- Cytochrome P450 enzyme substrate: CYP2D6 and CYP3A4
- Action to be taken: Caution with close monitoring
- Rationale: In vitro studies in hepatocytes indicated that CYP3A4 may contribute to fingolimod metabolism in the case of strong induction of CYP3A4. Ketoconazole is a potent inhibitor of CYP3A. Co-administration of ketoconazole with a single dose of fingolimod 5mg led to a 70% increase in the systemic exposure of fingolimod and fingolimod-phosphate. In vitro studies showed that marijuana can inhibit CYP3A4 enzyme. Based on available data patients should be monitored closely who use fingolimod and marijuana concomitantly since the risk of adverse reactions from fingolimod is greater.
- Watanabe K, Yamaori S, Funahashi T, et al. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007;80:1415-1419.
- Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46:86-95.
- Gilenya (fingolimod) package insert. East Hanover, New Jersey: Novartis Pharmaceuticals Corporation; 2016 Feb.