RASAGILINE
SELEGILINE
- CytochromeP450 enzyme substrate: CYP1A2
- Action to be taken: Possible dose adjustment
- Rationale: Study with synthetic cannabinoids showed that synthetic cannabis may be a weak inhibitor of CYP1A2. Rasagiline plasma concentrations may increase up to 2 fold in patients using concomitant CYP1A2 inhibitors, resulting in the potential for increased adverse events from rasagiline. Dosage adjustments of rasagiline are required when CYP1A2 inhibitors are started in combination with rasagiline (recommended rasagiline adult dose is 0.5 mg PO once daily).
SELEGILINE
- Action to be taken: Possible dose adjustment
- Rationale: The metabolism of selegiline is not fully understood. An in vitro study examining the effect of selegiline and its metabolites on CYP enzymes showed that furafylline and ketoconazole, known inhibitors for CYP1A2 and CYP3A4, respectively, inhibited the formation of selegiline metabolites suggesting that CYP1A2 and CYP3A4 contribute to the metabolism of selegiline. In vitro studies showed that marijuana is also a CYP3A4 inhibitor. Therefore based on available data, caution should be used when marijuana is administered with selegiline.
References
- Ashino, T. Hakukawa K, et al. Inhibitory effect of synthetic cannabinoids on CYP1A activity in mouse liver microsomes. The journal of toxicological sciences. Volume 39, Issue 6, Pages 815 -820, 2014
- Azilect (rasagiline mesylate) tablets. Kansas City, MO: Teva Neurosciences, Inc.; 2014
- Taavitsainen, P., Anttila, M., Nyman, L., Karnani, H., Salonen, J. S. and Pelkonen, O. (2000), Selegiline Metabolism and Cytochrome P450 Enzymes:In vitro Study in Human Liver Microsomes. Pharmacology & Toxicology, 86: 215–221. doi:10.1034/j.1600-0773.2000.pto860504.
- 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.
- Eldepryl(selegiline) package insert. Somerset Pharmaceuticals Inc. Tampa, FL 2008