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Ergot Alkaloids

ERGOTAMINE OR ERGOTAMINE + CAFFEINE
  • Cytochrome P450 enzyme substrate: CYP3A4
  • Action to be taken: Caution with close monitoring for ergot toxicity (e.g., severe peripheral vasospasm with possible ischemia, potentially leading to gangrene, cyanosis, stroke, numbness of the extremities and/or other serious effects)15
  • Rationale: Ergotamine and cannabis are both substantially metabolized via CYP3A4. Furthermore cannabis shows weak inhibition of this enzyme. The risk of ergot toxicity (e.g., severe peripheral vasospasm with possible ischemia, potentially leading to gangrene, cyanosis, stroke, numbness of the extremities and/or other serious effects) is potentially increased by the use of CYP3A4 inhibitors. Clinicians should review the effects on CYP3A4 of other agents considered for concomitant use with ergotamine.

DIHYDROERGOTAMINE
  • Cytochrome P450 enzyme substrate: CYP3A4
  • Action to be taken: Caution with close monitoring for ergot toxicity (e.g., severe peripheral vasospasm with possible ischemia, potentially leading to gangrene, cyanosis, stroke, numbness of the extremities and/or other serious effects)15
  • Rationale: Ergotamine is substantially metabolized via CYP3A4. Furthermore cannabis shows weak inhibition of this enzyme. The risk of ergot toxicity (e.g., severe peripheral vasospasm with possible ischemia, potentially leading to gangrene, cyanosis, stroke, numbness of the extremities and/or other serious effects) is potentially increased by the use of CYP3A4 inhibitors. Clinicians should review the effects on CYP3A4 of other agents considered for concomitant use with ergotamine.
References
  1. Cafergot® (caffeine; ergotamine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2002 June.
  2. Migranal® (dihydroergotamine mesylate) nasal spray package insert. Aliso Viejo, CA: Valeant Pharmaceuticals; 2007 Jun.
  3. D.H.E. 45® (dihydroergotamine mesylate) package insert. Stein, Switzerland: Novartis Pharmaceuticals AG; 2002 Sep.
  4. 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.
  5. 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.​​

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Last Updated: May 2018.
  • Home
  • Company
    • About Us
    • Services
  • Support
    • For Patients >
      • Qualifying Conditions
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      • How Marijuana Works
      • Side Effects and Safety
      • Approved Formulations and Dosing
      • Dispensaries
      • Caregivers
      • How to Register ?
      • FAQ
    • For Clinicians >
      • Research
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