Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIWGYB74T)
  Drug Name Tolazamide Drug Info Miconazole Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidiabetic Agents Antifungal Agents
  Structure

 Mechanism of Tolazamide-Miconazole Interaction (Severity Level: Major)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tolazamide Miconazole
      Mechanism CYP450 2C9 substrate CYP450 2C9 inhibitor
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C9
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Structure Sequence
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPV
Gene Name CYP2C9
Uniprot ID CP2C9_HUMAN
KEGG Pathway hsa:1559
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). 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:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:7574697, PubMed:15766564, PubMed:19965576, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9866708, PubMed:9435160). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Tolazamide caused by Miconazole mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised when sulfonylureas are used concomitantly with azole antifungal agents that inhibit CYP450 2C9. Blood glucose should be closely monitored, and the sulfonylurea dosage adjusted as necessary. Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, and tachycardia. If hypoglycemia occurs, patients should initiate appropriate remedial therapy immediately, discontinue the azole antifungal agent, and contact their physician.

References
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11 Product Information. Amaryl (glimepiride). Hoechst Marion-Roussel Inc, Kansas City, MO.
12 Product Information. Diflucan (fluconazole). Roerig Division, New York, NY.
13 Product Information. Glucotrol (glipizide). Pfizer US Pharmaceuticals, New York, NY.
14 Product Information. Micronase (glyburide). Pharmacia and Upjohn, Kalamazoo, MI.
15 Product Information. Monistat (miconazole). Ortho Pharmaceutical Corporation, Raritan, NJ.
16 Product Information. Noxafil (posaconazole). Schering-Plough Corporation, Kenilworth, NJ.
17 Product Information. VFEND (voriconazole). Pfizer U.S. Pharmaceuticals, New York, NY.
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