Drug Interactions between clofazimine and Olinvyk

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Coadministration with moderate or potent inhibitors of CYP450 2D6 and/or 3A4 may increase the plasma concentrations and adverse opioid effects of oliceridine, which is primarily metabolized by both isoenzymes in vitro. In addition, oliceridine concentrations may decrease following discontinuation of a concomitant moderate or potent CYP450 2D6 or 3A4 inhibitor, possibly resulting in decreased opioid efficacy or withdrawal syndrome. The effect of a CYP450 2D6 inhibitor on the pharmacokinetics of oliceridine has not been studied. However, it may be similar to that reported in CYP450 2D6 poor metabolizers, whose plasma clearance of oliceridine is reduced by approximately 50% compared to those who are nonpoor CYP450 2D6 metabolizers. The clearance may be further reduced with the addition of a CYP450 3A4 inhibitor. When a single 0.25 mg dose of oliceridine was given to poor metabolizers of CYP450 2D6 following pretreatment with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily for 5 days), oliceridine systemic exposure (AUC) increased by approximately 80% while peak plasma concentration (Cmax) was not significantly affected. Furthermore, mean oliceridine clearance decreased to approximately 30% of that observed in nonpoor metabolizers of CYP450 2D6. The interaction has not been studied with other, less potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is recommended if oliceridine is used in combination with moderate or potent inhibitors of CYP450 2D6 or 3A4. If concomitant use is considered necessary, patients may require less frequent dosing of oliceridine and should be closely monitored for respiratory depression, sedation, and QT prolongation. If a moderate or potent CYP450 2D6 or 3A4 inhibitor is discontinued, an increase of the oliceridine dosage may be considered while monitoring for signs of opioid withdrawal until stable drug effects are achieved. Due to the prolonged duration of CYP450 2D6 inhibition by the moderate CYP450 2D6 inhibitor rolapitant, prolonged monitoring for adverse effects of oliceridine for at least 28 days after administration of rolapitant may be required.