Reyataz

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Reyataz

Classes

Protease Inhibitors

Administration
Oral Administration

Administer with food to enhance absorption.

Oral Solid Formulations

Oral capsules
Capsules must be swallowed whole. Do not open the capsules.[28142]
 
Oral powder
Preferably, mix atazanavir powder with food such as applesauce or yogurt. The powder may also be mixed with a beverage (milk, infant formula, or water) for infants old enough to drink from a cup. For young infants (younger than 6 months) who cannot eat solid food or drink from a cup, atazanavir powder should be mixed with infant formula and given using an oral dosing syringe.
Mixing with food: Using a spoon, mix the appropriate number of oral powder packets into a minimum of 1 tablespoon of food. Feed the mixture to the child, and then add an additional tablespoon of food to the container, mix, and feed the child the residual mixture.
Mixing with a beverage: Using a spoon, mix the appropriate number of oral powder packets with a minimum of 30 mL of the beverage in a small drinking cup. Have the child drink the mixture. Add 15 mL more of beverage to the drinking cup, mix, and have the child drink the residual mixture. If water is used, food should also be given at the same time.
Mixing with liquid infant formula using an oral dosing syringe: Using a spoon, mix the appropriate number of oral powder packets with 10 mL of prepared liquid infant formula in a small medicine cup. Draw up the full amount of the mixture into an oral syringe and administer into either the right or left inner cheek of the infant. Pour an additional 10 mL of formula into the cup and rinse off the remaining oral powder in a cup. Draw up the residual mixture and administer it to the infant.
Administer ritonavir immediately after atazanavir powder administration.
Storage: Administer the entire mixture (mixed in food or beverage) within 1 hour of preparation; mixture may be left at a temperature of 20 to 30 degrees C (68 to 86 degrees F) during the 1 hour. Ensure that the patient consumes all of the food or beverage that contains the powder.[28142]

Adverse Reactions
Severe

AV block / Early / 0-5.9
cholecystitis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
interstitial nephritis / Delayed / Incidence not known
diabetic ketoacidosis / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known

Moderate

hyperbilirubinemia / Delayed / 16.0-58.0
hyperamylasemia / Delayed / 14.0-33.0
lipodystrophy / Delayed / 5.0-30.0
hypercholesterolemia / Delayed / 6.0-25.0
jaundice / Delayed / 5.0-15.0
elevated hepatic enzymes / Delayed / 2.0-9.0
neutropenia / Delayed / 3.0-9.0
hypertriglyceridemia / Delayed / 4.0-8.0
anemia / Delayed / 0-5.0
hyperglycemia / Delayed / 5.0-5.0
thrombocytopenia / Delayed / 2.0-2.0
depression / Delayed / 2.0-2.0
cholestasis / Delayed / Incidence not known
cholelithiasis / Delayed / Incidence not known
bundle-branch block / Early / Incidence not known
QT prolongation / Rapid / Incidence not known
PR prolongation / Rapid / Incidence not known
edema / Delayed / Incidence not known
nephrolithiasis / Delayed / Incidence not known
diabetes mellitus / Delayed / Incidence not known
bleeding / Early / Incidence not known
hematoma / Early / Incidence not known

Mild

cough / Delayed / 21.0-21.0
rash / Early / 14.0-20.0
fever / Early / 2.0-18.0
nausea / Early / 3.0-14.0
vomiting / Early / 3.0-12.0
diarrhea / Early / 1.0-9.0
headache / Early / 1.0-8.0
rhinorrhea / Early / 6.0-6.0
abdominal pain / Early / 4.0-4.0
myalgia / Early / 4.0-4.0
insomnia / Early / 0-3.0
dizziness / Early / 0-2.0
gynecomastia / Delayed / Incidence not known
breast enlargement / Delayed / Incidence not known
Cushingoid features / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
maculopapular rash / Early / Incidence not known
arthralgia / Delayed / Incidence not known

Common Brand Names

Reyataz

Dea Class

Rx

Description

Protease inhibitor
Used for the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents
Advantages include a unique resistance profile and fewer lipid abnormalities compared to other PIs

Dosage And Indications
For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents.
NOTE: When transitioning between formulations, a change in dose may be necessary. Consult dosing for each specific formulation prior to prescribing.
For the treatment of HIV in protease inhibitor-experienced patients. Oral dosage (oral capsules) Adults

300 mg PO with ritonavir 100 mg PO once daily. Increase dose to 400 mg PO with ritonavir 100 mg PO once daily if administered concomitantly with both an H2-blocker and tenofovir. Do not exceed an H2-blocker dose equivalent to famotidine 20 mg twice daily, and give the H2 blocker dose simultaneously with and/or at least 10 hours after the atazanavir dose. Do not co-administer with proton pump inhibitors or efavirenz.

Pregnant Females in the second or third trimester

300 mg PO with ritonavir 100 mg PO once daily per product labeling. HIV guidelines suggest giving 400 mg with ritonavir 100 mg PO once daily in all pregnant patients during the second/third trimesters. The manufacturer states to increase the dose only with concomitant use of an H2-blocker or tenofovir. Do not exceed an H2-blocker dose equivalent to famotidine 20 mg twice daily, and give the H2-blocker dose simultaneously with and/or at least 10 hours after the atazanavir dose. Data are insufficient to recommend concurrent use of atazanavir with both an H2-blocker and tenofovir in treatment-experienced pregnant women.

Children and Adolescents 6 to 17 years weighing 35 kg or more

300 mg PO with ritonavir 100 mg PO every 24 hours. Although specific dosage adjustments for pediatric patients are not specified in the product labeling, the manufacturer makes the general recommendation to increase the dose to 400 mg PO with ritonavir 100 mg PO once daily if administered concomitantly with both an H2-blocker and tenofovir in adult patients. Do not exceed an H2-blocker dose equivalent to famotidine 20 mg twice daily, and give the H2 blocker dose simultaneously with and/or at least 10 hours after the atazanavir dose. Do not co-administer with proton pump inhibitors or efavirenz.

Children and Adolescents 6 to 17 years weighing 15 to 34 kg

200 mg PO with ritonavir 100 mg PO every 24 hours. The product labeling does not provide dosing recommendations for pediatric patients who are receiving concomitant efavirenz, tenofovir, H2-blockers, or proton pump inhibitors or in patients not receiving ritonavir for boosting.

Oral dosage (oral powder) Adults

300 mg PO with ritonavir 100 mg PO every 24 hours. Increase dose to 400 mg PO with ritonavir 100 mg PO once daily if administered concomitantly with both an H2-blocker and tenofovir. Do not exceed an H2-blocker dose equivalent to famotidine 20 mg twice daily, and give the H2 blocker dose simultaneously with and/or at least 10 hours after the atazanavir dose. Do not co-administer with proton pump inhibitors or efavirenz.

Children and Adolescents weighing 25 kg or more

300 mg PO with ritonavir 100 mg PO every 24 hours. Although specific dosage adjustments for pediatric patients are not specified in the product labeling, the manufacturer makes the general recommendation to increase the dose to 400 mg PO plus ritonavir 100 mg PO once daily when combined with both an H2-blocker and tenofovir in adult patients.[28142] Do not exceed an H2-blocker dose equivalent to famotidine 20 mg twice daily, and give the H2 blocker dose simultaneously with and/or at least 10 hours after the atazanavir dose. Do not co-administer with proton pump inhibitors or efavirenz.[28142] [42452]

Children weighing 15 to 24 kg

250 mg PO with ritonavir 80 mg PO every 24 hours. The product labeling does not provide dosing recommendations for pediatric patients who are receiving concomitant tenofovir or H2-blockers.

Infants and Children 3 months and older weighing 5 to 14 kg

200 mg PO with ritonavir 80 mg PO every 24 hours. The product labeling does not provide dosing recommendations for pediatric patients who are receiving concomitant tenofovir or H2-blockers.

For the treatment of HIV in anti-retroviral treatment-naive patients. Oral dosage (oral capsules) Adults

300 mg PO with ritonavir 100 mg PO once daily; alternatively 400 mg PO once daily for patients unable to tolerate ritonavir. Increase the dose to 400 mg PO plus ritonavir 100 mg PO once daily when combined with efavirenz. No dosage adjustment is needed with concomitant H2-blockers or proton pump inhibitors (PPIs); however, ritonavir must be administered with concomitant PPIs. Atazanavir/ritonavir should be given simultaneously with and/or at least 10 hours after the H2-blocker dose. Alternatively, in patients unable to tolerate ritonavir, administer atazanavir alone at least 2 hours before or 10 hours after the H2-blocker dose. In patients receiving ritonavir, do not exceed an H2-blocker dose equivalent to famotidine 40 mg twice daily; in patients NOT receiving ritonavir, do not exceed a single dose of an H2-blocker equivalent to famotidine 20 mg or a total daily dose of an H2-blocker equivalent to famotidine 40 mg. Administer the PPI dose approximately 12 hours prior to the atazanavir dose. Do not exceed a PPI dose equivalent to omeprazole 20 mg daily.

Pregnant Females in the second or third trimester

300 mg PO with ritonavir 100 mg PO once daily per product labeling. Do not administer atazanavir without ritonavir in pregnant women or during the postpartum period. HIV guidelines suggest giving 400 mg with ritonavir 100 mg PO once daily during the second/third trimesters.

Adolescents weighing 40 kg or more

300 mg PO every 24 hours with ritonavir 100 mg PO every 24 hours. In treatment-naive patients who cannot tolerate ritonavir, the FDA-approved labeling recommends 400 mg PO every 24 hours (without ritonavir); however, guidelines do NOT recommend unboosted atazanavir, as higher doses of atazanavir may be needed in adolescents to achieve target drug concentrations.[28142] [42452] In a pharmacokinetic study, 620 mg/m2 PO every 24 hours administered without ritonavir achieved protocol-defined pharmacokinetic targets in a cohort of 21 adolescents (median age = 14.6 years, IQR = 2.9).[54408] Although specific dosage adjustments for pediatric patients are not specified in the product labeling, the manufacturer makes the general recommendation to increase the dose to 400 mg PO plus ritonavir 100 mg PO once daily when combined with efavirenz in adult patients. No dosage adjustment is needed with concomitant H2-blockers or proton pump inhibitors (PPIs). Atazanavir/ritonavir should be given simultaneously with or at least 10 hours after the H2-blocker dose; do not exceed an H2-blocker dose equivalent to famotidine 40 mg twice daily. Administer the PPI dose approximately 12 hours prior to the atazanavir dose. Do not exceed a PPI dose equivalent to omeprazole 20 mg daily.[28142]

Adolescents weighing 35 to 39 kg

300 mg PO with ritonavir 100 mg PO every 24 hours. Although specific dosage adjustments for pediatric patients are not specified in the product labeling, the manufacturer makes the general recommendation to increase the dose to 400 mg PO plus ritonavir 100 mg PO once daily when combined with efavirenz in adult patients. No dosage adjustment is needed with concomitant H2-blockers or proton pump inhibitors (PPIs). Atazanavir/ritonavir should be given simultaneously with or at least 10 hours after the H2-blocker dose; do not exceed an H2-blocker dose equivalent to famotidine 40 mg twice daily. Administer the PPI dose approximately 12 hours prior to the atazanavir dose. Do not exceed a PPI dose equivalent to omeprazole 20 mg daily.

Adolescents weighing less than 35 kg

200 mg PO with ritonavir 100 mg PO every 24 hours. The product labeling does not provide dosing recommendations for pediatric patients who are receiving concomitant efavirenz, H2-blockers, or proton pump inhibitors or in patients not receiving ritonavir for boosting.

Children 6 to 12 years weighing 35 kg or more

300 mg PO with ritonavir 100 mg PO every 24 hours. Although specific dosage adjustments for pediatric patients are not specified in the product labeling, the manufacturer makes the general recommendation to increase the dose to 400 mg PO plus ritonavir 100 mg PO once daily when combined with efavirenz in adult patients. No dosage adjustment is needed with concomitant H2-blockers or proton pump inhibitors (PPIs). Atazanavir/ritonavir should be given simultaneously with or at least 10 hours after the H2-blocker dose; do not exceed an H2-blocker dose equivalent to famotidine 40 mg twice daily. Administer the PPI dose approximately 12 hours prior to the atazanavir dose. Do not exceed a PPI dose equivalent to omeprazole 20 mg daily.

Children 6 to 12 years weighing 15 to 34 kg

200 mg PO with ritonavir 100 mg PO every 24 hours.The product labeling does not provide dosing recommendations for pediatric patients who are receiving concomitant efavirenz, H2-blockers, or proton pump inhibitors or in patients not receiving ritonavir for boosting.

Oral dosage (oral powder) Adults

300 mg PO with ritonavir 100 mg PO every 24 hours. Increase the dose to 400 mg PO plus ritonavir 100 mg PO once daily when combined with efavirenz. No dosage adjustment is needed with concomitant H2-blockers or proton pump inhibitors. Atazanavir/ritonavir should be given simultaneously with or at least 10 hours after the H2-blocker dose; do not exceed an H2-blocker dose equivalent to famotidine 40 mg twice daily. Administer the PPI dose approximately 12 hours prior to the atazanavir dose. Do not exceed a PPI dose equivalent to omeprazole 20 mg daily.

Children and Adolescents weighing 25 kg or more

300 mg PO with ritonavir 100 mg PO every 24 hours. Although specific dosage adjustments for pediatric patients are not specified in the product labeling, the manufacturer makes the general recommendation to increase the dose to 400 mg PO plus ritonavir 100 mg PO once daily when combined with efavirenz in adult patients. No dosage adjustment is needed with concomitant H2-blockers or proton pump inhibitors (PPIs). Atazanavir/ritonavir should be given simultaneously with or at least 10 hours after the H2-blocker dose; do not exceed an H2-blocker dose equivalent to famotidine 40 mg twice daily. Administer the PPI dose approximately 12 hours prior to the atazanavir dose. Do not exceed a PPI dose equivalent to omeprazole 20 mg daily.

Children weighing 15 to 24 kg

250 mg PO with ritonavir 80 mg PO every 24 hours. The product labeling does not provide dosing recommendations for pediatric patients who are receiving concomitant efavirenz, H2-receptor blockers, or proton pump inhibitors or in patients not receiving ritonavir for boosting.

Infants and Children 3 months and older weighing 10 to 14 kg

200 mg PO with ritonavir 80 mg PO every 24 hours. The product labeling does not provide dosing recommendations for pediatric patients who are receiving concomitant efavirenz, H2-receptor blockers, or proton pump inhibitors or in patients not receiving ritonavir for boosting.

Infants and Children 3 months and older weighing 5 to 9 kg

200 mg PO with ritonavir 80 mg PO every 24 hours. For patients unable to tolerate 200 mg, the dose may be reduced to 150 mg PO every 24 hours; however, HIV viral load must be closely monitored. The product labeling does not provide dosing recommendations for pediatric patients who are receiving concomitant efavirenz, tenofovir, H2-receptor blockers, or proton pump inhibitors or in patients not receiving ritonavir for boosting.

For human immunodeficiency virus (HIV) prophylaxis† after occupational exposure. Oral dosage Adults

The World Health Organization (WHO) recommends atazanavir 300 mg PO once daily boosted with ritonavir 100 mg PO once daily in combination with tenofovir and either emtricitabine or lamivudine as preferred HIV post-exposure prophylaxis (PEP) regimens. The US Public Health Service guidelines and the New York State Department of Health AIDS Institute (NYSDOH AI) recommend atazanavir/ritonavir with either tenofovir or zidovudine and either emtricitabine or lamivudine as alternative PEP regimens. According to PEP guidelines, individuals potentially exposed to HIV should receive a 3-drug regimen for a total of 28 days; however if tolerability is a concern, use of a 2-drug regimen may be considered and is preferred to prophylaxis discontinuation. Begin prophylaxis as soon as possible, ideally within 2 hours of exposure. If initiation of prophylaxis is delayed (beyond 36 hours or 72 hours after exposure), efficacy of the antiretroviral regimen may be diminished and treatment should be determined on a case-by-case basis. Exposures for which PEP is indicated include: skin puncture by a sharp object that has been contaminated with blood, body fluid, or other infectious material; bite from a patient with visible bleeding in the mouth which causes bleeding by the exposed worker; splash of blood, body fluid, or other infectious material onto the workers mouth, nose, or eyes; exposure of blood, body fluid, or other infectious material on a workers non-intact skin (i.e., open wound, chapped skin, abrasion, dermatitis).

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

A reduced dosage of atazanavir without ritonavir may be needed for patients with hepatic impairment. Atazanavir should not be used in patients with severe hepatic dysfunction (Child-Pugh Class C). A reduced dosage of 300 mg PO once daily should be considered for patients with moderate hepatic insufficiency (Child-Pugh Class B). Ritonavir boosting is not recommended in patients with hepatic impairment.

Renal Impairment

No dosage adjustments are required for patients with any degree of renal impairment who are NOT managed with hemodialysis.
 
Intermittent hemodialysis
Treatment-naive adult patients with end stage renal disease that is managed with hemodialysis should receive an atazanavir dose of 300 mg with ritonavir 100 mg. Treatment-experienced patients with end stage renal disease that is managed with hemodialysis should not receive atazanavir. Pediatric patients are not specifically addressed.

Drug Interactions

Abacavir; Dolutegravir; Lamivudine: (Moderate) Caution is warranted when atazanavir is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and uridine glucuronyltransferase (UGT). Atazanavir is an inhibitor of CYP3A4 and UGT1A1.
Abemaciclib: (Major) If coadministration with atazanavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If atazanavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of atazanavir. Abemaciclib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and atazanavir; significantly increased acalabrutinib exposure may occur. Acalabrutinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In healthy subjects, the Cmax and AUC values of acalabrutinib were increased by 3.9-fold and 5.1-fold, respectively, when acalabrutinib was coadministered with another strong inhibitor for 5 days.
Acarbose: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with atazanavir may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Atazanavir is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like atazanavir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If atazanavir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. If atazanavir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like atazanavir can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If atazanavir is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Adagrasib: (Moderate) Monitor for an increase in adagrasib-related adverse effects during concomitant use of atazanavir. Avoid concomitant use during adagrasib therapy initiation (approximately 8 days); concomitant use before steady state is achieved may increase adagrasib exposure and the risk for adagrasib-related adverse reactions. Adagrasib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use of a single 200 mg dose of adagrasib with another strong CYP3A inhibitor increased adagrasib exposure by approximately 4-fold, however, no clinically significant differences in pharmacokinetics are predicted at steady state.
Adefovir: (Major) Patients who are concurrently taking adefovir with antiretrovirals like the protease inhibitors, are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Ado-Trastuzumab emtansine: (Major) Avoid coadministration of atazanavir with ado-trastuzumab emtansine if possible due to the risk of elevated exposure to the cytotoxic component of ado-trastuzumab emtansine, DM1. Delay ado-trastuzumab emtansine treatment until atazanavir has cleared from the circulation (approximately 3 half-lives of atazanavir) when possible. If concomitant use is unavoidable, closely monitor patients for ado-trastuzumab emtansine-related adverse reactions. The cytotoxic component of ado-trastuzumab emtansine, DM1, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5; atazanavir is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted.
Albuterol; Budesonide: (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Aldesleukin, IL-2: (Moderate) Caution is warranted when atazanavir is administered with aldesleukin, IL-2 as there is a potential for elevated concentrations of atazanavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; atazanavir is a substrate of CYP3A4.
Alfentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If the protease inhibitor is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like protease inhibitors can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If the protease inhibitor is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Alfuzosin: (Contraindicated) Concurrent use of alfuzosin and protease inhibitors is contraindicated due to increased alfuzosin exposure. Alfuzosin is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. When coadministered with another strong CYP3A inhibitor, the AUC of alfuzosin was increased by 2.5-fold to 3.2-fold.
Aliskiren: (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor. Aliskiren is a substrate of CYP3A4.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor. Aliskiren is a substrate of CYP3A4.
Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with atazanavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and atazanavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Alogliptin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Alogliptin; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Alogliptin; Pioglitazone: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Alosetron: (Major) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4, such as alosetron. Serious drug interactions may occur. If these drugs must be coadministered, monitor patient response and adjust the dose of alosetron if necessary.
Alpha-glucosidase Inhibitors: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors.
Alprazolam: (Contraindicated) Coadministration of atazanavir and alprazolam is contraindicated due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with atazanavir, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased alprazolam exposure by 2.7- to 3.98-fold.
Aluminum Hydroxide: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Aluminum Hydroxide; Magnesium Carbonate: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Aluminum Hydroxide; Magnesium Trisilicate: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Amiodarone: (Major) Therapeutic monitoring of amiodarone concentrations is recommended when administered concurrently with atazanavir. If atazanavir is boosted with ritonavir, concurrent use of amiodarone is contraindicated. Use of all 3 drugs together may significantly increase amiodarone concentrations and increase the risk for serious or life-threatening cardiac arrhythmias. Atazanavir and ritonavir are CYP3A4 inhibitors; amiodarone is metabolized by this enzyme.
Amitriptyline: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Atorvastatin: (Major) Use caution and the lowest atorvastatin dose necessary if atorvastatin must be coadministered with atazanavir. When atazanavir is boosted with cobicistat, use of atorvastatin is not recommended. The risk of developing myopathy or rhabdomyolysis increases when these drugs are used together. Monitor patients for any signs or symptoms of muscle pain, weakness, or tenderness especially in the initial months of therapy and any time the dosage of either drug is titrated upward. The serious risk of myopathy or rhabdomyolysis should be weighed carefully against the benefits of combined statin and atazanavir therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. Increased atorvastatin serum concentrations may occur due to atazanavir inhibition of CYP3A4 metabolism. In addition, atorvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an OATP1B1 inhibitor. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Celecoxib: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Valsartan: (Moderate) Concurrent use of atazanavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of atazanavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amobarbital: (Major) Coadministration of amobarbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. If atazanavir and amobarbital are used together, the patient must be closely monitored for antiviral efficacy.
Amoxapine: (Moderate) Atazanavir competitively inhibits the enzymes CYP3A4, CYP1A2 and CYP2C9. Concentrations of drugs that are substrates of these enzymes, such as tricyclic antidepressants, may be increased with concomitant atazanavir use. Amoxapine is related to the tricyclic antidepressants, and until more data is available, similar caution is advised when using amoxapine with atazanavir.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Major) Coadministration with atazanavir increases clarithromycin serum concentrations. Use caution if these drugs are coadministered, as increased clarithromycin concentrations may cause QT prolongation; a 50% dosage reduction of clarithromycin is recommended. In addition, atazanavir significantly reduces the concentration of 14-OH clarithromycin, the active metabolite of clarithromycin; consider alternative agents for indications other than infections due to Mycobacterium avium complex (MAC).
Anagrelide: (Moderate) Anagrelide is partially metabolized by CYP1A2. Coadministration of anagrelide with drugs that inhibit CYP1A2, such as atazanavir, could theoretically decrease the elimination of anagrelide and increase the risk of side effects or toxicity. Monitor for increased adverse effects if anagrelide is coadministered with atazanavir.
Antacids: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Apalutamide: (Contraindicated) Atazanavir is contraindicated for use with apalutamide due to decreased plasma concentrations of atazanavir, which may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Apalutamide is a strong CYP3A4 inducer and atazanavir is a CYP3A4 substrate. When coadministered with another strong CYP3A4 inducer, the Cmax of atazanavir was reduced by 53%, the AUC by 72%, and the Cmin by 98%.
Apixaban: (Major) Apixaban is a substrate of CYP3A4 and CYP2C8; atazanavir is a CYP3A4 substrate/inhibitor and a minor inhibitor of CYP2C8. Coadministration of these drugs may increase apixaban plasma concentrations and risk of adverse events such as bleeding. Avoid concurrent administration if possible; if concurrent administration is required, monitor for signs of bleeding.
Aprepitant, Fosaprepitant: (Major) The manufacturer of aprepitant, fosaprepitant recommends avoiding concomitant use with atazanavir due to substantially increased exposure of aprepitant. Increased atazanavir exposure may also occur with multi-day regimens of oral aprepitant for several days after administration. Atazanavir is a strong CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of a single oral dose of aprepitant (125 mg) on day 5 of a 10-day ketoconazole regimen (strong CYP3A4 inhibitor) increased the aprepitant AUC approximately 5-fold, and increased the mean terminal half-life by approximately 3-fold. Atazanavir is also a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of atazanavir. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Major) Recommendations for managing aripiprazole and atazanavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; atazanavir is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and atazanavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; atazanavir is a strong CYP3A inhibitor.
Artemether; Lumefantrine: (Moderate) Atazanavir is a substrate/inhibitor and artemether is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased artemether concentrations. Concomitant use warrants caution due to the potential for increased side effects. (Moderate) Atazanavir is a substrate/inhibitor and lumefantrine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased lumefantrine concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation.
Asciminib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with atazanavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Asenapine: (Moderate) Caution is warranted when atazanavir is administered with asenapine as there is a potential for increased aspenapine concentrations. Asenapine is a substrate of CYP3A4. Atazanavir is an inhibitor of CYP3A4. In addition, asenapine is substrate for uridine glucoronyltransferase (UGT); atazanavir is a UGT1A1 inhibitor.
Aspirin, ASA; Butalbital; Caffeine: (Major) Coadministration of butalbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. If atazanavir and butalbital are used together, the patient must be closely monitored for antiviral efficacy.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Aspirin, ASA; Omeprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. If atazanavir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like atazanavir can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If atazanavir is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atogepant: (Major) Avoid use of atogepant and atazanavir when atogepant is used for chronic migraine. Limit the dose of atogepant to 10 mg PO once daily for episodic migraine if coadministered with atazanavir. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of CYP3A and OATP1B1/3; atazanavir is a strong CYP3A inhibitor and an OATP1B1 inhibitor. Coadministration with a strong CYP3A inhibitor resulted in a 5.5-fold increase in atogepant overall exposure and a 2.15-fold increase in atogepant peak concentration.
Atorvastatin: (Major) Use caution and the lowest atorvastatin dose necessary if atorvastatin must be coadministered with atazanavir. When atazanavir is boosted with cobicistat, use of atorvastatin is not recommended. The risk of developing myopathy or rhabdomyolysis increases when these drugs are used together. Monitor patients for any signs or symptoms of muscle pain, weakness, or tenderness especially in the initial months of therapy and any time the dosage of either drug is titrated upward. The serious risk of myopathy or rhabdomyolysis should be weighed carefully against the benefits of combined statin and atazanavir therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. Increased atorvastatin serum concentrations may occur due to atazanavir inhibition of CYP3A4 metabolism. In addition, atorvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an OATP1B1 inhibitor.
Atorvastatin; Ezetimibe: (Major) Use caution and the lowest atorvastatin dose necessary if atorvastatin must be coadministered with atazanavir. When atazanavir is boosted with cobicistat, use of atorvastatin is not recommended. The risk of developing myopathy or rhabdomyolysis increases when these drugs are used together. Monitor patients for any signs or symptoms of muscle pain, weakness, or tenderness especially in the initial months of therapy and any time the dosage of either drug is titrated upward. The serious risk of myopathy or rhabdomyolysis should be weighed carefully against the benefits of combined statin and atazanavir therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. Increased atorvastatin serum concentrations may occur due to atazanavir inhibition of CYP3A4 metabolism. In addition, atorvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an OATP1B1 inhibitor.
Atovaquone: (Major) Concurrent administration of atazanavir plus ritonavir with atovaquone; proguanil has shown to decrease the atovaquone AUC by 46% and the proguanil AUC by 41%. Consider alternative malaria prophylaxis.
Atovaquone; Proguanil: (Major) Concurrent administration of atazanavir plus ritonavir with atovaquone; proguanil has shown to decrease the atovaquone AUC by 46% and the proguanil AUC by 41%. Consider alternative malaria prophylaxis.
Avacopan: (Major) Reduce the dose of avacopan to 30 mg once daily if concomitant use of atazanavir is necessary. Concomitant use may increase avacopan exposure and risk for avacopan-related adverse effects. Avacopan is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased avacopan overall exposure 2.19-fold.
Avanafil: (Major) Concomitant use of avanafil and atazanavir is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; atazanavir is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; atazanavir would be expected to have similar effects.
Avapritinib: (Major) Avoid coadministration of avapritinib with atazanavir due to the risk of increased avapritinib-related adverse reactions. Avapritinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 600% at steady-state.
Axitinib: (Major) Avoid coadministration of axitinib with atazanavir due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately half; subsequent doses can be increased or decreased based on individual safety and tolerability. Resume the original dose of axitinib approximately 3 to 5 half-lives after atazanavir is discontinued. Axitinib is a CYP3A4/5 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4/5 inhibitor significantly increased the plasma exposure of axitinib in healthy volunteers.
Azelastine; Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as atazanavir, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, atazanavir may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions, such as QT prolongation and hepatotoxicity.
Belinostat: (Contraindicated) Avoid concomitant administration of belinostat with strong UGT1A1 inhibitors such as atazanavir, as belinostat is primarily metabolized by UGT1A1. Coadministration with strong UGT1A1 inhibitors may increase belinostat exposure and result in increased toxicities.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with atazanavir may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of atazanavir in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Atazanavir is a strong inhibitor of CYP3A4.
Beta-adrenergic blockers: (Moderate) Atazanavir can prolong the PR interval. Coadministration with other agents that prolong the PR interval, like beta blockers, may result in elevated risk of conduction disturbances and atrioventricular block.
Betamethasone: (Moderate) Monitor for corticosteroid-related adverse effects if coadministration is necessary. Consider using an alternative treatment to betametasone, such as a corticosteroid less affected by CYP3A4 (i.e., beclomethasone or prednisolone), particularly if long term use is indicated. Atazanavir is a strong CYP3A4 inhibitor and betamethasone is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Concomitant use of bictegravir and atazanavir may result in increased bictegravir plasma concentrations, which may increase the risk of adverse effects. Monitor for increased toxicity if these drugs are used together. Bictegravir is a substrate of CYP3A4 and UGT1A1; atazanavir is a strong inhibitor of CYP3A4 and an inhibitor of UGT1A1. (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Bortezomib: (Moderate) In vitro studies with human liver microsomes indicate that bortezomib is a significant substrate for CYP3A4. Agents that inhibit CYP3A4, such atazanavir, may increase the exposure to bortezomib and increase the risk for toxicity. The manufacturer warns that patients who are receiving bortezomib concurrently with potent CYP3A4 inhibitors should be closely monitored for potential toxicity. Additionally, atazanavir can cause peripheral neuropathy. It may be prudent to monitor patients for signs and symptoms of neuropathy.
Bosentan: (Major) Do not administer bosentan with anti-retroviral protease inhibitors that are not boosted with ritonavir as decreased protease inhibitor concentrations are expected. In addition, administration of anti-retroviral protease inhibitors with bosentan may increase bosentan serum concentrations due to the inhibition of the CYP3A4 isoenzyme. In patients who have been receiving protease inhibitor therapy for at least 10 days, initiate bosentan at the recommended initial dose once daily or every other day based on tolerability. For patients on bosentan who need protease inhibitor therapy, discontinue use of bosentan at least 36 hours prior to starting protease inhibitor therapy. After 10 days of the protease inhibitor therapy, bosentan may be restarted at the recommended initial dose once daily or every other day based on tolerability. Bosentan is a substrate for organic anion transport protein (OATP), CYP3A, and CYP2C9. In healthy subjects, initial and steady state trough plasma concentrations of bosentan were approximately 48-fold and 5-fold higher, respectively, after coadministration of bosentan 125 mg twice daily PO and lopinavir; ritonavir 400/100 mg twice daily PO compared to those measured after bosentan alone. This is most likely explained by inhibition by lopinavir of OATP-mediated uptake into hepatocytes; toxicity of bosentan is possible. Monitor for potential adverse effects of bosentan during coadministration with CYP2C9 or CYP3A4 inhibitors; excessive bosentan dosage may result in hypotension or elevated hepatic enzyme. Additionally, bosentan is a significant inducer of CYP3A4 and CYP2C9 hepatic enzymes. Theoretically, bosentan may increase the clearance of the protease inhibitors and potentially lead to a reduction of anti-retroviral efficacy. However, this interaction has not been studied.
Bosutinib: (Major) Avoid concomitant use of bosutinib and atazanavir; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and atazanavir is a moderate CYP3A4 inhibitor. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor.
Brentuximab vedotin: (Minor) Concomitant administration of brentuximab vedotin and atazanavir may increase the exposure of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin. The manufacturer suggests that potent CYP3A4 inhibitors, such as atazanavir, may alter MMAE exposure as MMAE is a CYP3A4 substrate. Monitor patients for adverse reactions.
Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as atazanavir. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Because brexpiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a moderate to strong CYP3A4 inhibitor and moderate to strong CYP2D6 inhibitor should have their brexpiprazole dose reduced to one-quarter (25%) of the usual dose. If the co-administered CYP inhibitor is discontinued, adjust the brexpiprazole dose to its original level.
Brigatinib: (Major) Avoid coadministration of brigatinib with atazanavir if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 50% without breaking tablets (i.e., from 180 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of atazanavir, resume the brigatinib dose that was tolerated prior to initiation of atazanavir. Brigatinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively.
Brincidofovir: (Moderate) Postpone the administration of atazanavir for at least three hours after brincidofovir administration and increase monitoring for brincidofovir-related adverse reactions (i.e., elevated hepatic enzymes and bilirubin, diarrhea, other gastrointestinal adverse events) if concomitant use of brincidofovir and atazanavir is necessary. Brincidofovir is an OATP1B1 substrate and atazanavir is an OATP1B1 inhibitor. In a drug interaction study, the mean AUC and Cmax of brincidofovir increased by 374% and 269%, respectively, when administered with another OATP1B1 inhibitor.
Bromocriptine: (Major) When bromocriptine is used for diabetes, avoid coadministration with atazanavir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; atazanavir is a strong inhibitor of CYP3A4.
Budesonide: (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Budesonide; Formoterol: (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Bupivacaine Liposomal: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects.
Bupivacaine: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects.
Bupivacaine; Epinephrine: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects.
Bupivacaine; Lidocaine: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity. (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects.
Bupivacaine; Meloxicam: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects. (Moderate) The plasma concentrations of meloxicam may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while meloxicam is a CYP3A4 substrate.
Buprenorphine: (Major) Atazanavir-induced inhibition of CYP3A4 may increase the AUCs of buprenorphine by 93% and norbuprenorphine 76%. When buprenorphine is coadministered with atazanavir/ritonavir the AUCs of buprenophine and norbuprenorphine are increased by 66% and 105%, respectively. Serious drug interactions have been reported following administration of sublingual buprenorphine with atazanavir and atazanavir/ritonavir; although not clinically studied, atazanavir-induced inhibition of UGT1A1 may increase the potential for interaction with orally administered buprenorphine. If atazanavir plus ritonavir must be coadministered with buprenorphine, monitor patient response, including sedation and cognitive effects, and adjust the dose of buprenorphine if necessary. Buprenorphine administered with atazanavir plus ritonavir is not expected to decrease atazanavir concentrations; however, if buprenorphine is administered with atazanavir in the absence of ritonavir, atazanavir concentrations may be decreased. Do not administer atazanavir with buprenorphine with unboosted atazanavir.
Buprenorphine; Naloxone: (Major) Atazanavir-induced inhibition of CYP3A4 may increase the AUCs of buprenorphine by 93% and norbuprenorphine 76%. When buprenorphine is coadministered with atazanavir/ritonavir the AUCs of buprenophine and norbuprenorphine are increased by 66% and 105%, respectively. Serious drug interactions have been reported following administration of sublingual buprenorphine with atazanavir and atazanavir/ritonavir; although not clinically studied, atazanavir-induced inhibition of UGT1A1 may increase the potential for interaction with orally administered buprenorphine. If atazanavir plus ritonavir must be coadministered with buprenorphine, monitor patient response, including sedation and cognitive effects, and adjust the dose of buprenorphine if necessary. Buprenorphine administered with atazanavir plus ritonavir is not expected to decrease atazanavir concentrations; however, if buprenorphine is administered with atazanavir in the absence of ritonavir, atazanavir concentrations may be decreased. Do not administer atazanavir with buprenorphine with unboosted atazanavir.
Buspirone: (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like atazanavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
Butalbital; Acetaminophen: (Major) Coadministration of butalbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. If atazanavir and butalbital are used together, the patient must be closely monitored for antiviral efficacy.
Butalbital; Acetaminophen; Caffeine: (Major) Coadministration of butalbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. If atazanavir and butalbital are used together, the patient must be closely monitored for antiviral efficacy.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Coadministration of butalbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. If atazanavir and butalbital are used together, the patient must be closely monitored for antiviral efficacy. (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Coadministration of butalbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. If atazanavir and butalbital are used together, the patient must be closely monitored for antiviral efficacy. (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with atazanavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and atazanavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Cabotegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering atazanavir with rilpivirine due to an increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Atazanavir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Cabozantinib: (Major) Avoid concomitant use of cabozantinib and atazanavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with atazanavir 2 to 3 days after discontinuation of atazanavir. Cabozantinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Calcifediol: (Moderate) Dose adjustment of calcifediol may be necessary during coadministration with atazanavir. Additionally, serum 25-hydroxyvitamin D, intact PTH, and calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with atazanavir. Atazanavir, which is a cytochrome P450 inhibitor, may inhibit enzymes involve

d in vitamin D metabolism (CYP24A1 and CYP27B1) and may alter serum concentrations of calcifediol.
Calcium Carbonate: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid. (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Calcium Carbonate; Magnesium Hydroxide: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Calcium Carbonate; Simethicone: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Calcium; Vitamin D: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Canagliflozin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Canagliflozin; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Capmatinib: (Moderate) Monitor for an increase in capmatinib-related adverse reactions if coadministration with atazanavir is necessary. Capmatinib is a CYP3A substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%.
Carbamazepine: (Major) Coadministration of carbamazepine and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. Avoid coadministration of atazanavir with carbamazepine unless atazanavir is boosted with ritonavir. In addition, coadministration of atazanavir and ritonavir with carbamazepine may result in increased carbamazepine concentrations. If atazanavir and carbamazepine are used together, the patient must be closely monitored for antiviral efficacy and carbamazepine toxicity; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When a strong CYP3A4 inhibitor, such as atazanavir, is initiated in a patient who is on a stable dose of cariprazine, reduce the cariprazine dosage by half. For adult patients taking cariprazine 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For adult patients taking cariprazine 1.5 mg daily, the dosing frequency should be adjusted to every other day. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased. When initiating cariprazine in an adult patient who is stable on a strong CYP3A4 inhibitor, the patient should be administered 1.5 mg of cariprazine on Day 1 and on Day 3 with no dose administered on Day 2. From Day 4 onward, the dose should be administered at 1.5 mg daily, then increased to a maximum dose of 3 mg daily. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased.
Ceritinib: (Major) Avoid concomitant use of ceritinib with atazanavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After atazanavir is discontinued, resume the dose of ceritinib taken prior to initiating atazanavir. Ceritinib is a CYP3A substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Chloramphenicol: (Moderate) Caution is warranted when atazanavir is administered with chloramphenicol as there is a potential for elevated concentrations of atazanavir. Chloramphenicol is a CYP3A4 inhibitor; atazanavir is a substrate of CYP3A4.
Chlordiazepoxide: (Major) CYP3A4 inhibitors, such as protease inhibitors, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity. A decrease in the chlordiazepoxide dose may be needed.
Chlordiazepoxide; Amitriptyline: (Major) CYP3A4 inhibitors, such as protease inhibitors, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity. A decrease in the chlordiazepoxide dose may be needed. (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Chlordiazepoxide; Clidinium: (Major) CYP3A4 inhibitors, such as protease inhibitors, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity. A decrease in the chlordiazepoxide dose may be needed.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with atazanavir may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Atazanavir is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like atazanavir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If atazanavir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Ciclesonide: (Moderate) Coadministration of ciclesonide with atazanavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Cidofovir: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis.
Cilostazol: (Major) Reduce the dose of cilostazol to 50 mg twice daily when coadministered with protease inhibitors and monitor for an increase in cilostazol-related adverse reactions. Concurrent use may increase cilostazol exposure. Cilostazol is a CYP3A substrate; protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a strong CYP3A inhibitor increased the cilostazol AUC by 117%. Coadministration with a moderate CYP3A inhibitor increased the AUC of cilostazol (single dose) by 73%; the AUC of 4-trans-hydroxycilostazol increased by 141%.
Cimetidine: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Cinacalcet: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of atazanavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Cisapride: (Contraindicated) Concomitant use of protease inhibitors and cisapride is contraindicated; use increases cisapride exposure and the risk for cisapride-related adverse effects such as QT/QTc prolongation and torsade de pointes (TdP). Cisapride is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Concomitant use of cisapride with CYP3A inhibitors also is disallowed under the Propulsid Limited Access Program.
Clarithromycin: (Major) Coadministration with atazanavir increases clarithromycin serum concentrations. Use caution if these drugs are coadministered, as increased clarithromycin concentrations may cause QT prolongation; a 50% dosage reduction of clarithromycin is recommended. In addition, atazanavir significantly reduces the concentration of 14-OH clarithromycin, the active metabolite of clarithromycin; consider alternative agents for indications other than infections due to Mycobacterium avium complex (MAC).
Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of atazanavir as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4.
Clobazam: (Major) Coadministration of atazanavir with clobazam is not recommended. There is a potential for elevated clobazam concentrations and altered atazanavir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Clobazam is a substrate of CYP3A4. Clobazam is also a weak inducer of CYP3A4. The active metabolite of clobazam, N-desmethylclobazam, is a dose-dependent inducer of CYP3A4. Atazanavir is an inhibitor/substrate of CYP3A4.
Clomipramine: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Clonazepam: (Moderate) Monitor for increased sedation and respiratory depression if clonazepam is coadministered with protease inhibitors; adjust the dose of clonazepam if necessary. The systemic exposure of clonazepam may be increased resulting in an increase in treatment-related adverse reactions. Clonazepam is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors.
Clorazepate: (Major) CYP3A4 inhibitors, such as protease inhibitors, may reduce the metabolism of N-desmethyldiazepam, the active metabolite of clorazepate, and increase the potential for benzodiazepine toxicity. Monitor patients closely who receive concurrent therapy.
Clozapine: (Moderate) Caution is advisable during concurrent use of atazanavir and clozapine. Atazanavir is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of clozapine. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with a CYP3A4 inhibitor should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with atazanavir due to the risk of cobimetinib toxicity. Cobimetinib is a CYP3A substrate in vitro, and atazanavir is a strong inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), another strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Cocaine: (Moderate) Caution is warranted when atazanavir is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4.
Codeine: (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with atazanavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of atazanavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If atazanavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Atazanavir is a strong inhibitor of CYP3A4.
Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and atazanavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Atazanavir can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken atazanavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
Conivaptan: (Contraindicated) Coadministration of conivaptan and atazanavir is contraindicated due to the potential for increased conivaptan exposure. Conivaptan is a sensitive CYP3A substrate; atazanavir is a strong CYP3A inhibitor. In a drug interaction study, coadministration of a strong CYP3A inhibitor increased the exposure of oral conivaptan by 11-fold.
Conjugated Estrogens: (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Conjugated Estrogens; Bazedoxifene: (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Conjugated Estrogens; Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with atazanavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Copanlisib: (Major) Avoid the concomitant use of copanlisib and atazanavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; atazanavir is a strong CYP3A inhibitor.
Crizotinib: (Major) Avoid concomitant use of atazanavir and crizotinib due to increased plasma concentrations of crizotinib, which may increase the incidence and severity of adverse reactions. If concomitant use is necessary for adults with non-small cell lung cancer (NSCLC) or inflammatory myofibroblastic tumor (IMT), reduce the dose of crizotinib to 250 mg PO once daily. If concomitant use is necessary for young adult or pediatric patients with anaplastic large cell lymphoma or pediatric patients with IMT, reduce the dose of crizotinib to 250 mg PO twice daily for BSA of 1.7 m2 or more; 200 mg PO twice daily for BSA of 1.17 to 1.69 m2; and 250 mg PO once daily for BSA of 0.81 to 1.16 m2; do not use this combination in patients with a BSA of 0.6 to 0.8 m2. Resume the original crizotinib dose after discontinuation of atazanavir. Crizotinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with one strong CYP3A inhibitor increased the AUC of single-dose crizotinib by 216%. Concomitant use with another strong CYP3A inhibitor increased the steady-state AUC of crizotinib by 57% compared to crizotinib alone.
Cyclophosphamide: (Moderate) Monitor for an increase in cyclophosphamide-related adverse reactions if coadministration with protease inhibitors is necessary. Use of protease inhibitor-based regimens was found to be associated with a higher incidence of infections and neutropenia in patients receiving cyclophosphamide, doxorubicin, and etoposide (CDE) than the use of a Non-Nucleoside Reverse Transcriptase Inhibitor-based regimen. Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites.
Cyclosporine: (Moderate) An interaction is anticipated to occur with protease inhibitors and cyclosporine, as CYP3A4 is inhibited by protease inhibitors and cyclosporine is a CYP3A4 substrate. Closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate if coadministration with an anti-retroviral protease inhibitor is necessary. In a study of 18 HIV-infected patients who underwent renal or hepatic transplant and received concomitant therapy with protease inhibitors and cyclosporine, there was a 3-fold increase in cyclosporine AUC resulting in an 85% reduction in cyclosporine dose over a 2-year period. In another study, HIV-infected, liver and kidney transplant patients required 4- to 5-fold reductions in cyclosporine dose and approximate 50% increases in dosing interval when cyclosporine was coadministered with protease inhibitors. Consider a reduction in cyclosporine dose to 25 mg every 1 to 2 days when coadministered with a boosted protease inhibitor. Cyclosporine toxicity, consisting of fatigue, headache, and GI distress, has been reported by a patient receiving cyclosporine and saquinavir. After receiving saquinavir for 3 days, the cyclosporine trough concentration increased from 150 to 200 mcg/mL up to 580 mcg/mL. Dosages of both agents were decreased by 50% leading to resolution of symptoms.
Dabrafenib: (Major) Coadministration of atazanavir with dabrafenib is not recommended as there is a potential for elevated dabrafenib concentrations and decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Atazanavir is metabolized by CYP3A4; dabrafenib is a moderate CYP3A4 inducer. In addition, darbrafenib is a substrate for CYP2C8; atazanavir is a weak CYP2C8 inhibitor.
Daclatasvir: (Moderate) Monitor for daclatasvir-related adverse effects during concomitant use of atazanavir. When daclatasvir is used with ritonavir or cobicistat boosted atazanavir, reduce the daclatasvir dose to 30 mg once daily. Concomitant use may increase daclatasvir concentrations and the risk for daclatasvir-related adverse effects. Daclatasvir is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Danazol: (Moderate) Danazol is a CYP3A4 inhibitor, and serum concentrations of atazanavir, a CYP3A4 substrate, may increase with co-administration. Co-administer these drugs with caution due to the potential for atazanavir toxicity.
Dapagliflozin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Dapagliflozin; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Dapagliflozin; Saxagliptin: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as atazanavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Daridorexant: (Major) Avoid concomitant use of daridorexant and atazanavir. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased daridorexant overall exposure by over 400%.
Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg PO when administered with atazanavir due to increased darifenacin exposure. Darifenacin is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor.
Darunavir: (Contraindicated) Coadministration of atazanavir with darunavir; cobicistat is not recommended, as more than one antiretroviral would require pharmacokinetic enhancement (boosting). Pharmacokinetic data are not available to provide appropriate dosage recommendations, and use of these drugs together may lead to loss of antiretroviral efficacy and development of resistance.
Darunavir; Cobicistat: (Contraindicated) Coadministration of atazanavir with darunavir; cobicistat is not recommended, as more than one antiretroviral would require pharmacokinetic enhancement (boosting). Pharmacokinetic data are not available to provide appropriate dosage recommendations, and use of these drugs together may lead to loss of antiretroviral efficacy and development of resistance.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Coadministration of atazanavir with darunavir; cobicistat is not recommended, as more than one antiretroviral would require pharmacokinetic enhancement (boosting). Pharmacokinetic data are not available to provide appropriate dosage recommendations, and use of these drugs together may lead to loss of antiretroviral efficacy and development of resistance. (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Dasatinib: (Major) Avoid coadministration of dasatinib and atazanavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to atazanavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of atazanavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If atazanavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with atazanavir. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Delavirdine: (Moderate) Delavirdine and atazanavir are both substrates and inhibitors of CYP3A4. Coadministration may result in increased plasma concentrations of either drug. It is not clear if any dosage adjustments are needed.
Desipramine: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Desogestrel; Ethinyl Estradiol: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) Studies evaluating use of atazanavir with desogestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of desogestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Dexamethasone: (Moderate) Monitor for steroid-related adverse reactions and a decrease in atazanavir efficacy if concomitant use of dexamethasone and atazanavir is necessary. If long term coadministration is required, consider using an alternative corticosteroid, such as prednisone or prednisolone. Concomitant use may increase dexamethasone concentrations and decrease atazanavir exposure. Dexamethasone is a CYP3A substrate and CYP3A inducer; atazanavir is a CYP3A substrate and strong CYP3A inhibitor. Another strong CYP3A inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Dexlansoprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Dextromethorphan; Quinidine: (Major) Caution is advised when administering quinidine with atazanavir. If atazanavir is boosted with ritonavir, concurrent use of quinidine is contraindicated. Use of all 3 drugs together may significantly increase quinidine concentrations and increase the risk for QT prolongation and serious or life-threatening cardiac arrhythmias. Atazanavir and ritonavir are CYP3A4 inhibitors; quinidine is metabolized by this enzyme.
Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with protease inhibitors is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP3A4 substrate and protease inhibitors are moderate to strong CYP3A4 inhibitors.
Diclofenac: (Moderate) Caution is warranted when atazanavir is administered with diclofenac as there is a potential for elevated diclofenac concentrations. Diclofenac is a substrate of CYP3A4; atazanavir is an inhibitor of CYP3A4.
Diclofenac; Misoprostol: (Moderate) Caution is warranted when atazanavir is administered with diclofenac as there is a potential for elevated diclofenac concentrations. Diclofenac is a substrate of CYP3A4; atazanavir is an inhibitor of CYP3A4.
Didanosine, ddI: (Moderate) Separate the administration of atazanavir and didanosine, ddI by giving atazanavir 2 hours before or 1 hour after buffered didanosine. Atazanavir solubility decreases as gastric pH increases. Concomitant administration of atazanavir and buffered didanosine, ddI products resulted in a 4-fold decrease in the AUC of atazanavir. Didanosine chewable/dispersible buffered tablets contain calcium carbonate and magnesium hydroxide, and didanosine buffered powder for oral solution contains dibasic sodium phosphate, sodium citrate, and citric acid. No change in the AUC of enteric-coated didanosine occurred with concurrent use of atazanavir.
Dienogest; Estradiol valerate: (Major) Studies evaluating use of atazanavir with dienogest have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of dienogest. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Digoxin: (Moderate) Atazanavir can prolong the PR interval and pharmacodynamic interactions between atazanavir and drugs that also prolong the PR interval, such as digoxin, cannot be ruled out; caution is advised when these drugs are used together; monitor the patient for appropriate clinical responses.
Dihydroergotamine: (Contraindicated) Coadministration of ergot alkaloids with potent inhibitors of CYP3A4, like anti-retroviral protease inhibitors is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Several case reports have established the clinical significance of this interaction in the medical literature. In some cases, fatal interactions have occurred.
Diltiazem: (Major) Coadministration of atazanavir with diltiazem may result in increased plasma concentrations of either drug. Concurrent atazanavir use led to a 2-fold increase in the AUC of diltiazem. A 50% dose reduction of diltiazem should be considered and ECG monitoring is recommended when diltiazem is used with atazanavir. Additionally, atazanavir can prolong the PR interval, especially with high serum concentrations. Greater lengthening of the PR interval with the combined use of diltiazem and atazanavir as compared to either alone has been documented.
Diphenhydramine; Naproxen: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme.
Disopyramide: (Major) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of disopyramide and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur.
Disulfiram: (Moderate) The plasma concentrations of disulfiram may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while disulfiram is a CYP3A4 substrate.
Docetaxel: (Major) Avoid coadministration of docetaxel with atazanavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
Dofetilide: (Major) Coadministration of CYP3A4 inhibitors, such as atazanavir, with dofetilide may decrease the metabolism of dofetilide, thereby increasing the potential for QT prolongation. Dofetilide is a Class III antiarrhythmic agent that has a well-established risk of QT prolongation and torsade de pointes (TdP). Plasma dofetilide concentrations are correlated with the risk of drug-induced proarrhythmias.
Dolutegravir: (Moderate) Caution is warranted when atazanavir is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and uridine glucuronyltransferase (UGT). Atazanavir is an inhibitor of CYP3A4 and UGT1A1.
Dolutegravir; Lamivudine: (Moderate) Caution is warranted when atazanavir is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and uridine glucuronyltransferase (UGT). Atazanavir is an inhibitor of CYP3A4 and UGT1A1.
Dolutegravir; Rilpivirine: (Moderate) Caution is warranted when atazanavir is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and uridine glucuronyltransferase (UGT). Atazanavir is an inhibitor of CYP3A4 and UGT1A1. (Moderate) Close clinical monitoring is advised when administering atazanavir with rilpivirine due to an increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Atazanavir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Donepezil: (Moderate) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4, such as donepezil.
Donepezil; Memantine: (Moderate) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4, such as donepezil.
Doravirine: (Minor) Coadministration of doravirine and atazanavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; atazanavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. (Minor) Coadministration of doravirine and atazanavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; atazanavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doxazosin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with atazanavir. Atazanavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
Doxepin: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Doxercalciferol: (Moderate) Protease inhibitors may decrease efficacy of doxercalciferol. Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors, including protease inhibitors, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if these drugs are administered together.
Doxorubicin Liposomal: (Major) Atazanavir is a strong CYP3A4 inhibitor; doxorubicin is a major substrate of CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of atazanavir and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) Atazanavir is a strong CYP3A4 inhibitor; doxorubicin is a major substrate of CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of atazanavir and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronabinol: (Major) Use caution if coadministration of dronabinol with atazanavir is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dronedarone: (Moderate) Concomitant use of dronedarone with atazanavir may increase dronedarone concentrations. Coadministration with atazanavir; cobicistat is contraindicated. Dronedarone is metabolized by CYP3A. Atazanavir is an inhibitor CYP3A4. No data exist regarding the appropriate dose adjustment needed to allow safe administration of dronedarone with CYP3A4 inhibitors; therefore, use caution when coadministering dronedarone with CYP3A4 inhibitors such as atazanavir.
Droperidol: (Moderate) Droperidol is metabolized by CYP3A4 and with the potential to cause QT prolongation. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of droperidol and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and droperidol.
Drospirenone: (Contraindicated) Coadministration of drospirenone and atazanavir boosted with cobicistat is contraindicated. Taking these drugs concurrently increases drospirenone systemic concentrations, which may result in hyperkalemia.
Drospirenone; Estetrol: (Contraindicated) Coadministration of drospirenone and atazanavir boosted with cobicistat is contraindicated. Taking these drugs concurrently increases drospirenone systemic concentrations, which may result in hyperkalemia.
Drospirenone; Estradiol: (Contraindicated) Coadministration of drospirenone and atazanavir boosted with cobicistat is contraindicated. Taking these drugs concurrently increases drospirenone systemic concentrations, which may result in hyperkalemia. (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Drospirenone; Ethinyl Estradiol: (Contraindicated) Coadministration of drospirenone and atazanavir boosted with cobicistat is contraindicated. Taking these drugs concurrently increases drospirenone systemic concentrations, which may result in hyperkalemia. (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Contraindicated) Coadministration of drospirenone and atazanavir boosted with cobicistat is contraindicated. Taking these drugs concurrently increases drospirenone systemic concentrations, which may result in hyperkalemia. (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Dutasteride: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Dutasteride; Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Duvelisib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with atazanavir. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; atazanavir is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as atazanavir.
Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, more study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
Efavirenz: (Major) Due to induction of the CYP3A4 isoenzyme by efavirenz, coadministration results in significantly decreased atazanavir AUC and Cmin. Do not coadminister these drugs to treatment-experienced patients. Coadministration is acceptable in treatment-naive patients weighing at least40 kg as a regimen of atazanavir 400 mg with ritonavir 100 mg given once daily with food and efavirenz 600 mg given once daily on an empty stomach.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Due to induction of the CYP3A4 isoenzyme by efavirenz, coadministration results in significantly decreased atazanavir AUC and Cmin. Do not coadminister these drugs to treatment-experienced patients. Coadministration is acceptable in treatment-naive patients weighing at least40 kg as a regimen of atazanavir 400 mg with ritonavir 100 mg given once daily with food and efavirenz 600 mg given once daily on an empty stomach. (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Due to induction of the CYP3A4 isoenzyme by efavirenz, coadministration results in significantly decreased atazanavir AUC and Cmin. Do not coadminister these drugs to treatment-experienced patients. Coadministration is acceptable in treatment-naive patients weighing at least40 kg as a regimen of atazanavir 400 mg with ritonavir 100 mg given once daily with food and efavirenz 600 mg given once daily on an empty stomach. (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Elacestrant: (Major) Avoid concomitant use of elacestrant and atazanavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Elagolix: (Contraindicated) Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as atazanavir is contraindicated. Coadministration may increase elagolix plasma concentrations and decrease atazanavir concentrations. Elagolix is a substrate of CYP3A and OATP1B1, and a weak to moderate CYP3A4 inducer. Atazanavir is a strong inhibitor of CYP3A and a CYP3A4 substrate, and it inhibits OATP1B1. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as atazanavir is contraindicated. Coadministration may increase elagolix plasma concentrations and decrease atazanavir concentrations. Elagolix is a substrate of CYP3A and OATP1B1, and a weak to moderate CYP3A4 inducer. Atazanavir is a strong inhibitor of CYP3A and a CYP3A4 substrate, and it inhibits OATP1B1. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Elbasvir; Grazoprevir: (Contraindicated) Concurrent administration of elbasvir; grazoprevir with atazanavir is contraindicated. Use of these drugs together is expected to significantly increase the plasma concentrations of elbasvir and grazoprevir, and may result in adverse effects (i.e., elevated ALT concentrations). Atazanavir is an inhibitor of the hepatic enzyme CYP3A and the organic anion transporting protein (OATP). Elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a substrate of OATP1B1/3. (Contraindicated) Concurrent administration of elbasvir; grazoprevir with atazanavir is contraindicated. Use of these drugs together is expected to significantly increase the plasma concentrations of elbasvir and grazoprevir, and may result in adverse effects (i.e., elevated ALT concentrations). Atazanavir is an inhibitor of the hepatic enzyme CYP3A and the organic anion transporting protein (OATP1B1). Elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a substrate of OATP1B1/3.
Eletriptan: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
Elexacaftor; tezacaftor; ivacaftor: (Major) If atazanavir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to twice a week in the morning, approximately 3 to 4 days apart (i.e., Day 1 and Day 4) when coadministered with atazanavir; omit the evening dose of ivacaftor. Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; atazanavir is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased elexacaftor exposure by 2.8- fold, tezacaftor exposure by 4.5-fold, and ivacaftor exposure by 15.6-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with atazanavir; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor/ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); atazanavir is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Eliglustat: (Major) Coadministration of atazanavir and eliglustat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). Use of these agents together is also contraindicated in any patient also receiving a moderate or strong CYP2D6 inhibitor, such as ritonavir. In extensive CYP2D6 metabolizers (EMs), coadministration of eliglustat and atazanavir requires dosage adjustment of eliglustat to 84 mg PO once daily. Atazanavir is a strong CYP3A inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Use of these drugs together may result in increased plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is greatest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A.
Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering weak inhibitors of CYP2C8, such as atazanavir, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Eluxadoline: (Major) When administered concurrently with atazanavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); atazanavir is an OATP1B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of atazanavir boosted with ritonavir and elvitagravir results in significantly elevated plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is: elvitegravir 85 mg PO once daily with atazanavir/ritonavir 300/100 mg PO once daily. No data are available for use of other dosage. (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of atazanavir boosted with ritonavir and elvitagravir results in significantly elevated plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is: elvitegravir 85 mg PO once daily with atazanavir/ritonavir 300/100 mg PO once daily. No data are available for use of other dosage. (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Empagliflozin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Empagliflozin; Linagliptin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy, such as linagliptin, should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Empagliflozin; Linagliptin; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy, such as linagliptin, should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Empagliflozin; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring is advised when administering atazanavir with rilpivirine due to an increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Atazanavir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Close clinical monitoring is advised when administering atazanavir with rilpivirine due to an increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Atazanavir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Emtricitabine; Tenofovir alafenamide: (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Encorafenib: (Major) Avoid coadministration of encorafenib and atazanavir due to increased encorafenib exposure. If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of atazanavir. If atazanavir is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of atazanavir. Encorafenib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 3-fold and 68%, respectively.
Entrectinib: (Major) Avoid coadministration of entrectinib with atazanavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If atazanavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of atazanavir. Entrectinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Enzalutamide: (Contraindicated) Coadministration of atazanavir with strong inducers of CYP3A4, such as enzalutamide, is contraindicated. Taking these drugs together could decrease atazanavir concentrations, and may lead to a reduction in antiretroviral activity.
Eplerenone: (Contraindicated) Coadministration of atazanavir and eplerenone is contraindicated. Atazanavir potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and atazanavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If atazanavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
Ergoloid Mesylates: (Contraindicated) Coadministration of ergot alkaloids with potent inhibitors of CYP3A4, like anti-retroviral protease inhibitors is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Several case reports have established the clinical significance of this interaction in the medical literature. In some cases, fatal interactions have occurred.
Ergot alkaloids: (Contraindicated) Coadministration of ergot alkaloids with potent inhibitors of CYP3A4, like anti-retroviral protease inhibitors is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Several case reports have established the clinical significance of this interaction in the medical literature. In some cases, fatal interactions have occurred.
Ergotamine: (Contraindicated) Coadministration of ergot alkaloids with potent inhibitors of CYP3A4, like anti-retroviral protease inhibitors is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Several case reports have established the clinical significance of this interaction in the medical literature. In some cases, fatal interactions have occurred.
Ergotamine; Caffeine: (Contraindicated) Coadministration of ergot alkaloids with potent inhibitors of CYP3A4, like anti-retroviral protease inhibitors is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Several case reports have established the clinical significance of this interaction in the medical literature. In some cases, fatal interactions have occurred.
Erlotinib: (Major) Avoid the coadministration of erlotinib with atazanavir due to the risk of increased erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of erlotinib with another strong CYP3A4 inhibitor increased the erlotinib AUC by 67%.
Ertugliflozin; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Ertugliflozin; Sitagliptin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Eslicarbazepine: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as atazanavir, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of atazanavir if coadministered with eslicarbazepine.
Esomeprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Estazolam: (Moderate) In vitro studies with human liver microsomes indicate that the biotransformation of estazolam to the major circulating metabolite 4-hydroxy-estazolam is mediated by CYP3A. In theory, CYP3A4 inhibitors, such as protease inhibitors, may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity (i.e., prolonged sedation and respiratory depression).
Esterified Estrogens: (Moderate) Monitor for an increase in estrogen-related adverse effects during concomitant atazanavir use and adjust estrogen dose as appropriate based on response. Atazanavir has been shown to inhibit the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens.
Esterified Estrogens; Methyltestosterone: (Moderate) Monitor for an increase in estrogen-related adverse effects during concomitant atazanavir use and adjust estrogen dose as appropriate based on response. Atazanavir has been shown to inhibit the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens.
Estradiol: (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Estradiol; Levonorgestrel: (Major) Studies evaluating use of atazanavir with levonorgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Estradiol; Norethindrone: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Estradiol; Norgestimate: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norgestimate are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Estradiol; Progesterone: (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events. (Moderate) Use caution if coadministration of atazanavir with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Atazanavir is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Eszopiclone: (Major) The adult dose of eszopiclone should not exceed 2 mg/day during co-administration of potent CYP3A4 inhibitors, such as anti-retroviral protease inhibitors. CYP3A4 is a primary metabolic pathway for eszopiclone, and increased systemic exposure to eszopiclone increases the risk of next-day psychomotor or memory impairment, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethinyl Estradiol; Norelgestromin: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Ethinyl Estradiol; Norgestrel: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) Studies evaluating use of atazanavir with norgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of norgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Ethosuximide: (Moderate) Atazanavir may inhibit the metabolism of ethosuximide and may necessitate up to a 50% dose reduction of ethosuximide.
Ethotoin: (Major) Ethotoin may increase the metabolism of atazanavir and lead to decreased antiretroviral efficacy. The appropriate drug-dose adjustments necessary to ensure optimum levels of both antiretroviral and anticonvulsant drugs are unknown. Consider using alternative anticonvulsant, or monitoring atazanavir concentrations and boosting with ritonavir if necessary. If atazanavir is added to anticonvulsant therapy, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or seizure control. Monitoring of serum concentrations of these drugs is recommended when given concomitantly with atazanavir.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) Studies evaluating use of atazanavir with ethynodiol diacetate have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of ethynodiol diacetate. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Etonogestrel; Ethinyl Estradiol: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Etravirine: (Moderate) Etravirine should not be coadministered with atazanavir, unless atazanavir is boosted with ritonavir. Concomitant use of etravirine and unboosted atazanavir results in significant decreases in atazanavir exposure. Coadministration of etravirine and atazanavir (boosted with ritonavir) causes a decrease in atazanavir Cmin (38%); however, the decrease is not considered clinically relevant, and this drug combination can be administred together without dose adjustments.
Everolimus: (Major) Avoid coadministration of everolimus with atazanavir due to the risk of increased everolimus-related adverse reactions. If concomitant use is unavoidable in patients receiving everolimus for either kidney or liver transplant, closely monitor everolimus whole blood trough concentrations. Everolimus is a sensitive CYP3A4 substrate and P-glycoprotein (P-gp) substrate. Atazanavir is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4/P-gp inhibitor increased the AUC of everolimus by 15-fold.
Ezetimibe; Simvastatin: (Contraindicated) The coadministration of anti-retroviral protease inhibitors with simvastatin is contraindicated. Taking these drugs together may significantly increase the serum concentration of simvastatin; thereby increasing the risk of myopathy and rhabdomyolysis. One report has demonstrated that ritonavir plus saquinavir therapy markedly increases the AUC for simvastatin by 3059%. Simvastatin is a substrate for CYP3A4 and the drug transporter organic anion transporting polypeptide (OATP1B1); protease inhibitors are CYP3A4 and OATP inhibitors.
Famotidine: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Fedratinib: (Major) Avoid coadministration of fedratinib with atazanavir as concurrent use may increase fedratinib exposure. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If atazanavir is discontinued, increase the fedratinib dose as follows: 300 mg PO once daily for 2 weeks and then 400 mg PO once daily thereafter as tolerated. Fedratinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
Felbamate: (Major) Coadministration of felbamate with atazanavir is not recommended. Plasma concentrations of atazanavir may be reduced if these drugs are administered concurrently, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Felbamate is a CYP3A4 inducer; atazanavir is a substrate of CYP3A4.
Felodipine: (Moderate) Concurrent use of felodipine and protease inhibitors should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Concurrent use of a strong CYP3A inhibitor increased felodipine AUC and half-life by approximately 8-fold and 2-fold, respectively. Concurrent use of a moderate CYP3A inhibitor increased felodipine AUC and half-life by approximately 2.5-fold and 2-fold, respectively.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. If atazanavir is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like atazanavir can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If atazanavir is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Fesoterodine: (Major) Limit the dose of fesoterodine to 4 mg once daily in adults and pediatric patients weighing more than 35 kg if coadministered with anti-retroviral protease inhibitors. Avoid use of fesoterodine and protease inhibitors in pediatric patients weighing 25 to 35 kg. Concurrent use may increase fesoterodine exposure. Fesoterodine is a CYP3A4 substrate and protease inhibitors are strong CYP3A4 inhibitors. Coadministration with another strong CYP3A4 inhibitor led to approximately a doubling of the overall exposure of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine.
Finasteride; Tadalafil: (Major) For the treatment of erectile dysfunction, do not exceed 10 mg of tadalafil within 72 hours of atazanavir for the 'as needed' dose or 2.5 mg daily for the 'once-daily' dose. Avoid the use of tadalafil for pulmonary hypertension during the initiation of atazanavir therapy. Stop tadalafil at least 24 hours prior to starting atazanavir. After at least 1 week of atazanavir therapy, resume tadalafil at 20 mg once daily. Increase to 40 mg once daily based on tolerability. Tadalafil is metabolized by CYP3A4, and atazanavir is a potent inhibitor of CYP3A4. Substantially increased tadalafil plasma concentrations may result in increased adverse events including hypotension, syncope, visual changes, and prolonged erection. Although the manufacturer of tadalafil provides recommended dosing for coadministration with ritonavir only, the FDA recommends the same dosage adjustment for the coadministration of tadalafil with all protease inhibitors.
Finerenone: (Contraindicated) Concomitant use of finerenone and atazanavir is contraindicated. Concomitant use may increase finerenone exposure and the risk for finerenone-related adverse reactions. Finerenone is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased overall exposure to finerenone by more than 400%.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as atazanavir, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Flurazepam: (Moderate) Monitor for an increase in flurazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with protease inhibitors is necessary. Concurrent use may increase flurazepam exposure. Flurazepam is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors.
Flurbiprofen: (Moderate) Caution is warranted when atazanavir is administered with flurbiprofen as there is a potential for elevated flubriprofen concentrations. Flurbiprofen is a substrate of uridine glucoronyltransferase (UGT). Atazanavir is an UGT1A1 inhibitor.
Flutamide: (Major) Caution is warranted when atazanavir is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Atazanavir is a CYP3A4 substrate and inhibitor.
Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Salmeterol: (Major) Avoid concomitant use of salmeterol with atazanavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Umeclidinium; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Moderate) Caution is warranted when atazanavir is administered with umeclidinium; vilanterol as there is a potential for elevated umeclidinium; vilanterol concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Umeclidinium; vilanterol is a substrate of CYP3A4. Atazanavir is an inhibitor of CYP3A4.
Fluticasone; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Moderate) Caution is warranted when atazanavir is administered with umeclidinium; vilanterol as there is a potential for elevated umeclidinium; vilanterol concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Umeclidinium; vilanterol is a substrate of CYP3A4. Atazanavir is an inhibitor of CYP3A4.
Fluvastatin: (Moderate) Concurrent use of atazanavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Atazanavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, atazanavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Fluvoxamine: (Minor) Fluvoxamine is a CYP3A4 inhibitor, and serum concentrations of atazanavir, a CYP3A4 substrate, may increase with co-administration. Co-administer these drugs with caution due to the potential for atazanavir toxicity.
Food: (Major) Advise patients to avoid cannabis use during protease inhibitor treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A substrates and protease inhibitors are strong CYP3A inhibitors. Concomitant use of a cannabinoid product containing THC and CBD at an approximate 1:1 ratio with another strong CYP3A inhibitor increased THC, 11-OH-THC, and CBD peak exposures by 1.3-, 3-, and 1.9-fold respectively. (Major) Atazanavir needs to be taken with a light snack or meal, such as dry toast with jelly, apple juice, and coffee with skim milk in order to enhance oral absorption. However, administration with food high in calories and fat can result in a decrease in the AUC of atazanavir.
Formoterol; Mometasone: (Moderate) Coadministration of mometasone with atazanavir may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Fosamprenavir: (Major) Avoid concurrent use of fosamprenavir and atazanavir. Concomitant use may decrease the exposure of atazanavir and increase the exposure of fosamprenavir; appropriate doses for this combination with respect to safety and efficacy have not been established.
Fosphenytoin: (Major) Coadministration of fosphenytoin and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. Avoid coadministration of atazanavir with fosphenytoin unless atazanavir is boosted with ritonavir. Coadministration may also result in decreased phenytoin concentrations. If atazanavir and fosphenytoin are used together, the patient must be closely monitored for antiviral efficacy and decreased fosphenytoin efficacy; clinical monitoring of phenytoin concentrations with dosage titration if necessary is also warranted.
Fostamatinib: (Moderate) Monitor for fostamatinib toxicities that may require fostamatinib dose reduction (i.e., elevated hepatic enzymes, neutropenia, high blood pressure, severe diarrhea) if given concurrently with a strong CYP3A4 inhibitor. Concomitant use of fostamatinib with a strong CYP3A4 inhibitor increases exposure to the major active metabolite, R406, which may increase the risk of adverse reactions. R406 is extensively metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with atazanavir is necessary. Gefitinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
Gilteritinib: (Major) Consider an alternative to atazanavir during treatment with gilteritinib. Concurrent use may increase gilteritinib exposure resulting in treatment-related adverse events. If coadministration is required, frequently monitor for gilteritinib adverse reactions. Interrupt therapy and reduce the gilteritinib dose if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study.
Glasdegib: (Major) Consider an alternative to atazanavir during treatment with glasdegib. Concurrent use may increase glasdegib exposure resulting in treatment-related adverse events including QT prolongation. If coadministration cannot be avoided, monitor for increased adverse events; more frequent ECG monitoring is recommended. Glasdegib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study.
Glecaprevir; Pibrentasvir: (Contraindicated) Coadministration of glecaprevir with atazanavir is contraindicated due to an increased risk of ALT elevations. (Contraindicated) Coadministration of pibrentasvir with atazanavir is contraindicated due to an increased risk of ALT elevations.
Glipizide; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Glyburide; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Granisetron: (Minor) The plasma concentrations of granisetron may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate.
Grapefruit juice: (Moderate) Grapefruit or grapefruit juice ingestion may theoretically increase atazanavir serum concentrations. The possible increase in atazanavir bioavailability would be most likely due to inhibition of the CYP3A4 isoenzyme in the gut. Individuals should not drastically alter their intake of grapefruit or grapefruit juice or should avoid concurrent use unless advised differently by their health care professional.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like atazanavir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If atazanavir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) Atazanavir may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. If atazanavir is discontinued, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and atazanavir is a strong CYP3A4 inhibitor.
H2-blockers: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Haloperidol: (Moderate) Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of the listed drugs and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and these drugs. Haloperidol is metabolized by CYP3A4 and with the potential to cause QT prolongation. Avoid use of atazanavir with haloperidol when possible. Downward dosage adjustment of haloperidol may be necessary.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like atazanavir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If atazanavir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like atazanavir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If atazanavir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like atazanavir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If atazanavir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like atazanavir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If atazanavir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Ibrexafungerp: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with atazanavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ibrutinib: (Major) Avoid concomitant use of ibrutinib and atazanavir; ibrutinib plasma concentrations may increase resulting in severe ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). Ibrutinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased ibrutinib exposure by 5.7-fold to 24-fold.
Ibuprofen; Famotidine: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. If atazanavir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like atazanavir can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If atazanavir is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Idelalisib: (Major) Coadministration of idelalisib with atazanavir may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib and atazanavir are both CYP3A4 substrates and strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold. Atazanavir exposure was increased when administered with some strong CYP3A inhibitors but not others.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with atazanavir is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Atazanavir is a strong CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Major) The plasma concentrations of iloperidone may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as cardiovascular or CNS effects, is recommended during coadministration. A dose reduction of iloperidone may be necessary. Atazanavir is a CYP3A4 inhibitors; iloperidone is a CYP3A4 substrate.
Imatinib: (Major) Protease Inhibitors inhibit cytochrome P450 CYP3A4 and may decrease the metabolism of imatinib and increase imatinib concentrations leading to an increased incidence of adverse reactions. In addition, because imatinib inhibits CYP2C9, CYP2D6, and CYP3A4/5, the metabolism of protease inhibitors may be decreased by imatinib. Close monitoring of the antiviral and antineoplastic responses is recommended.
Imipramine: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Incretin Mimetics: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Indinavir: (Contraindicated) Atazanavir is an inhibitor of CYP3A and is associated with indirect (unconjugated) hyperbilirubinemia. Indinavir is a substrate of CYP3A4 and is also associated with increased unconjugated bilirubin. Due to the potential interactions and the increased risk of hyperbilirubinemia, the concomitant use of atazanavir and indinavir is contraindicated; however, the combination has not been studied.
Infigratinib: (Major) Avoid concomitant use of infigratinib and atazanavir. Coadministration may increase infigratinib exposure, increasing the risk for adverse effects. Infigratinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of infigratinib by 622%.
Insulins: (Moderate) Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment.
Interferons: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Irinotecan Liposomal: (Major) Avoid administration of atazanavir during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Coadministration is contraindicated if atazanavir is boosted with cobicistat. Irinotecan is a CYP3A4 substrate and its active metabolite, SN-38, is a substrate of UGT1A1. Atazanavir is a UGT1A1 inhibitor and a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and UGT1A1 inhibitor increased exposure to both irinotecan and its active metabolite, SN-38.
Irinotecan: (Major) Avoid administration of atazanavir during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Coadministration is contraindicated if atazanavir is boosted with cobicistat. Irinotecan is a CYP3A4 substrate and its active metabolite, SN-38, is a substrate of UGT1A1. Atazanavir is a UGT1A1 inhibitor and a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and UGT1A1 inhibitor increased exposure to both irinotecan and its active metabolite, SN-38.
Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium with atazanavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; atazanavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated atazanavir concentrations would also be expected with coadministration, as atazanavir is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Atazanavir is contraindicated for use with rifampin. Rifampin induces CYP isoenzymes, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Isoniazid, INH; Rifampin: (Contraindicated) Atazanavir is contraindicated for use with rifampin. Rifampin induces CYP isoenzymes, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Isradipine: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with protease inhibitors is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors.
Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with atazanavir as istradefylline exposure and adverse effects may increase. Atazanavir is a strong CYP3A4 inhibitor. Istradefylline exposure was increased by 2.5-fold when administered with a strong inhibitor in a drug interaction study.
Itraconazole: (Major) Coadministration of atazanavir and itraconazole may result in increased serum concentrations of itraconazole. While clinically significant interactions are not expected with atazanavir monotherapy, the addition of cobicistat to atazanavir may cause a significant interaction and therefore, atazanavir; cobicistat should be avoided in combination with itraconazole. Atazanavir is a CYP3A4 inhibitor and itraconazole is a CYP3A4 substrate. Caution and close monitoring of the anticipated responses are recommended when coadministered.
Ivabradine: (Contraindicated) Coadministration of ivabradine and atazanvir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If atazanavir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with atazanavir due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of ivosidenib to 250 mg PO once daily. Monitor ECGs for QTc prolongation and monitor electrolytes, correcting any electrolyte abnormalities as clinically appropriate. If atazanavir is discontinued, wait at least 5 half-lives of atazanavir before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivosidenib single-dose AUC to 269% of control, with no change in Cmax.
Ixabepilone: (Major) Avoid concurrent use of ixabepilone and atazanavir due to increased ixabepilone exposure, which may increase the risk of adverse reactions. If concomitant use is unavoidable, reduce the dose of ixabepilone to 20 mg/m2. Ixabepilone is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ixabepilone exposure by 79%.
Ketoconazole: (Major) Avoid atazanavir for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may increase exposure of ketoconazole and increase the risk of adverse effects. If concomitant use is necessary, monitor closely for ketoconazole-related adverse reactions; a ketoconazole dose reduction may be necessary. Ketoconazole is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Lacosamide: (Moderate) Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as atazanavir, since further PR prolongation is possible. If concurrent use is necessary, an ECG is recommended prior to initiation of lacosamide and after the drug is titrated to the maintenence dose. Patients receiving intravenous lacosamide should be closely monitored due to the potential for profound bradycardia and AV block during coadministration.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Lamotrigine: (Major) Adjustments in lamotrigine maintenance dose regimens may be necessary with concomitant use of atazanavir boosted with ritonavir. No dose adjustments during dose escalation are necessary. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and atazanavir with ritonavir induces glucuronidation. Daily doses of atazanavir/ritonavir (300 mg/100 mg) in healthy volunteers reduced the AUC and Cmax of a single lamotrigine dose (100 mg) by approximately 32% and 6%, respectively. The lamotrigine half-life decreased by 27%. Concurrent use of lamotrigine and unboosted atazanavir is not expected to alter the plasma concentration of lamotrigine, and no dose adjustment of lamotrigine is necessary when administered without ritonavir.
Lansoprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Major) Coadministration with atazanavir increases clarithromycin serum concentrations. Use caution if these drugs are coadministered, as increased clarithromycin concentrations may cause QT prolongation; a 50% dosage reduction of clarithromycin is recommended. In addition, atazanavir significantly reduces the concentration of 14-OH clarithromycin, the active metabolite of clarithromycin; consider alternative agents for indications other than infections due to Mycobacterium avium complex (MAC).
Lapatinib: (Major) Avoid coadministration of lapatinib with atazanavir due to increased plasma concentrations of lapatinib. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily. If atazanavir is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased lapatinib exposure by 3.6-fold and increased the half-life of lapatinib by 1.7-fold.
Larotrectinib: (Major) Avoid coadministration of larotrectinib with atazanavir due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If atazanavir is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of atazanavir. Larotrectinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of larotrectinib by 4.3-fold in a drug interaction study.
Lefamulin: (Major) Avoid coadministration of atazanavir with oral lefamulin due to increased lefamulin exposure; atazanavir may be administered with intravenous lefamulin. Lefamulin is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and atazanavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong/moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lenacapavir: (Major) Avoid concomitant use of lenacapavir and atazanavir boosted with ritonavir or cobicistat and consider alternative therapy. Concomitant use may increase lenacapavir exposure and the risk for lenacapavir-related adverse reactions. Lenacapavir is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use of lenacapavir with atazanavir boosted cobicistat was observed to increase lenacapavir overall exposure by 4.21-fold.
Leniolisib: (Major) Avoid concomitant use of leniolisib and atazanavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of atazanavir; monitor for potential reduction in efficacy. Atazanavir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of atazanavir; monitor for potential reduction in efficacy. Atazanavir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Moderate) Administering atazanavir concurrently with letermovir may result in elevated concentrations of both drugs. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Closely monitor for adverse events, including tachycardia, atrial fibrillation, hepatotoxicity, kidney stones, and gastrointestinal events. Atazanavir is an inhibitor of the organic anion-transporting polypeptides (OATP1B1), and a substrate of CYP3A4. Letermovir is an OATP1B1 substrate and a moderate CYP3A4 inhibitor. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Leuprolide; Norethindrone: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Levamlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Levoketoconazole: (Major) Avoid atazanavir for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may increase exposure of ketoconazole and increase the risk of adverse effects. If concomitant use is necessary, monitor closely for ketoconazole-related adverse reactions; a ketoconazole dose reduction may be necessary. Ketoconazole is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Levonorgestrel: (Major) Studies evaluating use of atazanavir with levonorgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Levonorgestrel; Ethinyl Estradiol: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) Studies evaluating use of atazanavir with levonorgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) Studies evaluating use of atazanavir with levonorgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) Studies evaluating use of atazanavir with levonorgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Lidocaine: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Lidocaine; Epinephrine: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Lidocaine; Prilocaine: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity. (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects.
Linagliptin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy, such as linagliptin, should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Linagliptin; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy, such as linagliptin, should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Lomitapide: (Contraindicated) Concomitant use of atazanavir and lomitapide is contraindicated. If treatment with atazanavir is unavoidable, lomitapide should be stopped during the course of treatment. Atazanavir is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and atazanavir is contraindicated; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of lonafarnib by 425%.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with atazanavir. Concurrent use ma y increase loperamide exposure. Loperamide is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with atazanavir. Concurrent use may increase loperamide exposure. Loperamide is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Lopinavir; Ritonavir: (Minor) Coadministration of atazanavir with ritonavir results in higher atazanavir concentrations; reduced adult doses of atazanavir 300 mg once daily are recommended when ritonavir (100 mg once daily) is given concomitantly. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including atazanavir) has not been evaluated. Atazanavir is a CYP3A4 substrate; ritonavir is a strong inhibitor of CYP3A4.
Lorazepam: (Moderate) Monitor for an increase in lorazepam-related adverse reactions and consider reducing the dose of lorazepam if concomitant use of lorazepam and atazanavir is necessary. Avoid lorazepam extended-release capsules and utilize lorazepam immediate-release dosage forms that can be easily titrated. Lorazepam is an UGT substrate and atazanavir is an UGT inhibitor.
Lorlatinib: (Major) Avoid coadministration of lorlatinib with atazanavir due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions of lorlatinib; exposure to atazanavir may also decrease. If concomitant use is unavoidable, reduce the starting dose of lorlatinib from 100 mg to 75 mg once daily, or from 75 mg to 50 mg once daily. If atazanavir is discontinued, resume the original dose of lorlatinib after 3 plasma half-lives of atazanavir. Lorlatinib is a CYP3A4 substrate and a moderate CYP3A4 inducer. Atazanavir is a CYP3A4 substrate and a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lorlatinib exposure by 42%. Concomitant administration of atazanavir with CYP3A4 inducers may decrease plasma concentrations, reducing efficacy and increasing the potential for viral resistance.
Losartan: (Minor) Caution is warranted when atazanavir is administered with losartan as there is a potential for elevated losartan concentrations. Losartan is a substrate of CYP3A4; atazanavir is an inhibitor of CYP3A4.
Losartan; Hydrochlorothiazide, HCTZ: (Minor) Caution is warranted when atazanavir is administered with losartan as there is a potential for elevated losartan concentrations. Losartan is a substrate of CYP3A4; atazanavir is an inhibitor of CYP3A4.
Lovastatin: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Lumacaftor; Ivacaftor: (Major) If atazanavir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Lumacaftor; ivacaftor is expected to decrease the therapeutic efficacy of atazanavir; avoid concurrent use. If concomitant use cannot be avoided, consider limiting concurrent use to regimens in which atazanavir is boosted with ritonavir and monitor antiretroviral efficacy carefully. Lumacaftor; ivacaftor dosage adjustment is not required when atazanavir is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking atazanavir, reduce the dose of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking atazanavir. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Atazanavir is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Lumacaftor's induction of CYP3A may decrease the systemic exposure of atazanavir and decrease its therapeutic efficacy. Although atazanavir is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor is expected to decrease the therapeutic efficacy of atazanavir; avoid concurrent use. If concomitant use cannot be avoided, consider limiting concurrent use to regimens in which atazanavir is boosted with ritonavir and monitor antiretroviral efficacy carefully. Lumacaftor; ivacaftor dosage adjustment is not required when atazanavir is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking atazanavir, reduce the dose of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking atazanavir. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Atazanavir is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Lumacaftor's induction of CYP3A may decrease the systemic exposure of atazanavir and decrease its therapeutic efficacy. Although atazanavir is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
Lumateperone: (Major) Reduce the dose of lumateperone to 10.5 mg once daily if concomitant use with atazanavir is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor increased lumateperone exposure by approximately 4-fold.
Lurasidone: (Major) Atazanavir is a moderate inhibitor of CYP3A4 and has the potential for interactions with substrates of CYP3A4 such as lurasidone. Concurrent use of these medications may lead to an increased risk of lurasidone-related adverse reactions. If a moderate inhibitor of CYP3A4 is being prescribed and lurasidone is added in an adult patient, the recommended starting dose of lurasidone is 20 mg/day and the maximum recommended daily dose of lurasidone is 80 mg/day. If a moderate CYP3A4 inhibitor is added to an existing lurasidone regimen, reduce the lurasidone dose to one-half of the original dose. Patients should be monitored for efficacy and toxicity. Concurrent use of lurasidone and atazanavir boosted with ritonavir or atazanavir; cobicistat is contraindicated.
Lurbinectedin: (Major) Avoid concomitant use of lurbinectedin and atazanavir due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Magnesium Hydroxide: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Maprotiline: (Moderate) Atazanavir competitively inhibits the enzymes CYP3A4, CYP1A2 and CYP2C9. Concentrations of drugs that are substrates of these enzymes (e.g., tricyclic antidepressants) may be increased with concomitant atazanavir use. According to the manufacturer of atazanavir, coadministration of atazanavir in a patient on a tricyclic antidepressant (TCA) may result in increased serum concentrations of the TCA, and the two drugs should be coadministered with caution due to a potential for serious adverse events. Monitor the patient for anticholinergic effects (e.g., sedation, confusion, constipation) associated with TCA use. The manufacturer recommends TCA concentration monitoring if atazanavir is used concomitantly with a TCA. Maprotiline is related to the tricyclic antidepressants, and until more data is available, similar caution is advised when using maprotiline with atazanavir.
Maraviroc: (Major) Coadministration of maraviroc, a CYP3A and OATP1B1 substrate, with atazanavir, a strong CYP3A4 inhibitor and in vitro inhibitor of OATP1B1, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with atazanavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with atazanavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of atazanavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and atazanavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with atazanavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
Mefloquine: (Moderate) Mefloquine is metabolized by CYP3A4. Atazanavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Meloxicam: (Moderate) The plasma concentrations of meloxicam may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while meloxicam is a CYP3A4 substrate.
Mepivacaine: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects.
Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Metformin; Repaglinide: (Moderate) Coadministration of repaglinide and protease inhibitors may increase or decrease glucose concentrations and increase repaglinide AUC; if coadministration is necessary, repaglinide dosage adjustment may be necessary and increased frequency of glucose monitoring is recommended. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. In addition, repaglinide is a substrate of the hepatic isoenzyme CYP3A4 and the drug transporter organic anion transporting polypeptide (OATP1B1); protease inhibitors are potent CYP3A4 inhibitors and inhibitors of OATP. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Metformin; Rosiglitazone: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Metformin; Saxagliptin: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as atazanavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Metformin; Sitagliptin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Methadone: (Moderate) Caution is advised with the coadministration of atazanavir and methadone as concurrent use may result in increased concentrations of methadone. Methadone is primarily metabolized by CYP3A4; atazanavir is a CYP3A4 inhibitor. No clinically significant drug interaction was observed when atazanavir was coadministered with a stable maintenance dose of methadone. However, if coadministered, patients should be regularly monitored for excessive methadone-related side effects, as the theoretical possibility for atazanavir to inhibit methadone metabolism does exist.
Methylergonovine: (Contraindicated) Coadministration of ergot alkaloids with potent inhibitors of CYP3A4, like anti-retroviral protease inhibitors is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Several case reports have established the clinical significance of this interaction in the medical literature. In some cases, fatal interactions have occurred.
Methylprednisolone: (Moderate) Coadministration of methylprednisolone with atazanavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Methylprednisolone is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Midazolam: (Major) Protease inhibitors may increase midazolam concentrations; the risk for midazolam-related adverse effects varies by midazolam dosage form and route of administration. Oral midazolam use is contraindicated. Intranasal midazolam should be avoided when possible. Additional monitoring and a dosage reduction may be necessary with parenteral midazolam. Midazolam is a CYP3A substrate and protease inhibitors are CYP3A inhibitors. Protease inhibitors have been shown to increase oral midazolam AUCs by up to 3-fold, resulting in clinically significant potentiation of sedation.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and atazanavir due to the risk of increased midostaurin exposure which may increase the incidence and severity of adverse reactions. If concomitant use cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity, particularly during the first week of midostaurin therapy for those with systemic mastocytosis/mast cell leukemia and during the first week of each cycle for those with acute myeloid leukemia. Midostaurin is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of one strong CYP3A4 inhibitor with a single dose of midostaurin increased the exposure of midostaurin and its active metabolites CGP62221 and CGP52421 by 10.4-fold, 3.5-fold, and 1.2-fold, respectively. Coadministration of another strong CYP3A4 inhibitor with twice daily doses of midostaurin increased Day 28 trough concentrations of midostaurin, CGP62221, and CGP52421 by 2.1-fold, 1.2-fold, and 1.3-fold respectively compared with day 21 trough levels with midostaurin alone.
Mifepristone: (Major) Caution is advised when administering atazanavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with atazanavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving atazanavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with atazanavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and atazanavir are substrates and strong inhibitors of CYP3A4.
Miglitol: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors.
Mirtazapine: (Moderate) Concurrent administration of mirtazapine and atazanavir may result in elevated mirtazapine plasma concentrations. If these drugs are coadministered, monitor patients for adverse effects associated with mirtazapine, such as constipation, drowsiness, dizziness, and QT prolongation, and decrease the dose if necessary. Mirtazapine is a substrate of CYP3A4 and protease inhibitors are potent inhibitors of CYP3A4.
Mirvetuximab Soravtansine: (Moderate) Closely monitor for mirvetuximab soravtansine-related adverse reactions if concomitant use of atazanavir is necessary. DM4, the cytotoxic component of mirvetuximab soravtansine, is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use may increase unconjugated DM4 exposure.
Mitapivat: (Major) Avoid coadministration of mitapivat with atazanavir due to increased risk of adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with other strong CYP3A inhibitors increased mitapivat overall exposure by 3.6 to 4.9-fold.
Mitotane: (Contraindicated) Atazanavir is contraindicated for use with mitotane. Mitotane is a strong CYP3A4 inducer and atazanavir is a CYP3A4 substrate; coadministration significantly reduces plasma concentrations of atazanavir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. When coadministered with another strong CYP3A4 inducer (rifampin 600 mg daily; n = 16), the ratio of atazanavir pharmacokinetic parameters was significantly affected as follows (where 1 = no change): Cmax, 0.47 (90% CI, 0.41 to 0.53), AUC, 0.28 (90% CI, 0.25 to 0.32), and Cmin, 0.02 (90% CI, 0.02 to 0.03).
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and atazanavir. Concomitant use may increase mobocertinib exposure and the risk for adverse reactions such as QT prolongation. Mobocertinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Use of a strong CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 374% to 419%.
Modafinil: (Major) Coadministration of atazanavir with modafinil is not recommended as there is a potential for elevated modafinil concentrations and decreased atazanavir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Modafinil is a CYP3A4 substrate/inducer. Atazanavir is an inhibitor/substrate of CYP3A4.
Mometasone: (Moderate) Coadministration of mometasone with atazanavir may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Nafcillin: (Major) Caution is warranted when atazanavir is administered with nafcillin as there is a potential for decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Nafcillin is an inducer of CYP3A4. Atazanavir is a CYP3A4 substrate.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with atazanavir. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; atazanavir is a CYP3A4 inhibitor.
Naloxegol: (Contraindicated) Concomitant use of naloxegol with atazanavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as atazanavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with atazanavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Naproxen: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme.
Naproxen; Esomeprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme.
Naproxen; Pseudoephedrine: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme.
Nateglinide: (Moderate) Concurrent administration of nateglinide with some protease inhibitors may result in elevated nateglinide plasma concentrations via inhibition of CYP2C9. Ritonavir may induce CYP2C9 leading to a reduction of nateglinide concentrations. Monitor blood glucose concentrations during coadministration as hypoglycemia or hyperglycemia could occur. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Monitor blood glucose concentrations during coadministration. Caution and close monitoring are advised if these drugs are administered together.
Nebivolol; Valsartan: (Moderate) Concurrent use of atazanavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Nefazodone: (Major) Nefazodone and atazanavir are both substrates and inhibitors of CYP3A4. Coadministration could result in increased plasma concentrations of either drug; caution and close monitoring are recommended.
Neratinib: (Major) Avoid concomitant use of atazanavir with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 381%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4 since the plasma concentrations of the primary substrate can increase; the inhibitory effect on CYP3A4 can last for multiple days. Atazanavir is partially metabolized by CYP3A4. In addition, netupitant is mainly metabolized by CYP3A4. Coadministration of netupitant; palonosetron with a strong CYP3A4 inhibitor can significantly increase the systemic exposure to netupitant. Atazanavir is a strong CYP3A4 inhibitor. No dosage adjustment is necessary for single dose administration of netupitant; palonosetron. (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor; palonosetron is a substrate of CYP3A4.
Nevirapine: (Major) Do not coadminister atazanavir and nevirapine. Coadministration leads to substantially decreased atazanavir concentrations and increased nevirapine concentrations, which could lead to toxicity.
Niacin; Simvastatin: (Contraindicated) The coadministration of anti-retroviral protease inhibitors with simvastatin is contraindicated. Taking these drugs together may significantly increase the serum concentration of simvastatin; thereby increasing the risk of myopathy and rhabdomyolysis. One report has demonstrated that ritonavir plus saquinavir therapy markedly increases the AUC for simvastatin by 3059%. Simvastatin is a substrate for CYP3A4 and the drug transporter organic anion transporting polypeptide (OATP1B1); protease inhibitors are CYP3A4 and OATP inhibitors.
Nicardipine: (Moderate) Anti-retroviral protease inhibitors may decrease the hepatic CYP metabolism of calcium-channel blockers (mainly through CYP3A4 inhibition) resulting in increased calcium-channel blocker concentrations. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
Nifedipine: (Moderate) Atazanavir may interact with certain calcium-channel blockers that undergo significant metabolism via CYP3A4, including nifedipine. Cautious dose titration of amlodipine should be considered; the patient should be monitored for the proper clinical responses to calcium-channel blocker therapy.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and atazanavir. If coadministration is required, monitor patients closely for prolongation of the QT interval and reduce the nilotinib dose to 300 mg once daily in patients with resistant or intolerant Ph+ CML or to 200 mg once daily in patients with newly diagnosed Ph+ CML. If atazanavir is discontinued, a washout period should be allowed before adjusting the nilotinib dosage upward to the indicated dose. Nilotinib is a substrate of CYP3A4 and atazanavir is a strong inhibitor of CYP3A4.
Nimodipine: (Moderate) Anti-retroviral protease inhibitors are CYP3A4 inhibitors and may decrease the hepatic metabolism of nimodipine, leading to increased plasma concentrations of nimodipine. In addition, ritonavir and calcium channel blockers both prolong the PR interval and the manufacturer for ritonavir recommends caution during coadministration. Monitor therapeutic response and for adverse effects, such as hypotension. Decreased calcium-channel blocker doses may be warranted.
Nirmatrelvir; Ritonavir: (Minor) Coadministration of atazanavir with ritonavir results in higher atazanavir concentrations; reduced adult doses of atazanavir 300 mg once daily are recommended when ritonavir (100 mg once daily) is given concomitantly. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including atazanavir) has not been evaluated. Atazanavir is a CYP3A4 substrate; ritonavir is a strong inhibitor of CYP3A4.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Nizatidine: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Norethindrone: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Norethindrone; Ethinyl Estradiol: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Norgestimate; Ethinyl Estradiol: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norgestimate are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Norgestrel: (Major) Studies evaluating use of atazanavir with norgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of norgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms.
Nortriptyline: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Olanzapine: (Moderate) Caution is warranted when atazanavir is administered with olanzapine as there is a potential for elevated olanzapine concentrations. Olanzapine is a substrate of uridine glucoronyltransferase (UGT). Atazanavir is an inhibitor of UGT1A1.
Olanzapine; Fluoxetine: (Moderate) Caution is warranted when atazanavir is administered with olanzapine as there is a potential for elevated olanzapine concentrations. Olanzapine is a substrate of uridine glucoronyltransferase (UGT). Atazanavir is an inhibitor of UGT1A1.
Olanzapine; Samidorphan: (Moderate) Caution is warranted when atazanavir is administered with olanzapine as there is a potential for elevated olanzapine concentrations. Olanzapine is a substrate of uridine glucoronyltransferase (UGT). Atazanavir is an inhibitor of UGT1A1.
Olaparib: (Major) Avoid coadministration of olaparib with atazanavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after atazanavir is discontinued. Olaparib is a CYP3A substrate and atazanavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and atazanavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and atazanavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If atazanavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Olopatadine; Mometasone: (Moderate) Coadministration of mometasone with atazanavir may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and atazanavir. If concomitant use is necessary, decrease omaveloxolone dose to 50 mg once daily. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased omaveloxolone overall exposure by 4-fold.
Omeprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Omeprazole; Amoxicillin; Rifabutin: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Major) Reduce the rifabutin dose to 150 mg PO once daily and monitor for adverse effects, such as uveitis and neutropenia, if concomitant use with atazanavir is necessary. Avoid concurrent use of rifabutin and atazanavir boosted with cobicistat. Although the FDA-approved labeling recommends reducing the rifabutin dose by at least 75% (to a maximum 150 mg every other day or 3 times per week), lower rifabutin exposure has been reported in persons living with HIV than in healthy subjects and acquired rifamycin resistance has been reported in these persons receiving 3 times weekly regimens. Monitor response and consider therapeutic drug monitoring (TDM) when rifabutin is used with atazanavir boosted with ritonavir and adjust dose accordingly. Rifabutin is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with atazanavir/ritonavir increased the AUC of rifabutin by approximately 110%.
Omeprazole; Sodium Bicarbonate: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Ondansetron: (Moderate) The plasma concentrations of ondansetron may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Atazanavir is an inhibitor of CYP3A4. Ondansetron is a CYP3A4 substrate.
Oritavancin: (Major) Atazanavir is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of atazanavir may be reduced if these drugs are administered concurrently.
Orlistat: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
Osilodrostat: (Major) Reduce the dose of osilodrostat by one-half during coadministration of atazanavir; concurrent use may increase osilodrostat exposure and the risk of osilodrostat-related adverse reactions. Osilodrostat is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor.
Ospemifene: (Moderate) Caution is warranted when atazanavir is administered with ospemifene as there is a potential for elevated concentrations of ospemifene. Clinical monitoring for ospemifene-related adverse effects is recommended during coadministration. Atazanavir is an inhibitor of CYP3A4 and ospemifene is a substrate for CYP3A4.
Oxcarbazepine: (Major) Oxcarbazepine may increase the metabolism of atazanavir and lead to decreased antiretroviral efficacy. Treatment failures have been reported with other protease inhibitors when carbamazepine was used concomitantly. If atazanavir is added to anticonvulsant therapy, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or seizure control. Monitor serum concentrations.
Oxybutynin: (Moderate) Monitor for an increase in oxybutynin-related adverse reactions if coadministration with protease inhibitors is necessary. Oxybutynin is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased mean oxybutynin plasma concentrations by approximately 2-fold. Concomitant use with moderate CYP3A inhibitors may alter the mean pharmacokinetic parameters of oxybutynin, although the clinical relevance of these potential interactions is unknown.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of atazanavir is necessary. If atazanavir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like atazanavir can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If atazanavir is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Paclitaxel: (Moderate) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4 including paclitaxel. If atazanavir and paclitaxel must be coadministered, the dosage of paclitaxel may need to be downwardly adjusted and conversely, upward dosage adjustment of paclitaxel may be required when atazanavir is discontinued.
Pacritinib: (Contraindicated) Concurrent use of pacritinib with ataz anavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Palbociclib: (Major) Avoid coadministration of atazanavir with palbociclib; significantly increased palbociclib exposure may occur. If concomitant use cannot be avoided, reduce the dose of palbociclib to 75 mg PO once daily and monitor for increased adverse reactions. If atazanavir is discontinued, increase the palbociclib dose (after 3 to 5 half-lives of atazanavir) to the dose used before initiation of atazanavir. Palbociclib is primarily metabolized by CYP3A4 and atazanavir is a strong CYP3A4 inhibitor. In a drug interaction trial, coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of palbociclib by 87% and 34%, respectively.
Palonosetron: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor; palonosetron is a substrate of CYP3A4.
Palovarotene: (Major) Avoid concomitant use of palovarotene and atazanavir due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. Palovarotene is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased palovarotene overall exposure by 3-fold.
Pantoprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Paricalcitol: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
Pazopanib: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as atazanavir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 and CYP2C8 substrate, and atazanavir, a CYP3A4 and CYP2C8 inhibitor and a substrate for CYP3A4, may result in altered pazopanib and/or atazanavir concentrations.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and atazanavir due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If atazanavir is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of atazanavir. Pemigatinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased pemigatinib exposure by 88%.
Perampanel: (Major) Caution is warranted when atazanavir is administered with perampanel as there is a potential for elevated perampanel concentrations and decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Perampanel is a substrate and inducer of CYP3A4. Atazanavir is a CYP3A4 substrate and inhibitor.
Perindopril; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Perphenazine; Amitriptyline: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and atazanavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease atazanavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If atazanavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of atazanavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; atazanavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Phenobarbital: (Major) Coadministration of phenobarbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. Avoid coadministration of atazanavir with phenobarbital unless atazanavir is boosted with ritonavir. Coadministration may also result in decreased phenobarbital concentrations. If atazanavir and phenobarbital are used together, the patient must be closely monitored for antiviral efficacy and decreased phenobarbital efficacy; clinical monitoring of phenobarbital concentrations with dosage titration if necessary is also warranted.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Coadministration of phenobarbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. Avoid coadministration of atazanavir with phenobarbital unless atazanavir is boosted with ritonavir. Coadministration may also result in decreased phenobarbital concentrations. If atazanavir and phenobarbital are used together, the patient must be closely monitored for antiviral efficacy and decreased phenobarbital efficacy; clinical monitoring of phenobarbital concentrations with dosage titration if necessary is also warranted.
Phentermine; Topiramate: (Moderate) Caution is warranted when atazanavir is administered with topiramate as there is a potential for decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Atazanavir is a substrate of CYP3A4.
Phenytoin: (Major) Coadministration of phenytoin and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. Avoid coadministration of atazanavir with phenytoin unless atazanavir is boosted with ritonavir. Coadministration may also result in decreased phenytoin concentrations. If atazanavir and phenytoin are used together, the patient must be closely monitored for antiviral efficacy and decreased phenytoin efficacy; clinical monitoring of phenytoin concentrations with dosage titration if necessary is also warranted.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends that the pimavanserin dose be reduced to 10 mg/day PO in patients receiving strong inhibitors of CYP3A4 such as atazanavir. If these agents are used in combination, the patient should be carefully monitored for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, loss of balance or coordination, and QT prolongation.
Pimozide: (Contraindicated) Coadministration of pimozide with protease inhibitors is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Pimozide is thought to be metabolized through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Elevated pimozide plasma levels are probable when coadministered with CYP450 inhibitors, such as the protease inhibitors. Increased plasma concentrations of pimozide have been associated with QT prolongation and serious cardiovascular adverse events including death due to TdP.
Pioglitazone; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Pirfenidone: (Moderate) Caution is warranted when atazanavir is administered with pirfenidone as there is a potential for elevated concentrations of atazanavir. Clinical monitoring for adverse effects is recommended during coadministration. Atazanavir is a substrate CYP3A4. Pirfenidone is a CYP3A4 inhibitor.
Pirtobrutinib: (Major) Avoid concomitant use of pirtobrutinib and atazanavir due to the risk of increased pirtobrutinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pirtobrutinib dose by 50 mg. If the current pirtobrutinib dosage is 50 mg once daily, interrupt pirtobrutinib treatment for the duration of atazanavir use. Resume the previous dose of pirtobrutinib after atazanavir is discontinued for 5 half-lives. Pirtobrutinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant with another strong CYP3A inhibitor increased pirtobrutinib overall exposure by 49%.
Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of atazanavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Ponatinib: (Major) Avoid coadministration of ponatinib and atazanavir due to the potential for increased ponatinib exposure. If concurrent use cannot be avoided, reduce the ponatinib dose to the next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg). If the patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid the use of atazanavir and consider alternative therapy. After atazanavir has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting atazanavir. Ponatinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%.
Posaconazole: (Major) The concurrent use of posaconazole and atazanavir should be avoided, if possible, due to the potential for atazanavir-related toxicities. If coadministered, frequently monitor for increased side effects from atazanavir. Dosage adjustment recommendations are not available. Both drugs are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of atazanavir. In one study, coadministration of posaconazole (400 mg PO twice daily) with atazanavir (300 mg PO daily) resulted in significant increases in atazanavir mean Cmax (155% increase) and mean AUC (268% increase). Further, administering posaconazole (400 mg PO twice daily) to volunteers receiving atazanavir boosted with ritonavir (300 mg/100 mg PO daily) also resulted in an increase in the mean Cmax (53% increase) and AUC (146% increase) of atazanavir.
Pralsetinib: (Major) Avoid concomitant use of atazanavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Pramlintide: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors.
Pravastatin: (Moderate) Concurrent use of atazanavir with pravastatin may result in elevated pravasatin serum concentrations. Pravastatin is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an inhibitor of OATP1B1. Monitor for increased toxicities if these drugs are given together, such as myopathy.
Prednisone: (Moderate) Coadministration of prednisone with atazanavir may cause elevated prednisone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Prednisone is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Prilocaine: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects.
Prilocaine; Epinephrine: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects.
Primidone: (Major) Coadministration of primidone and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. Avoid coadministration of atazanavir with primidone unless atazanavir is boosted with ritonavir. Primidone is metabolized to phenobarbital and coadministration may also result in decreased phenobarbital concentrations. If atazanavir and primidone are used together, the patient must be closely monitored for antiviral efficacy and decreased primidone efficacy; clinical monitoring of phenobarbital concentrations with dosage titration if necessary is also warranted.
Probenecid; Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and atazanavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Atazanavir can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken atazanavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
Progesterone: (Moderate) Use caution if coadministration of atazanavir with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Atazanavir is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Propafenone: (Major) Avoid coadministration of atazanavir and propafenone when possible. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of propafenone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and propafenone.
Proton pump inhibitors: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Protriptyline: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Quazepam: (Major) CYP3A4 inhibitors, such as protease inhibitors, may reduce the metabolism of quazepam and increase the potential for benzodiazepine toxicity. A decrease in the quazepam dose may be needed.
Quetiapine: (Major) Avoid concurrent use of quetiapine and anti-retroviral protease inhibitors, such as atazanavir. Atazanavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of atazanavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If atazanavir is discontinued, increase the quetiapine dose by 6-fold.
Quinidine: (Major) Caution is advised when administering quinidine with atazanavir. If atazanavir is boosted with ritonavir, concurrent use of quinidine is contraindicated. Use of all 3 drugs together may significantly increase quinidine concentrations and increase the risk for QT prolongation and serious or life-threatening cardiac arrhythmias. Atazanavir and ritonavir are CYP3A4 inhibitors; quinidine is metabolized by this enzyme.
Quinine: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
Quizartinib: (Major) Avoid concomitant use of atazanavir with quizartinib due to the risk of increased quizartinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of quizartinib to 26.5 mg for patients taking a daily dose of 53 mg, and to 17.7 mg for patients taking a daily dose of 35.4 mg or 26.5 mg; interrupt quizartinib therapy for the duration of the strong CYP3A inhibitor use for patients already taking a daily dose of 17.7 mg. Quizartinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of quizartinib by 94%.
Rabeprazole: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Ramelteon: (Moderate) The serum concentrations of ramelteon may increase when ramelteon is administered with strong CYP3A4 inhibitors like the anti-retroviral protease inhibitors. Because there is the potential for multiple CYPP450 enzyme inhibition interactions between protease inhibitors and ramelteon, caution should be used if these 2 drugs are coadministered. The patient should be monitored closely for toxicity even though ramelteon has a wide therapeutic index.
Ranitidine: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Ranolazine: (Major) Coadministration of ranolazine and atazanavir; cobicistat is contraindicated. A dose reduction may be required if ranolazine is coadminsitered with atazanavir alone. According to the manufacturer, the ranolazine dosage should be limited to 500 mg PO twice daily for patients receiving drugs known to be moderate CYP3A inhibitors. Ranolazine is metabolized mainly by CYP3A. Although not specifically mentioned by the manufacturer, atazanavir is known to inhibit CYP3A4. A reduction in the ranolazine dose may be prudent if these two agents are administered concurrently.
Red Yeast Rice: (Contraindicated) The risk of myopathy, including rhabdomyolysis, may be increased when anti-retroviral protease inhibitors are given in combination with most HMG-CoA reductase inhibitors. Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, coadministration of red yeast rice with anti-retroviral protease inhibitors is not recommended.
Regorafenib: (Major) Avoid coadministration of regorafenib with atazanavir due to increased plasma concentrations of regorafenib and decreased plasma concentrations of the active metabolites M-2 and M-5, which may lead to increased toxicity. Regorafenib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased regorafenib exposure by 33% and decreased exposure of M-2 and M-5 by 93% each.
Relugolix; Estradiol; Norethindrone acetate: (Major) Atazanavir may decrease the metabolism of oral contraceptives and non-oral combination contraceptives; the mean exposure and minimum serum concentrations of ethinyl estradiol and norethindrone are increased when administered with atazanavir 400 mg daily. However, if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased; data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Moderate) Atazanavir has been shown to decrease the metabolism of ethinyl estradiol; a similar interaction may occur with other estrogens used for hormone replacement therapy. Patients should be instructed to report any estrogen- related adverse events.
Repaglinide: (Moderate) Coadministration of repaglinide and protease inhibitors may increase or decrease glucose concentrations and increase repaglinide AUC; if coadministration is necessary, repaglinide dosage adjustment may be necessary and increased frequency of glucose monitoring is recommended. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. In addition, repaglinide is a substrate of the hepatic isoenzyme CYP3A4 and the drug transporter organic anion transporting polypeptide (OATP1B1); protease inhibitors are potent CYP3A4 inhibitors and inhibitors of OATP.
Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as atazanavir boosted with ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Revefenacin: (Major) Coadministration of revefenacin with atazanavir is not recommended because it could lead to an increase in systemic exposure of the active metabolite of revefenacin and an increase in potential for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1 and OATP1B3; atazanavir is an in vitro inhibitor of OATP1B1.
Ribavirin: (Major) The concomitant use of ribavirin and anti-retroviral protease inhibitors should be done with caution as both can cause hepatic damage. Most protease inhibitors have been associated with episodes of liver toxicity, with lopinavir/low-dose ritonavir, fosamprenavir/low-dose ritonavir, and nelfinavir being less hepatotoxic and tipranavir/low-dose ritonavir being the most hepatotoxic. Hyperbilirubinemia is often associated with atazanavir and/or indinavir therapy but does not reflect liver damage and is related to the inhibition of UDP glucuronosyltransferase. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
Ribociclib: (Contraindicated) Coadministration of ribociclib with atazanavir is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to atazanavir may also increase. Ribociclib is a strong CYP3A4 inhibitor and is extensively metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor and CYP3A4 substrate.
Ribociclib; Letrozole: (Contraindicated) Coadministration of ribociclib with atazanavir is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to atazanavir may also increase. Ribociclib is a strong CYP3A4 inhibitor and is extensively metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor and CYP3A4 substrate.
Rifabutin: (Major) Reduce the rifabutin dose to 150 mg PO once daily and monitor for adverse effects, such as uveitis and neutropenia, if concomitant use with atazanavir is necessary. Avoid concurrent use of rifabutin and atazanavir boosted with cobicistat. Although the FDA-approved labeling recommends reducing the rifabutin dose by at least 75% (to a maximum 150 mg every other day or 3 times per week), lower rifabutin exposure has been reported in persons living with HIV than in healthy subjects and acquired rifamycin resistance has been reported in these persons receiving 3 times weekly regimens. Monitor response and consider therapeutic drug monitoring (TDM) when rifabutin is used with atazanavir boosted with ritonavir and adjust dose accordingly. Rifabutin is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with atazanavir/ritonavir increased the AUC of rifabutin by approximately 110%.
Rifampin: (Contraindicated) Atazanavir is contraindicated for use with rifampin. Rifampin induces CYP isoenzymes, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Rifapentine: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Rilpivirine: (Moderate) Close clinical monitoring is advised when administering atazanavir with rilpivirine due to an increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Atazanavir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Rimegepant: (Major) Avoid coadministration of rimegepant with atazanavir; concurrent use may significantly increase rimegepant exposure. Rimegepant is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of rimegepant with another strong CYP3A4 inhibitor increased rimegepant exposure by 4-fold.
Ripretinib: (Moderate) Monitor patients more frequently for ripretinib-related adverse reactions if coadministered with atazanavir. Coadministration may increase the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions. Ripretinib and DP-5439 are metabolized by CYP3A4 and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ripretinib and DP-5439 exposure by 99%.
Risperidone: (Major) Avoid coadministration of atazanavir and risperidone when possible. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of risperidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and risperidone.
Ritonavir: (Minor) Coadministration of atazanavir with ritonavir results in higher atazanavir concentrations; reduced adult doses of atazanavir 300 mg once daily are recommended when ritonavir (100 mg once daily) is given concomitantly. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including atazanavir) has not been evaluated. Atazanavir is a CYP3A4 substrate; ritonavir is a strong inhibitor of CYP3A4.
Rivaroxaban: (Moderate) Close monitoring for increased bleeding is recommended when rivaroxaban is administered with atazanavir. If atazanavir is boosted with ritonavir, concurrent use of rivaroxaban should be avoided. Taking these drugs together may significantly increase rivaroxaban concentrations. Atazanavir and ritonavir are CYP3A4 inhibitors; rivaroxaban is metabolized by this enzyme. Additionally, rivaroxaban is a P-glycoprotein (P-gp) substrate; ritonavir is a P-gp inhibitor.
Romidepsin: (Moderate) The concomitant use of romidepsin, a CYP3A4 substrate, and atazanavir, a strong CYP3A4 inhibitor, may increase romidepsin plasma exposure. If these agents are used together, monitor patients for signs and symptoms of romidepsin toxicity including hematologic toxicity, infection, and electrocardiogram changes; therapy interruption or discontinuation or a dosage reduction may be required if toxicity develops.
Ropivacaine: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
Rosuvastatin: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with atazanavir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Rosuvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an OATP1B1 inhibitor. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis.
Rosuvastatin; Ezetimibe: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with atazanavir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Rosuvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an OATP1B1 inhibitor. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis.
Ruxolitinib: (Major) Reduce the ruxolitinib dosage when coadministered with atazanavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur. No dose adjustments are necessary for patients with graft-versus-host disease; however, monitor blood counts more frequently for toxicity and adjust ruxolitinib dosage for adverse reactions. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Avoid the use of atazanavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. Ruxolitinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor.
Sacituzumab Govitecan: (Major) Avoid coadministration of sacituzumab govitecan and atazanavir due to the risk of increased sacituzumab govitecan exposure which may increase the risk of adverse reactions. The cytotoxic component of sacituzumab govitecan, SN-38, is metabolized by UGT1A1 and atazanavir is a UGT1A1 inhibitor. Formal drug interaction studies with sacituzumab govitecan have not been conducted but the concomitant use of UGT1A1 inhibitors is expected to increase SN-38 exposure.
Sacubitril; Valsartan: (Moderate) Concurrent use of atazanavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Salmeterol: (Major) Avoid concomitant use of salmeterol with atazanavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Saquinavir: (Contraindicated) Concurrent administration of saquinavir boosted with ritonavir and atazanavir is contraindicated due to the risk of life threatening cardiac arrhythmias. Saquinavir boosted with ritonavir prolongs the QT and PR intervals in a dose-dependent fashion, and the impact of coadministering the combination with other drugs that prolong the PR interval, such as atazanavir, is not known. In addition, administration of atazanavir (300 mg daily) with saquinavir (1600 mg daily) and ritonavir (100 mg daily) resulted in an increased saquinavir AUC (by 60%). When administered with atazanavir, and in the presence of a high fat meal, there is a 4- to 7-fold increase in the AUC of saquinavir (soft-gelatin capsules, Fortovase).
Saxagliptin: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as atazanavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Secobarbital: (Major) Coadministration of secobarbital and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. If atazanavir and secobarbital are used together, the patient must be closely monitored for antiviral efficacy.
Segesterone Acetate; Ethinyl Estradiol: (Major) If ethinyl estradiol is administered with atazanavir boosted with ritonavir, it is recommended that the dose of ethinyl estradiol be at least 35 mcg. However, the dose of ethinyl estradiol should be no more than 30 mcg when administered with atazanavir that is NOT boosted by ritonavir. The mean exposure and minimum serum concentrations of ethinyl estradiol are increased when administered with atazanavir; but if atazanavir is boosted with ritonavir, mean exposure of ethinyl estradiol will be decreased. Data are limited regarding use of atazanavir with cobicistat. Instruct women to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. (Minor) Coadministration of segesterone and strong CYP3A4 inhibitors such as atazanavir may increase the serum concentration of segesterone.
Selumetinib: (Major) Avoid coadministration of selumetinib and atazanavir due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If atazanavir is discontinued, resume the original selumetinib dose after 3 elimination half-lives of atazanavir. Selumetinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selumetinib exposure by 49%.
Sildenafil: (Major) Sildenafil is contraindicated for use with atazanavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Silodosin: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
Simvastatin: (Contraindicated) The coadministration of anti-retroviral protease inhibitors with simvastatin is contraindicated. Taking these drugs together may significantly increase the serum concentration of simvastatin; thereby increasing the risk of myopathy and rhabdomyolysis. One report has demonstrated that ritonavir plus saquinavir therapy markedly increases the AUC for simvastatin by 3059%. Simvastatin is a substrate for CYP3A4 and the drug transporter organic anion transporting polypeptide (OATP1B1); protease inhibitors are CYP3A4 and OATP inhibitors.
Siponimod: (Moderate) Concomitant use of siponimod and atazanavir may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Sitagliptin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Sodium Bicarbonate: (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Sofosbuvir; Velpatasvir: (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with atazanavir. In an interaction study, use of these drugs together resulted in a 142% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of organic anion transporting polypeptide (OATP1B1), and to a lesser extent CYP3A and CYP2C8; atazanavir is an inhibitor of OATP1B1, CYP3A4, and CYP2C8.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of voxilaprevir and atazanavir. Taking these medications together may increase voxilaprevir plasma concentrations, potentially increasing the risk for adverse events. Voxilaprevir is a substrate for the drug transporter Organic Anion Transporting Polypeptides 1B1 (OATP1B1). Atazanavir is an OATP1B1 inhibitor. (Moderate) Monitor for velpatasvir-related adverse events when administering velpatasvir with atazanavir. In an interaction study, use of these drugs together resulted in a 142% increase in velpatasvir exposure; however, because data have not correlated velpatasvir exposure with toxicity, no dose adjustments are recommended. Velpatasvir is a substrate of organic anion transporting polypeptide (OATP1B1), and to a lesser extent CYP3A and CYP2C8; atazanavir is an inhibitor of OATP1B1, CYP3A4, and CYP2C8.
Solifenacin: (Major) Do not exceed a dose of 5 mg per day of solifenacin in patients receiving atazanavir as concurrent use may increase solifenacin exposure. Solifenacin is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased solifenacin exposure by 2.7-fold.
Sonidegib: (Major) Avoid concomitant use of sonidegib and atazanavir as increased sonidegib plasma are expected, resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. Atazanavir is a strong CYP3A4 inhibitor and may significantly increase the level of the CYP3A4 substrate, sonidegib. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of sonidegib by 2.2-fold and 1.5-fold, respectively.
Sotorasib: (Moderate) Monitor for decreased efficacy of atazanavir if coadministered with sotorasib. Concurrent use may decrease the plasma concentrations of atazanavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Atazanavir is a CYP3A substrate and sotorasib is a moderate CYP3A4 inducer.
Sparsentan: (Major) Avoid concomitant use of sparsentan and atazanavir. Concomitant use may increase sparsentan exposure and the risk for sparsentan-related adverse effects. Sparsentan is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased sparsentan overall exposure by 174%.
St. John's Wort, Hypericum perforatum: (Contraindicated) Coadministration of protease inhibitors and St. John's wort is contraindicated due to the risk of decreased plasma concentrations of the antiviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and St. John's wort is a strong CYP3A4 inducer.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if protease inhibitors must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of protease inhibitors is necessary. If protease inhibitors is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a CYP3A inhibitor like protease inhibitors can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If protease inhibitors is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Sulfonylureas: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Sumatriptan; Naproxen: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme.
Sunitinib: (Major) Avoid coadministration of atazanavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
Suvorexant: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with atazanavir. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and atazanavir is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
Tacrolimus: (Major) Decrease tacrolimus dose and closely monitor tacrolimus serum concentrations if coadministration with atazanavir is necessary; additional dosage reductions may be required. Concurrent use may increase tacrolimus serum concentrations and increase the risk of toxicity. Consider a tacrolimus dose reduction to 0.5 mg to 1 mg once per week when coadministered with a protease inhibitor. In one study, the tacrolimus half-life increased to 10.6 days in one patient and 20.6 days in another following coadministration of tacrolimus and lopinavir; ritonavir. Up to 80% reductions in tacrolimus dosages and 7-fold increase in dosage intervals were needed when tacrolimus was coadministered with protease inhibitors in studies. Tacrolimus is a sensitive CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor.
Tadalafil: (Major) For the treatment of erectile dysfunction, do not exceed 10 mg of tadalafil within 72 hours of atazanavir for the 'as needed' dose or 2.5 mg daily for the 'once-daily' dose. Avoid the use of tadalafil for pulmonary hypertension during the initiation of atazanavir therapy. Stop tadalafil at least 24 hours prior to starting atazanavir. After at least 1 week of atazanavir therapy, resume tadalafil at 20 mg once daily. Increase to 40 mg once daily based on tolerability. Tadalafil is metabolized by CYP3A4, and atazanavir is a potent inhibitor of CYP3A4. Substantially increased tadalafil plasma concentrations may result in increased adverse events including hypotension, syncope, visual changes, and prolonged erection. Although the manufacturer of tadalafil provides recommended dosing for coadministration with ritonavir only, the FDA recommends the same dosage adjustment for the coadministration of tadalafil with all protease inhibitors.
Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided.
Tapentadol: (Moderate) Caution is warranted when atazanavir is administered with tapentadol as there is a potential for elevated tapentadol concentrations. Tapentadol is a substrate of uridine glucoronyltransferase (UGT). Atazanavir is an inhibitor of UGT1A1.
Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and atazanavir. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as atazanavir, may increase exposure to tasimelteon with the potential for adverse reactions.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with atazanavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telmisartan; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with protease inhibitors is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Temsirolimus: (Major) Avoid coadministration of atazanavir with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider reducing the dose of temsirolimus to 12.5 mg per week. Allow a washout period of approximately 1 week after discontinuation of atazanavir before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor did not significantly affect temsirolimus exposure, but increased the AUC and Cmax of sirolimus by 3.1-fold and 2.2-fold, respectively.
Teniposide: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Atazanavir is an inhibitor of CYP3A4. Teniposide is a CYP3A4 substrate.
Tenofovir Alafenamide: (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Tenofovir Alafenamide: (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with t enofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering atazanavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8 and CYP3A4; atazanavir is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
Tezacaftor; Ivacaftor: (Major) If atazanavir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with atazanavir; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor/ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); atazanavir is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Theophylline, Aminophylline: (Moderate) Caution is warranted when atazanavir is administered with theophylline; aminophylline as there is a potential for elevated theophylline concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Theophylline is a substrate of CYP3A4; atazanavir is a CYP3A4 inhibitor.
Thiazolidinediones: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
Thiotepa: (Major) Avoid the concomitant use of thiotepa and atazanavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; atazanavir is a strong CYP3A4 inhibitor.
Tiagabine: (Moderate) The plasma concentrations of tiagabine may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while tiagabine is a CYP3A4 substrate.
Ticagrelor: (Moderate) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as atazanavir. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with atazanavir substantially increases ticagrelor exposure which may increase the bleeding risk.
Tinidazole: (Major) The plasma concentrations of tinidazole may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Tipranavir: (Contraindicated) Concurrent administration of tipranavir (in the FDA approved dosage regimen) with atazanavir ('boosted' with ritonavir 100 mg) results in decreased atazanavir and increased tipranavir concentrations. These drugs should not be coadministered.
Tisotumab Vedotin: (Moderate) Monitor for tisotumab vedotin-related adverse reactions if concomitant use with atazanavir is necessary due to increased monomethyl auristatin E (MMAE) exposure which may increase the incidence and severity of adverse reactions. MMAE, the active component of tisotumab vedotin, is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Clinical drug interaction studies have not been conducted for tisotumab vedotin. However, coadministration of another antibody-drug conjugate that contains MMAE with a strong CYP3A inhibitor increased unconjugated MMAE exposure by 34%.
Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with atazanavir. In patients receiving 5 mg or less twice daily, reduce to once daily dosing; in patients receiving 10 mg twice daily, reduce to 5 mg twice daily; in patients receiving 22 mg once daily of the extended-release (XR) formulation, switch to 11 mg XR once daily; in patients receiving 11 mg XR once daily, switch to the immediate-release formulation at a dose of 5 mg once daily. Tofacitinib exposure is increased when coadministered with atazanavir. Atazanavir is a strong CYP3A4 inhibitor; tofacitinib is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased tofacitinib exposure by 2-fold.
Tolterodine: (Major) Reduce the dose of immediate-release tolterodine to 1 mg twice daily and extended-release tolterodine to 2 mg once daily if coadministered with atazanavir. Concurrent use may increase tolterodine exposure. Atazanavir is a strong CYP3A4 inhibitor. In CYP2D6 poor metabolizers, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor CYP2D6 metabolizers, reduced doses of tolterodine are advised when administered with strong CYP3A4 inhibitors. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the tolterodine AUC by 2.5-fold in CYP2D6 poor metabolizers.
Tolvaptan: (Contraindicated) The concomitant use of tolvaptan and atazanavir is contraindicated. Concurrent use is expected to increase tolvaptan exposure. Tolvaptan is a sensitive CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Coadministration of another strong CYP3A4 inhibitor increased tolvaptan exposure 5-fold. No data exists regarding the appropriate dose adjustment needed to allow safe administration of tolvaptan with strong CYP3A4 inhibitors.
Topiramate: (Moderate) Caution is warranted when atazanavir is administered with topiramate as there is a potential for decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Atazanavir is a substrate of CYP3A4.
Toremifene: (Major) Avoid coadministration of atazanavir with toremifene if possible due to increased plasma concentrations of toremifene which may result in QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner, and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased toremifene exposure by 2.9-fold; exposure to N-demethyltoremifene was reduced by 20%.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with atazanavir due to the risk of increased trabectedin exposure. Trabectedin is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
Trandolapril; Verapamil: (Moderate) Coadministration of ritonavir with verapamil may increase the serum concentrations of verapamil, potentially resulting in verapamil toxicity. The manufacturer for ritonavir recommends caution when coadministering this combination. A similar effect could be expected with other anti-retroviral protease inhibitors, which are also inhibitors of CYP3A4.
Trazodone: (Major) Avoid coadministration of trazodone with atazanavir due to the potential for increased trazodone exposure and associated adverse effects including QT prolongation. If concurrent use cannot be avoided, consider a reduced dose of trazodone based on tolerability. Trazodone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of trazodone alone.
Triamcinolone: (Moderate) Atazanavir may inhibit the CYP3A4 metabolism of triamcinolone, resulting in increased plasma triamcinolone concentrations and reduced serum cortisol concentrations. There have been reports of clinically significant drug interactions in patients receiving another strong CYP3A4 inhibitor with triamcinolone, resulting in systemic corticosteroid effects including, but not limited to, Cushing syndrome and adrenal suppression. Consider the benefit-risk of concomitant use and monitor for systemic corticosteroid side effects. Consider using an alternative treatment to triamcinolone, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). In some patients, a corticosteroid dose adjustment may be needed. If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal.
Triazolam: (Contraindicated) Coadministration of triazolam, a primary CYP3A4 substrate, with strong CYP3A4 inhibitors, such as protease inhibitors, is contraindicated by the manufacturer of triazolam due to the risk for increased and prolonged sedation and respiratory depression. Concurrent use is expected to produce large increases in systemic exposure to triazolam, with the potential for serious adverse effects.
Tricyclic antidepressants: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Trimipramine: (Moderate) According to the manufacturer, concurrent use of tricyclic antidepressants (TCAs) and atazanavir may result in elevated TCA plasma concentration, and could increase the potential for serious adverse effects. If these drugs are administered together, carefully titrate the TCA dose based on a clinical assessment of antidepressant response. Patients on a stable dose of TCA who start treatment with atazanavir should be monitored for TCA-associated anticholinergic effects (e.g., sedation, confusion, constipation). In addition to clinical monitoring, the manufacturer suggests obtaining TCA serum concentrations (where available) as an adjunct to assessing the potential for interactions.
Ubrogepant: (Contraindicated) Coadministration of ubrogepant and atazanavir is contraindicated as concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor resulted in a 9.7-fold increase in the exposure of ubrogepant.
Ulipristal: (Minor) Ulipristal is a substrate of CYP3A4 and atazanavir is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
Umeclidinium; Vilanterol: (Moderate) Caution is warranted when atazanavir is administered with umeclidinium; vilanterol as there is a potential for elevated umeclidinium; vilanterol concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Umeclidinium; vilanterol is a substrate of CYP3A4. Atazanavir is an inhibitor of CYP3A4.
Upadacitinib: (Major) During concomitant use of upadacitinib and atazanavir reduce the upadacitinib dosage to 15 mg once daily. During induction for ulcerative colitis and Crohn's disease reduce the upadacitinib dosage to 30 mg once daily. Concomitant use may increase upadacitinib exposure and risk for adverse effects. Concomitant use with another strong CYP3A inhibitor increased upadacitinib overall exposure 1.75-fold.
Valproic Acid, Divalproex Sodium: (Major) Caution is warranted when atazanavir is administered with valproic acid as there is a potential for elevated valproic acid concentrations and altered concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Valproic acid is a substrate of uridine glucoronyltransferase (UGT). Atazanavir is an inhibitor of UGT1A1. In addition valproic acid is a weak inhibitor and inducer (in vitro) of CYP3A4; atazanavir is a CYP3A4 substrate.
Valsartan: (Moderate) Concurrent use of atazanavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of atazanavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with atazanavir due to increased vardenafil exposure. Use reduced doses of no more than 2.5 mg every 72 hours of vardenafil oral tablets with increased monitoring for adverse reactions. Vardenafil is primarily metabolized by CYP3A4/5; atazanavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to16-fold.
Vemurafenib: (Major) Avoid the concomitant use of vemurafenib and atazanavir; vemurafenib exposure may be increased resulting in an increased risk of adverse events, including QT prolongation. If use with atazanavir cannot be avoided, consider a vemurafenib dose reduction; monitor patients closely for the development of adverse events and dose reduce or discontinue therapy based on manufacturer guidance. Vemurafenib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of vemurafenib by 40%.
Venetoclax: (Major) Coadministration of atazanavir with venetoclax is contraindicated during the initiation and ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); consider an alternative medication or adjust the venetoclax dose with close monitoring for toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) in patients receiving a steady daily dose of venetoclax if concurrent use is necessary. In patients with acute myeloid leukemia (AML), reduce the venetoclax dose and monitor for toxicity during concurrent use. Resume the original venetoclax dose 2 to 3 days after discontinuation of atazanavir. Specific venetoclax dosage adjustments are as follows: CLL/SLL patients at steady daily dose: 100 mg/day. AML patients: 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, then 100 mg/day starting on day 4. Venetoclax is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of strong CYP3A4 inhibitors increased the venetoclax AUC by 90% to 690% in drug interaction studies.
Verapamil: (Moderate) Coadministration of ritonavir with verapamil may increase the serum concentrations of verapamil, potentially resulting in verapamil toxicity. The manufacturer for ritonavir recommends caution when coadministering this combination. A similar effect could be expected with other anti-retroviral protease inhibitors, which are also inhibitors of CYP3A4.
Vilazodone: (Major) Because CYP3A4 is the primary isoenzyme involved in the metabolism of vilazodone, the manufacturer of vilazodone recommends that the daily dose not exceed 20 mg/day during concurrent use of a strong CYP3A4 inhibitor, such as atazanavir. The original vilazodone dose can be resumed when the CYP3A4 inhibitor is discontinued.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with atazanavir is necessary. Vinblastine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor.
Vincristine Liposomal: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Vincristine: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with atazanavir is necessary. Vinorelbine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor.
Voclosporin: (Contraindicated) Concomitant use of voclosporin and atazanavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of atazanavir and vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of atazanavir reducing its efficacy.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of atazanavir and vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of atazanavir reducing its efficacy. (Major) Coadministration with atazanavir increases clarithromycin serum concentrations. Use caution if these drugs are coadministered, as increased clarithromycin concentrations may cause QT prolongation; a 50% dosage reduction of clarithromycin is recommended. In addition, atazanavir significantly reduces the concentration of 14-OH clarithromycin, the active metabolite of clarithromycin; consider alternative agents for indications other than infections due to Mycobacterium avium complex (MAC).
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and atazanavir. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with atazanavir, a CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Voriconazole: (Major) Avoid concurrent use of voriconazole and atazanavir boosted with ritonavir, unless the benefits justify the risks. If used together, health care providers are advised to monitor for loss of virologic and fungal efficacy, as well as potential voriconazole-related adverse effects. In one drug-drug interaction study, coadministration resulted in decreased atazanavir pharmacokinetic parameters (AUC, Cmax, Cmin). The pharmacokinetic parameter of voriconazole were also altered; however the effect depended a functional CYP2C19 allele. In this study, the pharmacokinetic parameters of voriconazole were reduced in patients with at least one function CYP2C19 allele, and elevated in patients without a function CYP2C19 allele. No pharmacokinetic data are available for concurrent use of voriconazole and unboosted atazanavir.
Warfarin: (Moderate) Monitor the INR and adjust the dose as necessary if warfarin is coadministered with atazanavir. Concurrent use may increase the INR and the risk of bleeding. Atazanavir is a CYP3A4 inhibitor and the R-enantiomer of warfarin is a 3A4 substrate. The S-enantiomer exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zafirlukast: (Moderate) Zafirlukast is a CYP3A4 inhibitor, and serum concentrations of atazanavir, a CYP3A4 substrate, may increase with coadministration. Coadminister these drugs with caution due to the potential for atazanavir toxicity.
Zaleplon: (Moderate) Zaleplon is partially metabolized by CYP3A4, and concurrent use of strong CYP3A4 inhibitors, such as atazanavir, may decrease the clearance of zaleplon. Routine dosage adjustments of zaleplon are not required. Dosage adjustments should be made on an individual basis according to efficacy and tolerability.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with atazanavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of atazanavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Ziprasidone: (Major) Avoid coadministration when possible. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of ziprasidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and ziprasidone. Downward dosage adjustment of ziprasidone may be necessary.
Zolmitriptan: (Moderate) Caution is warranted when atazanavir is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; atazanavir is a CYP3A4 inhibitors.
Zolpidem: (Moderate) Consider decreasing the dose of zolpidem if coadministration with protease inhibitors is necessary. Zolpidem is a CYP3A4 substrate and protease inhibitors are strong CYP3A4 inhibitors. Coadministration with strong CYP3A4 inhibitors increased the AUC of zolpidem by 34% to 70%.

How Supplied

Atazanavir/Atazanavir Sulfate/Reyataz Oral Cap: 150mg, 200mg, 300mg
Reyataz Oral Pwd F/Recon: 50mg

Maximum Dosage
Adults

300 mg/day PO with ritonavir and 400 mg/day PO without ritonavir for oral capsules; 300 mg/day PO for oral powder. 

Geriatric

300 mg/day PO with ritonavir and 400 mg/day PO without ritonavir for oral capsules; 300 mg/day PO for oral powder. 

Adolescents

40 kg or more: 300 mg/day PO with ritonavir and 400 mg/day PO without ritonavir for oral capsules; 300 mg/day PO for oral powder.
35 to 39 kg: 300 mg/day PO for oral capsules and oral powder.
25 to 34 kg: 200 mg/day PO for oral capsules; 300 mg/day PO for oral powder.

Children

Oral capsules
6 to 12 years weighing 35 kg or more: 300 mg/day PO.
6 to 12 years weighing 15 to 34 kg: 200 mg/day PO.
1 to 5 years or weighing less than 15 kg: Safety and efficacy have not been established.
 
Oral powder
25 kg or more: 300 mg/day PO.
15 to 24 kg: 250 mg/day PO.
5 to 14 kg: 200 mg/day PO.

Infants

3 to 11 months weighing 5 to 14 kg: 200 mg/day PO for oral powder.
3 to 11 months weighing less than 5 kg: Safety and efficacy have not been established.
1 to 2 months: Not recommended due to the risk of hyperbilirubinemia.

Neonates

Not recommended due to the risk of hyperbilirubinemia.

Mechanism Of Action

Atazanavir inhibits the human immunodeficiency virus (HIV) type 1 aspartic protease, which is an enzyme involved in the replication of HIV. Protease plays a key role in the post-translational processing of the gag and gag-pol gene products into key structural proteins and replication enzymes of HIV-1. During the later stages of the HIV growth cycle, the gag and gag-pol gene products are first translated into polyproteins and become immature budding particles. Protease is responsible for cleaving these precursor molecules to produce the final structural proteins of a mature virion core and to activate reverse transcriptase for a new round of infection. Thus, protease is necessary for the production of mature virions. Protease inhibition renders the virus noninfectious. Because HIV protease inhibitors inhibit the HIV replication cycle after translation and before assembly, they are active in acutely and chronically infected cells, and in cells not normally affected by dideoxynucleoside reverse transcriptase inhibitors (i.e., monocytes and macrophages). The EC90 (90% effective concentration) of atazanavir is 9 to 15 nM. In vitro, atazanavir produces additive to moderately synergistic antiviral effects when combined with the reverse transcriptase inhibitors stavudine, zidovudine, tenofovir, zalcitabine, lamivudine, or didanosine, or the protease inhibitors saquinavir, nelfinavir, indinavir, ritonavir, lopinavir, or amprenavir.
 
Resistance to atazanavir can occur as a result of amino acid changes; the most common being I50L, N88S and 184V. Atazanavir resistance appears to be more likely if an isolate is resistant to 3 or more protease inhibitors. Among clinical isolates with a variety of protease inhibitor resistance profiles and genotypic patterns, the median atazanavir fold change for isolates resistant to 1 to 5 protease inhibitors was 1.6-, 2.1-, 4-, 6.2-, and 22-fold, respectively. Atazanavir has a distinct resistance profile; there is no obvious pattern of cross-resistance between atazanavir and any other protease inhibitor. Protease inhibitor-naive patients that developed atazanavir resistance mostly had development of the 150L mutation, which did not confer resistance and even increased susceptibility of the strain to other protease inhibitors. However, protease inhibitor-experienced patients often had development of mutations that conferred resistance to atazanavir and other protease inhibitors. Atazanavir-resistant virus remained sensitive to saquinavir and somewhat sensitive (0.1- to 71-fold reduction) to nelfinavir, indinavir, ritonavir, and amprenavir. Conversely, nelfinavir-, saquinavir-, and amprenavir-resistant strains remained sensitive to atazanavir. Indinavir- and ritonavir-resistant strains showed 6- to 9-fold reductions in sensitivity to atazanavir. In antiretroviral-experienced patients with prior virologic failure, coadministration of atazanavir with ritonavir is recommended. However, the number of baseline primary protease inhibitor mutations present affects the virologic response of atazanavir with ritonavir; if a patient displays 3 to 4 baseline primary protease inhibitor mutations the approximate response rate to atazanavir with ritonavir is 40%, and if a patient displays 5 or more baseline primary protease inhibitor mutations there is no apparent response to atazanavir with ritonavir.

Pharmacokinetics

Atazanavir is administered orally. It is 86% bound to albumin and 89% bound to alpha-1-acid glycoprotein. Atazanavir is extensively metabolized by the liver. The cytochrome P450 (CYP450) system, specifically CYP3A4, is the main metabolic pathway. None of the identified metabolites are active. After chronic receipt of 400 mg daily with a light meal, the mean elimination half-life is 7 hours. About 7% of radiotagged atazanavir is recovered in the feces and approximately 20% of the administered dose is recovered unchanged. Only 13% of radiotagged atazanavir appears in the urine and approximately 7% of the administered dose is recovered unchanged; renal elimination is not a significant elimination pathway. Atazanavir demonstrates nonlinear pharmacokinetics with greater than dose-proportional increases in AUC and Cmax values over the dose range of 200 to 800 mg once daily. Steady state is achieved between 4 to 8 days with an accumulation of approximately 2.3-fold.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C8, organic anion transporting polypeptide (OATP1B1), uridine glucoronyltransferase (UGT1A1)
Atazanavir is an inhibitor of the hepatic enzymes CYP3A and CYP2C8 (weak), and the drug transporters UGT1A1 and OATP1B1. It is a substrate of CYP3A4. Clinically significant interactions are not expected between atazanavir and substrates of CYP2C19, CYP2C9, CYP2D6, CYP2B6, CYP2A6, CYP1A2, or CYP2E1.

Oral Route

Atazanavir is rapidly absorbed with a Tmax of approximately 2.5 hours. Administration with food enhances bioavailability and reduces pharmacokinetic variability. Administration of a single 400 mg dose with a light meal (357 kcal, 8.2 g of fat, and 10.6 g of protein) resulted in an increase of 70% in the AUC and of 57% in the Cmax relative to the fasted state. Administration of a single 400 mg dose with a high-fat meal (721 kcal, 37.3 g of fat, and 29.4 g of protein) resulted in a 35% increase in AUC and no change in Cmax compared to fasting state. Administration with either type of meal decreased the coefficient of variation of AUC and Cmax by approximately one-half compared to the fasting state. Administration of a single 300 mg dose and ritonavir with a light meal (336 kcal, 5.1 g fat, 9.3 g protein) resulted in a 33% increase in the AUC and a 40% increase in the Cmax relative to the fasting state. Administration of a single 300 mg dose and ritonavir with a high-fat meal (951 kcal, 54.7 g fat, 35.9 g protein) did not affect the AUC compared to fasting conditions and the Cmax as well as the 24-hour concentration was within 11% of fasting values. The 24-hour concentration after a high-fat meal was increased by approximately 33% due to delayed absorption and the median Tmax increased from 2 to 5 hours. Administration with either type of meal decreased the coefficient of variation of AUC and Cmax by approximately 25% compared to the fasting state.

Pregnancy And Lactation
Pregnancy

Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. Atazanavir-containing regimens are recommended as alternative treatment options for use in pregnant patients and those trying to conceive. Atazanavir should be boosted with ritonavir during pregnancy, as drug levels are too low if given unboosted or boosted with cobicistat. The FDA-approved dose is 300 mg PO plus ritonavir 100 mg PO once daily; increase to 400 mg plus ritonavir 100 mg once daily during the second and third trimesters in treatment-experienced patients who are also taking either an H2-blocker or tenofovir. Atazanavir is not recommended for treatment-experienced patients who are taking BOTH an H2-blocker and tenofovir during the second and third trimesters. HIV guidelines suggest giving 400 mg plus ritonavir 100 mg PO once daily in all pregnant patients during the second and third trimesters. No dosage adjustment is necessary in postpartum patients; however, patients should be monitored closely for adverse effects because atazanavir exposure may be higher during the first 2 months after delivery. Available data from the Antiretroviral Pregnancy Registry, which includes more than 1,460 first trimester exposures, have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When atazanavir exposure occurred in the first trimester, the prevalence of defects was 2.5% (95% CI: 1.7 to 3.4). It should be taken into consideration that atazanavir is frequently associated with hyperbilirubinemia; all newborns exposed to atazanavir in utero should be monitored closely for hyperbilirubinemia during the first few days of life. In addition, healthcare professionals are advised to monitor for signs of lactic acidosis as severe, sometimes fatal, cases have occurred in pregnant patients who received atazanavir in combination with nucleoside analogues; nucleoside analogues are known to be associated with the development of lactic acidosis. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at deliver. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to atazanavir; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.

HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission; thus, replacement feeding is recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). There are limited data regarding the use of atazanavir during breast-feeding. In 1 small study involving 3 lactating women, the median ratio of atazanavir human breast milk to plasma concentration was 13%. Other antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.