Drug Interactions between delavirdine and Mycobutin

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 such as rifabutin may significantly decrease the plasma concentrations of delavirdine, which is primarily metabolized by the isoenzyme. In addition, delavirdine may increase the plasma concentrations of rifabutin by inhibiting its metabolism via CYP450 3A4. In seven HIV-infected subjects, administration of delavirdine (400 mg three times a day for 30 days) in combination with rifabutin (300 mg once daily on days 16 through 30) decreased delavirdine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by approximately 75%, 84% and 95%, respectively, compared to administration of delavirdine alone. Oral clearance of delavirdine also increased by about 5-fold in the presence of rifabutin. On the other hand, when rifabutin (300 mg once daily for 15 to 99 days) was coadministered with delavirdine (400 to 1000 mg three times a day for 45 to 129 days) in 5 study subjects, rifabutin Cmax, AUC, and Cmin increased by 128%, 230%, and 450%, respectively. This may increase the risk and/or severity of rifabutin-related adverse effects such as leukopenia, uveitis, arthralgia, joint disorder, and skin discoloration.

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