Drug Interactions between clofazimine and OxyContin

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of oxycodone, which is substantially metabolized by the isoenzyme. Increased oxycodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. According to some manufacturers, oxycodone systemic exposure (AUC) was, on average, approximately 2.4-times higher (range 1.5 to 3.4) during coadministration with itraconazole (200 mg orally for 5 days); 1.8 times higher (range 1.3 to 2.3) during coadministration with telithromycin (800 mg orally for 4 days); 3.6 times higher (range 2.7 to 5.6) during coadministration with voriconazole (200 mg twice daily for 4 days); and 1.7 times higher (range 1.1 - 2.1) during coadministration with grapefruit juice (200 mL three times daily for 5 days). Because oxycodone is also partially metabolized by CYP450 2D6, the magnitude of interaction may be even greater with concomitant use of a CYP450 3A4 and a CYP450 2D6 inhibitor, or concomitant use of a drug that is a dual inhibitor of both isoenzymes.

MANAGEMENT: Extreme caution is advised if oxycodone is prescribed with CYP450 3A4 inhibitors, particularly potent and moderate inhibitors (e.g., azole antifungal agents, protease inhibitors, aprepitant, ciprofloxacin, chloramphenicol, clarithromycin, cobicistat, conivaptan, crizotinib, delavirdine, diltiazem, dronedarone, erythromycin, fusidic acid, idelalisib, imatinib, mibefradil, mifepristone, nefazodone, netupitant, quinupristin-dalfopristin, telithromycin, verapamil) or weak inhibitors that also inhibit CYP450 2D6 (e.g., abiraterone, amiodarone, cimetidine, mavorixafor, pazopanib, ranolazine). Some authorities advise that the oxycodone dose may need to be adjusted. A fatal overdose may occur following the initiation of a CYP450 3A4 inhibitor in patients already receiving oxycodone. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Following discontinuation of the CYP450 3A4 inhibitor, patients should be monitored for reduced efficacy of oxycodone or development of withdrawal symptoms due to reduced plasma oxycodone levels.