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Dabigatran levels in omeprazole versus pantoprazole-treated patients with atrial fibrillation: is there a difference?

  • Tomáš Bolek
  • Matej SamošEmail author
  • Ingrid Škorňová
  • Martin Schnierer
  • Peter Lipták
  • Peter Bánovčin
  • Lukáš Urban
  • Ján Staško
  • Peter Kubisz
  • Peter Galajda
  • Marián Mokán
Letter to the Editor

To the Editor:

Proton pump inhibition (PPI) administrated with dabigatran etexilate reduces the risk of gastrointestinal (GI) bleeding on long-term dabigatran therapy [1]. However, we have previously demonstrated [2] that PPI (with omeprazole or pantoprazole) significantly reduces the trough and peak on-treatment levels in dabigatran-treated patients with atrial fibrillation (AF). Similar observation of significantly lower dabigatran levels in PPI-treated patients was subsequently published in Japanese patients with AF [3]. Now, it is not entirely clear whether this is a “class effect” or a “drug effect.” In fact, there are differences in PPI pharmacokinetics, such as differences in bioavailability, elimination half-life, and metabolism, which may translate into differences in interaction [4]. Therefore, we decided to compare the effect of omeprazole PPI versus pantoprazole PPI on dabigatran etexilate trough and peak levels in patients with AF.

We performed a pilot, prospective,...

Notes

Funding

This study was supported by project APVV (Slovak Research and Development Agency) 16-0020.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval and inform consent

This research was done according to ethical standards and was approved by the local ethical committee (Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava). The patient agreed to participate in the research and signed informed consent for study participation.

Supplementary material

228_2019_2647_MOESM1_ESM.docx (13 kb)
ESM 1 (DOCX 13 kb)

References

  1. 1.
    Chan EW, Lau WC, Leung WK, Mok MT, He Y, Tong TS, Wong IC (2015) Prevention of dabigatran-related gastrointestinal bleeding with gastroprotective agents: a population-based study. Gastroenterology 149:586–95.e3CrossRefGoogle Scholar
  2. 2.
    Bolek T, Samoš M, Stančiaková L, Ivanková J, Škorňová I, Staško J, Galajda P, Kubisz P, Mokáň M (2017) The impact of proton pump inhibition on dabigatran levels in patients with atrial fibrillation. Am J Ther.  https://doi.org/10.1097/MJT.0000000000000599 [article in press]
  3. 3.
    Kuwayama T, Osanai H, Ajioka M, Tokuda K, Ohashi H, Tobe A, Yoshida T, Masutomi T, Kambara T, Inoue Y, Nakashima Y, Asano H, Sakai K (2017) Influence of proton pump inhibitors on blood dabigatran concentrations in Japanese patients with non-valvular atrial fibrillation. J Arrhythm 33:619–623CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Wedemeyer RS, Blume H (2014) Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf 37:201–211CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Samoš M, Stančiaková L, Ivanková J, Staško J, Kovář F, Dobrotová M, Galajda P, Kubisz P, Mokáň M (2015) Monitoring of dabigatran therapy using Hemoclot(®) Thrombin Inhibitor assay in patients with atrial fibrillation. J Thromb Thrombolysis 39:95–100CrossRefGoogle Scholar
  6. 6.
    Ollier E, Hodin S, Basset T, Accassat S, Bertoletti L, Mismetti P, Delavenne X (2015) In vitro and in vivo evaluation of drug-drug interaction between dabigatran and proton pump inhibitors. Fundam Clin Pharmacol 29:604–614CrossRefGoogle Scholar
  7. 7.
    Bolek T, Samoš M, Škorňová I, Stančiaková L, Korpallová B, Galajda P, Staško J, Kubisz P, Mokán M (2019) How to proceed with long-term anticoagulation in patient after total gastrectomy and atrial fibrillation? Eur J Clin Pharmacol 75:285–286CrossRefGoogle Scholar
  8. 8.
    Stangier J (2008) Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 47:285–295CrossRefGoogle Scholar
  9. 9.
    Stangier J, Stahle H, Rathgen K (2005) Effect of food and pantoprazole on the bioavailability of the direct thrombin inhibitor dabigatran in healthy subjects. J Thromb Haemost 3(Suppl. 1):P1612Google Scholar
  10. 10.
    Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, Ezekowitz MD, Nehmiz G, Wang S, Wallentin L, RE-LY Investigators (2014) The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 63:321–328CrossRefGoogle Scholar
  11. 11.
    Chin TW, Loeb M, Fong IW (1995) Effects of an acidic beverage (Coca-Cola) on absorption of ketoconazole. Antimicrob Agents Chemother 39:1671–1675CrossRefPubMedCentralGoogle Scholar
  12. 12.
    Bolek T, Samoš M, Škorňová I, Stančiaková L, Staško J, Korpallová B, Galajda P, Kubisz P, Mokáň M (2019) Does proton pump inhibition change the on-treatment anti-Xa activity in xabans-treated patients with atrial fibrillation? A pilot study. J Thromb Thrombolysis 47:140–145CrossRefGoogle Scholar
  13. 13.
    Henriksen DP, Stage TB, Hansen MR, Rasmussen L, Damkier P, Pottegard A (2015) The potential drug-drug interaction between proton pump inhibitors and warfarin. Pharmacoepidemiol Drug Saf 24:1337–1340CrossRefGoogle Scholar
  14. 14.
    Bolek T, Samoš M, Škorňová I, Kovář F, Galajda P, Staško J, Kubisz P, Mokáň M (2018) Proton pump inhibition in patients treated with novel antithrombotic drugs: should we worry about thrombosis? J Cardiovasc Pharmacol 72:71–76CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Tomáš Bolek
    • 1
  • Matej Samoš
    • 1
    Email author
  • Ingrid Škorňová
    • 2
  • Martin Schnierer
    • 3
  • Peter Lipták
    • 3
  • Peter Bánovčin
    • 3
  • Lukáš Urban
    • 1
  • Ján Staško
    • 2
  • Peter Kubisz
    • 2
  • Peter Galajda
    • 1
  • Marián Mokán
    • 1
  1. 1.Department of Internal Medicine I, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovak Republic
  2. 2.National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovak Republic
  3. 3.Department of Gastroenterology, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovak Republic

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