Drug Interactions between mefloquine and st. john's wort

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of mefloquine. The proposed mechanism is increased drug solubility in the presence of food. In 20 healthy volunteers, administration of a single 750 mg oral dose of mefloquine 30 minutes following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of mefloquine by 73% and 40%, respectively, compared to administration in the fasting state. The Cmax and AUC of the carboxylic acid metabolite were also increased by 35% and 33%, respectively, compared to fasting. In addition, the time to reach peak plasma concentration (Tmax) of mefloquine was significantly shorter after food intake (17 hours) than in the fasting state (36 hours). There was no difference in the elimination half-life of mefloquine and metabolite, or the Tmax for the metabolite.

MANAGEMENT: To ensure maximal oral absorption, mefloquine should be administered immediately after a meal with at least 8 ounces of water.

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.