Drug Interactions between dronedarone and levamlodipine

MONITOR: Coadministration of dronedarone and a calcium channel blocker (CCB) may result in increased plasma concentrations of both drugs. Dronedarone and most CCBs are substrates of CYP450 3A4. In addition, dronedarone and certain CCBs such as diltiazem and verapamil are also moderate inhibitors of the isoenzyme, thus competitive and noncompetitive metabolic inhibition may occur. According to the product labeling, dronedarone increased systemic exposure (AUC) to diltiazem, nifedipine and verapamil by 1.4- to 1.5-fold, while diltiazem and verapamil increased dronedarone AUC by approximately 1.4- to 1.7-fold. Pharmacodynamically, CCBs with depressant effects on the sinus and AV nodes (particularly diltiazem, verapamil, and bepridil) could also potentiate dronedarone's effects on cardiac conduction.

MANAGEMENT: Caution is advised if dronedarone is coadministered with a CCB. The dosage of the CCB should start low and increased only after ECG verification of good tolerability. Patients should be advised to promptly report potential symptoms of toxicity such as excessive fatigue; edema or swelling of the lower extremities; sudden, unexplained weight gain; fainting; difficulty breathing; chest pain or tightness; bradycardia; arrhythmia; or hypotension as indicated by dizziness, fainting, or orthostasis.