NEVIRAPINE (Viramune).

Nevirapine is supplied in 200 mg tablets that are white, oval and biconvex. One side is embossed with "54 193," with a single-line bisect separating the "54" and "193." The opposite side has a single-line bisect. Other dose formulations of nevirapine are available. Dosing may vary.

"A study reported at the recent Chicago conference suggests that women are more likely to develop rash, especially severe rash, as a side effect of the anti-HIV drug nevirapine compared to men."

Project Inform Perspectives, April 11, 1999

"Two studies published in The Lancet medical journal showed that a single dose of nevirapine to both the mother and infant was cheaper and more effective than the normal multi-dose treatment with zidovudine."

Reuters NewMedia, September 6, 1999

Also known as: NVP, BI-RG-587

Background and description. Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), manufactured by Boehringer Ingelheim Pharmaceuticals, Inc. and distributed by Roxanne Laboratories, Inc. Nevirapine was granted accelerated approval for use in combination with nucleoside reverse transcriptase inhibitors (NRTIs) by the US Food & Drug Administration (FDA) in June 1996.

Dose. Nevirapine is supplied in tablet and oral suspension. The dose for the tablet formulation is 200 mg (1 tablet) for the first 14 days; followed by 200 mg (1 tablet) twice a day.

Guidelines classification. The Panel on Clinical Practices for the Treatment of HIV Infection recommends nevirapine as an "alternative" NNRTI.

Food restrictions. Nevirapine may be taken with or without food.

Storage. Nevirapine should be stored at 59 [degrees] to 86 [degrees] F

Side effects and toxicity. The most common and potentially serious side effect of nevirapine is rash. If rash develops, it usually does so within 6 weeks of starting the drug. If a rash develops within the first 2 weeks of therapy, the dose of nevirapine should not be increased until the rash resolves. A patient experiencing a severe rash or a rash accompanied by fever, blistering, oral lesions, conjunctivitis, swelling, muscle or joint aches or general malaise should immediately stop taking nevirapine. Such symptoms may indicate a life-threatening condition called Stevens-Johnson syndrome. Cases of hepatitis, including cases resulting in death, have been reported with the use of nevirapine. Patients experiencing moderate or severe liver function test abnormalities should interrupt therapy until liver function tests return to normal. If the abnormalities return upon re-administration of nevirapine, the drug should be permanently discontinued.

Drug interactions. Nevirapine lowers the levels of rifampin (Rifadin, Rimactane) but there is insufficient data to recommend a dose adjustment. Combining nevirapine and rifabutin (Mycobutin) results in lower levels of both drugs. Some experts recommend increasing the dose of rifabutin to 450 mg. The manufacturer recommends that rifampin or rifabutin be used in combination with nevirapine only "if clearly indicated and with careful monitoring." Ketoconazole (Nizoral) should not be co-administered with nevirapine, nor should women take oral contraceptives (or other hormonal contraceptives) with the drug. Nevirapine should not be combined with the hard-gel formulation of saquinavir (Invirase). Nevirapine decreases the levels of indinavir (Crixivan) and increasing the dose of indinavir to 1000 mg every 8 hours is recommended. There are no data regarding the interaction between amprenavir (Agenerase) and nevirapine.

Resistance and cross-resistance. Resistance to nevirapine is associated with mutations at positions 103 and 181. Mutations at positions 106, 108, 188 and 190 can also occur. Mutations at positions 103 and 181 lead to broad cross-resistance to all approved NNRTIs.

Clinical data. The pivotal trial for nevirapine was ACTG 241, which enrolled patients with over 6 months of prior NRTI experience. Patients were randomized to receive nevirapine/zidovudine (Retrovir)/didanosine (Videx) or zidovudine/didanosine. At 4 weeks the mean reduction in the 3-drug arm was 1.0 log versus 0.5 log in the 2-drug arm. By 48 weeks viral loads had returned to baseline with the viral load in the 3-drug arm being 0.25 log less than in the 2-drug arm, BI Trial 1046 or INCAS studied nevirapine in anti-retroviral naive patients comparing the following regimens: nevirapine/zidovudine/didanosine compared to nevirapine/zidovudine or zidovudine/didanosine. At week 52 there was a significant difference in the number of patients with viral loads below 400 copies/mL among the arms. In the triple-therapy arm 51% of the patients had viral loads below 400 copies/mL compared to less than 6% in the other 2 arms. The mean CD4 T cell count increase from baseline was 139 cells/[mm.sup.3] in the triple-therapy arm versus less than 90 cells/[mm.sup.3] in the other 2 arms.

Patient assistance. The patient assistance program can be reached at 800.274.8651.