Nevirapine

Nevirapine is an oral non-nucleoside reverse transcriptase inhibitor used for HIV-1 infection, now rarely in adults but still widely for infant prophylaxis to prevent mother-to-child transmission. It carries boxed warnings for life-threatening hepatotoxicity and severe skin reactions, which are most likely in the first 18 weeks and in women with higher CD4 counts. A mandatory 14-day lead-in dose reduces rash risk.

Class. Non-nucleoside reverse transcriptase inhibitor.

Mechanism. Binds directly to HIV-1 reverse transcriptase and blocks its activity without activation. A single mutation (Y181C or K103N) causes high-level resistance, and a single dose can select it.

Pharmacokinetics. Oral bioavailability over 90%, unaffected by food. Half life 25 to 30 hours with repeated doses (45 hours after a single dose). It induces CYP3A4 and CYP2B6, including its own metabolism (hence the lead-in).

HIV-1 infection (adults). - Lead-in: 200 mg orally once daily for 14 days. - Then 200 mg twice daily (or 400 mg extended-release once daily after the lead-in on immediate-release tablets). - Do not start in women with CD4 over 250 cells/microlitre or men with CD4 over 400 cells/microlitre unless the benefit clearly outweighs the risk.

Children. 150 mg/m² once daily for 14 days, then 150 mg/m² twice daily (maximum 200 mg twice daily); weight-banded dispersible tablets.

Infant prophylaxis. - Birth weight 2.0 to 2.49 kg: 10 mg once daily; 2.5 kg or more: 15 mg once daily; birth to 6 weeks (low risk) or 12 weeks (high risk).

Interruptions. If doses are missed for more than 7 days, restart the 14-day lead-in.

Loading dose, maintenance dose and titration. The 14-day lead-in at 200 mg once daily is mandatory before full dosing. Maximum: 400 mg daily.

Main alternative. Dolutegravir (adults) or efavirenz.

Contraindications. Hypersensitivity; moderate or severe liver impairment; previous severe rash or hepatitis on nevirapine; ALT over 5 times the upper limit of normal before starting.

Serious adverse effects. Hepatotoxicity including fatal hepatic necrosis, Stevens-Johnson syndrome and toxic epidermal necrolysis, hypersensitivity syndrome with fever and eosinophilia, and immune reconstitution syndrome.

Common adverse effects. Rash, nausea, headache, fever and fatigue.

Interactions. - Rifampicin lowers nevirapine levels substantially; avoid. - Protease inhibitors, ketoconazole, itraconazole, methadone and oral hormonal contraceptives are lowered. - Fluconazole raises levels and hepatotoxicity risk. - Artemether-lumefantrine: lowered levels.

Common prescribing errors. Skipping the lead-in, escalating despite a rash, restarting without the lead-in after a gap, and using it in women with higher CD4 counts.

Special groups. - Pregnancy: acceptable but hepatotoxicity is more frequent in women with CD4 over 250 cells/microlitre. - Breastfeeding: compatible. - Children: weight-banded dispersible tablets; infant prophylaxis dosing by birth weight. - Older adults: usual dose; check liver tests. - Kidney impairment: no adjustment; dialysis patients receive an extra dose after dialysis. - Liver impairment: contraindicated in moderate or severe disease.

Regional points. Dolutegravir has replaced it in adults, but nevirapine remains in infant prophylaxis programmes; single-dose use in labour has left some women with resistant virus.

Formulations. Tablets 200 mg; extended-release tablets 400 mg; oral suspension 10 mg/mL; dispersible tablets 50 mg; fixed-dose combination with zidovudine and lamivudine.

Administration. With or without food. Do not escalate beyond 200 mg once daily during the lead-in if a rash develops.

Baseline. HIV test, CD4 count, liver tests, hepatitis B and C status, pregnancy test.

Monitoring. Liver tests at 2, 4, 8 and 12 weeks and then every 3 months; skin examination and symptoms at every contact during the first 18 weeks.

Stopping thresholds. Stop permanently for ALT over 3 times the upper limit of normal with symptoms, or over 5 times without; for severe rash, rash with fever or mucosal involvement; or for hypersensitivity. Do not restart.

Referral and escalation. Admission for suspected hepatitis or Stevens-Johnson syndrome.