DEXAMETHASONE

• Cytochrome P450 enzyme substrate: CYP3A4
• Action to be taken: Caution with close monitoring of side effects
• Rationale: Dexamethasone is found to be a CYP3A4 inducer. Drugs which inhibit CYP3A4 have the potential to result in increased plasma concentrations of corticosteroids. In vitro studies showed that marijuana is a CYP3A4 substrate and inhibitor. Ketoconazole has been reported to significantly decrease the metabolism of certain corticosteroids by up to 60%, leading to an increased risk of corticosteroid side effects. 

METHYLPREDNISOLONE

• Cytochrome P450 enzyme substrate: CYP3A4
• P-gp substrate
• Action to be taken: Caution with close monitoring of side effects
• Rationale: Drugs which inhibit cytochrome P450 3A4 have the potential to result in increased plasma concentrations of corticosteroids. In vitro studies showed that marijuana is a CYP3A4 inhibitor. Ketoconazole has been reported to significantly decrease the metabolism of certain corticosteroids by up to 60%, leading to an increased risk of corticosteroid side effects. Itraconazole inhibits methylprednisolone through CYP3A4 inhibition. Several published reports state that this decreases the clearance and increases the elimination half-life of methylprednisolone, resulting in increased exposure of methylprednisolone. 
  

PREDNISONE

• Cytochrome P450 enzyme substrate: CYP3A4
• P-gp substrate
• Action to be taken: Caution with close monitoring of side effects. Consider alternative corticosteroid
• Rationale: Plasma concentrations of prednisone may be elevated with darunavir; cobicstat, which are both CYP3A4 inhibitors. In vitro studies showed that marijuana is a CYP3A4 inhibitor.  An alternative corticosteroid should be considered. If it must be administered, clinical monitoring for adverse effects. 

References

1. 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.
2. 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.​
3. Solu-Medrol (methylprednisolone) package insert. Pfizer Inc. New York, NY, 2011
   
4. Lebrun-Vignes B, Archer VC, Diquet B, et al. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects. Br J Clin Pharmacol 2001;51:443—50.
5. Dilger K, Schwab M, Fromm MF. Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 2004; 10: 578-83.
6. Pascussi JM, Drocourt L, Gerbal-Chaloin S, Fabre JM, Maurel P, Vilarem MJ. Dual effect of dexamethasone on CYP3A4 gene expression in human hepatocytes. Sequential role of glucocorticoid receptor and pregnane X receptor. European journal of biochemistry / FEBS. 2001;268:6346.