Lexiva

Protease Inhibitors

Oral Administration Oral Solid Formulations

Tablets: May be taken with or without food. If administered with ritonavir, take with meals.

Oral Liquid Formulations

Oral Suspension: Administer to adults without food. Administer to pediatric patients with food. If emesis occurs within 30 minutes of administration, re-administer the dose. Shake vigorously before measuring a dose. Administer using a calibrated oral dosing syringe or dosing cup.

Severe

Stevens-Johnson syndrome / Delayed / 0-1.0
angioedema / Rapid / 0-1.0
myocardial infarction / Delayed / 0-1.0
diabetic ketoacidosis / Delayed / 0-1.0
hemolytic anemia / Delayed / 0-1.0

Moderate

hypertriglyceridemia / Delayed / 6.0-11.0
elevated hepatic enzymes / Delayed / 6.0-6.0
neutropenia / Delayed / 3.0-3.0
hyperglycemia / Delayed / 2.0-2.0
hypercholesterolemia / Delayed / 0-1.0
nephrolithiasis / Delayed / 0-1.0
diabetes mellitus / Delayed / 0-1.0
bleeding / Early / 0-1.0
lipodystrophy / Delayed / Incidence not known

Mild

vomiting / Early / 2.0-60.0
rash / Early / 8.0-19.0
nausea / Early / 7.0-7.0
diarrhea / Early / 5.0-5.0
headache / Early / 2.0-2.0
fatigue / Early / 2.0-2.0
abdominal pain / Early / 1.0-1.0
paresthesias / Delayed / 0-1.0
pruritus / Rapid / Incidence not known
maculopapular rash / Early / Incidence not known

Lexiva

Rx

Protease inhibitor (PI)
For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents
Prodrug of amprenavir; improved solubility compared to amprenavir allows for reduced pill burden

For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents. For the treatment of HIV in protease inhibitor-experienced patients. Oral dosage Adults

700 mg, with ritonavir (100 mg), PO twice daily. Administration without ritonavir, or the once-daily administration regimen, is not recommended.

Adult pregnant females

700 mg with ritonavir (100 mg) PO twice daily may be considered for virologically suppressed (HIV RNA less than 50 copies/mL) pregnant women who were already on a stable twice daily fosamprenavir; ritonavir regimen prior to pregnancy. Data regarding use of other fosamprenavir regimens during pregnancy are not available. Closely monitor viral loads to ensure viral suppression is maintained.[29012] HIV guidelines recommend switching women who become pregnant while taking fosamprenavir to an alternative treatment regimen.[23512]

Children and Adolescents weighing 20 kg or more

18 mg/kg/dose (Max: 700 mg/dose) PO twice daily plus ritonavir 3 mg/kg/dose (Max: 100 mg/dose) PO twice daily. Patients weighing at least 39 kg may receive tablets.

Children weighing 15 to 19 kg

23 mg/kg/dose PO twice daily plus ritonavir 3 mg/kg/dose PO twice daily.

Infants and Children 6 months and older weighing 11 to 14 kg

30 mg/kg/dose PO twice daily plus ritonavir 3 mg/kg/dose PO twice daily.

Infants and Children 6 months and older weighing less than 11 kg

45 mg/kg/dose PO twice daily plus ritonavir 7 mg/kg/dose PO twice daily.

For the treatment of HIV in protease inhibitor-naive patients. Oral dosage Adults

1,400 mg with ritonavir (either 100 mg or 200 mg) PO once daily, 1,400 mg PO twice daily (without ritonavir), or 700 mg with ritonavir (100 mg) PO twice daily. If administered as once daily dose with efavirenz, increase the ritonavir dosage to 300 mg.

Children and Adolescents weighing 20 kg or more

18 mg/kg/dose (Max: 700 mg/dose) PO twice daily plus ritonavir 3 mg/kg/dose (Max: 100 mg/dose) PO twice daily. Patients weighing at least 39 kg may receive tablets. The HIV guidelines do not recommend unboosted fosamprenavir in pediatric patients due to low drug exposures; however, the product labeling includes a dose of 30 mg/kg/dose (Max: 1,400 mg/dose) PO twice daily without ritonavir as an alternative in children 2 years and older.

Children weighing 15 to 19 kg

23 mg/kg/dose PO twice daily plus ritonavir 3 mg/kg/dose PO twice daily. The HIV guidelines do not recommend unboosted fosamprenavir in pediatric patients due to low drug exposures; however, the product labeling includes a dose of 30 mg/kg/dose PO twice daily without ritonavir as an alternative in children 2 years and older.

Infants and Children 6 months and older weighing 11 to 14 kg

30 mg/kg/dose PO twice daily plus ritonavir 3 mg/kg/dose PO twice daily. The HIV guidelines do not recommend unboosted fosamprenavir in pediatric patients due to low drug exposures; however, the product labeling includes a dose of 30 mg/kg/dose PO twice daily without ritonavir as an alternative in children 2 years and older.

Infants and Children 6 months and older weighing less than 11 kg

45 mg/kg/dose PO twice daily plus ritonavir 7 mg/kg/dose PO twice daily. The HIV guidelines do not recommend unboosted fosamprenavir in pediatric patients due to low drug exposures; however, the product labeling includes a dose of 30 mg/kg/dose PO twice daily without ritonavir as an alternative in children 2 years and older.

Infants 4 weeks to 5 months

The HIV guidelines do not recommend fosamprenavir with ritonavir in infants younger than 6 months due to low drug exposures in this population. Fosamprenavir should only be administered to infants born at 38 weeks gestation or greater and who have attained a post-natal age of 28 days. The FDA-approved dosage is 45 mg/kg/dose PO twice daily plus ritonavir 7 mg/kg/dose PO twice daily for infants less than 11 kg and 30 mg/kg/dose PO twice daily plus ritonavir 3 mg/kg/dose PO twice daily for infants 11 to 14 kg.

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

As an alternative to preferred regimens, guidelines recommend fosamprenavir 1,400 mg PO once daily boosted with ritonavir 100 mg PO once daily, in combination with tenofovir and either emtricitabine or lamivudine. For patients unable to receive tenofovir, fosamprenavir/ritonavir (1,400 mg/100 mg) PO daily may be administered in combination with zidovudine and either lamivudine or emtricitabine. According to HIV post-exposure prophylaxis (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

Hepatic Impairment

For adults with mild hepatic impairment (Child-Pugh score of 5—6), use with caution at a reduced dose of 700 mg twice daily without ritonavir (in treatment-naive patients only) or 700 mg twice daily plus ritonavir 100 mg once daily (treatment-naive or experienced patients). For adults with moderate hepatic impairment (Child-Pugh score of 7—9), use with caution at a reduced dose of 700 mg twice daily without ritonavir (in treatment-naive patients only) or 450 mg twice daily plus ritonavir 100 mg once daily (treatment-naive or experienced patients). For adults with severe hepatic impairment (Child-Pugh score of 10—15), use with caution at a reduced dose of 350 mg twice daily without ritonavir (in treatment-naive patients only) or 300 mg twice daily plus ritonavir 100 mg once daily (treatment-naive or experienced patients). For pediatric patients with hepatic impairment, no data are available to define dosing recommendations.

Renal Impairment

Dosing in patients with renal impairment has not been studied. Less than 2% is excreted unchanged in the urine, therefore, the effect of renal impairment on elimination should be minimal.

Abacavir; Dolutegravir; Lamivudine: (Major) Avoid concurrent use of dolutegravir and fosamprenavir boosted with ritonavir in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For INSTI-naive adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with fosamprenavir/ritonavir. Use of these drugs together results in decreased dolutegravir plasma concentrations.
Abemaciclib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with fosamprenavir is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with fosamprenavir. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
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) Consider a reduced dose of dihydrocodeine with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. If fosamprenavir is discontinued, consider increasing the dihydrocodeine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Concomitant use of dihydrocodeine with fosamprenavir 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 fosamprenavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Fosamprenavir is a moderate inhibitor of CYP3A, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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 fosamprenavir is necessary. If fosamprenavir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with moderate CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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 increased fosamprenavir toxicity if coadministered with adagrasib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
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 fosamprenavir 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 fosamprenavir has cleared from the circulation (approximately 3 half-lives of fosamprenavir) 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; fosamprenavir is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted.
Afatinib: (Major) Increase the daily dose of afatinib by 10 mg as tolerated if the concomitant use with fosamprenavir is necessary; resume the previous dose of afatinib 2 to 3 days after discontinuation of fosamprenavir. Afatinib is a P-glycoprotein (P-gp) substrate and fosamprenavir is a P-gp inducer; coadministration may decrease plasma concentrations of afatinib. Pre-treatment with another strong P-gp inducer decreased afatinib exposure by 34%.
Albuterol; Budesonide: (Major) Avoid coadministration of oral budesonide with fosamprenavir due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
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) Caution is advised when administering aliskiren with fosamprenavir, as concurrent use may alter the plasma concentrations of aliskiren. Aliskiren is a substrate for the hepatic isoenzyme CYP3A4 and the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advised when administering aliskiren with fosamprenavir, as concurrent use may alter the plasma concentrations of aliskiren. Aliskiren is a substrate for the hepatic isoenzyme CYP3A4 and the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with fosamprenavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and fosamprenavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and fosamprenavir 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: (Moderate) Fosamprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P450 3A4. Although drug interaction studies have not been conducted, the serum concentrations of alosetron may be increased with concomitant administration of fosamprenavir.
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: (Major) Avoid coadministration of alprazolam and fosamprenavir due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with fosamprenavir, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased alprazolam exposure by 1.6- to 1.98-fold.
Amiodarone: (Moderate) Monitor for an increase in adverse reactions from both drugs during concomitant use of amiodarone and fosamprenavir. Concomitant use may increase the exposure of both drugs. Amiodarone and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
Amitriptyline: (Moderate) An increased plasma concentration of amitriptyline is seen when coadministered with fosamprenavir; therapeutic concentration monitoring is recommended when coadministered.
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) Do not exceed 20 mg/day of atorvastatin if coadministration with fosamprenavir is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Use the lowest possible atorvastatin dose. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Protease inhibitors inhibit the CYP3A4 metabolism of atorvastatin. (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) 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) 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.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with clarithromycin. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Antacids: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after antacids. Coadministration may decrease the exposure of fosamprenavir and impair its efficacy.
Apalutamide: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with apalutamide. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and apalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Apixaban: (Major) Avoid the concomitant administration of apixaban and drugs that are both strong inducers of CYP3A4 and P-gp, such as fosamprenavir. Concomitant administration of apixaban and fosamprenavir results in decreased exposure to apixaban and an increase in the risk of stroke.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of fosamprenavir and aprepitant/fosaprepitant due to substantially increased exposure of aprepitant. The exposure of fosamprenavir may also be increased. Fosaprepitant is rapidly converted to aprepitant; therefore, a similar interaction is likely. Aprepitant and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors. Administration of a moderate CYP3A inhibitor increased the aprepitant AUC by 2-fold.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of fosamprenavir. Patients receiving both a CYP2D6 inhibitor plus fosamprenavir may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; fosamprenavir is a moderate CYP3A inhibitor.
Armodafinil: (Major) Caution is advised when administering armodafinil with fosamprenavir, as concurrent use may reduce the plasma concentrations of both drugs. Armodafinil is an inducer of the hepatic isoenzyme CYP3A4 and a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a substrate of CYP3A4.
Artemether; Lumefantrine: (Major) Artemether; lumefantrine is an inhibitor and fosamprenavir is a substrate/inhibitor of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased fosamprenavir concentrations. Additionally, artemether; lumefantrine is a substrate and fosamprenavir is an inhibitor of the CYP3A4 isoenzyme; therefore, concomitant use may lead to increased artemether; lumefantrine concentrations. Concomitant use warrants caution due to the potential for increased side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after oral sodium bicarbonate. Coadministration of antacids, such as sodium bicarbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. If fosamprenavir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with moderate CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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.
Atazanavir: (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.
Atazanavir; Cobicistat: (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. (Major) Coadministration of cobicistat with fosamprenavir is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations. Cobicistat is not interchangeable with ritonavir as a boosting agent to fosamprenavir.
Atorvastatin: (Major) Do not exceed 20 mg/day of atorvastatin if coadministration with fosamprenavir is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Use the lowest possible atorvastatin dose. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Protease inhibitors inhibit the CYP3A4 metabolism of atorvastatin.
Atorvastatin; Ezetimibe: (Major) Do not exceed 20 mg/day of atorvastatin if coadministration with fosamprenavir is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Use the lowest possible atorvastatin dose. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Protease inhibitors inhibit the CYP3A4 metabolism of atorvastatin.
Avanafil: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving fosamprenavir. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Administration of another moderate CYP3A inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Avapritinib: (Major) Avoid coadministration of avapritinib with fosamprenavir due to the risk of increased avapritinib-related adverse reactions. If concurrent use is unavoidable, reduce the starting dose of avapritinib from 300 mg PO once daily to 100 mg PO once daily in patients with gastrointestinal stromal tumor or from 200 mg PO once daily to 50 mg PO once daily in patients with advanced systemic mastocytosis. Avapritinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration of avapritinib 300 mg PO once daily with another moderate CYP3A inhibitor is predicted to increase the overall exposure of avapritinib by 210% at steady-state.
Axitinib: (Major) Avoid coadministration of axitinib with fosamprenavir 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 fosamprenavir is discontinued. Axitinib is a CYP3A4/5 substrate and fosamprenavir 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 fosamprenavir 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; fosamprenavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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.
Barbiturates: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with barbiturates. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and barbiturates are strong CYP3A inducers. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as fosamprenavir, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, fosamprenavir may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions, such as QT prolongation and hepatotoxicity.
Benzhydrocodone; Acetaminophen: (Moderate) Consider a reduced dose of benzhydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A substrate, and coadministration with moderate CYP3A inhibitors like fosamprenavir 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 benzhydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If fosamprenavir 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 benzhydrocodone.
Berotralstat: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with berotralstat. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor.
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. Amprenavir is a strong CYP3A4 inhibitor and betamethasone is a CYP3A4 substrate. Fosamprenavir is a prodrug of amprenavir. 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.
Betrixaban: (Major) Avoid concomitant administration of betrixaban and fosamprenavir. Concomitant administration of betrixaban and fosamprenavir results in decreased plasma concentrations of betrixaban that may be insufficient to achieve the intended therapeutic effect. Betrixaban is P-glycoprotein (P-gp) substrate and fosamprenavir is a P-gp inducer.
Bexarotene: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with bexarotene. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Bortezomib: (Moderate) In vitro studies with human liver microsomes indicate that bortezomib is a significant substrate for CYP3A4. Agents that inhibit CYP3A4, such fosamprenavir, 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.
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 fosamprenavir as bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. 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 CYP3A inhibitor.
Brexpiprazole: (Moderate) Use caution if coadministration of fosamprenavir with brexpiprazole is necessary, as the systemic exposure of brexpiprazole may be increased resulting in an increase in brexpiprazole-related adverse reactions. Reduce the dose of brexpiprazole to one-quarter (25%) of the usual dose if brexpiprazole and fosamprenavir are coadministered with a moderate to strong inhibitor of CYP2D6 or if the patient is a poor metabolizer of CYP2D6. If fosamprenavir is discontinued, adjust the brexpiprazole dosage to its original level. Brexpiprazole is a CYP3A and CYP2D6 substrate; fosamprenavir is a moderate CYP3A inhibitor. Concomitant use of moderate CYP3A inhibitors with a strong or moderate CYP2D6 inhibitor increased the exposure of brexpiprazole compared to use of brexpiprazole alone.
Brigatinib: (Major) Avoid coadministration of brigatinib with fosamprenavir 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 40% without breaking tablets (i.e., from 180 mg to 120 mg; from 120 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of fosamprenavir, resume the brigatinib dose that was tolerated prior to initiation of fosamprenavir. Brigatinib is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the AUC of brigatinib by approximately 40%.
Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of fosamprenavir. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A; fosamprenavir is a moderate inhibitor of CYP3A. Coadministration with another moderate CYP3A inhibitor increased bromocriptine exposure by 2.8-fold.
Budesonide: (Major) Avoid coadministration of oral budesonide with fosamprenavir due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Budesonide; Formoterol: (Major) Avoid coadministration of oral budesonide with fosamprenavir due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid coadministration of oral budesonide with fosamprenavir due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Bupivacaine Liposomal: (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Bupivacaine: (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Bupivacaine; Epinephrine: (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with fosamprenavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Bupivacaine; Meloxicam: (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Buprenorphine: (Moderate) Concomitant use of buprenorphine and fosamprenavir can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when fosamprenavir is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping fosamprenavir, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If fosamprenavir is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A and fosamprenavir is a CYP3A inhibitor.
Buprenorphine; Naloxone: (Moderate) Concomitant use of buprenorphine and fosamprenavir can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when fosamprenavir is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping fosamprenavir, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If fosamprenavir is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A and fosamprenavir is a CYP3A inhibitor.
Buspirone: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with fosamprenavir is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and fosamprenavir is added or removed from therapy. Buspirone is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with fosamprenavir 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 fosamprenavir is a strong CYP3A4 inhibitor; data also suggest that fosamprenavir has the potential to induce CYP3A4. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%; concomitant use with a strong CYP3A4 inducer decreased cabazitaxel exposure by 17%.
Cabotegravir; Rilpivirine: (Moderate) Coadministration of rilpivirine with fosamprenavir may result in increased plasma concentrations of rilpivirine, leading to an increase in rilpivirine-related adverse effects. Rilpivirine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Cabozantinib: (Major) Avoid concomitant use of cabozantinib and fosamprenavir 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 fosamprenavir 2 to 3 days after discontinuation of fosamprenavir. Cabozantinib is a CYP3A substrate and fosamprenavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Calcium Carbonate: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after calcium carbonate. Coadministration of antacids, such as calcium carbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after calcium carbonate. Coadministration of antacids, such as calcium carbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after calcium carbonate. Coadministration of antacids, such as calcium carbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after calcium carbonate. Coadministration of antacids, such as calcium carbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Calcium Carbonate; Simethicone: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after calcium carbonate. Coadministration of antacids, such as calcium carbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Calcium; Vitamin D: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after calcium carbonate. Coadministration of antacids, such as calcium carbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Canagliflozin: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if canagliflozin is coadministered with fosamprenavir. 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.
Canagliflozin; Metformin: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if canagliflozin is coadministered with fosamprenavir. 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. (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 treatment-related adverse reactions if coadministration of capmatinib with fosamprenavir is necessary. Capmatinib is a CYP3A substrate and a P-glycoprotein (P-gp) inhibitor. Fosamprenavir is a strong CYP3A4 inhibitor and a P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%. Inhibitors of P-gp may increase fosamprenavir exposure.
Carbamazepine: (Moderate) Monitor for decreased efficacy of fosamprenavir during coadministration of carbamazepine. Additionally, monitor carbamazepine concentrations closely as increased side effects may occur; dose adjustments may be needed. Concomitant use may result in decreased plasma concentrations of fosamprenavir and increased carbamazepine concentrations. Fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When strong CYP3A4 inhibitors, such as amprenavir or fosamprenavir, are 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 a 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.
Carvedilol: (Moderate) Caution is advised when administering carvedilol with fosamprenavir, as concurrent use may result in elevated fosamprenavir and reduced carvedilol plasma concentrations. Carvedilol is an inhibitor and substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer and substrate.
Celecoxib; Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with fosamprenavir is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of fosamprenavir, a moderate CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Cenobamate: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with cenobamate. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and cenobamate is a moderate CYP3A inducer.
Ceritinib: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with ceritinib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Chloramphenicol: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with chloramphenicol. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
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) An increased plasma concentration of amitriptyline is seen when coadministered with fosamprenavir; therapeutic concentration monitoring is recommended when coadministered.
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 fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Consider a reduced dose of dihydrocodeine with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. If fosamprenavir is discontinued, consider increasing the dihydrocodeine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Concomitant use of dihydrocodeine with fosamprenavir 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 fosamprenavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Fosamprenavir is a moderate inhibitor of CYP3A, 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 fosamprenavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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.
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%.
Ciprofloxacin: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with ciprofloxacin. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor.
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: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with clarithromycin. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of fosamprenavir as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; fosamprenavir is a strong inhibitor of CYP3A4.
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) Consider a clozapine dose reduction if coadministered with fosamprenavir and monitor for adverse reactions. If fosamprenavir is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP3A and fosamprenavir is a moderate CYP3A inhibitor.
Cobicistat: (Major) Coadministration of cobicistat with fosamprenavir is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations. Cobicistat is not interchangeable with ritonavir as a boosting agent to fosamprenavir.
Cobimetinib: (Major) Avoid using cobimetinib and fosamprenavir together for more than 14 days due to the risk for cobimetinib toxicity. For short-term coadministration, defined as 14 days or less of combination therapy, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg per day; consider alternative therapy for patients already taking a reduced dose of cobimetinib (40 or 20 mg per day). After discontinuation of fosamprenavir, resume cobime

tinib 60 mg per day. Cobimetinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Simulations have demonstrated that a short course of cobimetinib 20 mg once daily taken with a moderate CYP3A inhibitor produces similar concentrations to cobimetinib 60 mg per day alone.
Codeine: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with fosamprenavir 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 fosamprenavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fosamprenavir 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. Fosamprenavir is a moderate inhibitor of CYP3A4.
Colchicine: (Major) Avoid concomitant use of colchicine and fosamprenavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Conivaptan: (Moderate) Monitor for increased toxicity of fosamprenavir if coadministered with conivaptan. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Conjugated Estrogens; Medroxyprogesterone: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Copanlisib: (Major) Avoid the concomitant use of copanlisib and fosamprenavir if possible due to an unpredictable effect on copanlisib exposure. 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) and/or decreased copanlisib efficacy. Copanlisib is a CYP3A substrate; fosamprenavir is a strong CYP3A4 inhibitor with the potential to also induce CYP3A4.
Crizotinib: (Moderate) Monitor for an increase in adverse reactions from both drugs if crizotinib is coadministered with fosamprenavir. Concomitant use may increase the exposure of both drugs. Crizotinib and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
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.
Dabigatran: (Major) In general, avoid coadministration of dabigatran with P-glycoprotein (P-gp) inducers, such as fosamprenavir. Concomitant administration of dabigatran and rifampin, another P-gp inducer, resulted in a significant decrease in dabigatran AUC and Cmax.
Dabrafenib: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with dabrafenib. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with fosamprenavir, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of fosamprenavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Danazol: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with danazol. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
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: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if saxagliptin is coadministered with fosamprenavir. 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. (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.
Dapsone: (Minor) Fosamprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P450 3A4. Although drug interaction studies have not been conducted, the serum concentrations of dapsone may be increased with concomitant administration of fosamprenavir.
Daridorexant: (Major) Limit the daridorexant dose to 25 mg if coadministered with fosamprenavir. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use of another moderate CYP3A inhibitor increased daridorexant overall exposure 2.4-fold.
Darifenacin: (Moderate) Monitor for increased toxicity of darifenacin if coadministered with fosamprenavir. Coadministration may increase the exposure of darifenacin. Darifenacin is a sensitive CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor.
Darunavir: (Moderate) Monitor for an increase in adverse reactions from both drugs if concomitant use of darunavir and fosamprenavir is necessary. Concomitant use may increase the exposure of both drugs and the risk for adverse effects. Darunavir boosted with ritonavir or cobicistat is a CYP3A substrate and strong CYP3A inhibitor; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor.
Darunavir; Cobicistat: (Major) Coadministration of cobicistat with fosamprenavir is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations. Cobicistat is not interchangeable with ritonavir as a boosting agent to fosamprenavir. (Moderate) Monitor for an increase in adverse reactions from both drugs if concomitant use of darunavir and fosamprenavir is necessary. Concomitant use may increase the exposure of both drugs and the risk for adverse effects. Darunavir boosted with ritonavir or cobicistat is a CYP3A substrate and strong CYP3A inhibitor; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of cobicistat with fosamprenavir is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations. Cobicistat is not interchangeable with ritonavir as a boosting agent to fosamprenavir. (Moderate) Monitor for an increase in adverse reactions from both drugs if concomitant use of darunavir and fosamprenavir is necessary. Concomitant use may increase the exposure of both drugs and the risk for adverse effects. Darunavir boosted with ritonavir or cobicistat is a CYP3A substrate and strong CYP3A inhibitor; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor.
Dasatinib: (Major) Avoid coadministration of dasatinib and fosamprenavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to fosamprenavir 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 fosamprenavir 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 fosamprenavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; fosamprenavir 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 fosamprenavir. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A substrate; fosamprenavir is a moderate inhibitor of CYP3A.
Delavirdine: (Contraindicated) The coadministration of fosamprenavir with delavirdine is contraindicated. Coadministration may lead to loss of virologic response and possible resistance to delavirdine. In addition, the coadministration of delavirdine and fosamprenavir results in increased serum concentrations of fosamprenavir's active metabolite, amprenavir.
Desogestrel; Ethinyl Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Dexamethasone: (Moderate) Monitor for a decrease in fosamprenavir efficacy during concurrent use of fosamprenavir and dexamethasone. If long term coadministration is required, consider using an alternative corticosteroid, such as prednisone or prednisolone. Concomitant use may decrease fosamprenavir exposure leading to potential loss of virologic control. Fosamprenavir is a CYP3A4 substrate and dexamethasone is a weak CYP3A inducer.
Dextromethorphan; Quinidine: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with fosamprenavir is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
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.
Didanosine, ddI: (Moderate) It is recommended that the administration of fosamprenavir and buffered medications such as didanosine, ddI, be separated by at least 1 hour.
Dienogest; Estradiol valerate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Digoxin: (Moderate) Caution is advised when administering digoxin with fosamprenavir, as concurrent use may result in reduced digoxin plasma concentrations. Digoxin is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
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: (Moderate) Monitor blood pressure, heart rate, and for increased fosamprenavir-related adverse reactions if concurrent use of diltiazem and fosamprenavir is necessary. Concomitant use may increase the exposure of both drugs. Diltiazem and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
Disopyramide: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if concurrent use of fosamprenavir is necessary. Concomitant use may increase the exposure of disopyramide. Disopyramide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other moderate CYP3A inhibitors.
Docetaxel: (Major) Avoid coadministration of docetaxel with fosamprenavir 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 fosamprenavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
Dofetilide: (Moderate) Monitor for an increase in dofetilide-related adverse reactions, including QT prolongation, if coadministration with fosamprenavir is necessary as concurrent use may increase dofetilide exposure. Fosamprenavir is a moderate CYP3A inhibitor. Dofetilide is a minor CYP3A substrate; however, because there is a linear relationship between dofetilide plasma concentration and QTc, concomitant administration of CYP3A inhibitors may increase the risk of arrhythmia (torsade de pointes).
Dolutegravir: (Major) Avoid concurrent use of dolutegravir and fosamprenavir boosted with ritonavir in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For INSTI-naive adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with fosamprenavir/ritonavir. Use of these drugs together results in decreased dolutegravir plasma concentrations.
Dolutegravir; Lamivudine: (Major) Avoid concurrent use of dolutegravir and fosamprenavir boosted with ritonavir in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For INSTI-naive adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with fosamprenavir/ritonavir. Use of these drugs together results in decreased dolutegravir plasma concentrations.
Dolutegravir; Rilpivirine: (Major) Avoid concurrent use of dolutegravir and fosamprenavir boosted with ritonavir in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For INSTI-naive adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with fosamprenavir/ritonavir. Use of these drugs together results in decreased dolutegravir plasma concentrations. (Moderate) Coadministration of rilpivirine with fosamprenavir may result in increased plasma concentrations of rilpivirine, leading to an increase in rilpivirine-related adverse effects. Rilpivirine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Donepezil: (Moderate) Fosamprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P450 3A4, such as donepezil.
Donepezil; Memantine: (Moderate) Fosamprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P450 3A4, such as donepezil.
Doravirine: (Minor) Coadministration of doravirine and fosamprenavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; fosamprenavir 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: (Minor) Coadministration of doravirine and fosamprenavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; fosamprenavir 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 fosamprenavir. Fosamprenavir 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.
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) Avoid coadministration of doxorubicin with fosamprenavir due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a major substrate of CYP3A and fosamprenavir is a moderate CYP3A inhibitor. Concurrent use of CYP3A inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with fosamprenavir due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a major substrate of CYP3A and fosamprenavir is a moderate CYP3A inhibitor. Concurrent use of CYP3A inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronabinol: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with fosamprenavir. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor.
Dronedarone: (Moderate) Monitor for an increase in adverse reactions from both drugs if concurrent use of dronedarone and fosamprenavir is necessary. Concomitant use may increase the exposure of both drugs. Dronedarone and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
Drospirenone: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Drospirenone; Estetrol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Drospirenone; Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Drospirenone; Ethinyl Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
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: (Moderate) Monitor for an increase in adverse reactions from both drugs if concurrent use of duvelisib and fosamprenavir is necessary. Concomitant use may increase the exposure of both drugs. Duvelisib and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
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) Appropriate doses of unboosted fosamprenavir when coadministered with efavirenz have not been established. When fosamprenavir plus ritonavir is administered once daily and given in combination with efavirenz, the dose of ritonavir must be increased by 100 mg/day (300 mg total). No change in the ritonavir dose is required when efavirenz is administered with fosamprenavir plus ritonavir twice daily. Systemic concentrations of fosamprenavir are reduced when administered concurrently with efavirenz. Fosamprenavir is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Appropriate doses of unboosted fosamprenavir when coadministered with efavirenz have not been established. When fosamprenavir plus ritonavir is administered once daily and given in combination with efavirenz, the dose of ritonavir must be increased by 100 mg/day (300 mg total). No change in the ritonavir dose is required when efavirenz is administered with fosamprenavir plus ritonavir twice daily. Systemic concentrations of fosamprenavir are reduced when administered concurrently with efavirenz. Fosamprenavir is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Appropriate doses of unboosted fosamprenavir when coadministered with efavirenz have not been established. When fosamprenavir plus ritonavir is administered once daily and given in combination with efavirenz, the dose of ritonavir must be increased by 100 mg/day (300 mg total). No change in the ritonavir dose is required when efavirenz is administered with fosamprenavir plus ritonavir twice daily. Systemic concentrations of fosamprenavir are reduced when administered concurrently with efavirenz. Fosamprenavir is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Elacestrant: (Major) Avoid concomitant use of elacestrant and fosamprenavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Elagolix: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with elagolix. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir. (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with elagolix. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with fosamprenavir. Use of these drugs together may cause changes in the plasma concentrations of elbasvir, which could result in decreased virologic response or adverse reactions (i.e., hepatotoxicity). Fosamprenavir is a strong inhibitor and moderate inducer of CYP3A; elbasvir is a substrate of CYP3A. (Major) If possible, avoid concurrent administration of grazoprevir with fosamprenavir. Use of these drugs together may cause changes in the plasma concentrations of grazoprevir, which could result in decreased virologic response or adverse reactions (i.e., hepatotoxicity). Fosamprenavir is a strong inhibitor and moderate inducer of CYP3A; grazoprevir is a substrate of CYP3A. In addition, concentrations of fosamprenavir (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
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) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with fosamprenavir; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); fosamprenavir is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If fosamprenavir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to every other day in the morning when coadministered with fosamprenavir; omit the ivacaftor evening dose and administer in the morning every other day alternating with elexacaftor; tezacaftor; ivacaftor (i.e., recommended dose of elexacaftor; tezacaftor; ivacaftor on day 1 in the morning and recommended dose of ivacaftor on day 2 in the morning). Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; fosamprenavir is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure by 2.9-fold. Simulation suggests a moderate inhibitor may increase elexacaftor and tezacaftor exposure by 2.3-fold and 2.1-fold, respectively.
Eliglustat: (Major) Avoid coadministration of eliglustat with fosamprenavir in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Concurrent use is contraindicated in EMs and IMs also receiving a strong or moderate CYP2D6 inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate; fosamprenavir is a moderate inhibitor of CYP3A. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of cobicistat with fosamprenavir is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations. Cobicistat is not interchangeable with ritonavir as a boosting agent to fosamprenavir. (Moderate) Coadministration of fosamprenavir boosted with ritonavir and elvitegravir results in an unknown effect on the plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is: elvitegravir 150 mg PO once daily with fosamprenavir/ritonavir 700/100 mg PO twice daily. No data are available for use of other doses.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of cobicistat with fosamprenavir is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations. Cobicistat is not interchangeable with ritonavir as a boosting agent to fosamprenavir. (Moderate) Coadministration of fosamprenavir boosted with ritonavir and elvitegravir results in an unknown effect on the plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is: elvitegravir 150 mg PO once daily with fosamprenavir/ritonavir 700/100 mg PO twice daily. No data are available for use of other doses.
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) Closely monitor for changes in glycemic control and hyperglycemia if linagliptin is coadministered with fosamprenavir. 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. (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; Metformin: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if linagliptin is coadministered with fosamprenavir. 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. (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.
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) Coadministration of rilpivirine with fosamprenavir may result in increased plasma concentrations of rilpivirine, leading to an increase in rilpivirine-related adverse effects. Rilpivirine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of rilpivirine with fosamprenavir may result in increased plasma concentrations of rilpivirine, leading to an increase in rilpivirine-related adverse effects. Rilpivirine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Encorafenib: (Major) Avoid coadministration of encorafenib and fosamprenavir due to increased encorafenib exposure. If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of fosamprenavir. If fosamprenavir is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of fosamprenavir. Encorafenib is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 2-fold and 45%, respectively.
Entrectinib: (Major) Avoid coadministration of entrectinib with fosamprenavir due to increased entrectinib exposure which may increase the risk for entrectinib-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 200 mg PO once daily. If fosamprenavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of fosamprenavir. Entrectinib is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor is predicted to increase the overall exposure of entrectinib by 3-fold.
Enzalutamide: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with enzalutamide. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and enzalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with fosamprenavir in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving fosamprenavir, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. Measure serum creatinine and serum potassium within 3 to 7 days of initiating fosamprenavir and periodically thereafter. Eplerenone is a CYP3A substrate. Fosamprenavir is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and fosamprenavir 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 fosamprenavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and fosamprenavir 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 coadministration of erlotinib with fosamprenavir if possible due to the increased risk of 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 fosamprenavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure 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.
Erythromycin: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with erythromycin. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Eslicarbazepine: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with eslicarbazepine. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
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).
Estradiol; Levonorgestrel: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Estradiol; Norethindrone: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Estradiol; Norgestimate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Estradiol; Progesterone: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Estrogens: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing estrogens with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the estrogen and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of estrogens and fosamprenavir boosted with ritonavir.
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) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Ethinyl Estradiol; Norgestrel: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Al ternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Ethosuximide: (Moderate) Fosamprenavir may inhibit the metabolism of ethosuximide and may necessitate up to a 50% dose reduction of ethosuximide.
Ethotoin: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with phenytoin or fosphenytoin. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Etonogestrel: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Etonogestrel; Ethinyl Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Etravirine: (Major) Avoid concurrent use of etravirine and fosamprenavir. Concomitant use of etravirine with fosamprenavir without low-dose ritonavir may cause a significant increase in the plasma concentrations of fosamprenavir. Appropriate dose adjustments for combination therapy with etravirine and fosamprenavir boosted with ritonavir have not been established.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with fosamprenavir is necessary. The dose of everolimus may need to be reduced. Everolimus is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
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.
Fedratinib: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with fedratinib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor.
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.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as fosamprenavir, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of fosamprenavir during coadministration with fenofibric acid.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. If fosamprenavir is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A substrate, and coadministration with CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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) Monitor for an increase in tadalafil-related adverse reactions if coadministration with fosamprenavir is necessary. The prescribing information for fosamprenavir recommends to avoid coadministration of tadalafil for the treatment of pulmonary hypertension and to stop tadalafil at least 24 hours prior to starting fosamprenavir. After at least 1 week of fosamprenavir therapy, resume tadalafil at 20 mg once daily. Increase to 40 mg once daily based on tolerability. For the treatment of erectile dysfunction, the prescribing information for fosamprenavir recommends to not exceed 10 mg tadalafil within 72 hours of fosamprenavir for the 'as needed' dose or 2.5 mg daily for the 'once-daily' dose. Tadalafil is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Although specific interactions have not been studied, moderate CYP3A inhibitors would likely increase tadalafil exposure.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or fosamprenavir; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased overall exposure to finerenone by 248%.
Flecainide: (Major) Concurrent use of fosamprenavir boosted with ritonavir and flecainide is contraindicated. When administered with ritonavir, fosamprenavir is expected to increase plasma concentrations of flecainide, causing the potential for serious and/or life threatening adverse reactions, including cardiac arrhythmia.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and fosamprenavir is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of fosamprenavir, start flibanserin at least 2 weeks after the last dose of fosamprenavir. If initiating fosamprenavir following flibanserin use, start fosamprenavir at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fluconazole: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with fluconazole. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
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.
Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and fosamprenavir 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; fosamprenavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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 fosamprenavir. 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 fosamprenavir is a moderate CYP3A inhibitor. (Major) Coadministration of inhaled fluticasone propionate and fosamprenavir 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; fosamprenavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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 fosamprenavir 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; fosamprenavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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) Concomitant use of umeclidinium and fosamprenavir may result in decreased umeclidinium plasma concentrations. Umeclidinium is a substrate of the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp. (Moderate) Concomitant use of vilanterol and fosamprenavir may result in altered vilanterol plasma concentrations. Vilanterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Fluticasone; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and fosamprenavir 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; fosamprenavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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) Concomitant use of vilanterol and fosamprenavir may result in altered vilanterol plasma concentrations. Vilanterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Fluvastatin: (Moderate) Concurrent use of fosamprenavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Fosamprenavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, fosamprenavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Fluvoxamine: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with fluvoxamine. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor.
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.
Formoterol; Mometasone: (Moderate) Concomitant administration of fosamprenavir and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with fosamprenavir long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor.
Fosphenytoin: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with phenytoin or fosphenytoin. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
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; fosamprenavir is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and fosamprenavir due to the risk of decreased ganaxolone efficacy. If concomitant use is unavoidable, consider increasing ganaxolone dose without exceeding the maximum daily dose. Ganaxolone is a CYP3A4 substrate and fosamprenavir is a moderate CYP3A4 inducer.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with fosamprenavir is necessary. Gefitinib is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
Gilteritinib: (Major) Consider an alternative to fosamprenavir 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; fosamprenavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study.
Glasdegib: (Major) Avoid coadministration of glasdegib and fosamprenavir as concurrent use may alter glasdegib exposure and lead to increased toxicity (e.g.,QT interval prolongation) and/or decreased efficacy. If coadministration cannot be avoided, monitor for increased adverse events; more frequent ECG monitoring may be prudent. Glasdegib is a substrate of CYP3A4; fosamprenavir is both a strong CYP3A4 inhibitor and may also be a moderate CYP3A4 inducer. The net effect of fosamprenavir on CYP3A4 substrates is unknown, but fosamprenavir increases the concentrations of some CYP3A4 substrates. Coadministration with strong CYP3A4 inhibitors is predicted to increase glasdegib exposure by 2.4-fold while coadministration with moderate CYP3A4 inducers is predicted to decrease glasdegib exposure by 55%.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of pibrentasvir and fosamprenavir as coadministration may decrease serum concentrations of pibrentasvir and/or increase serum concentrations of fosamprenavir. This may result in decreased efficacy of pibrentasvir and/or increased fosamprenavir-related adverse effects. Pibrentasvir is a substrate and inhibitor of P-glycoprotein (P-gp); fosamprenavir is a substrate and inducer of P-gp.
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.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during fosamprenavir treatment due to the risk of increased fosamprenavir exposure and adverse reactions. Fosamprenavir is a CYP3A substrate and grapefruit juice is a strong CYP3A inhibitor.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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) Decrease the dose of extended-release guanfacine by 50% if coadministration with fosamprenavir is necessary; if fosamprenavir is discontinued, the dose of extended-release guanfacine may be increased to the recommended level. Monitor patients closely for adverse effects including hypotension, drowsiness, lethargy, and bradycardia. Recommendations for immediate-release guanfacine are not available. Guanfacine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
H2-blockers: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with H2-blockers. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Haloperidol: (Moderate) Fosamprenavir is an inhibitor of CYP3A4. CYP3A4 is one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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.
Hydantoins: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with phenytoin or fosphenytoin. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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 fosamprenavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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 fosamprenavir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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.
Ibrutinib: (Major) If ibrutinib is coadministered with fosamprenavir, reduce the initial ibrutinib dosage to 280 mg/day PO in patients receiving ibrutinib for a B-cell malignancy. Resume ibrutinib at the previous dose if fosamprenavir is discontinued. No initial ibrutinib dosage reduction is necessary in patients receiving ibrutinib for chronic graft-versus-host disease. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection); modify the ibrutinib dosage as recommended if toxicity occurs. Ibrutinib is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A inhibitor, the AUC value of ibrutinib was increased by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. If fosamprenavir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with moderate CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with idelalisib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with fosamprenavir is necessary. Ifosfamide is metabolized by CYP3A to its active alkylating metabolites. Fosamprenavir is a moderate CYP3A inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Major) Concomitant use of iloperidone and fosamprenavir may result in altered iloperidone plasma concentrations. Iloperidone is a substrate of the hepatic isoenzyme CYP3A4. Amprenavir, the active metabolite of fosamprenavir, is a strong inhibitor and moderate inducer of CYP3A4.
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: (Major) Increased plasma concentrations of the tricyclic antidepressant imipramine are seen when coadministered with fosamprenavir; therapeutic concentration monitoring is recommended when coadministered.
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.
Infigratinib: (Major) Avoid concomitant use of infigratinib and fosamprenavir. Coadministration may increase infigratinib exposure, increasing the risk of adverse effects. Infigratinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
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 fosamprenavir during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates; fosamprenavir is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure of irinotecan and SN-38.
Irinotecan: (Major) Avoid administration of fosamprenavir during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates; fosamprenavir is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure of irinotecan and SN-38.
Isavuconazonium: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with isavuconazonium. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Concurrent use of fosamprenavir and rifampin is contraindicated due to the risk of decreased plasma concentrations of fosamprenavir, which may result in potential loss of virologic control. Fosamprenavir is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Isoniazid, INH; Rifampin: (Contraindicated) Concurrent use of fosamprenavir and rifampin is contraindicated due to the risk of decreased plasma concentrations of fosamprenavir, which may result in potential loss of virologic control. Fosamprenavir is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
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 fosamprenavir as istradefylline exposure and adverse effects may increase. Fosamprenavir 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: (Moderate) Monitor for increased toxicity of both drugs if fosamprenavir is coadministered with itraconazole; an itraconazole dose reduction may be needed for patients receiving more than 400 mg/day. Concurrent use may increase the plasma concentrations of both drugs. Fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor; itraconazole is a CYP3A substrate and strong CYP3A inhibitor.
Ivabradine: (Major) Avoid coadministration of ivabradine and fosamprenavir as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Ivacaftor: (Major) If fosamprenavir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with fosamprenavir due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. Ivosidenib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor is predicted to increase the ivosidenib single-dose AUC to 173% of control based on physiologically-based pharmacokinetic modeling, with no change in Cmax. Multiple doses of the moderate CYP3A inhibitor are predicted to increase the ivosidenib steady-state AUC to 152% of control and AUC to 190% of control.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of fosamprenavir is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Ketoconazole: (Moderate) Monitor for increased toxicity of both drugs if fosamprenavir is coadministered with ketoconazole; a ketoconazole dose reduction may be needed for patients receiving more than 400 mg/day. Concurrent use may increase the plasma concentrations of both drugs. Fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor; ketoconazole is a CYP3A substrate and strong CYP3A inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with clarithromycin. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Lapatinib: (Major) Avoid coadministration of lapatinib with fosamprenavir due to increased plasma concentrations of lapatinib. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily. If fosamprenavir is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate and fosamprenavir 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: (Moderate) Monitor for an increase in larotrectinib-related adverse reactions if concomitant use with fosamprenavir is necessary. Concomitant use may increase larotrectinib exposure. Larotrectinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase larotrectinib exposure by 2.7-fold.
Ledipasvir; Sofosbuvir: (Moderate) Caution is advised when administering sofosbuvir with fosamprenavir, as concurrent use may result in reduced sofosbuvir plasma concentrations. Sofosbuvir is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
Lefamulin: (Moderate) Monitor for an increase in adverse reactions from both drugs if oral lefamulin is administered with fosamprenavir. Concomitant use may increase the exposure of both drugs. An interaction is not expected with intravenous lefamulin. Lefamulin and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
Lemborexant: (Major) Avoid coadministration of lemborexant and fosamprenavir as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the lemborexant overall exposure by up to 4.5-fold.
Lenacapavir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with lenacapavir. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Letermovir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with letermovir. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and letermovir is a moderate CYP3A inhibitor. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine.
Leuprolide; Norethindrone: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
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: (Moderate) Monitor for increased toxicity of both drugs if fosamprenavir is coadministered with ketoconazole; a ketoconazole dose reduction may be needed for patients receiving more than 400 mg/day. Concurrent use may increase the plasma concentrations of both drugs. Fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor; ketoconazole is a CYP3A substrate and strong CYP3A inhibitor.
Levomilnacipran: (Major) The adult dose of levomilnacipran should not exceed 80 mg/day during concurrent use of strong CYP3A4 inhibitors. Amprenavir and fosamprenavir are considered strong inhibitors of CYP3A4. Levomilnacipran is partially metabolized by CYP3A4, and decreased metabolism of the drug can lead to an increased risk of adverse effects such as urinary retention.
Levonorgestrel: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Levonorgestrel; Ethinyl Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with fosamprenavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with fosamprenavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with fosamprenavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Linagliptin: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if linagliptin is coadministered with fosamprenavir. 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.
Linagliptin; Metformin: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if linagliptin is coadministered with fosamprenavir. 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. (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 fosamprenavir and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with fosamprenavir is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Although concomitant use of moderate CYP3A inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A inhibitor.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and fosamprenavir is contraindicated; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. The exposure of fosamprenavir may also be increased. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; fosamprenavir is a CYP3A4 substrate and moderate CYP3A4 inhibitor.
Loperamide: (Moderate) The plasma concentration of loperamide, a CYP3A4 and P-glycoprotein (P-gp) substrate, may be altered when administered concurrently with fosamprenavir, a potent inhibitor and inducer of CYP3A4 and inducer of P-gp. If these drugs are used together, monitor for both decreased loperamide efficacy and loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Loperamide; Simethicone: (Moderate) The plasma concentration of loperamide, a CYP3A4 and P-glycoprotein (P-gp) substrate, may be altered when administered concurrently with fosamprenavir, a potent inhibitor and inducer of CYP3A4 and inducer of P-gp. If these drugs are used together, monitor for both decreased loperamide efficacy and loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Lopinavir; Ritonavir: (Major) Concurrent use of fosamprenavir and lopinavir; ritonavir may alter the concentrations of both drugs. An increased rate of adverse reactions has been observed with coadministration of these medications. Appropriate doses of the combinations with respect to safety and efficacy have not been established. Coadministration of fosamprenavir (twice daily, boosted with ritonavir) and lopinavir; ritonavir tablets (400/100 mg) decreased the fosamprenavir AUC by 63% and increased the lopinavir; ritonavir AUC by 37%. Coadministration of fosamprenavir (1,400 mg twice daily) and lopinavir; ritonavir (533/133 mg twice daily) decreased the fosamprenavir AUC by 26%.
Lorlatinib: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with lorlatinib. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and lorlatinib is a moderate CYP3A inducer.
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 fosamprenavir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with lumacaftor; ivacaftor. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Lumacaftor; Ivacaftor: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with lumacaftor; ivacaftor. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Lumateperone: (Major) Avoid coadministration of lumateperone and fosamprenavir as concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor increased lumateperone exposure by approximately 2-fold.
Lurasidone: (Major) The recommended starting dose of lurasidone is 20 mg daily (maximum, 80 mg daily) if coadministration with fosamprenavir is necessary. Reduce the lurasidone dose to half of its original dose level if fosamprenavir is added to existing lurasidone therapy. Lurasidone is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased lurasidone exposure by 116%.
Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and fosamprenavir due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with fosamprenavir is necessary. Maraviroc is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors may result in increased maraviroc concentrations.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting fosamprenavir therapy. Avoid initiation of fosamprenavir in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable fosamprenavir therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Additionally, monitor for decreased fosamprenavir efficacy as concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a CYP3A substrate and moderate CYP3A inducer; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Medroxyprogesterone: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Mefloquine: (Moderate) Use mefloquine with caution if coadministration with fosamprenavir is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and fosamprenavir is a moderate CYP3A inhibitor.
Meperidine: (Moderate) Consider a reduced dose of meperidine with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. If fosamprenavir is discontinued, meperidine plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to meperidine. Meperidine is a substrate of CYP3A and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with fosamprenavir can increase meperidine exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of meperidine.
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: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if saxagliptin is coadministered with fosamprenavir. 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. (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) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of fosamprenavir is necessary. If fosamprenavir is di scontinued, methadone plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Methadone is a substrate of CYP3A, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with fosamprenavir can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone.
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) Concomitant use of methylprednisolone and fosamprenavir may result in altered methylprednisolone plasma concentrations. Monitor closely. Methylprednisolone is a substrate of CYP3A4. Amprenavir, the active metabolite of fosamprenavir, is a potent inhibitor of CYP3A4, but may also induce this enzyme to some degree. The net effect is likely increased methylprednisolone exposure.
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 fosamprenavir 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 fosamprenavir 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: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with mifepristone. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
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.
Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fosamprenavir may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Moderate) Concurrent administration of mirtazapine and fosamprenavir 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.
Mitapivat: (Moderate) Do not exceed mitapivat 20 mg PO twice daily during coadministration with fosamprenavir and monitor hemoglobin and for adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased mitapivat overall exposure by 2.6-fold.
Mitotane: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with mitotane. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and mitotane is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and fosamprenavir; reduce the dose of mobocertinib by approximately 50% and monitor the QT interval more frequently if use is necessary. Concomitant use may increase mobocertinib exposure and the risk for adverse reactions. Mobocertinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Use of a moderate CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 100% to 200%.
Modafinil: (Major) Caution is advised when administering modafinil with fosamprenavir, as concurrent use may reduce the plasma concentrations of fosamprenavir. Modafinil is an inducer of the hepatic isoenzyme CYP3A4. Amprenavir, the active metabolite of fosamprenavir, is a substrate of CYP3A4.
Mometasone: (Moderate) Concomitant administration of fosamprenavir and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with fosamprenavir long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor.
Morphine: (Moderate) Caution is advised when administering morphine with fosamprenavir, as concurrent use may result in reduced morphine plasma concentrations. Morphine is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
Morphine; Naltrexone: (Moderate) Caution is advised when administering morphine with fosamprenavir, as concurrent use may result in reduced morphine plasma concentrations. Morphine is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
Nafcillin: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with nafcillin. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and nafcillin is a moderate CYP3A inducer.
Naldemedine: (Moderate) Monitor for naldemedine-related adverse reactions if coadministered with fosamprenavir. Naldemedine plasma concentrations may increase during concomitant use. Naldemedine is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor.
Naloxegol: (Major) Avoid concomitant administration of naloxegol and fosamprenavir due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with fosamprenavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A 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 CYP3A 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.
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.
Nefazodone: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with nefazodone. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and nefazodone is a moderate CYP3A inhibitor.
Nelfinavir: (Moderate) Monitor for an increase in adverse reactions from both drugs if concurrent use of nelfinavir and fosamprenavir is necessary. Concomitant use may increase the exposure of both drugs. Nelfinavir is a CYP3A substrate and strong CYP3A inhibitor; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor.
Neratinib: (Major) Avoid concomitant use of fosamprenavir with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and fosamprenavir 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) Monitor for increased fosamprenavir toxicity if coadministered with netupitant. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor.
Nevirapine: (Major) Coadministration of nevirapine and fosamprenavir without ritonavir is not recommended as significant decreases in amprenavir concentrations (active metabolite) may occur. If fosamprenavir and ritonavir, given as the twice daily dosage regimen, are administered with nevirapine, no dosage adjustments are needed. Additionally, monitor for an increase in nevirapine-related adverse reactions if coadministration with fosamprenavir is necessary. Nevirapine is a CYP3A4 substrate and weak CYP3A inducer; fosamprenavir is a CYP3A substrate and strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
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) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with fosamprenavir as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor.
Nilotinib: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with nilotinib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor.
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.
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%.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Norethindrone: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Norethindrone; Ethinyl Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Norgestimate; Ethinyl Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Norgestrel: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Olaparib: (Major) Avoid coadministration of olaparib with fosamprenavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after fosamprenavir is discontinued. Olaparib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
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 fosamprenavir is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and fosamprenavir may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If fosamprenavir is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A substrate and fosamprenavir is a moderate CYP3A 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) Concomitant administration of fosamprenavir and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with fosamprenavir long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and fosamprenavir. If concomitant use is necessary, decrease omaveloxolone dose to 100 mg once daily; additional dosage reductions may be necessary. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased omaveloxolone overall exposure by 1.25-fold.
Omeprazole; Amoxicillin; Rifabutin: (Major) Reduce rifabutin dose to 150 mg PO once daily and monitor for adverse effects, such as uveitis and neutropenia, if concomitant use of fosamprenavir is necessary. Concomitant use may increase rifabutin exposure. There are no clinically significantly alterations in fosamprenavir pharmacokinetics. Rifabutin is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with fosamprenavir/ritonavir significantly increased the AUC of the active metabolite of rifabutin.
Omeprazole; Sodium Bicarbonate: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after oral sodium bicarbonate. Coadministration of antacids, such as sodium bicarbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Ondansetron: (Moderate) Concomitant use of ondansetron and fosamprenavir may result in altered ondansetron plasma concentrations. Ondansetron is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Oritavancin: (Major) Coadministration of oritavancin and fosamprenavir may result in increases or decreases in fosamprenavir exposure and may increase side effects or decrease efficacy of fosamprenavir. Fosamprenavir is metabolized by CYP3A4, CYP2D6, and CYP2C9. Oritavancin weakly induces CYP3A4 and CYP2D6, while weakly inhibiting CYP2C9. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
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 fosamprenavir; concurrent use may increase osilodrostat exposure and the risk of osilodrostat-related adverse reactions. Osilodrostat is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor.
Ospemifene: (Moderate) Coadministration of fosamprenavir and ospemifene may increase ospemifene systemic concentrations and increase the risk of ospemifene-related adverse reactions. Fosamprenavir is a prodrug for amprenavir. Amprenavir is a strong CYP3A4 inhibitor, and ospemifene is a CYP3A4 substrate. Strong CYP3A4 inhibitors increase the systemic exposure of ospemifene by approximately 1.4-fold.
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 fosamprenavir is necessary. If fosamprenavir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with moderate CYP3A inhibitors like fosamprenavir 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 fosamprenavir 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) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with fosamprenavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A 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 CYP3A inhibitors.
Pacritinib: (Major) Avoid concurrent use of pacritinib with fosamprenavir due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Palbociclib: (Major) Avoid coadministration of fosamprenavir 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 fosamprenavir is discontinued, increase the palbociclib dose (after 3 to 5 half-lives of fosamprenavir) to the dose used before initiation of fosamprenavir. Palbociclib is primarily metabolized by CYP3A4 and fosamprenavir 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.
Palovarotene: (Major) Avoid concomitant use of palovarotene and fosamprenavir due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. If concomitant use is necessary, decrease the palovarotene dose by half. Palovarotene is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased palovarotene overall exposure by 2.5-fold.
Panobinostat: (Major) Concomitant use of panobinostat and fosamprenavir may result in altered panobinostat plasma concentrations. Panobinostat is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
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.
Paroxetine: (Moderate) The combined use of fosamprenavir, boosted with ritonavir, and paroxetine significantly reduced plasma concentrations of paroxetine. Adjust paroxetine dosage based upon tolerability and efficacy of the combined regimen.
Pazopanib: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as amprenavir or fosamprenavir. 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 substrate for CYP3A4, and fosamprenavir, an inhibitor, an inducer, and a substrate of CYP3A4, may result in altered pazopanib and/or fosamprenavir concentrations.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and fosamprenavir 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 fosamprenavir is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of fosamprenavir. Pemigatinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase pemigatinib exposure by approximately 50% to 80%.
Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with fosamprenavir due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of fosamprenavir occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Fosamprenavir is a CYP3A4 inducer, and perampanel is a CYP3A4 substrate.
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) An increased plasma concentration of amitriptyline is seen when coadministered with fosamprenavir; therapeutic concentration monitoring is recommended when coadministered.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and fosamprenavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease fosamprenavir 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 fosamprenavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of fosamprenavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Phenytoin: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with phenytoin or fosphenytoin. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
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. Further, pimavanserin should be avoided in combination with moderate CYP3A4 inducers, Because fosamprenavir has both strong CYP3A4 inhibitory and moderate CYP3A4 inducer properties, the outcome of this potential interaction is unpredictable.
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) Concomitant use of pirfenidone and fosamprenavir may result in elevated fosamprenavir plasma concentrations. Pirfenidone is a mild in vitro inhibitor of the hepatic isoenzymes CYP2C9, CYP2D6, and CYP3A4, and an inhibitor of the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is substrate of P-gp, CYP2C9, CYP2D6, and CYP3A4.
Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of fosamprenavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; fosamprenavir 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 fosamprenavir 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 fosamprenavir and consider alternative therapy. After fosamprenavir has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting fosamprenavir. Ponatinib is a CYP3A4 substrate; fosamprenavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%.
Posaconazole: (Moderate) Monitor for breakthrough fungal infections and increased fosamprenavir toxicity if concomitant use of posaconazole and fosamprenavir is necessary. Concomitant use may decrease the plasma concentrations of posaconazole and increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with fosamprenavir decreased the AUC of posaconazole by 23%.
Pralsetinib: (Major) Avoid concomitant use of fosamprenavir 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 fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
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.
Praziquantel: (Major) In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Therefore, use of praziquantel with fosamprenavir, which is metabolized to a CYP3A4 inducer (amprenavir), should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
Prednisone: (Moderate) Concomitant use of prednisone and fosamprenavir may result in altered prednisone plasma concentrations. Prednisone is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and fosamprenavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Progesterone: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Progestins: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if coadministered with fosamprenavir; concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid use of propafenone and fosamprenavir if boosted with ritonavir or with another CYP2D6 inhibitor or in patients with CYP2D6 deficiency. Propafenone is a CYP3A and CYP2D6 substrate; fosamprenavir is a moderate CYP3A inhibitor.
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, a CYP3A4 substrate, and fosamprenavir, a potent CYP3A4 inhibitor, due to the potential for increased exposure to quetiapine. If administration of fosamprenavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. If fosamprenavir is discontinued, increase the quetiapine dose by 6-fold.
Quinidine: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with fosamprenavir is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Quinine: (Moderate) Monitor for quinine-related adverse reactions if coadministration with fosamprenavir is necessary. Concurrent use may increase quinine exposure. Quinine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Raltegravir: (Moderate) Coadministration of fosamprenavir with raltegravir may alter the serum concentrations of both medications. According to the manufacturer, the appropriate dose adjustments for coadministration have not been established. During clinical studies, ampenavir pharmacokinetic parameters were altered when various fosamprenavir doses (i.e., 700 mg BID, 1400 mg BID, 1400 mg daily) were administered concurrently with raltegravir 400 mg PO twice daily. The recorded amprenavir pharmacokinetic parameters ranged from a Cmax reduction of 27% to an increase of 27%, an AUC reduction of 36% to an increase of 13%, and a Cmin reduction of 17% to 50%.
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.
Ranolazine: (Major) Limit the dose of ranolazine to 500 mg twice daily if coadministration with fosamprenavir is necessary. Coadministration may increase the exposure of ranolazine. Ranolazine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased plasma levels of ranolazine by 50% to 130%.
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 fosamprenavir 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 fosamprenavir 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) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
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 fosamprenavir, 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.
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: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with ribociclib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with ribociclib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Rifabutin: (Major) Reduce rifabutin dose to 150 mg PO once daily and monitor for adverse effects, such as uveitis and neutropenia, if concomitant use of fosamprenavir is necessary. Concomitant use may increase rifabutin exposure. There are no clinically significantly alterations in fosamprenavir pharmacokinetics. Rifabutin is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with fosamprenavir/ritonavir significantly increased the AUC of the active metabolite of rifabutin.
Rifampin: (Contraindicated) Concurrent use of fosamprenavir and rifampin is contraindicated due to the risk of decreased plasma concentrations of fosamprenavir, which may result in potential loss of virologic control. Fosamprenavir is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
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) Coadministration of rilpivirine with fosamprenavir may result in increased plasma concentrations of rilpivirine, leading to an increase in rilpivirine-related adverse effects. Rilpivirine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with fosamprenavir; concurrent use may increase rimegepant exposure. Rimegepant is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Riociguat: (Major) Concomitant use of riociguat and fosamprenavir may result in altered riociguat plasma concentrations. Riociguat is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Risperidone: (Major) Concomitant use of risperidone and fosamprenavir may result in altered risperidone plasma concentrations. Risperidone is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Ritlecitinib: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with ritlecitinib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and fosamprenavir may result in elevated fosamprenavir and altered rivaroxaban exposures, which may increase bleeding risk or decrease efficacy of rivaroxaban. Fosamprenavir is an inhibitor and inducer of CYP3A4 and a substrate/inducer of P-glycoprotein (P-gp). Rivaroxaban is a substrate of CYP3A4 and a substrate/inhibitor of P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding and lack of efficacy.
Roflumilast: (Moderate) Monitor for an increase in roflumilast-related adverse reactions if concomitant use with fosamprenavir is necessary. Concurrent use may increase roflumilast exposure. Roflumilast is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the exposure of roflumilast by 70%.
Rolapitant: (Major) Use caution if fosamprenavir and rolapitant are used concurrently, and monitor for fosamprenavir-related adverse effects. Fosamprenavir is a CYP2D6 and P-glycoprotein (P-gp) substrate and rolapitant is a CYP2D6 and P-gp inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured. When rolapitant was administered with another P-gp substrate, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
Romidepsin: (Moderate) Concomitant use of romidepsin and fosamprenavir may result in altered romidepsin plasma concentrations. Romidepsin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4. 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.
Rosuvastatin: (Major) Fosamprenavir increases rosuvastatin plasma concentrations. If these drugs are to be coadministered, use the lowest possible dose of rosuvastatin, or consider treatment with an alternative HMG-CoA reductase inhibitor such as fluvastatin or pravastatin.
Rosuvastatin; Ezetimibe: (Major) Fosamprenavir increases rosuvastatin plasma concentrations. If these drugs are to be coadministered, use the lowest possible dose of rosuvastatin, or consider treatment with an alternative HMG-CoA reductase inhibitor such as fluvastatin or pravastatin.
Ruxolitinib: (Major) Reduce the ruxolitinib dosage when coadministered with fosamprenavir 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 fosamprenavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. Ruxolitinib is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor.
Salmeterol: (Major) Avoid concomitant use of salmeterol with fosamprenavir. 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 fosamprenavir is a moderate CYP3A inhibitor.
Saquinavir: (Minor) Use caution when administering saquinavir concurrently with amprenavir or fosamprenavir. Coadministration of fosamprenavir and saquinavir boosted with ritonavir resulted in a 15% decrease in the AUC of saquinavir. Further, concurrent administration of saquinavir and amprenavir results in a 32% decrease in the AUC of amprenavir. There are insufficient data to support any dosing recommendations. Patients should be closely monitored.
Saxagliptin: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if saxagliptin is coadministered with fosamprenavir. 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.
Segesterone Acetate; Ethinyl Estradiol: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and fosamprenavir due to the risk of increased selpercatinib exposure which may increase the risk of adverse reactions, including QT prolongation. If coadministration is unavoidable, reduce the dose of selpercatinib to 80 mg PO twice daily if original dose was 120 mg twice daily, and to 120 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If fosamprenavir is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of fosamprenavir. Selpercatinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors is predicted to increase selpercatinib exposure by 60% to 99%.
Selumetinib: (Major) Avoid coadministration of selumetinib and fosamprenavir 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 fosamprenavir is discontinued, resume the original selumetinib dose after 3 elimination half-lives of fosamprenavir. Selumetinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase selumetinib exposure by 41%.
Sildenafil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fosamprenavir is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. When used for pulmonary arterial hypertension, this combination is listed as a contraindication in the fosamprenavir FDA-approved labeling. Sildenafil is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. In a drug interaction study, coadministration with a moderate CYP3A inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Silodosin: (Moderate) Monitor for silodosin-related adverse reactions if coadministration with fosamprenavir is necessary. Silodosin is a substrate of CYP3A and fosamprenavir is a moderate CYP3A inhibitor. The effect of moderate CYP3A inhibitors has not been evaluated; however, plasma concentrations of silodosin may increase based on its interaction with strong CYP3A inhibitors.
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 fosamprenavir 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 CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP2C9/CYP3A dual inhibitor led to a 2-fold increase in the AUC 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: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after oral sodium bicarbonate. Coadministration of antacids, such as sodium bicarbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Sofosbuvir: (Moderate) Caution is advised when administering sofosbuvir with fosamprenavir, as concurrent use may result in reduced sofosbuvir plasma concentrations. Sofosbuvir is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with fosamprenavir. Taking these drugs together may significantly reduce the plasma concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); fosamprenavir is a P-gp inducer. Velpatasvir is also a substrate for CYP3A4; fosamprenavir is an inducer/inhibitor of CYP34. (Moderate) Caution is advised when administering sofosbuvir with fosamprenavir, as concurrent use may result in reduced sofosbuvir plasma concentrations. Sofosbuvir is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with fosamprenavir. Taking these drugs together may significantly reduce the plasma concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); fosamprenavir is a P-gp inducer. Velpatasvir is also a substrate for CYP3A4; fosamprenavir is an inducer/inhibitor of CYP34. (Moderate) Caution is advised when administering sofosbuvir with fosamprenavir, as concurrent use may result in reduced sofosbuvir plasma concentrations. Sofosbuvir is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
Solifenacin: (Major) If coadministered with fosamprenavir do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with fosamprenavir. Solifenacin is a CYP3A4 substrate and fosamp renavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and fosamprenavir as concurrent use may increase sonidegib exposure. Sonidegib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Physiologic-based pharmacokinetic (PBPK) simulations indicate a moderate 3A inhibitor would increase the sonidegib AUC by 1.8-fold if administered for 14 days and by 2.8-fold if the moderate CYP3A inhibitor is administered with sonidegib for more than 14 days.
Sotorasib: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with sotorasib. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and sotorasib is a moderate CYP3A inducer.
Sparsentan: (Moderate) Monitor for an increase in sparsentan-related adverse effects if concomitant use with fosamprenavir is necessary. Concomitant use may increase sparsentan exposure. Sparsentan is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sparsentan overall exposure by 70%.
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.
Sunitinib: (Major) Avoid coadministration of fosamprenavir 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 fosamprenavir 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 fosamprenavir. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor increased the suvorexant AUC by 2-fold.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate and watch for tacrolimus-related adverse reactions if coadministration with fosamprenavir is necessary. The dose of tacrolimus may need to be reduced. Tacrolimus is a sensitive CYP3A substrate with a narrow therapeutic range; fosamprenavir is a moderate CYP3A inhibitor.
Tadalafil: (Major) Monitor for an increase in tadalafil-related adverse reactions if coadministration with fosamprenavir is necessary. The prescribing information for fosamprenavir recommends to avoid coadministration of tadalafil for the treatment of pulmonary hypertension and to stop tadalafil at least 24 hours prior to starting fosamprenavir. After at least 1 week of fosamprenavir therapy, resume tadalafil at 20 mg once daily. Increase to 40 mg once daily based on tolerability. For the treatment of erectile dysfunction, the prescribing information for fosamprenavir recommends to not exceed 10 mg tadalafil within 72 hours of fosamprenavir for the 'as needed' dose or 2.5 mg daily for the 'once-daily' dose. Tadalafil is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Although specific interactions have not been studied, moderate CYP3A inhibitors would likely increase tadalafil exposure.
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.
Tasimelteon: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as amprenavir or fosamprenavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with fosamprenavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If fosamprenavir is discontinued, wait at least 3 half-lives of fosamprenavir before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A 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 fosamprenavir with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus); exposure to fosamprenavir may also increase. 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 fosamprenavir before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and fosamprenavir 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. Fosamprenavir is also a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use may lead to increased concentrations of fosamprenavir.
Teniposide: (Major) Concomitant use of teniposide and fosamprenavir may result in altered teniposide plasma concentrations. Teniposide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Terbinafine: (Moderate) Caution is advised when administering terbinafine with fosamprenavir. 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 alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Fosamprenavir is a substrate of CYP2D6 and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
Tezacaftor; Ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with fosamprenavir; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); fosamprenavir is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If fosamprenavir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
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 fosamprenavir 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; fosamprenavir is a strong CYP3A4 inhibitor.
Ticagrelor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with fosamprenavir. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a sensitive substrate of CYP3A; fosamprenavir is a moderate inhibitor of CYP3A.
Tinidazole: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with fosamprenavir is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Tipranavir: (Major) Avoid concurrent use of fosamprenavir and tipranavir. Concomitant use may decrease the exposure of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Coadministration with tipranavir decreased the exposure of fosamprenavir by 44%.
Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with fosamprenavir. 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 fosamprenavir. Fosamprenavir 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 fosamprenavir. Concurrent use may increase tolterodine exposure. Fosamprenavir 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: (Major) Avoid coadministration of fosamprenavir when tolvaptan is administered for hyponatremia. In patients with autosomal dominant polycystic kidney disease (ADPKD), reduce tolvaptan dosage if administered with fosamprenavir. In ADPKD patients receiving tolvaptan 90 mg every morning and 30 mg every evening, reduce the dose to 45 mg every morning and 15 mg every evening; for those receiving tolvaptan 60 mg every morning and 30 mg every evening, reduce the dose to 30 mg every morning and 15 mg every evening; for those receiving tolvaptan 45 mg every morning and 15 mg every evening, reduce the dose to 15 mg every morning and 15 mg every evening. Consider additional dosage reduction if the reduced dose is not tolerated. Tolvaptan is a sensitive CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased the tolvaptan AUC by 200%.
Toremifene: (Major) Avoid coadministration of fosamprenavir 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 fosamprenavir 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 fosamprenavir due to the risk of increased trabectedin exposure. Trabectedin is a CYP3A substrate and fosamprenavir 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.
Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with fosamprenavir is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of fosamprenavir, a moderate CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Tramadol; Acetaminophen: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with fosamprenavir is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of fosamprenavir, a moderate CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure, heart rate, and for increased fosamprenavir-related adverse reactions during coadministration of verapamil with fosamprenavir. Concomitant use may increase the exposure of both drugs. Verapamil and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
Trazodone: (Major) Avoid coadministration of trazodone with fosamprenavir 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; fosamprenavir 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) Fosamprenavir 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.
Tucatinib: (Moderate) Monitor for increased toxicity of fosamprenavir if coadministered with tucatinib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Ubrogepant: (Major) Limit the initial dose of ubrogepant to 50 mg and avoid a second dose within 24 hours if coadministered with fosamprenavir. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor resulted in a 3.5-fold increase in the exposure of ubrogepant.
Ulipristal: (Minor) Ulipristal is a substrate of CYP3A4 and fosamprenavir is a CYP3A4 inhibitor, and may be a CYP3A4 inducer. Concomitant use may increase the plasma concentration of ulipristal. With single doses of ulipristal for emergency contraception it is not clear this interaction will have clinical consequence. The potential for interaction has not been studied.
Umeclidinium: (Moderate) Concomitant use of umeclidinium and fosamprenavir may result in decreased umeclidinium plasma concentrations. Umeclidinium is a substrate of the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp.
Umeclidinium; Vilanterol: (Moderate) Concomitant use of umeclidinium and fosamprenavir may result in decreased umeclidinium plasma concentrations. Umeclidinium is a substrate of the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp. (Moderate) Concomitant use of vilanterol and fosamprenavir may result in altered vilanterol plasma concentrations. Vilanterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Valproic Acid, Divalproex Sodium: (Major) Caution is advised when administering fosamprenavir with valproic acid, divalproex sodium as there is a potential for altered fosamprenavir plasma concentrations. Valproic acid is an inducer of P-glycoprotein (P-gp) and a mild inducer and inhibitor of CYP3A4. Fosamprenavir is a substrate both CYP3A4 and P-gp.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with fosamprenavir due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Vemurafenib: (Major) Concomitant use of vemurafenib and fosamprenavir may result in altered concentrations of amprenavir and vemurafenib. Fosamprenavir is metabolized to the active drug amprenavir. Vemurafenib is an inhibitor of CYP2C9, CYP2D6, and P-glycoprotein (P-gp) and a substrate/inducer of CYP3A4. Amprenavir is a substrate of CYP2C9 and CYP2D6, a substrate/inducer of P-gp, and is a substrate/potent inhibitor/moderate inducer of CYP3A4. Avoid using these agents together if possible.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with fosamprenavir due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of fosamprenavir. Venetoclax is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor.
Verapamil: (Moderate) Monitor blood pressure, heart rate, and for increased fosamprenavir-related adverse reactions during coadministration of verapamil with fosamprenavir. Concomitant use may increase the exposure of both drugs. Verapamil and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
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 fosamprenavir. 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 fosamprenavir is necessary. Vinblastine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A 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 fosamprenavir is necessary. Vinorelbine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Voclosporin: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with fosamprenavir. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors is predicted to increase voclosporin exposure by 3-fold.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and fosamprenavir due to altered plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and fosamprenavir is both a strong CYP3A inhibitor and moderate CYP3A inducer. The net effect on CYP3A4 substrates is unclear. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of vonoprazan and fosamprenavir due to altered plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and fosamprenavir is both a strong CYP3A inhibitor and moderate CYP3A inducer. The net effect on CYP3A4 substrates is unclear. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer. (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with clarithromycin. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and fosamprenavir. Fosamprenavir may inhibit or induce CYP3A4 and may alter serum concentrations of other drugs metabolized by this enzyme. Increased or decreased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with fosamprenavir. Increased exposure to vorapaxar may increase the risk of bleeding complications while decreased exposure to vorapaxar may reduce efficacy.
Voriconazole: (Moderate) Monitor for increased adverse effects of both drugs if voriconazole is coadministered with fosamprenavir. Concomitant use may increase the exposure of both drugs. Voriconazole is a CYP3A substrate and strong CYP3A inhibitor; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased voriconazole exposure by 79%.
Voxelotor: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with voxelotor. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with fosamprenavir is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. The R-enantiomer of warfarin is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zaleplon: (Moderate) Zaleplon is partially metabolized by CYP3A4, and concurrent use of strong CYP3A4 inhibitors, such as fosamprenavir, 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 twice daily if coadministered with fosamprenavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of fosamprenavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A 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%.

Fosamprenavir/Fosamprenavir Calcium/Lexiva Oral Tab: 700mg
Lexiva Oral Susp: 1mL, 50mg

Adults

2,800 mg/day PO.

Geriatric

2,800 mg/day PO.

Adolescents

20 kg or more: 36 mg/kg/day (Max: 1,400 mg) PO with ritonavir; 60 mg/kg/day (Max: 2,800 mg) PO without ritonavir (not recommended by HIV guidelines).

Children

2 years or older and at least 20 kg: 36 mg/kg/day (Max: 1,400 mg) PO with ritonavir; 60 mg/kg/day (Max: 1,400 mg) PO without ritonavir (not recommended by HIV guidelines).
2 years or older and 15 kg to 19 kg: 46 mg/kg/day PO with ritonavir; 60 mg/kg/day PO without ritonavir (not recommended by HIV guidelines).
2 years or older and 11 kg to 14 kg: 60 mg/kg/day PO with ritonavir; 60 mg/kg/day PO without ritonavir (not recommended by HIV guidelines).
2 years or older and 10 kg: 90 mg/kg/day PO with ritonavir; 60 mg/kg/day PO without ritonavir (not recommended by HIV guidelines).
younger than 2 years and 15 kg to 19 kg: 46 mg/kg/day PO with ritonavir.
younger than 2 years and 11 kg to 14 kg: 60 mg/kg/day PO with ritonavir.
younger than 2 years and less than 11 kg: 90 mg/kg/day PO with ritonavir.

Infants

15 kg to 19 kg: 46 mg/kg/day PO with ritonavir. HIV guidelines do not recommend use in infants under 6 months of age.
11 kg to 14 kg: 60 mg/kg/day PO with ritonavir. HIV guidelines do not recommend use in infants under 6 months of age.
less than 11 kg: 90 mg/kg/day PO with ritonavir. HIV guidelines do not recommend use in infants under 6 months of age.

Neonates

Safety and efficacy have not been established.

Fosamprenavir is a prodrug of amprenavir. It is rapidly converted to amprenavir by cellular phosphatases following oral administration. Fosamprenavir has little or no antiviral activity in vitro; the in vitro antiviral activity observed with fosamprenavir is not measurable. Amprenavir inhibits the human immunodeficiency virus (HIV) type 1 aspartic protease enzyme. This enzyme plays a key role in the post-translational processing of the gag and gag-pol polyprotein precursors, key structural proteins and replication enzymes of HIV-1. Thus, by inhibiting HIV-1 protease, amprenavir impairs HIV viral replication and proliferation, resulting in the formation of immature non-infectious viral particles. When fosamprenavir is combined with the protease inhibitor ritonavir an additive inhibitory effect on HIV-1 is observed.
 
HIV-1 resistance has been observed in fosampreanavir treated patients. In fosamprenavir-resistant patients, or, more specifically, amprenavir-resistant patients, mutations occur most frequently at amino acid positions V32I, M46I/L, I47V, I50V, I54L/M, and I84V, as well as mutations in the p7/p1 and p1/p6 Gag and Gag-Pol polyprotein precursor cleavage sites. Some of these amprenavir resistance-associated mutations have also been detected in HIV-1 isolates from antiretroviral-naive patients treated with fosamprenavir.

Fosamprenavir, a phosphate ester prodrug of the antiretroviral protease inhibitor amprenavir, is administered orally as a tablet or suspension. Amprenavir is approximately 90% protein bound with a concentration-dependent binding that suggests a decreased binding with higher concentrations.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C9, CYP2D6, P-gp
Fosamprenavir is metabolized to the active drug amprenavir. Amprenavir is a strong inhibitor and a substrate of CYP3A4, an inducer and substrate of P-glycoprotein (P-gp), and a substrate of CYP2C9, and CYP2D6. Data also suggest that amprenavir induces CYP3A4. Caution should be used when coadministering medications that are substrates, inhibitors, or inducers of CYP3A4, or potentially toxic medications that are metabolized by CYP3A4. Amprenavir does not inhibit CYP2D6, CYP1A2, CYP2C9, CYP2C19, CYP2E1, or uridine glucuronosyltransferase (UDPGT).
 
After oral administration, fosamprenavir is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate prior to reaching circulation in the gut epithelium during absorption. Twenty-four metabolites have been identified; the majority of these metabolites are excreted in the feces. Excretion of unchanged amprenavir in urine and feces is minimal. Unchanged amprenavir in urine accounts for approximately 1% of the fosamprenavir dose; unchanged amprenavir was not detectable in feces. Since renal elimination of unchanged amprenavir represents approximately 1% of the administered dose, renal impairment is not expected to significantly impact the elimination of amprenavir. Following a single dose of 14C-amprenavir, approximately 14% and 75% can be accounted for as metabolites in urine and feces, respectively. The plasma elimination half-life of amprenavir is approximately 7.7 hours.

Oral Route

In general, the Tmax of amprenavir is reached at a median of 2.5 hours. Exposure (AUC) is similar after the administration of the tablets and suspension when administered at a fasted state; however, the Cmax of after administration of the suspension is 14.5% higher compared to the tablet. No significant changes in pharmacokinetic parameters are seen when the tablets are administered in a fed (standardized high-fat meal) versus fasted state. Administration of the oral suspension (1400 mg single dose) with food (standardized high-fat meal) results in a decreased Cmax (by 46%), a prolonged Tmax (by 0.72 hours), and a decreased AUC (by 28%), compared to administration in a fasted state.
 
Several dosing regimens are approved for use, and the regimens display similar pharmacokinetic parameters. When administered at a dose of 1400 mg twice daily, the following are observed: Cmax of 4.82 mcg/ml; Tmax of 1.3 hours; AUC of 33 mcg x hr/mL; and Cmin of 0.35 mcg/mL. When administered at a dose of 1400 mg with ritonavir 100 mg once daily, the following are observed: Cmax of 7.93 mcg/mL; Tmax of 1.5 hours; AUC of 66.4 mcg x hr/mL; and Cmin of 0.86 mcg/mL. When administered at a dose of 1400 mg with ritonavir 200 mg once daily, the following are observed: Cmax of 7.24 mcg/mL; Tmax of 2.1 hours; AUC of 69.4 mcg x hr/mL; and Cmin of 0.86 mcg/mL. When administered at a dose of 700 mg with ritonavir 100 mg twice daily, the following are observed: Cmax of 6.08 mcg/mL; Tmax of 1.5 hours; AUC of 79.2 mcg x hr/mL; and Cmin of 2.12 mcg/mL.

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. Due to lower systemic exposures of amprenavir during pregnancy, HIV treatment guidelines recommend against the use of fosamprenavir-containing regimens during pregnancy. According to the guidelines, patients who become pregnant while taking fosamprenavir should be switched to an alternative treatment regimen. However, according the FDA-approved labeling, virologically suppressed (HIV RNA less than 50 copies/mL) patients who were on twice-daily fosamprenavir 700 mg and ritonavir 100 mg regimen prior to becoming pregnant may continue this regimen during pregnancy if viral loads are closely monitored to ensure viral suppression is maintained. Data regarding the use of other fosamprenavir regimens during pregnancy are not available. Data regarding first trimester exposures to fosamprenavir are limited; therefore, an association between fosamprenavir and the potential for birth defects cannot be made. Available data from the Antiretroviral Pregnancy Registry (APR) associates first trimester exposure to fosamprenavir with 2 birth defects out of 109 live births. Data for second and third trimesters show 2 birth defects in 36 exposures. 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 delivery. 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 fosamprenavir; 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 fosamprenavir use during breast-feeding, and excretion into human breast milk is unknown. Antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.