Drug Interaction Report

MONITOR CLOSELY: Dronedarone may cause dose-related prolongation of the QT interval. Since hypokalemia and hypomagnesemia are known risk factors for arrhythmia associated with QT prolongation, coadministration of dronedarone with agents that can cause significant potassium and/or magnesium loss (e.g., potassium-wasting diuretics, amphotericin B, cation exchange resins) may increase the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Caution is advised if dronedarone must be used concomitantly with medications that can cause significant potassium and/or magnesium loss. Serum electrolytes should be evaluated at baseline and at regular intervals throughout the duration of therapy. Any abnormalities should be corrected prior to initiating therapy, and levels should be maintained within the normal range during treatment. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope. Dronedarone should be discontinued if QTc Bazett interval increases to 500 ms or greater.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of dronedarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration with grapefruit juice resulted in a 2.5-fold increase in dronedarone peak plasma concentration and a 3-fold increase in systemic exposure. Because dronedarone is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of dronedarone. The mechanism of interaction is unknown. According to the product labeling, the absolute bioavailability of dronedarone increases from about 4% when administered in the fasted state to approximately 15% when administered with a high-fat meal.

MANAGEMENT: Patients treated with dronedarone should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Dronedarone should be taken twice daily with the morning and evening meals.