Drug Interactions between iptacopan and Sezaby

MONITOR: Coadministration with inducers of CYP450 2C8, uridine diphosphate glucuronosyltransferase (UGT) 1A1, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and/or organic anion transporting polypeptide (OATP) 1B1/3 (e.g., rifampin) may decrease iptacopan plasma concentrations and may result in a loss of efficacy. The proposed mechanism is induction of CYP450 2C8-mediated metabolism of iptacopan, which is primarily metabolized by the isoenzyme, glucuronidation via UGT1A1, which is a minor elimination pathway, and the transporters P-gp, BCRP, and OATP1B1/3, for which iptacopan is a substrate. However, clinical data evaluating the interaction are not available.

MANAGEMENT: The potential for diminished pharmacologic effects of iptacopan should be considered during coadministration with CYP450 2C8, UGT1A1, P-gp, BCRP, and/or OATP1B1/3 inducers. The manufacturer recommends the pharmacologic effects of iptacopan should be monitored more closely, and the CYP450 2C8 inducer be discontinued if loss of therapeutic efficacy occurs. Additionally, the pharmacologic response to iptacopan should be monitored more closely whenever a CYP450 2C8 inducer is added to or withdrawn from therapy.