Objective  To understand the concomitant use of dabigatran etexilate in medical institutions, and provide reference for rational clinical use.

Methods  Based on the dabigatran etexilate drug instructions, along with relevant guidelines, literature, and professional databases, a retrospective study was conducted to analyze the potential drug-drug interactions among hospitalized patients who received dabigatran etexilate in a tertiary hospital from January 1, 2020 to June 30, 2022.

Results  A total of 1 965 medical records of patients using dabigatran etexilate were included, with 736 patients (1 088 cases) instances of potential drug-drug interactions, resulting in an incidence rate of 37.46%. The drug-drug interactions involved 41 types of drugs, mainly antiarrhythmics, antiplatelets, anticoagulants, and nonsteroidal anti-inflammatory drugs. Notably, the proportion of high-risk drug-drug interactions was 879 cases, accounting for 80.79%.

Conclusion  The findings of this study indicate that potential drug-drug interactions are prevalent during the clinical use of dabigatran etexilate. Clinicians should carefully consider the benefits and risks associated with its use in order to optimize medication treatment plans. Pharmacists should ensure the medication safety of patients through diligent pharmaceutical monitoring.

1.Arthur TMW, Britt WMB, Thomas M, et al. Contextualized drug-drug-interaction management improves clinical utility compared with basic drug-drug interaction management in hospitalized patients[J]. Clin Pharmacol Ther, 2022, 112(2): 382-390. DOI: 10.1002/cpt.2624.

2.周佳纯, 周琰, 苏瑞, 等. 非瓣膜性房颤射频消融术围术期抗凝药物治疗分析与评价 [J]. 中国药师, 2019, 22(6): 1081-1084. [Zhou JC, Zhou Y, Su R, et al. Analysis and evaluation of anticoagulation therapy in the perioperative period of radiofrequency ablation for nonvalvular atrial fibrillation[J]. China Pharmacist, 2019, 22(6): 1081-1084.] DOI: 1008-049X( 2019) 06-1081-04.

3.Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation[J]. Europace, 2021, 23(10): 1612-1676. DOI: 10.1093/europace/euab065.

4.Sandhu RK, Islam S, Dover DC, et al. Concurrent use of P-glycoprotein or ccytochrome 3A4 drugs and non-vitamin K antagonist oral anticoagulants in non-valvular atrial fibrillation[J]. Eur Heart J Qual Care Clin Outcomes, 2022, 8(2): 195-201. DOI: 10.1093/ehjqcco/qcab002.

5.Liesenfeld KH, Lehr T, Dansirikul C, et al. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RELY trial[J]. J Thromb Haemost, 2011, 9(11): 2168-2175. DOI: 10.1111/j.1538-7836. 2011.04498.x.

6.Antonijevic NM, Zivkovic ID, Jovanovic LM, et al. Dabigatran-metabolism, pharmacologic properties and drug interactions[J]. Curr Drug Metab, 2017, 18(7): 622-635. DOI: 10.2174/1389200218666170427113504.

7.Skov K, Falskov B, Jensen EA, et al. Supratheraputic rivaroxaban levels: a persistent drug-drug interaction after discontinuation of amiodarone[J]. Basic Clin Pharmacol Toxicol, 2020, 127(4): 351-353. DOI: 10.1111/bcpt.13419.

8.Siddiqui FM, Qureshi AI. Dabigatran etexilate, a new oral direct thrombin inhibitor, for stroke prevention in patients with atrial fibrillation[J]. Expert Opin Pharmacother，2010, 11(8): 1403-1411. DOI: 10.1517/14656566.2010.482931.

9.Wiggins BS, Northup A, Johnson D, et al. Reduced anticoagulant effect of dabigatran in a patient receiving concomitant phenytoin[J]. Pharmacotherapy, 2016, 36(2): e5-e7. DOI: 10.1002/phar.1698.

10.Zamek-Gliszczynski MJ, Patel M, Yang X, et al. Intestinal P-gp and putative hepatic OATP1B induction: international transporter consortium perspective on drug development implications[J]. Clin Pharmacol Ther, 2021, 109(1): 55-64. DOI: 10.1002/cpt.1916.

11.Härtter S, Sennewald R, Schepers C, et al. Pharmacokinetic and pharmacodynamic effects of comedication of clopidogrel and dabigatran etexilate in healthy male volunteers[J]. Eur J Clin Pharmacol, 2013, 69(3): 327-339. DOI: 10.1007/s00228-012-1304-8.

12.Ferri N, Colombo E, Tenconi M, et al. Drug-drug interactions of direct oral anticoagulants (DOACs): from pharmacological to clinical practice[J]. Pharmaceutics, 2022, 14(6): 1120. DOI: 10.3390/pharmaceutics14061120.

13.Mar PL, Gopinathannair R, Gengler BE, et al. Drug interactions affecting oral anticoagulant use[J]. Circ Arrhythm Electrophysiol, 2022, 15(6): e007956. DOI: 10.1161/CIRCEP.121.007956.

14.Xu WL, Lv MN, Wu SY, et al. Severe bleeding risk of direct oral anticoagulants versus vitamin K antagonists for stroke prevention and treatment in patients with atrial fibrillation: a systematic review and network meta-analysis[J]. Cardiovasc Drugs Ther, 2023, 37(2): 363-377. DOI: 10.1007/s10557-021-07232-9.

15.张桂芳, 陆社桂, 熊淑华, 等. 达比加群酯联合塞来昔布致上消化道出血1例 [J]. 中国新药与临床杂志, 2016, 35(8): 596-598. [Zhang GF, Lu SG, Xiong SH, et al. One case of gastrointestinal bleeding caused by combination of dabigatran etexilate and celecoxib[J].Chinese Journal of New Drugs and Clinical Remedies, 2016, 8(35): 596-597.] DOI: 10.14109/j.cnki.xyylc.2016. 08.015.