Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIZA6TI8F)
  Drug Name Sumatriptan Drug Info Isocarboxazid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Vasoconstrictor Agents Antidepressants
  Structure

 Mechanism of Sumatriptan-Isocarboxazid Interaction (Severity Level: Major)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Sumatriptan Isocarboxazid
      Mechanism Monoamine oxidase substrate Monoamine oxidase inhibitor
      Key Mechanism Factor 1
Factor Name Monoamine oxidase Structure Sequence
Protein Family Flavin monoamine oxidase family
Protein Function
Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Sumatriptan caused by Isocarboxazid mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management Concomitant use of rizatriptan, sumatriptan, or zolmitriptan with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine) is considered contraindicated. At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with 5-HT1 receptor agonists. If concurrent therapy is necessary, almotriptan, frovatriptan and naratriptan may be preferred due to the lack of a significant pharmacokinetic interaction with MAOIs. However, patients should be closely monitored for adverse effects related to excessive serotonergic activity.

References
1 Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5. [PMID: 9861909]
2 De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5. [PMID: 4379192]
3 Diamond S "The use of sumatriptan in patients on monoamine oxidase inhibitors." Neurology 45 (1995): 1039-40. [PMID: 7783861]
4 Fleishaker JC, Ryan KK, Jansat JM, et al. "Effect of MAO-A inhibition on the pharmacokinetics of almotriptan, an antimigraine agent in humans." Br J Clin Pharmacol 51 (2001): 437-41. [PMID: 11422001]
5 Gardner DM, Lynd LD "Sumatriptan contraindications and the serotonin syndrome." Ann Pharmacother 32 (1998): 33-8. [PMID: 9475817]
6 Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6. [PMID: 8909274]
7 Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763. [PMID: 9330840]
8 Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8. [PMID: 8257462]
9 Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7. [PMID: 5655478]
10 Product Information. Imitrex (sumatriptan). Glaxo Wellcome, Research Triangle Park, NC.
11 Product Information. Maxalt (rizatriptan). Merck & Co, Inc, West Point, PA.
12 Product Information. Zomig (zolmitriptan). Zeneca Pharmaceuticals, Wilmington, DE.
13 Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13. [PMID: 2035713]