Drug Interactions between clofazimine and voriconazole

MONITOR: Clofazimine may cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. According to the manufacturer, there have been cases of torsade de pointes with QT prolongation reported in patients receiving clofazimine at dosages higher than 100 mg/day or in combination with QT-prolonging medications. QT prolongation has also been reported in patients who received clofazimine with bedaquiline at the recommended dosage regimen for each drug. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is recommended if clofazimine is used in combination with other drugs that can prolong the QT interval. Consider monitoring electrocardiograms, particularly in patients receiving clofazimine dosages greater than 100 mg/day, and discontinue QT-prolonging medications if clinically significant ventricular arrhythmia is noted or if QTcF interval >=500 ms is observed. If syncope occurs, obtain an ECG to detect QT prolongation. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.