Stavudine does not inhibit the major cytochrome P450 isoforms CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4; therefore, it is unlikely that clinically significant drug interactions will occur with drugs metabolized through these pathways.

Because stavudine is not proteinbound, it is not expected to affect the pharmacokinetics of protein- bound drugs.

Tables 5 and 6 summarize the effects on AUC and Cmax, with a 95% confidence interval (CI) when available, following coadministration of ZERIT (stavudine) with didanosine, lamivudine, and nelfinavir. No clinically significant pharmacokinetic interactions were observed.

Table 5: Results of Drug Interaction Studies with ZERIT: Effects of Coadministered Drug on Stavudine Plasma AUC and Cmax Values

Table 6: Results of Drug Interaction Studies with ZERIT: Effects of Stavudine on Coadministered Drug Plasma AUC and Cmax Values

Clinical Studies

Combination Therapy

The combination use of ZERIT is based on the results of clinical studies in HIV-infected patients in double- and triple-combination regimens with other antiretroviral agents. One of these studies (START 1) was a multicenter, randomized, open-label study comparing ZERIT (40 mg twice daily) plus lamivudine plus indinavir to zidovudine plus lamivudine plus indinavir in 202 treatment-naive patients. Both regimens resulted in a similar magnitude of inhibition of HIV RNA levels and increases in CD4 cell counts through 48 weeks.

Monotherapy

The efficacy of ZERIT was demonstrated in a randomized, double-blind study (AI455-019, conducted 1992-1994) comparing ZERIT with zidovudine in 822 patients with a spectrum of HIV-related symptoms. The outcome in terms of progression of HIV disease and death was similar for both drugs.

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