Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI6C2PLZ9)
  Drug Name Fluvoxamine Drug Info Rabeprazole Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antiulcer Agents
  Structure

 Mechanism of Fluvoxamine-Rabeprazole Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Fluvoxamine Rabeprazole
      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 Rabeprazole caused by Fluvoxamine mediated inhibition of CYP450 enzyme

Recommended Action
      Management Although proton pump inhibitors are generally well tolerated, caution is advised if they are prescribed with fluvoxamine. Dosage adjustment should be considered in patients who experience excessive adverse effects such as drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth.

References
1 Christensen M, Tybring G, Mihara K, et al. "Low daily 10-mg and 20-mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19)." Clin Pharmacol Ther 71 (2002): 141-52. [PMID: 11907488]
2 Product Information. Aciphex (rabeprazole) Janssen Pharmaceuticals, Titusville, NJ.
3 Product Information. Nexium (esomeprazole) Astra-Zeneca Pharmaceuticals, Wilmington, DE.
4 Product Information. Prevacid (lansoprazole). TAP Pharmaceuticals Inc, Deerfield, IL.
5 Product Information. Prilosec (omeprazole). Merck & Co, Inc, West Point, PA.
6 Product Information. Protonix (pantoprazole) Wyeth-Ayerst Laboratories, Philadelphia, PA.
7 Yasui-Furukori N, Takahata T, Nakagami T, et al. "Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes." Br J Clin Pharmacol 57 (2004): 487-94. [PMID: 15025747]