SILDENAFIL
TADALAFIL
- Cytochrome P450 enzyme substrate: CYP3A4 and CYP2C9
- Action to be taken: Potential dose reduction
- Rationale: Sildenafil is metabolized principally by the hepatic cytochrome P450 (CYP3A4 (major route) and CYP2C9 (minor route) isoenzymes. Inhibitors of these isoenzymes may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects. In vitro studies have shown that cannabis undergoes metabolism by CYP450 enzymes, including CYP3A4 and CYP2C9. Furthermore certain cannabinoids have shown to have inhibitory action at these enzymes. Based on the available data, patients should be monitored for possible side effects of sildenafil.
TADALAFIL
- Cytochrome P450 enzyme substrate: CYP3A4
- Action to be taken: Potential dose reduction
- Rationale: In vitro studies have shown that cannabis undergoes metabolism by CYP450 enzymes, including CYP3A4 and CYP2C9. Furthermore certain cannabinoids have shown to have inhibitory action at these enzymes. In patients receiving concomitant potent CYP3A4 inhibitors, the “as needed” dose for erectile dysfunction should not exceed 10 mg within a 72 hour time period, and the “once-daily” dose for erectile dysfunction or benign prostatic hyperplasia should not exceed 2.5 mg.
References
- Cialis (tadalafil) package insert. Indianapolis, IN: Lilly ICOS, LLC; 2011
- Viagra® (sildenafil citrate) package insert. New York, NY: Pfizer; 2006
- Hansten P, Horn J. The Top 100 Drug Interactions: A Guide to Patient Management. includes table of CYP450 and drug transporter substrates and modifiers (appendices). H & H Publications, LLP 2014 edition
- 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.