Drug Interaction Report

MONITOR: Coadministration with delavirdine may significantly increase the plasma concentrations of nelfinavir. The mechanism is delavirdine inhibition of nelfinavir metabolism via CYP450 3A4 and 2C19. According to the delavirdine labeling, coadministration of delavirdine (400 mg three times a day) and nelfinavir (750 mg three times a day) for 7 days increased the mean peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of nelfinavir by 88%, 107% and 136%, respectively, compared to administration of nelfinavir alone. Plasma concentrations of the active metabolite, nelfinavir hydroxy-t-butylamide, were significantly reduced but were more than compensated for by the increased nelfinavir concentration. Delavirdine Cmax, AUC and Cmin decreased by 27%, 31% and 33%, respectively.

MANAGEMENT: Appropriate dosages for the combination of nelfinavir and delavirdine with respect to safety and efficacy have not been established. Patients should be monitored for toxicity such as elevations in liver function tests, neutropenia, and undue gastrointestinal disturbances, especially diarrhea.