Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 and uridine diphosphate glucuronosyltransferase (UGT) 1A1 inducers (e.g., rifampicin, phenytoin, carbamazepine), may decrease the systemic exposure of ponesimod. Experiments with human liver preparations indicate that metabolism of ponesimod to inactive metabolites occurs through a combination of non-CYP450 oxidative enzymes, multiple CYP450 (2J2, 3A4, 3A5, 4F3A, and 4F12) enzymes, and direct glucuronidation (mainly UGT1A1 and UGT2B7). Limited clinical data are available, and it is unclear whether this decrease in ponesimod systemic exposure would be considered of clinical relevance.

MANAGEMENT: Until more information is available, concomitant use of ponesimod with potent CYP450 3A4 and UGT1A1 inducers should generally be avoided.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.