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: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.