Drug Interaction Report

MONITOR: Mefloquine is a myocardial depressant and can cause ECG abnormalities. Theoretically, coadministration with other agents that can affect cardiac conduction (e.g., antiarrhythmic agents, beta blockers, calcium channel blockers, certain antihistamines, tricyclic antidepressants, phenothiazines, some neuroleptics) may result in additive effects and increased risk of ventricular arrhythmias including ventricular tachycardia and torsade de pointes. Parenteral studies in animals have shown that mefloquine possesses 20% of the antifibrillatory action of quinidine and can cause 50% of the increase in PR interval reported with quinine. ECG alterations reported with mefloquine include sinus bradycardia, sinus arrhythmia, first degree AV block, prolongation of the QTc interval, and abnormal T waves. According to mefloquine labeling, there has been one report of cardiopulmonary arrest, with full recovery, in a patient who was taking a beta blocker (propranolol).

MANAGEMENT: Caution and clinical monitoring are recommended if mefloquine is used in combination with other drugs that can prolong the QT interval or otherwise affect cardiac conduction. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes or other arrhythmia such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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

Administration with food may increase the bioavailability of paliperidone from the extended release tablets. In healthy ambulatory subjects, administration of a 12 mg paliperidone extended release tablet with a standard high-fat/high-caloric meal resulted in 60% and 54% increases, respectively, in the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of paliperidone compared to administration under fasting conditions. The clinical significance of these changes is unknown.

MANAGEMENT: Patients receiving paliperidone should be advised to avoid the consumption of alcohol. Since clinical trials establishing the safety and efficacy of paliperidone were carried out without regard to the timing of meals, presumably paliperidone may be administered with or without food.