VIRAMUNE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIRAMUNE (VIRAMUNE).
Non-nucleoside reverse transcriptase inhibitor (NNRTI); binds directly to HIV-1 reverse transcriptase, causing allosteric inhibition and blocking RNA-dependent and DNA-dependent DNA polymerase activities.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2B6; undergoes hydroxylation and glucuronidation. Also a CYP3A4 inducer. |
| Excretion | Renal: <5% unchanged; urinary metabolites: ~80% (glucuronides, hydroxylated metabolites); fecal: ~10%. |
| Half-life | Terminal elimination half-life: 25-30 hours (single dose); 20-25 hours at steady state due to autoinduction. Clinical context: Autoinduction of CYP3A4 reduces half-life after multiple doses. |
| Protein binding | 60% bound to plasma proteins (albumin and lipoproteins). |
| Volume of Distribution | 1.2-1.5 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral: >90% (tablet and oral suspension). |
| Onset of Action | Oral: Rapid absorption; peak plasma concentrations at 2-4 hours. Clinical effect (HIV RNA reduction) typically seen within 1-2 weeks. |
| Duration of Action | Duration of therapeutic effect: 12 hours (due to recommended twice-daily dosing). Clinical notes: Continuous suppression requires consistent adherence. |
| Molecular Weight | 266.3 |
200 mg orally once daily for 14 days, then 200 mg twice daily; alternatively, 400 mg extended-release once daily for 14 days, then 400 mg extended-release once daily.
| Dosage form | SUSPENSION |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min or ESRD not on dialysis, use with caution; no specific dose recommendation available. |
| Liver impairment | Child-Pugh Class A: No dose adjustment. Child-Pugh Class B: Contraindicated. Child-Pugh Class C: Contraindicated. |
| Pediatric use | For patients ≥3 months of age: 150 mg/m² orally once daily for 14 days, then 150 mg/m² twice daily; maximum 400 mg per day. |
| Geriatric use | No specific dose adjustment; monitor closely due to increased risk of adverse effects (e.g., hepatotoxicity, rash). |
| 1st trimester | Use only if clearly needed; no adequate studies in pregnant women. Animal studies show reproductive toxicity. |
| 2nd trimester | Use if benefit outweighs risk; monitor for hepatotoxicity and skin reactions. |
| 3rd trimester | Use if benefit outweighs risk; may cause neonatal withdrawal syndrome if used near term. |
Clinical note
Comprehensive clinical and safety monograph for VIRAMUNE (VIRAMUNE).
| Placental transfer | Extensive placental transfer; cord blood levels approximate maternal plasma levels. |
| Breastfeeding | Nevirapine is excreted in human milk; potential for adverse effects in nursing infants. Formula feeding recommended. |
| Lactation Rating |
■ FDA Black Box Warning
Severe, life-threatening hepatotoxicity including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure. Fatal cases have been reported, especially within the first 18 weeks of therapy. Also, severe skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions can occur.
| Serious Effects |
Hypersensitivity to nevirapine or any excipientsSevere hepatic impairment (Child-Pugh class C)Concomitant use with St. John's wortConcomitant use with rifampicin
| Precautions | Hepatotoxicity: monitor hepatic enzymes closely, especially during first 18 weeks; discontinue if severe hepatitis occurs., Severe skin reactions: discontinue if rash with systemic symptoms or blistering., Immune reconstitution syndrome: may occur during initial treatment., Resistance: cross-resistance with other NNRTIs., Drug interactions: induces CYP3A4, reducing levels of many drugs (e.g., oral contraceptives, methadone, warfarin). |
| Food/Dietary | No significant food interactions. Take with or without food; if gastrointestinal upset occurs, taking with food may help. |
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| L5 |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in humans based on cohort studies; animal studies show no fetal harm at systemic exposures similar to human therapeutic levels. First trimester exposure not associated with increased major malformations. Second and third trimester exposure: no specific fetal risks identified, but monitor for mitochondrial toxicity (theoretical). |
| Fetal Monitoring | Monitor maternal hepatic function (ALT, AST) at baseline and every 2 weeks for first 12 weeks, then monthly; watch for rash (including Stevens-Johnson syndrome). Fetal monitoring: standard antenatal ultrasound; assess for growth restriction if hepatotoxicity develops. Postnatal: monitor infant for nevirapine-related adverse effects (e.g., hepatotoxicity) if exposed. |
| Fertility Effects | No known adverse effects on male or female fertility; limited human data. In animal studies, no impairment of fertility observed at clinically relevant doses. |
| Clinical Pearls | Start with a 200 mg once-daily lead-in dose for 14 days to reduce rash risk; if no rash occurs, escalate to 200 mg twice daily. Monitor LFTs at baseline and every 2 weeks for first 2 months, then monthly for 3 months. Use with caution in women with CD4+ >250 cells/mm³ and men with CD4+ >400 cells/mm³ due to increased hepatotoxicity risk. Do not use as monotherapy. |
| Patient Advice | Take this medication exactly as prescribed; do not skip doses or change dosing without consulting your doctor. · During the first 14 days, take one tablet once daily; after that, take one tablet twice daily. · A serious rash may occur during the first few weeks; contact your healthcare provider immediately if you develop a rash. · You will need regular blood tests to monitor liver function. · If you miss a dose, take it as soon as you remember, unless it is almost time for the next dose; then skip the missed dose and resume regular schedule. · Use effective birth control while on this medication as it may reduce the effectiveness of hormonal contraceptives. · Do not breastfeed if you are HIV-positive and taking this medication. |