Drug Interactions between aprepitant and dronedarone

MONITOR: Coadministration of dronedarone with a drug that is both a substrate as well as inhibitor of CYP450 3A4 may result in increased plasma concentrations of both drugs. Dronedarone itself is also a substrate and moderate inhibitor of CYP450 3A4. Theoretically, competitive and/or noncompetitive metabolic inhibition may occur. 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.

MANAGEMENT: Caution is advised if dronedarone is prescribed in combination with a drug that is an inhibitor of CYP450 3A4. Pharmacologic response to dronedarone should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. Patients should be advised to seek medical attention if they experience symptoms that could indicate dronedarone toxicity such as excessive fatigue, fainting, difficulty breathing, chest pain or tightness, bradycardia, or symptoms of torsade de pointes such as dizziness, palpitations, irregular heartbeat, shortness of breath, and syncope. Likewise, clinical and/or laboratory monitoring may be appropriate for the coadministered drug following the addition or withdrawal of dronedarone, and the dosage adjusted as necessary.