Drug Interaction Report

GENERALLY AVOID: Coadministration with phenobarbital is expected to decrease the plasma concentrations of nelfinavir. The proposed mechanism involves induction of the CYP450 3A4-mediated metabolism of nelfinavir by phenobarbital, which is considered a potent inducer of the isoenzyme. However, the interaction has not been reported in the medical literature, and no data are available from pharmacokinetic studies.

MANAGEMENT: Given the lack of pharmacokinetic data and the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, it may be preferable to avoid using nelfinavir in combination with phenobarbital. Caution is advised if concomitant use is required. In patients already receiving nelfinavir as part of their HIV treatment regimen, close clinical and laboratory monitoring of antiretroviral response is recommended following the addition or discontinuation of phenobarbital.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.