Drug Interaction Report

MONITOR: Coadministration with potent CYP450 3A4 inducers may decrease the plasma concentrations of felbamate, which may be a substrate of the isoenzyme. Pharmacokinetic data may not be available for all potent inducers with respect to their effect on felbamate. However, the potent CYP450 3A4 inducers carbamazepine, phenobarbital, and phenytoin have all been shown to decrease felbamate plasma concentrations. Felbamate steady-state trough concentrations have decreased by approximately 40% and 45% when administered with carbamazepine and phenytoin, respectively, compared to the same dose of felbamate monotherapy. In addition, concomitant use of phenobarbital resulted in a 29% decrease in felbamate steady-state plasma concentrations as compared to felbamate monotherapy.

MANAGEMENT: Caution is advised if felbamate is used concomitantly with potent CYP450 3A4 inducers. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever a potent CYP450 3A4 inducer is added to or withdrawn from therapy with felbamate.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.