Drug Interactions between clofazimine and QM-260

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of quinine, which is primarily metabolized by the isoenzyme. In ten healthy volunteers, administration of a single 600 mg oral dose of quinine sulfate in combination with the potent CYP450 3A4 inhibitor troleandomycin (500 mg orally every 8 hours for 48 hours) significantly increased the mean quinine peak plasma concentration (Cmax), systemic exposure (AUC) and terminal elimination half-life by 26%, 90% and 63%, respectively, and decreased the mean oral clearance (Cl/F) by 45% compared to administration of quinine alone. Troleandomycin also reduced the average Cmax, AUC and apparent formation clearance of the main metabolite, 3-hydroxyquinine, by 75%, 58% and 81%, respectively. Likewise, in a study of nine healthy volunteers, administration of a single 500 mg oral dose of quinine hydrochloride in combination with another potent CYP450 3A4 inhibitor ketoconazole (100 mg twice daily for 3 days) resulted in a 45% increase in mean quinine AUC and a 31% decrease in mean oral clearance compared to administration of quinine alone. Clinically, high plasma levels of quinine may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death. Fatal torsade de pointes arrhythmia was reported in an elderly patient who received quinine in combination with erythromycin, a moderately potent CYP450 3A4 inhibitor, and dopamine. However, a causal relationship was not established in this case. The risk of other quinine toxicities such as cinchonism may also be increased.

MANAGEMENT: Caution is advised if quinine is used in combination with potent and moderate CYP450 3A4 inhibitors. Patients should be monitored closely for adverse reactions associated with quinine such as hematologic toxicities and cardiac arrhythmias including torsade de pointes and atrial fibrillation. Patients should be advised to contact their physician if they experience increased side effects such as headache, flushing, sweating, nausea, vomiting, diarrhea, abdominal pain, tinnitus, dizziness, vertigo, hearing impairment, blurred vision, vision impairment, and irregular heart rhythm.