Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIR92OY8S)
  Drug Name Warfarin Drug Info Dexlansoprazole Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anticoagulants Proton Pump Inhibitors
  Structure

 Mechanism of Warfarin-Dexlansoprazole Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Warfarin Dexlansoprazole
      Mechanism CYP450 2C19 substrate CYP450 2C19 inhibitor
      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).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Warfarin caused by Dexlansoprazole mediated inhibition of CYP450 enzyme

Recommended Action
      Management Given the potential for interaction and the high degree of interpatient variability with respect to warfarin metabolism, patients should be closely monitored during concomitant therapy with PPIs. The INR should be checked frequently and warfarin dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of PPI in patients who are stabilized on their warfarin regimen. The same precaution may be applicable during therapy with other oral anticoagulants. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

References
1 Ahmad S "Omeprazole-warfarin interaction." South Med J 84 (1991): 674-5. [PMID: 2035104]
2 Andersson T, HassanAlin M, Hasselgren G, Rohss K "Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole." Clin Pharmacokinet 40 (2001): 523-37. [PMID: 11510629]
3 Product Information. Aciphex (rabeprazole) Janssen Pharmaceuticals, Titusville, NJ.
4 Product Information. Coumadin (warfarin). DuPont Pharmaceuticals, Wilmington, DE.
5 Product Information. Dexilant (dexlansoprazole). Takeda Pharmaceuticals America, Lincolnshire, IL.
6 Product Information. Nexium (esomeprazole) Astra-Zeneca Pharmaceuticals, Wilmington, DE.
7 Product Information. Omeprazole (omeprazole). Mylan Pharmaceuticals Inc, Morgantown, WV.
8 Product Information. Prevacid (lansoprazole). TAP Pharmaceuticals Inc, Deerfield, IL.
9 Product Information. Protonix (pantoprazole) Wyeth-Ayerst Laboratories, Philadelphia, PA.
10 Steinijans VW, Huber R, Hartmann M, Zech K, Bliesath H, Wurst W, Radtke HW "Lack of pantoprazole drug interactions in man." Int J Clin Pharmacol Ther 32 (1994): 385-99. [PMID: 7981922]
11 Steinijans VW, Huber R, Hartmann M, Zech K, Bliesath H, Wurst W, Radtke HW "Lack of pantoprazole drug interactions in man: an updated review." Int J Clin Pharmacol Ther 34 (1 suppl) (1996): s31-50. [PMID: 8793602]
12 Steinijans VW, Huber R, Hartmann M, Zech K, Bliesath H, Wurst W, Radtke HW "Lack of pantoprazole drug interactions in man: an updated review." Int J Clin Pharmacol Ther 34 (1996): 243-62. [PMID: 8793611]
13 Sutfin T, Blamer K, Bostrom H, Eriksson S, Hoglund P, Paulsen O "Stereoselective interaction of omeprazole with warfarin in healthy men." Ther Drug Monit 11 (1989): 176-84. [PMID: 2718223]
14 Unge P, Svedberg LE, Nordgren A, et al. "A study of the interaction of omeprazole and warfarin in anticoagulated patients." Br J Clin Pharmacol 34 (1992): 509-12. [PMID: 1493083]
15 Wells PS, Holbrook AM, Crowther NR, Hirsh J "Interactions of warfarin with drugs and food." Ann Intern Med 121 (1994): 676-83. [PMID: 7944078]