Safety and interaction of direct oral anticoagulants with antiarrhythmic drugs
https://doi.org/10.15829/1560-4071-2021-4482
Abstract
The use of direct oral anticoagulants minimized the risks associated with vitamin K antagonist (warfarin) therapy. Currently, direct oral anticoagulants have priority over warfarin for the prevention of thromboembolic events in patients with atrial fibrillation and a number of other conditions requiring anticoagulant therapy. Direct oral anticoagulants along with antiarrhythmic therapy are the accepted strategy for atrial fibrillation treatment. At the same time, the effect of drug-drug interactions (DDI) between direct oral anticoagulants and antiarrhythmic drugs, which have common points of metabolic application, has not been fully elucidated. In order to provide effective and safe anticoagulant and antiarrhythmic therapy in patients with AF, it is important to understand the mechanisms and severity of DDI of direct oral anticoagulants and antiarrhythmic agents. This review discusses the issues of DDI of direct oral anticoagulants and antiarrhythmic drugs used to treat atrial fibrillation.
About the Authors
B. A. Tatarsky
Almazov National Medical Research Center
Russian Federation
Competing Interests:
Russian Federation
St. Petersburg.
Competing Interests:
None
N. V. Kazyonnova
Almazov National Medical Research Center
Russian Federation
Competing Interests:
Russian Federation
St. Petersburg.
Competing Interests:
None
References
1. Reiffel JA, Weitz JI, Reilly P, et al. DOAC monitoring, reversal agents, and postapproval safety and effectiveness evaluation: a cardiac safety research consortium think tank. Cardiac safety research consortium presenters and participants. Am Heart J. 2016;177:74-86. doi:10.1016/j.ahj.2016.04.010.
2. Yeh CH, Hogg K, Weitz JI. Overview of the new oral anticoagulants: opportunities and challenges. Arterioscler Thromb Vasc Biol. 2015;35(5):1056-65. doi:10.1161/ATVBAHA.115.303397.
3. Kundu A, Sardar P, Chatterjee S, et al. Minimizing the risk of bleeding with DOACs in the elderly. Drugs Aging. 2016;33(7):491-500. doi:10.1007/s40266-016-0376-z.
4. Eikelboom J, Merli G. Bleeding with direct oral anticoagulants vs warfarin: clinical experience. Am J Med. 2016;129(11S):S33-40. doi:10.1016/j.amjmed.2016.06.003.
5. Whitworth MM, Haase KK, Fike DS, et al. Utilization and prescribing patterns of direct oral anticoagulants. Int J Gen Med. 2017;10:87-94. doi:10.2147/IJGM.S129235.
6. Voukalis C, Lip GY, Shantsila E. Drug-drug interactions of nonvitamin K oral anticoagulants. Expert Opin Drug Metab Toxicol. 2016;12(12):1445-61. doi:10.1080/17425255.2016.1225037.
7. Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmcol Ther. 2013;138:103-41. doi:10.1016/j.pharmthera.2012.12.007.
8. Megan R, Obaidat A, Hogenbuch B. OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol. 2012;165:1260-87. doi:10.1111/j.1476-5381.2011.01724.x.
9. Lee CA, O'Connor MA, Ritchie TK, et al. Breast cancer resistance protein (ABCG2) in clinical pharmacokinetics and drug interactions: practical recommendations for clinical victim and perpetrator drug-drug interaction study design. Drug Metab Dispos. 2015;43:490-9. doi:10.1124/dmd.114.06217.
10. Rendic S, Di Carlo FJ. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev. 1997;29(1-20):413-580. doi:10.3109/03602539709037591.
11. Dan GA, Antoni Martinez-Rubio A, Agewal S, et al. Antiarrhythmic drugs-clinical use and clinical decision making: a consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Working Group on Cardiovascular Pharmacology, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and International Society of Cardiovascular Pharmacotherapy (ISCP). Europace. 2018;20(5):731-2an. doi:10.1093/europace/eux373.
12. Herink MC, Zhuo YF, Williams CD, et al. Clinical management of pharmacokinetic drug interactions with direct oral anticoagulants (DOACs). Drugs. 2019;79(15):1625-34. doi:10.1007/s40265-019-01183-0.
13. Zimetbaum P. Antiarrhythmic Drug Therapy for Atrial Fibrillation. Circulation. 2012;125:381-9. doi:10.1161/CIRCULATIONAHA.111.019927.
14. Ahrens I, Peter K, Lip GY, et al. Development and clinical applications of novel oral anticoagulants. Part II. Drugs under clinical investigation. Discov Med. 2012;13(73):445-50.
15. Wessler J, Grip L, Mendell J, et al. The P-Glycoprotein Transport System and Cardiovascular Drugs. J Am Coll Card. 2013;61:2495. doi:10.1016/j.jacc.2013.02.058.
16. Groenendaal D, Strabach G, Garcia-Hernandez A, et al. The pharmacokinetics of darexaban (YM150), an oral direct factor Xa inhibitor, are not affected by ketoconazole, a strong inhibitor of CYP3A and P-glycoprotein. Clin Pharmacol Drug Dev. 2014;3(3):194-201. doi:10.1111/j.1365-2125.2012.04346.x.
17. Wiggins BS, Dixon DL, Neyens RR, et al. Select Drug-Drug Interactions With Direct Oral Anticoagulants: JACC Review Topic of the Week. J Am Coll Cardiol. 2020;75(11):1341-50. doi:1016/j.jacc.2019.12.068.
18. Mendell J, Zahir H, Ridout G, et al. Drug-drug interaction studies of cardiovascular drugs (amiodarone, digoxin, quinidine, atorvastatin and verapamil) involving P-glycoprotein (P-gp), an efflux transporter, on the pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor (abstr). J Am Coll Cardiol. 2011;57:E1510. doi:10.1016/S0735-1097(11)61510-6.
19. Rodriques AD. Prioritization of clinical drug interaction studies using in vitro cytochrome P450 data: proposed refinement and expansion of the “rank order” approach. Drug Metab Lett. 2007;1:31-5. doi:10.2174/187231207779814247.
20. Konieczny K, Dorian P. Clinically Important Drug-Drug Interactions Between Antiarrhythmic Drugs and Anticoagulants. J Innov Cardiac Rhythm Manage. 2019;10(3):3552-9. doi:10.19102/icrm.2019.100304.
21. Canadian Pharmacists Association. Compendium of Pharmaceuticals and Specialties. 2018 edition. Toronto, Canada: Canadian Pharmacists Association. ISBN: 1772410047 (ISBN13: 9781772410044).
22. Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015;17(10):1467-507. doi:10.1093/europace/euv309.
23. Steffel J, Verhamme P, Potpara TS, et al. The 2018 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39:1330-93. doi:10.1093/eurheartj/ehy136.
24. Dabigatran etexilate mesylate (Pradaxa) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, 2018.
25. 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 RE-LY trial. J Thromb Haemost. 2011;9(11):2168-75. doi:10.1111/j.1538-7836.2011.04498.x.
26. Kubitza D, Becka M, Roth A, et al. Absence of clinically relevant interactions between rivaroxaban — an oral, direct Factor Xa inhibitor — and digoxin or atorvastatin in healthy subjects. J Int Med Res. 2012;40(5):1688-707. doi:10.1177/030006051204000508.
27. Lupercio L, Romero J, Peltzer B, et al. Efficacy and Safety Outcomes of Direct Oral Anticoagulants and Amiodarone in Patients with Atrial Fibrillation. Am J Med. 2018;131(5):573.e1-e8. doi:10.1016/j.amjmed.2017.11.047.
28. Hartter S, Sennewald R, Nehmiz G, et al. Oral bioavailability of dabigatran etexilate (Pradaxa) after co-medication with verapamil in healthy subjects. Br J Clin Pharmacol. 2013;75:1053-62. doi:10.1111/j.1365-2125.2012.04453.x.
29. Frost C, Wang J, Nepal S, et al. Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol. 2012;75:476-87. doi:10.1111/j.1365-2125.2012.04369.x.
30. Kim M, Son H, Noh K, et al. Effects of Verapamil and Diltiazem on the pharmacokinetics and pharmacodynamics of rivaroxaban. Pharmaceutics. 2019;11:E133. doi:10.3390/pharmaceutics11030133.
31. Hanigan S, Das J, Pogue K, et al. The Real World Use of Combined P-glycoprotein and Moderate CYP3A4 Inhibitors With Rivaroxaban or Apixaban Increases Bleeding. J Thromb Thrombolysis. 2020;49(4):636-43. doi:10.1007/s11239-020-02037-3.
32. Turakhia MP, Blankestijn PJ, Carrero JJ, et al. Chronic kidney disease and arrhythmias: conclusions froma Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Eur Heart J. 2018;39:2314-25. doi:10.1093/eurheartj/ehy060.
33. Caldeira D, Barra M, Santos AT, et al. Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis. Heart. 2014;100(7):550-6. doi:10.1136/heartjnl-2013-305288.
34. Khoury T, Ayman AR, Cohen J, et al. The complex role of anticoagulation in cirrhosis: an updated review of where we are and where we are going. Digestion. 2016;93(2):149-59. doi:10.1159/000442877.
35. Liakoni E, Ratz Bravo AE, Krahenbuhl S. Hepatotoxicity of new oral anticoagulants (DOACs). Drug Saf. 2015;38(8):711-20. doi:10.1007/s40264-015-0317-5.
36. Mekaj YH, Mekaj AY, Duci SB, et al. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag. 2015;24(11):967-77. doi:10.2147/TCRM.S84210.
Supplementary files
Review
For citations:
Tatarsky B.A., Kazyonnova N.V. Safety and interaction of direct oral anticoagulants with antiarrhythmic drugs. Russian Journal of Cardiology. 2021;26(7):4482. (In Russ.) https://doi.org/10.15829/1560-4071-2021-4482
Views:
941
Email this article 