Carbidopa + Levodopa
- Action to be taken: No action needed
- Rationale: Levodopa and carbidopa do not modulate the cytochrome P450 enzyme system. Data shows that marijuana is predominantly metabolized by CYP3A4 and. Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 and undergoes glucuronidation. In vivo study involving Parkinson's disease patients showed no clinically significant drug–drug interactions between donepezil and levodopa/carbidopa. Co-administration of levodopa/carbidopa and donepezil did not increase the incidence of adverse effects compared with administration of donepezil alone. This indicates that the adverse effects seen in patients receiving donepezil in addition to levodopa/carbidopa are consistent with the cholinomimetic effect of donepezil, and are not caused by an interaction between the two drugs. Therefore this suggest that the combination of medical marijuana and levodopa/carbidopa could be co-prescribed in patients with Parkinson's disease, where indicated.
- 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.
- Aricept (donepezil) package insert. Eisai Inc., Woodcliff Lake, NJ 2012
- Sinemet (carbidopa -levodopa) package insert. Bristol -Myers Squibb Company.
- Okereke CS, Kirby L, Kumar D, Cullen EI, Pratt RD, Hahne WA. Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson’s disease: assessment of pharmacokinetic changes and safety following multiple oral doses. British Journal of Clinical Pharmacology. 2004;58(Suppl 1):41-49. doi:10.1111/j.1365-2125.2004.01799.x.