ETRAVIRINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ETRAVIRINE (ETRAVIRINE).
Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to reverse transcriptase, causing allosteric inhibition of RNA-dependent and DNA-dependent DNA polymerase activities.
| Metabolism | Primarily hepatic via CYP3A4, CYP2C9, and CYP2C19; also undergoes glucuronidation (UGT1A1, UGT1A3, UGT2B7). Minor metabolite formation via N-demethylation. |
| Excretion | Fecal: ~93.7% (unchanged drug and metabolites; bile is the major route); Renal: ~1.2% (urinary, negligible unchanged drug). |
| Half-life | Terminal elimination half-life approximately 41 hours (range 20-70 hours) following multiple doses; supports once-daily dosing with a pharmacokinetic booster (e.g., ritonavir or cobicistat). |
| Protein binding | ~99.9% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 645 L (not weight-based; corresponds to extensive tissue distribution, >9 L/kg). |
| Bioavailability | Oral bioavailability is not precisely determined (only oral route available); absorption is enhanced with food (increase by 50% with a high-fat meal), but absolute bioavailability data are unavailable. |
| Onset of Action | Not applicable; etravirine is administered orally for chronic therapy; antiviral effect begins within days as viral load declines, but no immediate clinical effect. |
| Duration of Action | Sustained viral suppression over 24 hours with twice-daily dosing; clinical duration is long-term (chronic therapy); half-life allows re-dosing every 12 hours. |
| Molecular Weight | 435.5 |
400 mg orally twice daily after meals.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment including dialysis. |
| Liver impairment | Child-Pugh Class A and B: No dose adjustment. Child-Pugh Class C: Not recommended. |
| Pediatric use | Weight-based dosing: 4 to <8 kg: 12 mg twice daily; 8 to <10 kg: 17 mg twice daily; 10 to <12 kg: 22 mg twice daily; 12 to <14 kg: 27 mg twice daily; 14 to <16 kg: 32 mg twice daily; 16 to <18 kg: 40 mg twice daily; 18 to <20 kg: 40 mg twice daily; 20 to <25 kg: 50 mg twice daily; 25 to <30 kg: 62.5 mg twice daily; 30 to <40 kg: 75 mg twice daily; ≥40 kg: 100 mg twice daily. Administer after meals. |
| Geriatric use | No specific dose adjustment; use with caution due to greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy. |
| 1st trimester | Use only if benefit outweighs risk; no adequate studies in pregnant women. |
| 2nd trimester | Use only if benefit outweighs risk; no adequate studies in pregnant women. |
| 3rd trimester | Use only if benefit outweighs risk; no adequate studies in pregnant women. |
Clinical note
Comprehensive clinical and safety monograph for ETRAVIRINE (ETRAVIRINE).
| Placental transfer | Etravirine crosses the placenta in animal studies; human data limited. |
| Breastfeeding | Excreted in human milk; potential for HIV transmission and adverse effects in infant; avoid breastfeeding in HIV-infected women per CDC guidelines. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to etravirine or any component
| Precautions | Severe skin and hypersensitivity reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme), which may include fever, fatigue, arthralgia, conjunctivitis, hepatitis, eosinophilia, Hepatotoxicity, especially in patients with hepatitis B or C coinfection, Immune reconstitution syndrome, Hyperlipidemia, including elevated triglycerides and cholesterol |
| Food/Dietary | Etravirine should be taken with food. A high-fat meal increases exposure; however, consistent intake with food is recommended regardless of meal composition. No specific food restrictions. Grapefruit juice may affect CYP3A4 but interaction is not clinically significant; avoid excessive consumption. |
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| Teratogenic Risk | Etravirine is classified as Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. In animal studies, no evidence of teratogenicity was observed at exposures up to 2-fold (rats) and 5-fold (rabbits) human exposure at recommended clinical dose. However, due to limited human data, it should be used during pregnancy only if clearly needed. No specific fetal risks in first, second, or third trimester have been identified in human studies. |
| Fetal Monitoring | Monitor liver function tests (LFTs) and renal function periodically. Assess for rash, as severe hypersensitivity reactions may occur. Monitor HIV viral load and CD4 count during pregnancy if used for HIV. Fetal ultrasound may be considered for growth assessment, though no specific monitoring is mandated. |
| Fertility Effects | No human studies on fertility are available. Animal studies at doses producing systemic exposures similar to human therapeutic exposure showed no impairment of fertility in rats. No known effect on human fertility. |
| Clinical Pearls | Etravirine is a second-generation NNRTI with a higher genetic barrier to resistance than first-generation NNRTIs. It is effective against many NNRTI-resistant HIV strains. Administer with food to improve bioavailability. Caution in severe hepatic impairment (Child-Pugh C): not recommended. Monitor for severe skin reactions, including Stevens-Johnson syndrome, especially in the first 4-6 weeks. Co-administration with rifampin is contraindicated due to significant CYP3A4 induction. Potential for central nervous system side effects (e.g., peripheral neuropathy, dizziness). |
| Patient Advice | Take etravirine exactly as prescribed; do not miss doses. · Swallow the tablets whole with a glass of water; do not crush or chew. · Always take with food to improve absorption. · Report any severe skin reactions, such as rash with blistering or fever, immediately. · Etravirine does not cure HIV; you may still transmit the virus. · Avoid alcohol if you have liver problems. · Inform your doctor of all other medications, including over-the-counter and herbal products. · Etravirine may cause dizziness or trouble sleeping; avoid driving if affected. · Do not breastfeed while taking etravirine. |