Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI8ERPKXA)
  Drug Name Montelukast Drug Info Isoniazid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiasthmatic Agents Antitubercular Agents
  Structure

 Mechanism of Montelukast-Isoniazid Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Montelukast Isoniazid
      Mechanism CYP450 2C8 substrate CYP450 2C8 inhibitor
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C8
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Structure Sequence
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKVYGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRWKEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICSVVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALTRSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTETTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSDLVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFKKSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLPPSYQICFIPV
Gene Name CYP2C8
Uniprot ID CP2C8_HUMAN
KEGG Pathway hsa:1558
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:7574697, PubMed:15766564, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316).
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      Mechanism Description
  • Decreased metabolism of Montelukast caused by Isoniazid mediated inhibition of CYP450 enzyme

Recommended Action
      Management According to the product labeling, no dosage adjustment of montelukast is required when used in combination with gemfibrozil. However, it may be advisable to monitor patients for potentially increased adverse effects during coadministration with gemfibrozil or other CYP450 2C8/2C9 inhibitors.

References
1 Karonen T, Filppula A, Laitila J, Niemi M, Neuvonen PJ, Backman JT "Gemfibrozil Markedly Increases the Plasma Concentrations of Montelukast: A Previously Unrecognized Role for CYP2C8 in the Metabolism of Montelukast." Clin Pharmacol Ther (2010):. [PMID: 20592724]
2 Product Information. Singulair (montelukast). Merck & Co, Inc, West Point, PA.