Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may 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. No data are available for use with other, less potent inducers. Subtherapeutic levels of telithromycin and loss of effect may occur. Enzyme activities usually return to normal 14 days after discontinuation of the inducing agent.

MANAGEMENT: The potential for diminished therapeutic effects of telithromycin should be considered when prescribed with CYP450 3A4 inducers. Pharmacologic response to telithromycin should be monitored closely during coadministration, and alternative treatment given if an interaction is suspected. Whenever possible, telithromycin should preferably not be used during or within 2 weeks after discontinuation of treatment with a 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.