Nevirapine

Is used in combination with other antiretroviral drugs for the treatment of HIV-1 infections in adults and children. Due to potential severe hepatotoxicity, nevirapine should not be initiated in women with CD4+ T-cell counts greater than 250 cells/mm3 or in men with CD4+ T cell counts greater than 400 cells/mm3. Nevirapine is well absorbed orally, and its absorption is not affected by food and antacids. The lipophilic nature of nevirapine accounts for its entrance into the fetus and mother’s milk and for its distribution, including the CNS. Nevirapine is dependent upon metabolism for elimination, and most of the drug is excreted in urine as the glucuronide of hydroxylated metabolites Nevirapine is an inducer of the CYP3A4 family of CYP450 drug-metabolizing enzymes. Nevirapine increases the metabolism of protease inhibitors, but most combinations do not require dosage adjustment. Nevirapine increases the metabolism of a number of drugs, such as oral contraceptives, ketoconazole, methadone, metronidazole, quinidine, theophylline, and warfarin. The most frequently observed side effects are rash, fever, headache, and elevated serum transaminases and fatal hepatotoxicity. Severe dermatologic eff ects have been encountered, including StevensJohnson syndrome and toxic epidermal necrolysis. A 14-day titration period at half the dose is mandatory to reduce the risk of serious epidermal reactions and hepatotoxicity.Hypersensitivity reactions with nevirapine include a rash, which occurs in 15–20% of patients, especially female.Nevirapine blood levels are increased by cimetidine and macrolide antibiotics and decreased by enzyme inducers such as rifampin.