Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIDPS03VB)
  Drug Name Omeprazole Drug Info Fosphenytoin Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiulcer Agents Anticonvulsants
  Structure

 Mechanism of Omeprazole-Fosphenytoin Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Omeprazole Fosphenytoin
      Mechanism CYP450 2C19 inhibitor CYP450 2C19 substrate
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C19
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Structure Sequence
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKIYGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFMESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRGHMPYTDAVVHEVQRYIDLIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFKKSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVPPFYQLCFIPV
Gene Name CYP2C19
Uniprot ID CP2CJ_HUMAN
KEGG Pathway hsa:1557
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:20972997, PubMed:19965576). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307).
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      Mechanism Description
  • Decreased metabolism of Fosphenytoin caused by Omeprazole mediated inhibition of CYP450 enzyme

Recommended Action
      Management Clinical and laboratory monitoring may be appropriate whenever omeprazole is added to or withdrawn from therapy with phenytoin. Dosage adjustments may be considered if an interaction is suspected. Patients should be advised to notify their doctor if they experience symptoms of phenytoin toxicity (e.g., drowsiness, visual disturbances, change in mental status, seizures, nausea, or ataxia).

References
1 Andersson T "Omeprazole drug interaction studies." Clin Pharmacokinet 21 (1991): 195-212. [PMID: 1764870]
2 Cerner Multum, Inc. "Australian Product Information.".
3 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4 Gugler R, Jensen JC "Omeprazole inhibits oxidative drug metabolism: studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro." Gastroenterology 89 (1985): 1235-41. [PMID: 3932118]
5 Prichard PJ, Walt RP, Kitchingman GK, et al. "Oral phenytoin pharmacokinetics during omeprazole therapy." Br J Clin Pharmacol 24 (1987): 543-5. [PMID: 3689634]
6 Product Information. Prilosec (omeprazole). Merck & Co, Inc, West Point, PA.