Interaction between Warfarin and Proton Pump Inhibitors

DOI: 10.4236/ijcm.2014.514112   PDF   HTML   XML   5,295 Downloads   9,020 Views   Citations


Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin was prescribed from November 1, 2010 to October 30, 2011 were extracted from electronic health records. In retrospective analysis for 1 year, PPI were prescribed to 404 patients. Among them, 108 patients were taking warfarin for more than 6 weeks before and after PPI. The profile of these patients was analyzed: 63 patients took lansoprazole; 15 patients took omeprazole; 30 patients took rabeprazole. No statistical difference was observed among 3 groups in age, body weight, concomitant use of other drugs, and comorbidity. Warfarin dose and INR did not change after PPI. Multivariate stepwise logistic regression analysis revealed that upper quartile of increment of INR was associated with the presence of atrial fibrillation (OR 3.77, 95% CI 1.16 - 12.27). The patients who had warfarin for shorter periods before PPI, or those who had PPI first (n = 141) had similar dose of warfarin and INR. In all patients analyzed (n = 404), including patients whose follow-up periods were shorter than 6 weeks (n = 155), a patient had cerebral bleeding, and 2 patients had cerebral infarction. Conclusions: Unfavorable interaction between warfarin and PPI was negligible in clinical use. Relatively higher INR was achieved after PPI in the presence of atrial fibrillation.

Share and Cite:

Shirayama, T. , Shiraishi, H. , Kuroyanagi, A. , Hamaoka, T. , Imai, M. and Kojima, A. (2014) Interaction between Warfarin and Proton Pump Inhibitors. International Journal of Clinical Medicine, 5, 836-843. doi: 10.4236/ijcm.2014.514112.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Hart, R.G., Pearce, L.A. and Aguilar, M.I. (2007) Meta-Analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrialfibrillation. Annals of Internal Medicine, 146, 857-867.
[2] Ogawa, S., Koretsune, Y., Yasaka, M., Aizawa, Y., Atarashi, H., Inoue, H., et al. (2011) Antithrombotic Therapy in Atrial Fibrillation: Evaluation and Positioning of New Oral Anticoagulant Agents. Circulation Journal, 75, 1539-1547.
[3] Doufekias, E., Segal, A.Z. and Kizer, J.R. (2008) Cardiogenic and Aortogenic Brain Embolism. Journal of the American College of Cardiology, 51, 1049-1059.
[4] Lanza, F.L., Chan, F.K.L. and Quigley, E.M.M. (The Practice Parameters Committee of the American College of Gastroenterology) (2009) Guidelines for Prevention of NSAID-Related Ulcer Complications. American Journal of Gastroenterology, 104, 728-738.
[5] Hungin, A.P., Rubin, G.P. and O’Flanagan, H. (1999) Co-Prescription of H2 Receptor Blockers and Proton Pump Inhibitors with Warfarin in General Practice. Postgraduate Medical Journal, 75, 721-722.
[6] Li, X.Q., Andersson, T.B., Ahlström, M. and Weidolf, L. (2004) Comparison of Inhibitory Effects of the Proton Pump Inhibiting Drugs. Omeprazole, Edomeprazole, Lansoprazole, Pantoprazole and Rabereazole on Human Cytochrome P450 Activities. Drug Metabolism and Disposition, 32, 821-827.
[7] Zhou, Q. and Chan, E. (2003) Effect of Omeprazole on the Anticoagulant Activity and the Pharmacokinetics of Warfarin Enantiomers in Rats. European Journal of Pharmaceutical Sciences, 20, 439-449.
[8] Zhou, Q., Zhou, S. and Chan, E. (2005) Effect of Omeprazole on the Hydroxylation of Warfarin Enantiomers in Human: In-Vitro Studies with Liver Microsomes and cDNA-Expressed Cytochrome P450 Isozymes. Current Drug Metabolism, 6, 399-411.
[9] Hata, M., Hayasaka, M., Sezai, A., Niino, T., Yoda, M., Unosawa, S., et al. (2008) Proton Pump Inhibitors May Increase the Risk of Delayed Bleeding Complications after Open Heart Surgery If Used Concomitantly with Warfarin. The Thoracic and Cardiovascular Surgery, 56, 274-277.
[10] Uno, T., Sugimoto, K., Sugawara, K. and Tateishi, T. (2008) The Role of Cytochrome P2C19 in R-Warfarin Pharmacokinetics and Its Interaction with Omeprazole. Therapeutic Drug Monitoring, 30, 276-281.
[11] Teichert, M., van Noord, C., Uitterlinden, A.G., Hofman, A., Buhre, P.N., De Smet, P.A., et al. (2011) Proton Pump Inhibitors and the Risk of Overanticoagulation during Acenocoumarol Maintenance Treatment. British Journal of Haematology, 153, 379-385.
[12] Sutfin, T., Balmer, K., Boström, H., Eriksson, S., Höglund, P. and Paulsen, O. (1989) Stereoselective Interaction of Omeprazole with Warfarin in Healthy Men. Therapeutic Drug Monitoring, 11, 176-184.
[13] Unge, P., Svedberg, L.E., Nordgren, A., Blom, H., Andersson, T., Lagerström, P.O., et al. (1992) A Study of the Interaction of Omeprazole and Warfarin in Anticoagulated Patients. British Journal of Clinical Pharmacology, 34, 509-512.
[14] Moffett, B.S., Ung, M. and Bomgaars, L. (2012) Risk Factors for Elevated INR Values during Warfarin Therapy in Hospitalized Pediatric Patients. Pediatric Blood Cancer, 58, 941-944.
[15] Flockhart, D.A., O’Kane, D., Williams, M.S., Watson, M.S., Flockhart, D.A., Gage, B., et al. (2008) Pharmacogenetic Testing of CYP2C9 and VKORC1 Alleles for Warfarin. Genetics in Medicine, 10, 139-150.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.