Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 that also induce P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of apixaban, which is a substrate of both the isoenzyme and the efflux transporter. When apixaban was coadministered with 600 mg/day of rifampin, a dual P-gp and potent CYP450 3A4 inducer, mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 42% and 54%, respectively. Reduced efficacy, increased stroke rates, and paradoxically, an increased risk of bleeding have been reported in a clinical study in patients with atrial fibrillation taking apixaban with concomitant dual P-gp and potent CYP450 3A4 inducers compared with apixaban alone.

MANAGEMENT: Concomitant use of apixaban with dual P-gp and potent CYP450 3A4 inducers should generally be avoided, since efficacy of apixaban may be compromised.

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.