Triomune equivalent to branded HIV drugs

A coformulation of three antiretrovirals developed by the Indian manufacturer Cipla is the latest generic antiretroviral product to gain approval from the World Health Orgnaisation, it was announced today, as Cipla researchers presented bioequivalence data on the formulation at the Sixth International Congress on Drug Therapy in HIV Infection in Glasgow.

Triomune, a coformulation of nevirapine, d4T (stavudine) and 3TC (lamivudine) was developed by Cipla as a cheap and convenient alternative to dosing with separate agents. Cipla tested bioequivalence in 26 HIV-negative adult males in a randomised, blinded crossover study which compared plasma concentrations of the individual constituents of Triomune with those of the branded products, Zerit, Epivir and Viramune. Twenty-six plasma samples were collected from each volunteer between baseline and 288 hours after dosing.

Peak levels (C_max) and total exposure (AUC) were almost identical, at 97.4% to 104.8% of the concentrations achieved by the branded products, well within the margins specified by the European Union drug regulatory authorities for demonstrating bioequivalence.

Triomune is a fixed dose combination available with two different d4T doses (30mg or 40mg) according to body weight. Dosing with the individual antiretroviral agents is recommended during the first 14 days of therapy because nevirapine must be dosed at 200mg once daily for the first 14 days of treatment.

Cipla also recommends that if treatment with Triomune is interrupted, this should be done by switching to therapy with d4T and 3TC for several days before ceasing treatment entirely, due to the longer half-life of nevirapine. If the three drugs are stopped at the same time, there is a danger that sub-optimal nevirapine levels will persist (in the absence of any other antiretroviral pressure) for long enough to select nevirapine-resistant viruses.

Cipla has also produced a fixed dose combination of AZT, 3TC and nevirapine. The company is able to coformulate antiretrovirals which are marketed by different companies in Europe, North America and many other countries because Indian law only protects patents for processes, not products. Dr JA Gogtay, presenting the results, said that the coformulation of d4T and 3TC, theoretically antagonistic if coformulated in the same tablet, had been achieved by creating a two layer tablet, in which the d4T was separated from the 3TC and nevirapine. Triomune is being sold for approximately $300-350, the cheapest triple combination currently available.