Etravirine is a second-generation NNRTI with activity against HIV strains resistant to nevirapine and efavirenz. It is used in second-line regimens.
Also known as: Intelence, ETV
Rifampicin reduces etravirine levels by ~80% via potent CYP3A4/CYP2C19 induction. CONTRAINDICATED.
Rifampicin is the most potent enzyme inducer available, acting on multiple enzymes including CYP3A4, CYP2C19, CYP2C9 and UGT1A1. Etravirine is metabolised primarily by CYP3A4 and CYP2C19. Pharmacokinetic studies demonstrated that rifampicin reduces etravirine AUC by ~80% and Cmax by ~70%, virtually abolishing its antiretroviral activity. The etravirine label (Intelence) lists rifampicin as an absolute contraindication. Coadministration would almost certainly lead to virological failure and resistance selection. Alternative: rifabutin (weaker induction) with etravirine dose adjustment to 400 mg twice daily, or use another antiretroviral regimen that does not depend on etravirine.
Etravirine + rifampicin: contraindicated. ~80% reduction in etravirine levels via potent CYP3A4/CYP2C19 induction.
Rifampicin is one of the most potent enzyme inducers. Induction of CYP3A4 and CYP2C19 virtually abolishes etravirine levels, compromising antiretroviral efficacy.
Monitor viral load if rifabutin is used instead of rifampicin.
Virological failure virtually guaranteed if coadministered.
CONTRAINDICATED. Do not coadminister. Alternative: rifabutin (weaker induction) with etravirine dose adjustment to 400 mg twice daily.
DailyMed/FDA (NIH/NLM) — approved Etravirine (Intelence) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6a9cbc29-9f15-4b24-8d86-206b82887f3d ; approved Rifampicin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=04e52489-77af-4b7f-b20b-3c5742e7b75e
Etravirine has significantly increased absorption with fatty food (50% vs fasting).
Take after fatty meals. Tablets should be chewed or crushed.
DailyMed/FDA (NIH/NLM) — approved Etravirine (Intelence) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6a9cbc29-9f15-4b24-8d86-206b82887f3d
No documented disease interactions.
Limited human data. Animal studies did not demonstrate teratogenicity. Use with caution.
Can be used in the 2nd and 3rd trimesters with caution. 1st trimester data are limited.
Excreted in breast milk. Artificial feeding is recommended for HIV-positive mothers.
Reliable contraceptive methods are recommended.
DailyMed/FDA (NIH/NLM) — approved Etravirine (Intelence) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6a9cbc29-9f15-4b24-8d86-206b82887f3d
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Etravirine is a second-generation NNRTI effective against HIV strains resistant to first-generation NNRTIs.
Binds to multiple sites of HIV-1 reverse transcriptase, causing allosteric distortion that inhibits viral DNA synthesis. Non-competitive binding confers activity against strains with K103N and Y181C mutations.
Oral bioavailability: significantly increased by fatty food (50% vs fasting). Tmax: 2.5-4 hours. Tablets should be chewed or crushed.
Metabolised by CYP3A4, CYP2C9 and CYP2C19. Induced by rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital. Inhibited by cimetidine.
~41 hours. Elimination: 92% faeces (metabolites), 10% urine. Long half-life allows twice-daily dosing.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
