- Action to be taken: Caution. Monitor side effects of marijuana.
- Rationale: The major metabolic pathway of isoniazid in man is acetylation, but cytochrome P450 enzymes may also contribute to the metabolism of isoniazid. Isoniazid at clinically relevant concentrations reversibly inhibits CYP2C19 and CYP3A4 activities, and mechanistically inactivates CYP1A2, CYP2A6, CYP2C19 and CYP3A4 in human liver microsomes. Co-administration of isoniazid and drugs that are primarily metabolised by these CYP isoforms, particularly by CYP2C19 and CYP3A4, may result in significant drug interactions. Cannabis undergoes metabolism by CYP2C19 and CYP3A4, therefore combination of isoniazid and cannabis should be used in caution as isoniazid may increase serum concentrations of cannabis and its metabolites.
- Wen X, Wang J, Neuvonen PJ, Backman JT. Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. European journal of clinical pharmacology. 2002;57:799.
- 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.