Accelerated Approval of Nevirapine
Nevirapine was reviewed by the FDA Antiviral Drugs Advisory Committee on June 7, 1996. The Committee voted approval 8-0. When The Hopkins HIV Report went to press, the FDA had not yet cleared the accelerated approval of nevirapine, but the prior experience suggests this drug may be FDA-approved by the end of June. The following is a review of nevirapine:
Nevirapine must be used in combination with nucleoside analogues such as AZT (200 mg po bid) or ddC (0.75 mg tid). The greatest experience is with a) Nevirapine + AZT; b) Nevirapine + AZT + ddI; c) Nevirapine + AZT + ddC; experience is limited for Nevirapine + 3TC or d4T; protease inhibitors should not be given in combination with nevirapine.
Highlights of FDA presentation
Bioavailability: >90%, not influenced by food
T½ (post induction): 25-30 hrs; CNS penetration: 50-60% of serum levels
Elimination: Induces cytochrome p450 (auto-induction) to reduce nevirapine levels
steady state achieved at 4 wks; gluconaride metabolite excreted in urine.
Rash in 18% - morbilliform and pruritic usually on trunk and extremities; most are noted during first 4 wks of therapy; dose related: 59% with 400 mg/day without lead-in; 18% with 400 mg/day after 200 mg/day x 2 wks; 9% with 200 mg/day. Stevens Johnson syndrome - 0.5%Note: Rash during lead-in phase: delay full dose.
Rash during maintenance dose: treat through - most resolve;
Discontinue if rash is severe or is accompanied by systemic complications - fever, fatigue, etc.
No drug interactions noted with AZT, ddI or ddC
Induction of cytochrome p450 to produce action similar to rifampin, but weaker
This article was provided by Johns Hopkins AIDS Service. It is a part of the publication Hopkins HIV Report.