INTELENCE

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)s

Oral Administration

Administer orally after a meal to enhance absorption.

Oral Solid Formulations

For patients who are unable to swallow tablets whole, the tablets may be dispersed in a glass of water. Place the tablets in 5 mL of water or enough water to completely cover the tablets.
Stir well until the water looks milky.
Add approximately 15 mL more of liquid. Water may be used but other liquids such as orange juice or milk may improve the taste. Do not place the tablets in juice or milk without first adding water. Avoid the use of carbonated beverages or warm liquids more than 40 degrees C (104 degrees F).
Instruct the patient to drink the mixture immediately.
Rinse the glass with water, orange juice, or milk several times, and instruct the patient to completely swallow each rinse to ensure the entire dose is consumed.[33718]

Severe

hepatic failure / Delayed / 0-2.0
myocardial infarction / Delayed / 0-2.0
atrial fibrillation / Early / 0-2.0
hematemesis / Delayed / 0-2.0
seizures / Delayed / 0-2.0
bronchospasm / Rapid / 0-2.0
pancreatitis / Delayed / 0-2.0
renal failure (unspecified) / Delayed / 0-2.0
hemolytic anemia / Delayed / 0-2.0
conjunctivitis / Delayed / 0-1.0
rhabdomyolysis / Delayed / 0-1.0
stroke / Early / 0-0.5
Stevens-Johnson syndrome / Delayed / 0-0.1
toxic epidermal necrolysis / Delayed / 0-0.1
erythema multiforme / Delayed / 0-0.1
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

Moderate

hypercholesterolemia / Delayed / 8.0-20.0
hyperglycemia / Delayed / 4.0-15.0
hypertriglyceridemia / Delayed / 4.0-9.0
hyperbilirubinemia / Delayed / 7.1-7.1
hyperamylasemia / Delayed / 2.0-7.0
elevated hepatic enzymes / Delayed / 0-6.0
neutropenia / Delayed / 2.0-5.0
peripheral neuropathy / Delayed / 4.0-4.0
thrombocytopenia / Delayed / 0-3.0
hepatomegaly / Delayed / 0-2.0
steatosis / Delayed / 0-2.0
hepatitis / Delayed / 0-2.0
blurred vision / Early / 0-2.0
constipation / Delayed / 0-2.0
stomatitis / Delayed / 0-2.0
amnesia / Delayed / 0-2.0
confusion / Early / 0-2.0
dyspnea / Early / 0-2.0
anemia / Delayed / 0-2.0
leukopenia / Delayed / 1.0-2.0
hyperlipidemia / Delayed / 0-2.0
diabetes mellitus / Delayed / 0-2.0
lipodystrophy / Delayed / 0-0.5
gastritis / Delayed / 1.0
oral ulceration / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
angina / Early / Incidence not known

Mild

rash / Early / 10.0-15.0
maculopapular rash / Early / 15.0-15.0
vertigo / Early / 0-2.0
xerostomia / Early / 0-2.0
flatulence / Early / 0-2.0
gastroesophageal reflux / Delayed / 0-2.0
anorexia / Delayed / 0-2.0
syncope / Early / 0-2.0
hypoesthesia / Delayed / 0-2.0
tremor / Early / 0-2.0
drowsiness / Early / 0-2.0
paresthesias / Delayed / 0-2.0
nightmares / Early / 0-2.0
anxiety / Delayed / 0-2.0
abnormal dreams / Early / 0-2.0
gynecomastia / Delayed / 0-2.0
hyperhidrosis / Delayed / 0-2.0
night sweats / Early / 0-2.0
xerosis / Delayed / 0-2.0
diarrhea / Early / 2.0
fever / Early / Incidence not known
malaise / Early / Incidence not known
musculoskeletal pain / Early / Incidence not known
Cushingoid features / Delayed / Incidence not known

INTELENCE

Rx

Non-nucleoside reverse transcriptase inhibitor (NNRTI)
Used with other antiretroviral drugs to treat HIV-1 infections in treatment-experienced patients 2 years and older
Associated with severe and potentially life-threatening rashes

For use in combination with other antiretroviral agents to treat human immunodeficiency virus (HIV) infection in treatment-experienced patients. Oral dosage Adults

200 mg PO twice daily.

Children and Adolescents weighing 30 kg or more

200 mg PO twice daily.

Children and Adolescents weighing 25 to 29 kg

150 mg PO twice daily.

Children 2 to 12 years weighing 20 to 24 kg

125 mg PO twice daily.

Children 2 to 12 years weighing 10 to 19 kg

100 mg PO twice daily.

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

The US Public Health Service guidelines suggest etravirine 200 mg PO twice daily in combination with one of the following backbones (in order of preference) as acceptable alternative regimens for HIV post-exposure prophylaxis (PEP): tenofovir plus emtricitabine; tenofovir plus lamivudine; zidovudine plus lamivudine; zidovudine plus emtricitabine. However, according to the New York State Department of Health AIDS Institute (NYSDOH AI), data on use of etravirine containing regimens for PEP are lacking. The NYSDOH AI recommends use of etravirine only after consultation with a clinician experienced in the management of PEP. According to PEP guidelines, individuals potentially exposed to HIV should receive a 3-drug regimen for a total of 28 days; however if tolerability is a concern, use of a 2-drug regimen may be considered and is preferred to prophylaxis discontinuation. Begin prophylaxis as soon as possible, ideally within 2 hours of exposure. If initiation of prophylaxis is delayed (beyond 36 hours or 72 hours after exposure), efficacy of the antiretroviral regimen may be diminished and treatment should be determined on a case-by-case basis. Exposures for which PEP is indicated include: skin puncture by a sharp object that has been contaminated with blood, body fluid, or other infectious material; bite from a patient with visible bleeding in the mouth which causes bleeding by the exposed worker; splash of blood, body fluid, or other infectious material onto the workers mouth, nose, or eyes; exposure of blood, body fluid, or other infectious material on a workers non-intact skin (i.e., open wound, chapped skin, abrasion, dermatitis).

†Indicates off-label use

Hepatic Impairment

Dosage adjustments are not required for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. No data are available for patients with severe hepatic impairment (Child-Pugh Class C).

Renal Impairment

Dosage adjustments are not required for patients with renal impairment.
 
Hemodialysis or Peritoneal Dialysis
Etravirine is highly bound to plasma proteins and it is therefore unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis.

Abacavir; Dolutegravir; Lamivudine: (Major) Coadministration of dolutegravir with etravirine should be avoided, unless also administered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. When administered with etravirine (a CYP3A4 inducer), the plasma concentration of dolutegravir (a CYP3A4 substrate) is significantly reduced; however, this effect is diminished by the presence of one of the above mentioned protease inhibitors.
Abemaciclib: (Major) Avoid coadministration of etravirine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with etravirine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If etravirine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Etravirine is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with etravirine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If etravirine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with etravirine is necessary; consider increasing the dose of oxycodone as needed. If etravirine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Adagrasib: (Moderate) Monitor for an increase in etravirine-related adverse reactions if concomitant use of adagrasib is necessary. Etravirine is a CYP3A and CYP2C9 substrate and adagrasib is a strong CYP3A and moderate CYP2C9 inhibitor. Concomitant use of another strong CYP3A inhibitor increased etravirine exposure by 1.4-fold.
Adefovir: (Major) Patients who are concurrently taking adefovir with non-nucleoside reverse transcriptase 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).
Afatinib: (Moderate) If the concomitant use of etravirine and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of etravirine. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and etravirine is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Albuterol; Budesonide: (Moderate) Etravirine is a CYP3A4 inducer and a P-glycoprotein (PGP) inhibitor and budesonide is a CYP3A4 substrate and a substrate/inhibitor of PGP. Caution is warranted if these drugs are coadministered.
Amiodarone: (Major) Etravirine is an inducer of CYP3A4; amiodarone concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor amiodarone concentrations when possible.
Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Atorvastatin: (Moderate) Concomitant use of etravirine and atorvastatin decreases atorvastatin serum concentrations and increases concentrations of the metabolite, 2-OH-atorvastatin. Atorvastatin may be a substrate of the CYP3A4 isoenzyme and etravirine induces the CYP3A4 isoenzyme. According to the manufacturer of etravirine, atorvastatin can be given without any dose adjustments, although its dose may need to be altered based on clinical response. The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Benazepril: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Celecoxib: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Olmesartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of etravirine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
Apalutamide: (Major) The concomitant use of apalutamide with etravirine is not recommended due to significant decreases in etravirine plasma concentrations and, thus, possible loss of therapeutic effect. Etravirine is a CYP3A4, CYP2C19, and CYP2C9 substrate. Apalutamide is a strong CYP3A4 and CYP2C19 inducer, as well as a weak CYP2C9 inducer.
Aprepitant, Fosaprepitant: (Major) Use caution if etravirine and aprepitant, fosaprepitant are used concurrently, and monitor for a possible decrease in the efficacy of aprepitant as well as an increase in etravirine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Etravirine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of etravirine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Additionally, etravirine is a moderate CYP3A4 inducer and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen (a strong CYP3A4 inducer), the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold. The manufacturer of aprepitant recommends avoidance of administration with strong CYP3A4 inducers, but does not provide guidance for low-to-moderate inducers. Finally, aprepitant is a CYP2C9 inducer and etravirine is a CYP2C9 substrate. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant.
Aripiprazole: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during use of a CYP3A4 inducer, such as etravirine. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Artemether; Lumefantrine: (Major) Pharmacokinetic parameters (AUC, Cmax, Cmin) of artemether, a CYP3A4 substrate, are reduced when administered concurrently with etravirine, a CYP3A4 inducer. Although dose adjustments are not required, concomitant use warrants caution due to the potential for decreased antimalarial efficacy. (Major) Pharmacokinetic parameters (AUC, Cmax, Cmin) of lumefantrine, a CYP3A4 substrate, are reduced when administered concurrently with etravirine, a CYP3A4 inducer. Although dose adjustments are not required, concomitant use warrants caution due to the potential for decreased antimalarial efficacy.
Asciminib: (Moderate) Monitor for an increase in etravirine-related adverse reactions if concomitant use of asciminib 200 mg twice daily is necessary. Etravirine is a CYP2C9 substrate and asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with etravirine is necessary; consider increasing the dose of oxycodone as needed. If etravirine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Moderate) Etravirine should not be coadministered with atazanavir, unless atazanavir is boosted with ritonavir. Concomitant use of etravirine and unboosted atazanavir results in significant decreases in atazanavir exposure. Coadministration of etravirine and atazanavir (boosted with ritonavir) causes a decrease in atazanavir Cmin (38%); however, the decrease is not considered clinically relevant, and this drug combination can be administred together without dose adjustments.
Atazanavir; Cobicistat: (Major) Due to the potential for decreased antiretroviral efficacy and potential for adverse events, use of etravirine with cobicistat is not recommended. When these drugs are given together, the concentrations of cobicistat and etravirine may be decreased and increased, respectively. Both drugs are substrates for CYP3A4. Etravirine is also a CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. Coadministration of etravirine with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold. (Moderate) Etravirine should not be coadministered with atazanavir, unless atazanavir is boosted with ritonavir. Concomitant use of etravirine and unboosted atazanavir results in significant decreases in atazanavir exposure. Coadministration of etravirine and atazanavir (boosted with ritonavir) causes a decrease in atazanavir Cmin (38%); however, the decrease is not considered clinically relevant, and this drug combination can be administred together without dose adjustments.
Atogepant: (Major) Avoid use of atogepant and etravirine when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with etravirine. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Atorvastatin: (Moderate) Concomitant use of etravirine and atorvastatin decreases atorvastatin serum concentrations and increases concentrations of the metabolite, 2-OH-atorvastatin. Atorvastatin may be a substrate of the CYP3A4 isoenzyme and etravirine induces the CYP3A4 isoenzyme. According to the manufacturer of etravirine, atorvastatin can be given without any dose adjustments, although its dose may need to be altered based on clinical response. The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors.
Atorvastatin; Ezetimibe: (Moderate) Concomitant use of etravirine and atorvastatin decreases atorvastatin serum concentrations and increases concentrations of the metabolite, 2-OH-atorvastatin. Atorvastatin may be a substrate of the CYP3A4 isoenzyme and etravirine induces the CYP3A4 isoenzyme. According to the manufacturer of etravirine, atorvastatin can be given without any dose adjustments, although its dose may need to be altered based on clinical response. The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors.
Avacopan: (Major) Avoid concomitant use of avacopan and etravirine due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Avanafil: (Moderate) The concomitant use of avanafil and etravirine is not recommended. Coadministration may result in decreased avanafil concentrations. Avanafil is a substrate of and primarily metabolized by CYP3A4. Etravirine is an inducer of CYP3A4.
Avapritinib: (Major) Avoid coadministration of avapritinib with etravirine due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer is predicted to decrease the AUC and Cmax of avapritinib by 62% and 55%, respectively.
Axitinib: (Major) Avoid coadministration of axitinib with etravirine if possible due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and etravirine is a moderate CYP3A4 inducer.
Bedaquiline: (Major) Avoid concurrent use of etravirine with bedaquiline. Etravirine is a CYP3A4 inducer, which may result in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of etravirine with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and etravirine is a CYP2C19 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with etravirine may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of etravirine may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If etravirine is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Etravirine is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking etravirine. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Additionally, monitor for an increase in etravirine-related adverse reactions as concurrent use may also increase etravirine exposure. Berotralstat is a P-gp substrate and moderate CYP3A4 inhibitor; etravirine is a CYP3A4 substrate and P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving etravirine. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving etravirine. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; etravirine inhibits P-gp.
Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be doubled over 1 to 2 weeks when a strong CYP3A4 inducer, such as etravirine, is added to brexpiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the brexpiprazole dose should be reduced to the original level over 1 to 2 weeks.
Brigatinib: (Major) Avoid coadministration of brigatinib with etravirine due to decreased plasma exposure to brigatinib which may result in decreased efficacy. If concomitant use is unavoidable, after 7 days of concomitant treatment with etravirine, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose. After discontinuation of etravirine, resume the brigatinib dose that was tolerated prior to initiation of etravirine. Brigatinib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and etravirine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; etravirine is a moderate inducer of CYP3A4.
Budesonide: (Moderate) Etravirine is a CYP3A4 inducer and a P-glycoprotein (PGP) inhibitor and budesonide is a CYP3A4 substrate and a substrate/inhibitor of PGP. Caution is warranted if these drugs are coadministered.
Budesonide; Formoterol: (Moderate) Etravirine is a CYP3A4 inducer and a P-glycoprotein (PGP) inhibitor and budesonide is a CYP3A4 substrate and a substrate/inhibitor of PGP. Caution is warranted if these drugs are coadministered.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Etravirine is a CYP3A4 inducer and a P-glycoprotein (PGP) inhibitor and budesonide is a CYP3A4 substrate and a substrate/inhibitor of PGP. Caution is warranted if these drugs are coadministered.
Bupivacaine; Lidocaine: (Major) Etravirine is an inducer of CYP3A4; systemic lidocaine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor lidocaine concentrations when possible.
Bupivacaine; Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with etravirine is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and etravirine is a weak CYP2C9 inhibitor.
Buprenorphine: (Moderate) Etravirine may decrease the systemic exposure and therapeutic efficacy of buprenorphine; monitor for potential reduction in efficacy or buprenorphine withdrawal symptoms. Buprenorphine is a CYP3A substrate, and etravirine is a moderate CYP3A inducer.
Buprenorphine; Naloxone: (Moderate) Etravirine may decrease the systemic exposure and therapeutic efficacy of buprenorphine; monitor for potential reduction in efficacy or buprenorphine withdrawal symptoms. Buprenorphine is a CYP3A substrate, and etravirine is a moderate CYP3A inducer.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Cabotegravir; Rilpivirine: (Major) Coadministration of etravirine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Etravirine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Cannabidiol: (Moderate) Consider a dose reduction of etravirine as clinically appropriate, if etravirine-related adverse reactions occur when administered with cannabidiol. Etravirine a substrate of CYP2C9 and CYP2C19; cannabidiol has the potential to inhibit these isoenzymes.
Capmatinib: (Major) Avoid coadministration of capmatinib and etravirine due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased capmatinib exposure by 44%.
Carbamazepine: (Major) Coadministration of carbamazepine and etravirine is not recommended due to the potential for loss of virologic response and possible resistance to etravirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Etravirine may also alter plasma concentrations of carbamazepine. Consider alternative anticonvulsant treatment. Etravirine is a substrate of CYP3A4, CYP2C9, and CYP2C19; it also induces CYP3A4. Carbamazepine is a CYP3A4 substrate and an inducer of CYP3A4 (strong), CYP2C9, and CYP2C19.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as etravirine, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
Carvedilol: (Moderate) Etravirine is an inhibitor of the efflux transporter P-glycoprotein (PGP). Carvedilol is a P-glycoprotein substrate. Increased concentrations of carvedilol may occur if it is coadministered with etravirine; exercise caution.
Ceritinib: (Moderate) Monitor for an increase in etravirine-related adverse reactions if coadministration with ceritinib is necessary. Etravirine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with etravirine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If etravirine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Etravirine is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with etravirine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If etravirine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Citalopram: (Moderate) Limit the dose of citalopram to 20 mg/day if coadministered with etravirine. Concurrent use may increase citalopram exposure increasing the risk of QT prolongation. Citalopram is a sensitive CYP2C19 substrate; etravirine is a weak inhibitor of CYP2C19.
Clarithromycin: (Major) Coadministration of etravirine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
Clopidogrel: (Moderate) Monitor for reduced clopidogrel efficacy during concomitant use of etravirine. Clopidogrel is primarily metabolized to its active metabolite by CYP2C19; etravirine is a CYP2C19 inhibitor.
Clozapine: (Moderate) Caution is advisable during concurrent use of etravirine and clozapine. Etravirine is an inducer of CYP3A4, one of the isoenzymes responsible for the metabolism of clozapine. According to the manufacturer, patients receiving clozapine in combination with a weak to moderate CYP3A4 inducer should be monitored for loss of effectiveness. Consideration should be given to increasing the clozapine dose if necessary. If the inducer is discontinued, monitor for adverse reactions, and consider reducing the clozapine dose if necessary.
Cobicistat: (Major) Due to the potential for decreased antiretroviral efficacy and potential for adverse events, use of etravirine with cobicistat is not recommended. When these drugs are given together, the concentrations of cobicistat and etravirine may be decreased and increased, respectively. Both drugs are substrates for CYP3A4. Etravirine is also a CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. Coadministration of etravirine with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with etravirine due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro, and etravirine is a moderate inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer.
Codeine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with etravirine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If etravirine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Etravirine is a moderate CYP3A4 inducer.
Colchicine: (Major) Avoid concomitant use of colchicine and etravirine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, 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 the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and etravirine is a P-gp inhibitor.
Conivaptan: (Moderate) Monitor for an increase in etravirine-related adverse reactions if concomitant use of conivaptan is necessary. Etravirine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Minor) Monitor for an increase in etravirine-related adverse reactions if coadministration with crizotinib is necessary. Etravirine is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (Major) Coadministration with etravirine may result in altered cyclosporine concentrations. Coadminister these drugs with caution, carefully monitor cyclosporine concentrations and make dosage adjustments as needed.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with etravirine is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and etravirine is a P-gp inhibitor.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as etravirine. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Dapsone: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with etravirine is necessary. Dapsone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Daridorexant: (Major) Avoid concomitant use of daridorexant and etravirine. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Daridorexant is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use of another moderate CYP3A inducer decreased daridorexant overall exposure by over 50%.
Darunavir: (Minor) In Phase 3 clinical trials of etravirine, darunavir (boosted with ritonavir) was used as part of the background treatment regimen. Coadministration of etravirine and darunavir is considered safe and effective, and although coadministration does result in a decreased mean systemic exposure (AUC) of etravirine, by about 37%, no dosage adjustments are required.
Darunavir; Cobicistat: (Major) Due to the potential for decreased antiretroviral efficacy and potential for adverse events, use of etravirine with cobicistat is not recommended. When these drugs are given together, the concentrations of cobicistat and etravirine may be decreased and increased, respectively. Both drugs are substrates for CYP3A4. Etravirine is also a CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. Coadministration of etravirine with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold. (Minor) In Phase 3 clinical trials of etravirine, darunavir (boosted with ritonavir) was used as part of the background treatment regimen. Coadministration of etravirine and darunavir is considered safe and effective, and although coadministration does result in a decreased mean systemic exposure (AUC) of etravirine, by about 37%, no dosage adjustments are required.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Due to the potential for decreased antiretroviral efficacy and potential for adverse events, use of etravirine with cobicistat is not recommended. When these drugs are given together, the concentrations of cobicistat and etravirine may be decreased and increased, respectively. Both drugs are substrates for CYP3A4. Etravirine is also a CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. Coadministration of etravirine with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold. (Minor) In Phase 3 clinical trials of etravirine, darunavir (boosted with ritonavir) was used as part of the background treatment regimen. Coadministration of etravirine and darunavir is considered safe and effective, and although coadministration does result in a decreased mean systemic exposure (AUC) of etravirine, by about 37%, no dosage adjustments are required.
Deflazacort: (Major) Avoid concomitant use of deflazacort and etravirine. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; etravirine is a moderate inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
Delavirdine: (Major) The combined use of two NNRTIs has not been shown to be beneficial; thus, etravirine and delavirdine should not be coadministered.
Dexamethasone: (Moderate) Monitor for a decrease in etravirine efficacy during concurrent use of etravirine and dexamethasone. If long term coadministration is required, consider using an alternative corticosteroid, such as prednisone or prednisolone. Concomitant use may decrease etravirine exposure leading to potential loss of virologic control. Etravirine is a CYP3A substrate and dexamethasone is a weak CYP3A inducer.
Dextromethorphan; Quinidine: (Major) Etravirine is an inducer of CYP3A4; quinidine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor quinidine concentrations when possible.
Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with etravirine is necessary. Concurrent use may increase diazepam exposure.
Diclofenac: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as etravirine; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
Diclofenac; Misoprostol: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as etravirine; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
Digoxin: (Moderate) Etravirine is a P-glycoprotein (PGP) inhibitor and digoxin is a substrate for PGP transport. Digoxin Cmax may increase by 19% and the AUC may increase by 18%. For patients starting both etravirine and digoxin, the lowest dose of digoxin should initially be prescribed. For patients on a stable digoxin regimen and initiating etravirine, no initial dose adjustment of either drug is necessary; however, serum digoxin concentrations should be monitored and used for digoxin dose titration.
Diltiazem: (Moderate) Caution is warranted if diltiazem and etravirine are coadministered as diltiazem exposure may be decreased and etravirine exposure may be increased. Etravirine is a CYP3A4 inducer/substrate and diltiazem is a CYP3A4 substrate/inhibitor.
Disopyramide: (Major) Etravirine is an inducer of CYP3A4; disopyramide concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor disopyramide concentrations when possible.
Docetaxel: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and docetaxel is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Dolutegravir: (Major) Coadministration of dolutegravir with etravirine should be avoided, unless also administered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. When administered with etravirine (a CYP3A4 inducer), the plasma concentration of dolutegravir (a CYP3A4 substrate) is significantly reduced; however, this effect is diminished by the presence of one of the above mentioned protease inhibitors.
Dolutegravir; Lamivudine: (Major) Coadministration of dolutegravir with etravirine should be avoided, unless also administered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. When administered with etravirine (a CYP3A4 inducer), the plasma concentration of dolutegravir (a CYP3A4 substrate) is significantly reduced; however, this effect is diminished by the presence of one of the above mentioned protease inhibitors.
Dolutegravir; Rilpivirine: (Major) Coadministration of dolutegravir with etravirine should be avoided, unless also administered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. When administered with etravirine (a CYP3A4 inducer), the plasma concentration of dolutegravir (a CYP3A4 substrate) is significantly reduced; however, this effect is diminished by the presence of one of the above mentioned protease inhibitors. (Major) Coadministration of etravirine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Etravirine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Doravirine: (Contraindicated) Concurrent treatment with etravirine and doravirine is not recommended. Both medications are non-nucleoside reverse transcriptase inhibitors (NNRTIs), and using these drugs together would represent duplicate therapy. In addition, taking these drugs together may result in decreased doravirine exposure. Doravirine is a CYP3A4 substrate; etravirine is a CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Contraindicated) Concurrent treatment with etravirine and doravirine is not recommended. Both medications are non-nucleoside reverse transcriptase inhibitors (NNRTIs), and using these drugs together would represent duplicate therapy. In addition, taking these drugs together may result in decreased doravirine exposure. Doravirine is a CYP3A4 substrate; etravirine is a CYP3A4 inducer. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Doxorubicin Liposomal: (Major) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (P-gp) inhibitor; doxorubicin is a CYP3A4 and P-gp substrate. Inducers of CYP3A4 my decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp and/or CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of etravirine and doxorubicin if possible. If not possible, closely monitor for doxorubicin efficacy, as well as increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (P-gp) inhibitor; doxorubicin is a CYP3A4 and P-gp substrate. Inducers of CYP3A4 my decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp and/or CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of etravirine and doxorubicin if possible. If not possible, closely monitor for doxorubicin efficacy, as well as increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronabinol: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with etravirine is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP3A substrate; etravirine is a moderate CYP3A inducer.
Dronedarone: (Major) Dronedarone is metabolized by CYP3A and should not be coadministered with CYP3A4 inducers, such as etravirine. Concurrent use may result in reduced dronedarone plasma concentration and treatment effectiveness.
Duvelisib: (Major) Avoid concomitant use of duvelisib with etravirine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib; etravirine exposure may also increase. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When etravirine has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with etravirine. Duvelisib is a CYP3A substrate and a moderate CYP3A inhibitor. Etravirine is a CYP3A substrate and a moderate CYP3A inducer. Coadministration of duvelisib with etravirine for 12 days decreased duvelisib exposure by 35%.
Edoxaban: (Moderate) Coadministration of edoxaban and etravirine may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and etravirine is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of etravirine; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism.
Efavirenz: (Major) Concomitant use of etravirine with efavirenz may cause a significant decrease in etravirine plasma concentrations and, thus, a loss of therapeutic effect. Additionally, the combined use of two NNRTIs has not been shown to be beneficial; etravirine and other NNRTIs should not be coadministered.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of etravirine with efavirenz may cause a significant decrease in etravirine plasma concentrations and, thus, a loss of therapeutic effect. Additionally, the combined use of two NNRTIs has not been shown to be beneficial; etravirine and other NNRTIs should not be coadministered. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of etravirine with efavirenz may cause a significant decrease in etravirine plasma concentrations and, thus, a loss of therapeutic effect. Additionally, the combined use of two NNRTIs has not been shown to be beneficial; etravirine and other NNRTIs should not be coadministered. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Elacestrant: (Major) Avoid concurrent use of elacestrant and etravirine due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Elbasvir; Grazoprevir: (Major) Concurrent administration of elbasvir with etravirine should be avoided if possible. Etravirine is a moderate CYP3A inducer, while elbasvir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir, and may result in decreased virologic response. (Major) Concurrent administration of grazoprevir with etravirine should be avoided if possible. Etravirine is a moderate CYP3A inducer, while grazoprevir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of grazoprevir, and may result in decreased virologic response.
Eletriptan: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and eletriptan is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Due to the potential for decreased antiretroviral efficacy and potential for adverse events, use of etravirine with cobicistat is not recommended. When these drugs are given together, the concentrations of cobicistat and etravirine may be decreased and increased, respectively. Both drugs are substrates for CYP3A4. Etravirine is also a CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. Coadministration of etravirine with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Due to the potential for decreased antiretroviral efficacy and potential for adverse events, use of etravirine with cobicistat is not recommended. When these drugs are given together, the concentrations of cobicistat and etravirine may be decreased and increased, respectively. Both drugs are substrates for CYP3A4. Etravirine is also a CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. Coadministration of etravirine with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Empagliflozin; Linagliptin: (Moderate) Concomitant use of linagliptin with etravirine may result in decreased serum concentrations of linagliptin. Linagliptin is a substrate of hepatic isoenzyme CYP3A4; etravirine is a moderate inducer of CYP3A4. Caution and close monitoring for decreased efficacy of linagliptin are advised if these drugs are used together.
Empagliflozin; Linagliptin; Metformin: (Moderate) Concomitant use of linagliptin with etravirine may result in decreased serum concentrations of linagliptin. Linagliptin is a substrate of hepatic isoenzyme CYP3A4; etravirine is a moderate inducer of CYP3A4. Caution and close monitoring for decreased efficacy of linagliptin are advised if these drugs are used together.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Coadministration of etravirine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Etravirine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of etravirine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Etravirine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate

, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Encorafenib: (Major) Avoid coadministration of encorafenib and etravirine due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A4 auto-induction.
Entrectinib: (Major) Avoid coadministration of entrectinib with etravirine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Enzalutamide: (Major) The concomitant use of enzalutamide with etravirine is not recommended due to significant decreases in etravirine plasma concentrations and, thus, possible loss of therapeutic effect. Enzalutamide is a strong CYP3A4 inducer and etravirine is a CYP3A4 substrate.
Erdafitinib: (Major) If coadministration of erdafitinib and etravirine is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If etravirine must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If etravirine is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Erlotinib: (Moderate) There may be a risk of reduced erlotinib efficacy when coadministered with etravirine; however, the risk has not been clearly defined. If coadministration is necessary, consider increasing the erlotinib dose by 50 mg increments at 2-week intervals as tolerated, to a maximum of 450 mg. Erlotinib is a CYP3A4 substrate, and etravirine is a moderate CYP3A4 inducer.
Erythromycin: (Moderate) Use caution with the coadministration of etravirine and erythromycin as serum concentrations of both drugs may be increased. Etravirine is a CYP3A4 substrate and a P-glycoprotein (P-gp) inhibitor, while erythromycin is a CYP3A4 inhibitor and P-gp substrate.
Estrogens affected by CYP3A inducers: (Major) Women taking both estrogens and etravirine should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed etravirine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of etravirine. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on etravirine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and etravirine is a moderate CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with etravirine is necessary. The dose of everolimus may need to be adjusted. Everolimus is a sensitive CYP3A4 substrate as well as a P-glycoprotein (P-gp) substrate. Etravirine is a moderate CYP3A4 inducer as well as a P-gp inhibitor. Coadministration with CYP3A4 inducers may increase the metabolism of everolimus and decrease everolimus blood concentrations. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ezetimibe; Simvastatin: (Moderate) The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of etravirine and simvastatin (CYP3A4 substrate) may result in lower plasma concentrations of the HMG-CoA reductase inhibitor; dose adjustments for may be necessary.
Fedratinib: (Major) Avoid coadministration of fedratinib with etravirine as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer. Coadministration of fedratinib with another moderate CYP3A4 inducer decreased the overall exposure of fedratinib by 47%.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as etravirine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of etravirine during coadministration with fenofibric acid.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if coadministration with etravirine is necessary. If etravirine is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A4 inducer like etravirine with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Fexofenadine: (Moderate) Etravirine is an inhibitor of the efflux transporter P-glycoprotein (PGP). Fexofenadine is a P-glycoprotein substrate. Increased concentrations of fexofenadine may occur if it is coadministered with etravirine; exercise caution.
Fexofenadine; Pseudoephedrine: (Moderate) Etravirine is an inhibitor of the efflux transporter P-glycoprotein (PGP). Fexofenadine is a P-glycoprotein substrate. Increased concentrations of fexofenadine may occur if it is coadministered with etravirine; exercise caution.
Finasteride; Tadalafil: (Moderate) Etravirine is an inducer of CYP3A4; coadministration may result in decreased tadalafil concentrations. Dosage adjustments may be needed based on clinical efficacy.
Finerenone: (Major) Avoid concurrent use of finerenone and etravirine due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased overall exposure to finerenone by 80%.
Flecainide: (Major) Flecainide concentrations may be decreased when coadministered with etravirine. Coadminister these drugs with caution and monitor flecainide concentrations when possible.
Flibanserin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as etravirine, is not recommended. In one study, etravirine decreased flibanserin exposure by about 21%.
Fluconazole: (Moderate) Although the manufacturer of etravirine does not recommend a dosage change for either fluconazole or etravirine when these drugs are coadministered, caution and careful monitoring is recommended. Coadministration of etravirine and fluconazole significantly increased etravirine exposures. The amount of safety data at these increased etravirine exposures is limited. Fluconazole is a moderate CYP2C9 inhibitor and etravirine is a CYP2C9 substrate.
Fluvastatin: (Moderate) The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of fluvastatin (CYP2C9 substrate) may result in higher fluvastatin plasma concentrations; dose adjustments may be necessary.
Food: (Major) Advise patients to avoid cannabis use during etravirine treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoid delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP2C9 substrates and etravirine is a moderate CYP2C9 inhibitor.
Fosamprenavir: (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.
Fosphenytoin: (Major) Etravirine should not be coadministered with fosphenytoin due to the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV; substantial reductions in etravirine concentrations may occur.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and etravirine 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 etravirine is a moderate CYP3A4 inducer.
Glasdegib: (Major) Avoid coadministration of glasdegib and etravirine due to the potential for decreased glasdegib exposure and risk of decreased efficacy. If concurrent use cannot be avoided, increase the glasdegib dosage (i.e., from 100 mg PO daily to 200 mg PO daily; or from 50 mg PO daily to 100 mg PO daily). Resume the previous dose of glasdegib after etravirine has been discontinued for 7 days. Glasdegib is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer was predicted to decrease the glasdegib AUC value by 55%.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and etravirine as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); etravirine is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and etravirine as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); etravirine is an inhibitor of P-gp.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with etravirine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If etravirine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Guanfacine: (Major) Etravirine may significantly decrease guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered; if etravirine is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If etravirine is discontinued, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and etravirine is a moderate CYP3A4 inducer.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with etravirine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If etravirine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with etravirine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If etravirine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with etravirine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If etravirine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with etravirine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If etravirine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with etravirine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Ibrutinib: (Moderate) Use ibrutinib and etravirine together with caution; decreased ibrutinib levels may occur resulting in reduced ibrutinib efficacy. Monitor patients for signs of decreased ibrutinib efficacy if these agents are used together. Ibrutinib is a CYP3A4 substrate; etravirine is a moderate CYP3A inducer. Simulations suggest that coadministration with a moderate CYP3A4 inducer may decrease ibrutinib exposure by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with etravirine is necessary; consider increasing the dose of oxycodone as needed. If etravirine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with etravirine, a CYP3A substrate, as etravirine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with etravirine is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; etravirine is a moderate CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
Imatinib: (Moderate) Monitor for evidence of increased etravirine-related adverse effects if coadministered with imatinib. Etravirine exposure may be increased during concurrent use. Etravirine is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor.
Indinavir: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and indinavir is a CYP3A4 inhibitor/substrate and a PGP substrate. Caution is warranted if these drugs are coadministered.
Infigratinib: (Major) Avoid concurrent use of infigratinib and etravirine. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Isavuconazonium: (Major) Concomitant use of isavuconazonium with etravirine may result in increased serum concentrations of etravirine and decreased serum concentrations of isavuconazonium. Etravirine is a substrate and inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Etravirine should not be coadministered with rifampin, a potent inducer of CYP450 enzymes, as significant decreases in etravirine plasma concentrations and, thus, loss of therapeutic effect could occur.
Isoniazid, INH; Rifampin: (Major) Etravirine should not be coadministered with rifampin, a potent inducer of CYP450 enzymes, as significant decreases in etravirine plasma concentrations and, thus, loss of therapeutic effect could occur.
Itraconazole: (Moderate) Itraconazole is a potent inhibitor and a substrate of CYP3A4. Etravirine is a substrate and an inducer of CYP3A4. Coadministration with itraconazole may increase plasma concentrations of etravirine. Simultaneously, plasma concentrations of itraconazole may be decreased by etravirine. Dose adjustments for itraconazole may be necessary when coadministered with etravirine. Monitor patients closely for etravirine-related adverse effects and for efficacy of itraconazole.
Ketoconazole: (Moderate) Monitor for an increase in etravirine-related adverse reactions if coadministration with ketoconazole is necessary. Etravirine is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased etravirine exposure by 1.4-fold.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of etravirine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with etravirine is necessary. Lapatinib is a P-glycoprotein (P-gp) substrate and etravirine is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Larotrectinib: (Major) Avoid concurrent use of larotrectinib and etravirine due to the risk of decreased larotrectinib exposure which may reduce its efficacy. If concomitant use is necessary, double the dose of larotrectinib and monitor response. If etravirine is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of etravirine. Larotrectinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease larotrectinib exposure by 72%.
Lefamulin: (Major) Avoid coadministration of lefamulin with etravirine unless the benefits outweigh the risks due to unpredictable lefamulin exposure. Lefamulin is a CYP3A4 and P-gp substrate; etravirine is both a moderate inducer of CYP3A4 as well as a P-gp inhibitor. The net effect on lefamulin concentrations is unclear.
Lemborexant: (Major) Avoid coadministration of lemborexant and etravirine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and etravirine due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. The exposure of etravirine may also be increased. Lenacapavir is a CYP3A substrate and moderate CYP3A inhibitor and etravirine is a CYP3A substrate and moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced lenacapavir overall exposure by 56%.
Leniolisib: (Major) Avoid concomitant use of leniolisib and etravirine. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Lesinurad: (Moderate) Use lesinurad and etravirine together with caution; etravirine may increase the systemic exposure of lesinurad. Etravirine is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Lesinurad; Allopurinol: (Moderate) Use lesinurad and etravirine together with caution; etravirine may increase the systemic exposure of lesinurad. Etravirine is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Letermovir: (Major) Concurrent administration of letermovir and etravirine is not recommended. Use of these drugs together may decrease letermovir plasma concentrations, resulting in a potential loss of letermovir efficacy. Letermovir is a substrate of UDP-glucuronosyltransferase 1A1/3 (UGT1A1/3). Etravirine induces UGT1A1. Also, plasma concentrations of etravirine could be altered (increased or decreased) when administered concurrently with letermovir. Etravirine is a substrate of the enzymes CYP3A4, CYP2C9, and CYP2C19. Letermovir is an inducer of CYP2C9 and CYP2C19, and a moderate inhibitor of CYP3A4. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levamlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Levoketoconazole: (Moderate) Monitor for an increase in etravirine-related adverse reactions if coadministration with ketoconazole is necessary. Etravirine is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased etravirine exposure by 1.4-fold.
Lidocaine: (Major) Etravirine is an inducer of CYP3A4; systemic lidocaine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor lidocaine concentrations when possible.
Lidocaine; Epinephrine: (Major) Etravirine is an inducer of CYP3A4; systemic lidocaine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor lidocaine concentrations when possible.
Lidocaine; Prilocaine: (Major) Etravirine is an inducer of CYP3A4; systemic lidocaine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor lidocaine concentrations when possible.
Linagliptin: (Moderate) Concomitant use of linagliptin with etravirine may result in decreased serum concentrations of linagliptin. Linagliptin is a substrate of hepatic isoenzyme CYP3A4; etravirine is a moderate inducer of CYP3A4. Caution and close monitoring for decreased efficacy of linagliptin are advised if these drugs are used together.
Linagliptin; Metformin: (Moderate) Concomitant use of linagliptin with etravirine may result in decreased serum concentrations of linagliptin. Linagliptin is a substrate of hepatic isoenzyme CYP3A4; etravirine is a moderate inducer of CYP3A4. Caution and close monitoring for decreased efficacy of linagliptin are advised if these drugs are used together.
Lonafarnib: (Contraindicated) Concurrent use of etravirine and lonafarnib is contraindicated and may produce unpredictable effects on lonafarnib including an increase in lonafarnib-related adverse effects or reduced lonafarnib efficacy. Etravirine exposure and adverse effects may also increase. Lonafarnib is a CYP3A4 and CYP2C9 substrate and a strong CYP3A4 and moderate CYP2C19 inhibitor. Etravirine is a CYP3A4 and CYP2C19 substrate, an inducer of CYP3A4, and an inhibitor of CYP2C9. Per the manufacturer, lonafarnib use is contraindicated with strong and moderate CYP3A4 inducers.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with etravirine. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and etravirine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with etravirine. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and etravirine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Moderate) Concomitant use of etravirine with full-dose ritonavir (i.e., 600 mg twice daily) may cause a significant decrease in etravirine plasma concentration and, thus, a loss of therapeutic effect. Etravirine and full-dose ritonavir should not be coadministered.
Lorlatinib: (Major) Avoid concomitant use of lorlatinib and etravirine due to decreased plasma concentrations of both drugs, which may reduce efficacy and increase the potential for viral resistance. If concomitant use is necessary, increase the dose of lorlatinib to 125 mg PO once daily. Both drugs are CYP3A substrates and moderate inducers. Administration with another moderate CYP3A inducer decreased lorlatinib exposure by 23%.
Lovastatin: (Moderate) The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of etravirine and lovastatin (CYP3A4 substrate) may result in lower plasma concentrations of the HMG-CoA reductase inhibitor; dose adjustments may be necessary.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may reduce the efficacy of etravirine by significantly decreasing its systemic exposure; avoid concurrent use if possible. If concomitant use of etravirine is necessary, monitor antiretroviral efficacy, consider the use of therapeutic drug monitoring, and adjust drug dosages as necessary. Etravirine is a substrate of CYP3A4, CYP2C9, and CYP2C19 and a moderate inducer of CYP3A4. Ivacaftor is a sensitive CYP3A substrate and lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce CYP2C19 and induce and/or inhibit CYP2C9. Although induction of etravirine through the CYP3A and CYP2C19 pathways may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on CYP2C9-mediated metabolism is not clear. Although ivacaftor exposure could theoretically be further decreased when given with another CYP3A inducer, ivacaftor; lumacaftor dosage adjustments are not recommended with concomitant use of a moderate CYP3A inducer such as etravirine.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may reduce the efficacy of etravirine by significantly decreasing its systemic exposure; avoid concurrent use if possible. If concomitant use of etravirine is necessary, monitor antiretroviral efficacy, consider the use of therapeutic drug monitoring, and adjust drug dosages as necessary. Etravirine is a substrate of CYP3A4, CYP2C9, and CYP2C19 and a moderate inducer of CYP3A4. Ivacaftor is a sensitive CYP3A substrate and lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce CYP2C19 and induce and/or inhibit CYP2C9. Although induction of etravirine through the CYP3A and CYP2C19 pathways may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on CYP2C9-mediated metabolism is not clear. Although ivacaftor exposure could theoretically be further decreased when given with another CYP3A inducer, ivacaftor; lumacaftor dosage adjustments are not recommended with concomitant use of a moderate CYP3A inducer such as etravirine.
Lumateperone: (Major) Avoid coadministration of lumateperone and etravirine as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer.
Lurasidone: (Moderate) Because lurasidone is primarily metabolized by CYP3A4, decreased plasma concentrations of lurasidone may occur when the drug is co-administered with inducers of CYP3A4. Concurrent use of lurasidone and CYP3A4 inducers, such as etravirine, may lead to a decrease in efficacy of lurasidone. If lurasidone is used with a moderate CYP3A4 inducer, it may be necessary to increase the lurasidone dose after chronic treatment (7 days or more).
Macimorelin: (Major) Discontinue etravirine and allow a sufficient washout period to pass before administering macimorelin. Use of these drugs together can significantly decrease macimorelin plasma concentrations, and may result in a false positive test for growth hormone deficiency. No drug-drug interaction studies have been conducted; however, macimorelin is primarily metabolized by CYP3A4 and etravirine is a CYP3A4 inducer.
Maraviroc: (Major) Coadministration of maraviroc, a CYP3A substrate, and etravirine, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor significantly decreases maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with etravirine without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and etravirine is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
Mavacamten: (Contraindicated) Concurrent use of mavacamten and etravirine is contraindicated and may produce unpredictable effects on mavacamten including reduced mavacamten efficacy or an increased risk of mavacamten-related adverse effects such as heart failure due to systolic dysfunction. Etravirine exposure may also be decreased. Mavacamten is a substrate of CYP2C19 and CYP3A and a moderate inducer of CYP2C9, CYP2C19, and CYP3A; etravirine is a CYP2C9, CYP2C19, and CYP3A substrate, a weak CYP2C19 inhibitor, and a moderate CYP3A inducer.
Mefloquine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor. Mefloquine is a CYP3A4 substrate and PGP substrate/inhibitor. Caution is warranted if these drugs are coadministered.
Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with etravirine is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and etravirine is a weak CYP2C9 inhibitor.
Methadone: (Moderate) No methadone dosage adjustments are expected when coadministered with etravirine. However, clinical monitoring for withdrawal symptoms is recommended as methadone maintenance therapy may need to be adjusted in some patients.
Methylprednisolone: (Moderate) Monitor for decreased efficacy of methylprednisolone if coadministration with etravirine is necessary; plasma concentrations of methylprednisolone may decrease. Methylprednisolone is a CYP3A substrate and etravirine induces CYP3A.
Mexiletine: (Major) Mexiletine concentrations may be decreased when coadministered with etravirine. Coadminister these drugs with caution and monitor mexiletine concentrations when possible.
Mitapivat: (Major) Avoid coadministration of mitapivat with etravirine, if possible, due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. If concomitant use is necessary, up-titration of mitapivat may be required. Monitor hemoglobin and titrate the mitapivat dose based on response; do not exceed 100 mg PO twice daily. Mitapivat is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased mitapivat overall exposure by 55% to 60%.
Mitotane: (Major) The concomitant use of mitotane with etravirine is not recommended due to significant decreases in etravirine plasma concentrations and, thus, possible loss of therapeutic effect. Mitotane is a strong CYP3A4 inducer and etravirine is a CYP3A4 substrate.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and etravirine. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Use of a moderate CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 58%.
Morphine: (Moderate) Increased concentrations of morphine may occur if it is coadministered with etravirine; exercise caution. Etravirine is an inhibitor of the efflux transporter P-glycoprotein (P-gp). Morphine is a P-gp substrate.
Morphine; Naltrexone: (Moderate) Increased concentrations of morphine may occur if it is coadministered with etravirine; exercise caution. Etravirine is an inhibitor of the efflux transporter P-glycoprotein (P-gp). Morphine is a P-gp substrate.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with etravirine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and etravirine. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and etravirine is a weak CYP3A inducer and P-gp inhibitor.
Nelfinavir: (Major) Concurrent use of etravirine and nelfinavir without low-dose ritonavir is not recommended. Concomitant use may cause a significant increase in the plasma concentrations of nelfinavir.
Neratinib: (Major) Avoid concomitant use of etravirine with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another moderate CYP3A4 inducer may decrease neratinib exposure by 52%.
Nevirapine: (Major) Coadministration of nevirapine and etravirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a significant decrease in etravirine plasma concentrations and, thus, a loss of therapeutic effect. Etravirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Niacin; Simvastatin: (Moderate) The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of etravirine and simvastatin (CYP3A4 substrate) may result in lower plasma concentrations of the HMG-CoA reductase inhibitor; dose adjustments for may be necessary.
Nirmatrelvir; Ritonavir: (Moderate) Concomitant use of etravirine with full-dose ritonavir (i.e., 600 mg twice daily) may cause a significant decrease in etravirine plasma concentration and, thus, a loss of therapeutic effect. Etravirine and full-dose ritonavir should not be coadministered. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of etravirine is necessary. Concomitant use of nirmatrelvir and etravirine may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with etravirine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and etravirine is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Nortriptyline: (Moderate) Etravirine is an inhibitor of the efflux transporter P-glycoprotein (PGP). Nortriptyline is a P-glycoprotein substrate. Increased concentrations of nortriptyline may occur if it is coadministered with etravirine; exercise caution.
Olaparib: (Major) Avoid coadministration of olaparib with etravirine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and etravirine is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and etravirine due to the risk of decreased olutasidenib exposure which may reduce its efficacy. Olutasidenib is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and etravirine. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. Omaveloxolone is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) If a patient's antiretroviral treatment regimen contains etravirine and a protease inhibitor boosted with ritonavir (i.e., either darunavir or saquinavir with ritonavir), then rifabutin should not be coadministered due to the potential for significant reductions in etravirine exposure. However, if the antiretroviral regimen does not contain a protease inhibitor boosted with ritonavir, then rifabutin may be used (at a dose of 300 mg daily).
Ondansetron: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and ondansetron is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Oritavancin: (Major) Coadministration of oritavancin and etravirine may result in increases or decreases in etravirine exposure and may increase side effects or decrease efficacy of etravirine. Etravirine is metabolized by CYP3A4, CYP2C9, and CYP2C19. Oritavancin weakly induces CYP3A4, while weakly inhibiting CYP2C9 and CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
Orlistat: (Major) Monitor HIV RNA concentrations frequently during concurrent use of orlistat and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Discontinue orlistat if an increased HIV viral load is confirmed. Loss of virological control has been reported in persons with HIV infection taking orlistat with antiretrovirals, including NNRTIs. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the antiretroviral agent.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with etravirine is necessary; consider increasing the dose of oxycodone as needed. If etravirine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Paclitaxel: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and paclitaxel is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Pacritinib: (Major) Avoid concurrent use of pacritinib with etravirine due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Palovarotene: (Major) Avoid concomitant use of palovarotene and etravirine. Concurrent use may decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Pazopanib: (Moderate) Pazopanib is a substrate for and a weak inhibitor of CYP3A4. Coadministration of pazopanib and etravirine, a CYP3A4 substrate, may cause an increase in systemic concentrations of etravirine. In addition, etravirine is an inducer of CYP3A4 and may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and etravirine due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%.
Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with etravirine due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of etravirine occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Etravirine is a moderate CYP3A4 inducer, and perampanel is a CYP3A4 substrate.
Perindopril; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Phenobarbital: (Major) Etravirine should not be coadministered with phenobarbital due to the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV; substantial reductions in etravirine concentrations may occur.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Etravirine should not be coadministered with phenobarbital due to the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV; substantial reductions in etravirine concentrations may occur.
Phenytoin: (Major) Etravirine should not be coadministered with phenytoin due to the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV; substantial reductions in etravirine concentrations may occur.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends avoiding concomitant use of pimavanserin with moderate CYP3A4 inducers, such as etravirine. Moderate inducers of CYP3A4 reduce pimavanserin exposure, potentially decreasing the effectiveness of pimavanserin.
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and etravirine due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. If concomitant use is necessary, an empiric pirtobrutinib dosage increase is required. If the current dosage is 200 mg once daily, increase the dose to 300 mg; if the current dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg. Pirtobrutinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use with other moderate CYP3A inducers reduced pirtobrutinib overall exposure by 27% and 49%.
Ponesimod: (Major) Avoid concurrent use of ponesimod and etravirine and monitor for decreased ponesimod efficacy if use is necessary. Ponesimod is an UGT1A1 substrate and etravirine is an UGT1A1 inducer that may decrease ponesimod exposure.
Posaconazole: (Moderate) Posaconazole and etravirine should be coadministered with caution due to an increased potential for etravirine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of etravirine. Further, etravirine is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and etravirine, ultimately resulting in an increased risk of adverse events.
Pralsetinib: (Major) Avoid concomitant use of etravirine with pralsetinib due to the risk of altered pralsetinib exposure which may reduce its efficacy or increase the risk of adverse reactions. Pralsetinib is a CYP3A and P-gp substrate and etravirine is a moderate CYP3A inducer and P-gp inhibitor. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45% and coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pravastatin: (Moderate) Concomitant use of etravirine and pravastatin has no effect on the serum concentration of pravastatin; however, the risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase 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 etravirine, a CYP3A4 inducer, should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
Prednisone: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and prednisone is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Pretomanid: (Major) Avoid coadministration of pretomanid with etravirine as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy. Pretomanid is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased pretomanid exposure by 35%.
Primidone: (Major) Etravirine should not be coadministered with phenobarbital due to the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV; substantial reductions in etravirine concentrations may occur. Primidone is metabolized to phenobarbital, therefore a similar interaction would be expected with primidone.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and etravirine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, 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 the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and etravirine is a P-gp inhibitor.
Progestins: (Major) Women taking both progestins and etravirine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed etravirine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of etravirine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and etravirine is a strong CYP3A4 inducer.
Propafenone: (Moderate) Use caution with coadministration of propafenone and etravirine; concurrent use may decrease propafenone exposure and efficacy. Propafenone concentration monitoring is recommended, if available.
Quinidine: (Major) Etravirine is an inducer of CYP3A4; quinidine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor quinidine concentrations when possible.
Quinine: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4, and etravirine is a PGP inhibitor and CYP3A4 inducer. Therefore, quinine concentrations could be altered with coadministration. Monitor patients for effectiveness and increased adverse effects of quinine if these drugs are given together.
Quizartinib: (Major) Avoid concomitant use of etravirine with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the quizartinib overall exposure by 90%.
Raltegravir: (Major) Coadministration of etravirine with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A; etravirine is a UGT1A1 inducer. Coadministration may result in decreased raltegravir concentrations, although the effects of etravirine on the pharmacokinetics of raltegravir administered once daily have not been studied. Etravirine may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In drug interaction studies, etravirine had no clinically meaningful effect on the pharmacokinetics of raltegravir 400 mg twice daily.
Ranolazine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor. Ranolazine is a CYP3A4 substrate/inhibitor and PGP substrate/inhibitor. Caution is warranted if these drugs are coadministered.
Relugolix: (Major) Avoid concomitant use of relugolix and oral etravirine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer etravirine at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and etravirine is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral etravirine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer etravirine at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and etravirine is a P-gp inhibitor.
Ribavirin: (Moderate) The concomitant use of ribavirin and antiretroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. 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 an increase in etravirine-related adverse reactions if coadministration with ribociclib is necessary. Etravirine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold.
Ribociclib; Letrozole: (Moderate) Monitor for an increase in etravirine-related adverse reactions if coadministration with ribociclib is necessary. Etravirine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold.
Rifabutin: (Moderate) If a patient's antiretroviral treatment regimen contains etravirine and a protease inhibitor boosted with ritonavir (i.e., either darunavir or saquinavir with ritonavir), then rifabutin should not be coadministered due to the potential for significant reductions in etravirine exposure. However, if the antiretroviral regimen does not contain a protease inhibitor boosted with ritonavir, then rifabutin may be used (at a dose of 300 mg daily).
Rifampin: (Major) Etravirine should not be coadministered with rifampin, a potent inducer of CYP450 enzymes, as significant decreases in etravirine plasma concentrations and, thus, loss of therapeutic effect could occur.
Rifapentine: (Major) Etravirine should not be coadministered with rifapentine, a potent inducer of CYP450 enzymes, as significant decreases in etravirine plasma concentrations and, thus, loss of therapeutic effect could occur.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with etravirine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and etravirine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Major) Coadministration of etravirine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Etravirine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Rimegepant: (Major) Avoid coadministration of rimegepant with etravirine; concurrent use may alter rimegepant exposure. Rimegepant is a CYP3A4 and P-gp substrate and etravirine is a moderate CYP3A4 inducer and P-gp inhibitor.
Ripretinib: (Major) Avoid coadministration of ripretinib with etravirine. If concomitant use is unavoidable, increase the frequency of ripretinib dosing from 150 mg once daily to 150 mg twice daily; monitor for clinical response and tolerability. Resume once daily dosing of ripretinib 14 days after discontinuation of etravirine. Coadministration is predicted to decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A and etravirine is a moderate CYP3A inducer. Drug interaction modeling studies suggest coadministration with a moderate CYP3A inducer may decrease ripretinib exposure by 56%.
Ritlecitinib: (Moderate) Monitor for an increase in etravirine-related adverse reactions if concomitant use of ritlecitinib is necessary. Etravirine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Moderate) Concomitant use of etravirine with full-dose ritonavir (i.e., 600 mg twice daily) may cause a significant decrease in etravirine plasma concentration and, thus, a loss of therapeutic effect. Etravirine and full-dose ritonavir should not be coadministered.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and etravirine may result in increases or decreases in rivaroxaban exposure and may increase bleeding risk or decrease efficacy of rivaroxaban. Etravirine is an inducer of CYP3A4 and inhibitor of P-gp, and rivaroxaban is a substrate of CYP3A4 and P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding and lack of efficacy.
Roflumilast: (Moderate) Coadminister etravirine and roflumilast cautiously as this may lead to reduced systemic exposure to roflumilast. Etravirine induces CYP3A4 and roflumilast is a CYP3A4 substrate. In pharmacokinetic study, administration of a single dose of roflumilast in patients receiving another CYP3A4 inducer, rifampin, resulted in decreased roflumilast Cmax and AUC, as well as increased Cmax and decreased AUC of the active metabolite roflumilast N-oxide.
Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4 and P-glycoprotein (P-gp). Coadministration of a CYP3A4 inducer, like etravirine, may decrease systemic concentrations of romidepsin. Alternately, etravirine is an inhibitor of P-gp and may increase systemic concentrations of romidepsin. Use caution when concomitant administration of these agents is necessary.
Rosuvastatin: (Moderate) Concomitant use of etravirine and rosuvastatin has no effect on the serum concentration of rosuvastatin; however, the risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors.
Rosuvastatin; Ezetimibe: (Moderate) Concomitant use of etravirine and rosuvastatin has no effect on the serum concentration of rosuvastatin; however, the risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors.
Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as etravirine, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition.
Sacituzumab Govitecan: (Major) Avoid coadministration of sacituzumab govitecan and etravirine due to the risk of decreased sacituzumab govitecan exposure which may reduce its efficacy. The cytotoxic component of sacituzumab govitecan, SN-38, is metabolized by UGT1A1 and etravirine is a UGT1A1 inducer. Formal drug interaction studies with sacituzumab govitecan have not been conducted but the concomitant use of UGT1A1 inducers is expected to decrease SN-38 exposure.
Saquinavir: (Minor) The coadministration of etravirine and saquinavir (boosted with ritonavir) resulted in a 33% decrease in etravirine exposure (AUC). This reduction is similar to that seen in etravirine phase 3 clinical trials (when administered with daruanvir boosted with ritonavir), therefore, no dosage adjustments are necessary.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and etravirine due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease selpercatinib exposure by 40% to 70%.
Selumetinib: (Major) Avoid coadministration of selumetinib and etravirine due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease selumetinib exposure by 38%.
Sildenafil: (Moderate) Etravirine is an inducer of CYP3A4; coadministration may result in decreased sildenafil concentrations. Dosage adjustments may be needed based on clinical efficacy.
Silodosin: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and silodosin is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Simvastatin: (Moderate) The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of etravirine and simvastatin (CYP3A4 substrate) may result in lower plasma concentrations of the HMG-CoA reductase inhibitor; dose adjustments for may be necessary.
Siponimod: (Moderate) Concomitant use of siponimod and etravirine is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A substrate; etravirine is a moderate CYP3A inducer. Across different CYP2C9 genotypes, a moderate CYP3A inducer decreased the exposure of siponimod by up to 52% according to in silico evaluation.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of etravirine. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and etravirine is a weak CYP3A inducer and P-gp inhibitor.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with etravirine due to the potential for loss of antiviral efficacy. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with etravirine due to the potential for loss of antiviral efficacy. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer. (Major) Avoid coadministration of voxilaprevir (a CYP3A4 substrate) with moderate to strong inducers of CYP3A4, such as etravirine. Taking these drugs together may significantly decrease voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and etravirine; sonidegib levels may be decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate and etravirine is a CYP3A4 inducer. Physiologic-based pharmacokinetics (PBPK) simulations indicate that a moderate CYP3A4 inducer would decrease the sonidegib AUC by 56% if administered for 14 days and by 69% if the moderate CYP3A inducer is administered for more than 14 days.
Sotagliflozin: (Moderate) Monitor for a decrease in sotagliflozin efficacy during concomitant use of sotagliflozin and etravirine and adjust therapy as appropriate. Concomitant use may decrease sotagliflozin exposure. Sotagliflozin is a UGT substrate and etravirine is a UGT inducer. Concomitant use with another UGT inducer reduced sotagliflozin overall exposure by 45%.
Sotorasib: (Moderate) Concurrent use of etravirine and sotorasib may decrease plasma concentrations of etravirine, leading to a reduction of antiretroviral efficacy and the potential development of antiretroviral drug resistance. Although specific recommendations are unavailable for use with sotorasib, coadministration with other moderate CYP3A4 inducers is not recommended. Etravirine is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. Concurrent use of another moderate CYP3A4 inducer decreased etravirine exposure by approximately 35%.
St. John's Wort, Hypericum perforatum: (Major) St. John's wort should not be administered with etravirine as it may significantly decrease the plasma concentrations of etravirine. Such reductions in plasma concentrations of etravirine could lead to HIV treatment failures or the development of viral-resistance. St. John's wort appears to be an inducer of hepatic cytochrome P450 enzymes, particularly CYP3A4. Etravirine is a CYP3A4 substrate.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if etravirine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with etravirine is necessary; consider increasing the dose of sufentanil injection as needed. If etravirine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tacrolimus: (Major) Coadministration with etravirine may result in altered tacrolimus concentrations. Coadminister these drugs with caution, carefully monitoring tacrolimus concentrations and making dosage adjustments as needed.
Tadalafil: (Moderate) Etravirine is an inducer of CYP3A4; coadministration may result in decreased tadalafil concentrations. Dosage adjustments may be needed based on clinical efficacy.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with etravirine is necessary. Talazoparib is a P-gp substrate and etravirine is a P-gp inhibitor.
Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and etravirine. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as etravirine, may reduce the efficacy of tasimelteon.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with etravirine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Telmisartan; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as etravirine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with etravirine is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and etravirine is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of temsirolimus.
Teniposide: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and teniposide is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ticagrelor: (Moderate) Coadministration of ticagrelor and etravirine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and etravirine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
Tipranavir: (Major) Etravirine should not be coadministered with tipranavir. Concomitant use may cause a significant decrease in etravirine plasma concentration and, thus, a loss of therapeutic effect.
Topotecan: (Major) Avoid coadministration of etravirine with oral topotecan due to increased topotecan exposure; etravirine may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and etravirine is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Toremifene: (Moderate) Monitor for an increase in etravirine-related adverse reactions if coadministration with toremifene is necessary. Etravirine is a CYP2C9 substrate and toremifene is a weak CYP2C9 inhibitor.
Trandolapril; Verapamil: (Moderate) Monitor for an increase in etravirine-related adverse reactions and decreased verapamil efficacy if concomitant use is necessary. The exposure of both drugs may be altered. Etravirine is a CYP3A substrate and moderate CYP3A inducer and verapamil is a CYP3A substrate and moderate CYP3A inhibitor.
Tucatinib: (Moderate) Monitor for an increase in etravirine-related adverse reactions if coadministration with tucatinib is necessary. Etravirine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold.
Ubrogepant: (Major) Ubrogepant dose adjustment is necessary if coadministered with etravirine as concurrent use may decrease ubrogepant exposure and efficacy or increase ubrogepant exposure and side effects. Ubrogepant is a CYP3A4 and P-gp substrate; etravirine is a moderate CYP3A4 inducer and P-gp inhibitor.
Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and etravirine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
Vemurafenib: (Major) Concomitant use of vemurafenib and etravirine may result in altered concentrations of both drugs. Use caution and monitor patients for toxicity and efficacy. Vemurafenib is a substrate/inducer of CYP3A4, an inhibitor of CYP2C9, and a substrate/inhibitor of P-glycoprotein (P-gp). Etravirine is a substrate/inducer of CYP3A4, a substrate/inhibitor of CYP2C9, and an inhibitor of P-gp.
Venetoclax: (Major) Avoid the concomitant use of venetoclax and etravirine; venetoclax levels may be altered. Consider alternative agents. Venetoclax is a substrate of CYP3A4 and P-glycoprotein (P-gp) and etravirine is a moderate inducer of CYP3A4 and an inhibitor of P-gp. In a drug interaction study in healthy subjects (n = 10), the venetoclax Cmax and AUC values were decreased by 42% and 71%, respectively, following the co-administration of multiple doses of a strong CYP3A4 inducer. Use of venetoclax with a moderate CYP3A4 inducer has not been evaluated. In another drug interaction study (n = 11), the venetoclax Cmax and AUC values were increased by 106% and 78%, respectively, when a single dose of a P-gp inhibitor was co-administered in healthy subjects.
Verapamil: (Moderate) Monitor for an increase in etravirine-related adverse reactions and decreased verapamil efficacy if concomitant use is necessary. The exposure of both drugs may be altered. Etravirine is a CYP3A substrate and moderate CYP3A inducer and verapamil is a CYP3A substrate and moderate CYP3A inhibitor.
Vincristine Liposomal: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and vincristine is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Vincristine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and vincristine is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Voclosporin: (Major) Avoid coadministration of voclosporin with etravirine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and etravirine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and etravirine is a moderate CYP3A inducer. 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 etravirine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer. (Major) Coadministration of etravirine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and etravirine. Decreased serum concentrations of vorapaxar and thus decreased efficacy are possible when vorapaxar, a CYP3A4 substrate, is coadministered with etravirine, a CYP3A inducer.
Voriconazole: (Moderate) Monitor for an increase in etravirine-related adverse reactions if concomitant use of voriconazole is necessary. Etravirine is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Concomitant use with voriconazole increased etravirine exposure by 1.4-fold.
Voxelotor: (Major) Avoid coadministration of voxelotor and etravirine as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,000 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Additionally, monitor for an increase in etravirine-related adverse reactions during coadministration as exposure may be increased. Voxelotor is a substrate of CYP3A and moderate CYP3A inhibitor; etravirine is a CYP3A substrate and moderate CYP3A inducer. Coadministration of voxelotor with a moderate CYP3A inducer is predicted to decrease voxelotor exposure by up to 24%.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with etravirine is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. The active metabolite of warfarin, the S-enantiomer, is a CYP2C9 substrate and etravirine is a CYP2C9 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.
Zanubrutinib: (Major) Avoid concurrent use of zanubrutinib and etravirine due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if etravirine is discontinued. Zanubrutinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Zolpidem: (Moderate) It is advisable to closely monitor for reductions in zolpidem efficacy during co-administration of moderate CYP3A4 inducers, such as etravirine. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of significant decreases in systemic exposure and pharmacodynamics effects of zolpidem during co-administration of rifampin, a potent CYP3A4 inducer.

Etravirine/INTELENCE Oral Tab: 25mg, 100mg, 200mg

Adults

400 mg/day PO.

Geriatric

400 mg/day PO.

Adolescents

weighing 30 kg or more: 400 mg/day PO.
weighing 25 to 29 kg: 300 mg/day PO.

Children

2 to 12 years weighing 30 kg or more: 400 mg/day PO.
2 to 12 years weighing 25 to 29 kg: 300 mg/day PO.
2 to 12 years weighing 20 to 24 kg: 250 mg/day PO.
2 to 12 years weighing 10 to 19 kg: 200 mg/day PO.
less than 2 years or less than 10 kg: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type-1 (HIV-1). It binds directly to reverse transcriptase. This binding blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site.
In clinical trials, resistance-associated substitutions most frequently observed with etravirine therapy included: L100I, E138G, V179F, V179I, Y181C, and H221Y. Other NNRTI-resistance-associated substitutions emerging in less than 10% of etravirine treatment failures included: K101E/H/P, K103N/R, V106I/M, V108I, Y181I, Y188L, V189I, G190S/C, N348I, and R356K. These substitutions contributed to a median decrease in etravirine susceptibility of 40-fold from reference and 6-fold from baseline. Some NNRTI-resistant viruses may be susceptible to etravirine; use genotypic and phenotypic testing to guide treatment. Cross-resistance to delavirdine, efavirenz, and nevirapine is expected after virologic failure with etravirine. Also, cross-resistance to etravirine has been observed in doravirine-resistant infections.
Etravirine did not show antagonism when studied in combination with: the NNRTIs delavirdine, efavirenz, and nevirapine; the NRTIs abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine; the PIs amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir; the integrase strand transfer inhibitor raltegravir; the CCR5 co-receptor antagonist maraviroc; and the fusion inhibitor enfuvirtide (ENF).[33718]
Avoid the use of etravirine in patients with HIV-2, as HIV-2 is intrinsically resistant to NNRTIs. To identify the HIV strain, The 2014 Centers for Disease Control and Prevention guidelines for HIV diagnostic testing recommend initial HIV testing using an HIV-1/HIV-2 antigen/antibody combination immunoassay and subsequent testing using an HIV-1/HIV-2 antibody differentiation immunoassay.[46638]

Etravirine is administered orally. It is about 99.9% bound to plasma proteins, primarily to albumin (99.6%) and alpha 1-acid glycoprotein (97.66% to 99.02%) in vitro. Etravirine is primarily metabolized by the liver by CYP3A4, CYP2C9, and CYP2C19 isoenzymes; the metabolites, which are formed by methyl hydroxylation of the dimethylbenzonitrile moiety, are at least 90% less active than etravirine against wild-type HIV in cell culture. After single dose oral administration of 800 mg 14C-etravirine, 93.7% and 1.2% of the dose is recovered in the feces and urine, respectively. Unchanged etravirine accounts for 81.2% to 86.4% of the administered dose in feces, and it is not detected in urine. The mean terminal elimination half-life is about 41 (+/- 20) hours.
 
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C9, CYP2C19, P-glycoprotein (P-gp)
Etravirine is an inducer of CYP3A4 and inhibitor of CYP2C9, CYP2C19, and P-glycoprotein (P-gp). Coadministration with drugs that are substrates of these isoenzymes or transported by P-gp may alter the therapeutic effect or adverse reaction profile of the coadministered drug(s). Additionally, etravirine is a substrate of CYP3A4, CYP2C9, and CYP2C19. Coadministration with drugs that induce or inhibit any of these isoenzymes may alter the therapeutic effect or adverse reaction profile of etravirine.
 

Oral Route

Following etravirine administration, Tmax is reached in about 2.5 to 4 hours. The absolute oral bioavailability is unknown. Systemic exposure (AUC) is decreased by about 50% when administered under fasting conditions, as compared to administration following a meal; therefore, etravirine should always be taken after a meal. A range of meals have been studied, with total caloric intake ranging from 345 kilocalories with 17 grams fat to 1,160 kilocalories with 70 grams fat, and the systemic exposures are similar.

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. Data regarding administration of etravirine during pregnancy are too limited to rule out any potential association with birth defects (i.e., 1 birth defect noted in 73 live births); therefore, etravirine-containing regimens should not be initiated in pregnant patients. However, it may be appropriate to continue use of the drug in some virally suppressed pregnant patients. 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 etravirine; 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 undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). There are limited data regarding the use of etravirine during breast-feeding; however, the drug was found to be excreted in 1 small study involving 8 lactating women. In this study, treatment with etravirine was initiated on postpartum day 1, with plasma and breast milk drug concentrations drawn on days 5 and 14. On day 5, the breast milk to plasma ratio was 109%; on day 14, the breast milk to plasma ratio was 327%. This data suggest etravirine is excreted into and may accumulate in human breast milk. Other antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.