General Information

Viramune (nevirapine) is an antiretroviral drug.

Viramune is specifically indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adults and pediatric patients 15 days and older.

Viramune is supplied as tablets and an oral suspension. The recommended dosing is as follows:

Adults:

The recommended dose for Viramune is one 200 mg tablet daily for the first 14 days, followed by one 200 mg tablet twice daily, in combination with other antiretroviral agents. The 14-day lead-in period with Viramune 200 mg daily dosing must be strictly followed as the lead-in period has been observed to decrease the incidence of rash. If rash persists beyond the 14-day lead-in period, do not dose escalate to 200 mg twice daily. The 200 mg once-daily dosing regimen should not be continued beyond 28 days, at which point, an alternative regimen should be sought. For concomitantly administered antiretroviral therapy, the manufacturer’s recommended dosage and monitoring should be followed.

Pediatric Patients:

The recommended oral dose for pediatric patients 15 days and older is 150 mg/m2 once daily for 14 days followed by 150 mg/m2 twice daily thereafter. The total daily dose should not exceed 400 mg for any patient.

Mechanism of Action

Viramune is a non-nucleoside reverse transcriptase inhibitor (NNRTI), which has a different mechanism of action and a distinct side effect profile from other classes of currently approved antiretrovirals. While the nucleoside analogues prevent the growth of the DNA chain, non-nucleoside drugs directly inactivate the enzyme.

Side Effects

The most common adverse effect associated with the use of Viramune is rash.

The Viramune drug label comes with the following Black Box Warning: Fatal and non-fatal hepatotoxicity have been reported in patients taking Viramune. Discontinue immediately if clinical hepatitis or transaminase elevations combined with rash or other systemic symptoms occur. Do not restart Viramune after recovery. Fatal and non-fatal skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions, have been reported. Discontinue immediately if severe skin reactions, hypersensitivity reactions, or any rash with systemic symptoms occur. Check transaminase levels immediately for all patients who develop a rash in the first 18 weeks of treatment. Do not restart Viramune after recovery. Monitoring during the first 18 weeks of therapy is essential. Extra vigilance is warranted during the first 6 weeks of therapy, which is the period of greatest risk of these events.

Clinical Trial Results

In the first major study presented, ACTG 241, a randomized, double blind, placebo-controlled trial, researchers followed 398 subjects for 48 weeks at 16 participating investigational sites. All subjects entering the study had advanced HIV infection with CD4 cell counts of less than or equal to 350 (mean CD4 cell count for these patients was 153). The study compared the combination of AZT, ddI, and viramune to the combination of AZT, ddI, and placebo. Subjects in this trial had received extensive prior nucleoside therapy. The ACTG 241 study found that the combination of AZT, ddI, and viramune increased CD4 cell count significantly more than AZT, ddI, and placebo combination. In a substudy, viral markers were followed. In these subjects the combination of AZT, ddI, and viramune, reduced the viral load significantly more than AZT, ddI, and placebo, throughout the 48 weeks of the trial. The clinical significance of changes in viral RNA has not been established.

The second major study presented, BI 1046, an international randomized, double blind, placebo-controlled trial, investigated viramune in previously untreated subjects. The six-month results from this twelve-month study compared the combinations of AZT, ddI, and viramune; AZTand ddI; and viramune and AZT in 151 HIV-1 infected subjects with CD4 counts between 200 and 600. Changes in CD4 counts through 28 weeks: levels of CD4 in those randomized to AZT plus ddI plus viramune, and AZT plus ddI remained significantly above baseline; however there was no significant difference between these arms. The triple drug regimen containing viramune decreased the viral load below the limit of detection in about two-thirds of the subjects, which was significantly greater than either double therapy regimen.