Risk för måttligt minskad dabigatranexponering (cirka 30%).Risk för måttligt minskad dabigatranexponering (cirka 30%).
Normalt behövs ingen dosjustering. Överväg mätning av dabigatrannivåerna vid ischemiska biverkningar.Normalt behövs ingen dosjustering. Överväg mätning av dabigatrannivåerna vid ischemiska biverkningar.
Not established. Possibly decreased absorption of dabigatr......Not established. Possibly decreased absorption of dabigatran due to increase in gastric pH.
A decrease of approximately 30 % of AUC was observed when ......A decrease of approximately 30 % of AUC was observed when dabigatran was co-administered with pantoprazole. However, no effects on bleeding or efficacy of dabigatran were observed in clinical trials when pantoprazole and other proton pump inhibitors were co-administered with dabigatran (1). In one study co-administration with PPIs (lansoprazole, rabeprazole or esomeprazole) was found to significantly decrease the trough and peak dabigatran concentration. Despite this decrease, the dabigatran concentrations were still within the therapeutic range (2). Similar results have been shown in other studies, where concomitant use with PPIs resulted in a decrease in bioavailability of dabigatran (3-6) and one study where dabigatran trough concentration increased almost 70% two weeks after withdrawal of long term PPI-treatment (omeprazole or pantoprazole) (7), but the consensus was that the effects are unlikely to be clinically relevant and do not warrant dose adjustment of dabigatran (3-6). Co-administration of ranitidine with dabigatran had no clinically relevant effect on the extent of absorption of dabigatran (1). A prospective pilot study in 31 patients with non-valvular atrial fibrillation on dabigatran therapy showed significant differences in dabigatran trough concentration comparing patients treated with PPI (omeprazole or pantoprazole) and patients without PPI (58.8 ± 36.7 ng/mL vs. 110.72 ± 88.47 ng/mL, p < 0.05). There were also significant differences in dabigatran peak level between groups (88.0 ± 20.5 ng/mL vs. 174.4 ± 139.64 ng/mL, p < 0.05) (8). A similar study was conducted in 34 patients with atrial fibrillation on long-term dabigatran therapy. Omeprazole was administered (20 mg twice daily) to 12 patients, pantoprazole (40 mg once daily) to 12 patients and no PPI in 10 patients. The decision on PPI strategy was left to the attending physician in order to maintain the conditions of real-life clinical practice. There were significant differences in dabigatran trough (62.4 ± 51.1 ng/mL vs. 122.6 ± 77.1 ng/mL, p < 0.05) and peak levels (116.4 ± 51.2 ng/mL vs. 228.2 ± 140.7 ng/mL; p < 0.05), comparing omeprazole-treated patients with patients without PPI. The pantoprazole-treated patients also had significantly lower trough (60.3 ±53.1 ng/mL vs. 122.6 ± 77.1 ng/mL; p < 0.05) and peak (110.1 ± 49.2 ng/mL vs. 228.2 ± 140.7 ng/mL; p < 0.05) levels when compared with patients without PPI therapy. No significant differences in dabigatran trough or peak levels were found when omeprazole-treated and pantoprazole-treated patients were compared (9). However, there is still no study investigating the effect of PPIs on the clinical outcome and risk of ischemic adverse events in dabigatran-treated patients.
- Pradaxa (dabigatran). Boehringer Ingelheim. SPC, EPAR [www]. 2008.
- Kuwayama T, Osanai H, Ajioka M, Tokuda K, Ohashi H, Tobe A et al. Influence of proton pump inhibitors on blood dabigatran concentrations in Japanese patients with non-valvular atrial fibrillation. J Arrhythm. 2017;33:619-623.
- Liesenfeld KH, Lehr T, Dansirikul C, Reilly PA, Connolly SJ, Ezekowitz MD et al. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial. J Thromb Haemost. 2011;9:2168-75.
- Ollier E, Hodin S, Basset T, Accassat S, Bertoletti L, Mismetti P et al. In vitro and in vivo evaluation of drug-drug interaction between dabigatran and proton pump inhibitors. Fundam Clin Pharmacol. 2015.
- Stangier J, Eriksson BI, Dahl OE, Ahnfelt L, Nehmiz G, Stähle H et al. Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol. 2005;45:555-63.
- Stangier J, Stähle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet. 2008;47:47-59.
- Schnierer M, Samoš M, Bolek T, et al. The Effect of Proton Pump Inhibitor Withdrawal on Dabigatran Etexilate Plasma Levels in Patients With Atrial Fibrillation: A Washout Study. J Cardiovasc Pharmacol. 2020 Apr;75(4):333-5.
- Bolek T, Samoš M, Stančiaková L, Ivanková J, Škorňová I, Staško J et al. The Impact of Proton Pump Inhibition on Dabigatran Levels in Patients With Atrial Fibrillation. Am J Ther. 2019 May/Jun;26:e308-e313.
- Bolek T, Samoš M, Škorňová I, Schnierer M, Lipták P, Bánovčin P et al. Dabigatran levels in omeprazole versus pantoprazole-treated patients with atrial fibrillation: is there a difference?. Eur J Clin Pharmacol. 2019;75:875-877.