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: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.