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Possible drug-drug interaction between high-dose esomeprazole and phenprocoumon

  • Pharmacodynamics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

It is established that omeprazole increases (R)+ warfarin levels with around 10 %. Whether (es)omeprazole also increase the plasma levels of acenocoumarol or phenprocoumon is still uncertain. We analyzed whether addition of (es)omeprazole to acenocoumarol or phenprocoumon increases the international normalized ratio (INR) levels and the risk of overanticoagulation.

Methods

We analyzed all hospital admissions in four teaching hospitals. Patients who used coumarins and pantoprazole or (es)omeprazole simultaneously for at least four consecutive days were included in the study. We analyzed the highest INR level and whether patients had an INR level above six. We compared patients using omeprazole or esomeprazole with patients using pantoprazole, because for pantoprazole, no interaction has been reported.

Results

We analyzed 5747 admissions with 4540 patients using one of the drug combinations. For acenocoumarol (4578 admissions), no significant differences were found between users of esomeprazole, omeprazole, and pantoprazole. For phenprocoumon (1169 admissions), the highest INR measured was significantly higher in users of esomeprazole than in users of pantoprazole (4.7 versus 4.3; p = 0.035). No significant difference was found with omeprazole versus pantoprazole (4.3 versus 4.3; p = 0.66). A non-significant association was found between the esomeprazole dose and the highest INR level (p = 0.055). The risk of an INR above six did not differ significantly between esomeprazole and pantoprazole (27.7 % versus 22.9 %; p = 0.34).

Conclusions

The use of esomeprazole simultaneously with phenprocoumon during hospital admissions might increase the anticoagulant effect. The clinical relevance seems to be limited, because no statistically significant increased risk of overanticoagulation was found.

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Compliance with ethical standards

The authors declare that they have no conflict of interest.

For this type of study, formal consent is not required.

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Authors and Affiliations

  1. Pharmacy Foundation of Haarlem Hospitals, Boerhaavelaan 24, 2035 RC, Haarlem, The Netherlands

    M. L. Becker & R. T. M. van der Hoeven

  2. ATAL-MEDIAL Diagnostics Centers, Hoofddorp, The Netherlands

    W. P. J. Franken

  3. Sint Lucas Andreas Hospital, Amsterdam, The Netherlands

    F. Karapinar

  4. Amphia Hospital, Breda, The Netherlands

    R. Verzijl-Zeegers

  5. Universiteit Utrecht, Utrecht, The Netherlands

    T. Schalekamp

Authors
  1. M. L. Becker
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  2. W. P. J. Franken
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  3. F. Karapinar
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  4. R. Verzijl-Zeegers
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  5. T. Schalekamp
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  6. R. T. M. van der Hoeven
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Correspondence to M. L. Becker.

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Becker, M.L., Franken, W.P.J., Karapinar, F. et al. Possible drug-drug interaction between high-dose esomeprazole and phenprocoumon. Eur J Clin Pharmacol 71, 1461–1465 (2015). https://doi.org/10.1007/s00228-015-1912-1

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  • DOI: https://doi.org/10.1007/s00228-015-1912-1

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