CITALOPRAM

• Cytochrome P450 enzyme substrate: CYP2C19 and CYP3A4
• Action to be taken: Caution
• Rationale:In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of citalopram. In vitro studies have shown that cannabis is metabolized by CYP450 enzymes, mainly by CYP3A4 and CYP2C19. Furthermore, various in vitro studies have found cannabinoids to be weak inhibitors of CYP enzymes. However other studies have shown that CBD is a potent inhibitor of CYP3A4 and CYP2C19. Since CYP3A4 and 2C19 are the primary enzymes involved in the metabolism of citalopram, it is expected that potent inhibitors of 3A4 and potent inhibitors of CYP2C19 might decrease the clearance of citalopram. However, coadministration of citalopram and the potent 3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of citalopram. Because citalopram is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease citalopram clearance.
  

ESCITALOPRAM

• Cytochrome P450 enzyme substrate: CYP2C19 and CYP3A4
• Action to be taken: Caution
• Rationale: In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram. In vitro studies have shown that cannabis is metabolized by CYP450 enzymes, mainly by CYP3A4 and CYP2C19. Furthermore, various in vitro studies have found cannabinoids to be weak inhibitors of CYP enzymes. However other studies have shown that CBD is a potent inhibitor of CYP3A4 and CYP2C19. In vitro studies indicated that CYP3A4 and -2C19 are the primary enzymes involved in the metabolism of escitalopram. However, coad ministration of escitalopram (20mg) and ritonavir (600 mg), a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escital opram is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram clearance.
  

FLOUXETINE

• Cytochrome P450 enzyme substrate: CYP2D6 and CYP3A4
• Action to be taken: Caution with close monitoring for potential hypomania. Potential dose reduction
• Rationale: Smoking marijuana while taking fluoxetine might cause hypomania. In one report, a reversible hypomanic reaction occurred in patients who smoked marijuana while taking fluoxetine. Furthermore, marijuana is a weak CYP2D6 inhibitor and exposure of fluoxetine may be increased when taken with CYP2D6 inhibitors.

PAROXETINE

• Cytochrome P450 enzyme substrate: CYP2D6 and CYP3A4
• Action to be taken: Caution with close monitoring. Potential dose reduction
• Rationale: Paroxetine metabolism is mediated in part by CYP2D6, and the metabolites are primarily excreted in the urine and to some extent in the feces. Ritonavir is a CYP2D6 inhibitor; a dose reduction of paroxetine may be necessary during co-administration with ritonavir. Concurrent use could result in increases (up to 2-fold) in the AUC of paroxetine. In vitro studies have shown that certain cannabinoids are substrates for CYP2D6 as well as show weak inhibition at this enzyme. Based on available data caution and close monitoring are advised if these drugs are administered together.

SERTRALINE

• Cytochrome P450 enzyme substrate: CYP2B6, CYP2C9, CYP2D6, CYP3A4, and CYP2C19
• Action to be taken: Caution with close monitoring for signs of adverse events
• Rationale: Administering elbasvir; grazoprevir, a weak CYP3A inhibitor, may result in elevated sertraline plasma concentrations. In vitro studies show that cannabis is majorly metabolized by CYP3A4 with minor contribution from CYP2D6. Furthermore various cannabinoids show weak inhibition of these enzymes. There for if sertraline and cannabis are used together, closely monitor for signs of adverse events.

References

1. Paxil (paroxetine HCL) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2014
2. Marinol Prescribing Information. Solvay Pharmaceuticals, Rev March 2008. Available at: http://www.solvaypharmaceuticals-us.com/static/wma/pdf/1/3/2/5/0/004InsertText500012RevMar2008.pdf
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5. Celexa (citalopram) package insert. Forest Laboratories, Inc. St. Louis, MO 2009
6. Lexapro (escitalopram) package insert. Forest Laboratories, Inc. St. Louis, MO 2009
7. Prozac (fluoxetine hydrochloride delayed release capsules) package insert. Indianapolis, IN: Eli Lilly and Company; 2014
8. Zoloft (sertraline) package insert. New York, NY: Pfizer; 2014 Aug.Obach RS, Cox LM, Tremaine LM. Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos 2005;33:262-70.
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