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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ETRAVIRINE (ETRAVIRINE).
| Breastfeeding | It is not known whether etravirine is excreted in human breast milk. No M/P ratio is available. Due to the potential for HIV transmission and adverse effects in the infant, breastfeeding is not recommended in HIV-infected mothers. If used in non-HIV indications, caution is advised. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with other NNRTIs","Severe hepatic impairment (Child-Pugh class C)"]
| 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"] |
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| 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. |