Drug Interactions between Agenerase and delavirdine

CONTRAINDICATED: Coadministration with amprenavir or its prodrug, fosamprenavir, may significantly decrease the plasma concentrations of delavirdine. The exact mechanism of interaction has not been established. Conversely, delavirdine may increase the plasma concentrations of amprenavir by inhibiting CYP450 3A4 metabolism. In 9 subjects treated with delavirdine and amprenavir, both at 600 mg twice a day for 10 days, delavirdine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 47%, 61% and 88%, respectively, while the same values for amprenavir increased by 40%, 130% and 125%, respectively, compared to either drug administered alone. In another study, 11 healthy volunteers given delavirdine and amprenavir 600 mg each twice a day for 7 days achieved higher levels of amprenavir Cmax, AUC and Cmin by 18%, 30% and 90%, respectively, than when given amprenavir alone at 1200 mg twice a day. Delavirdine Cmax, AUC and Cmin decreased by 30%, 50% and 70%, respectively.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of delavirdine with amprenavir or fosamprenavir is considered contraindicated.