Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of telithromycin, which is primarily metabolized by the isoenzyme. When telithromycin was given with the potent CYP450 3A4 inducer rifampin in repeated doses, telithromycin peak plasma concentration (Cmax) and systemic exposure (AUC) decreased on average by 79% and 86%, respectively. A similar interaction is expected with other potent CYP450 3A4 inducers such as carbamazepine, enzalutamide, mitotane, phenytoin, phenobarbital, rifabutin, rifapentine and St. John's wort, potentially resulting in subtherapeutic levels of telithromycin and loss of effect. Enzyme activities usually return to normal 14 days after discontinuation of the inducing agent.

MANAGEMENT: Telithromycin should not be used during or within 2 weeks after discontinuation of treatment with a potent CYP450 3A4 inducer.

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.