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Published in: Drug Safety 9/2016

01-09-2016 | Review Article

Drug Interactions of Direct-Acting Oral Anticoagulants

Authors: John Leonard Fitzgerald, Laurence Guy Howes

Published in: Drug Safety | Issue 9/2016

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Abstract

In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion system, and several are metabolised, in part, by cytochrome P450 (CYP) 3A4. This current article assesses the interactions that do or may occur with the DOACs, particularly with respect to the P-gp and CYP3A4 systems.
Literature
1.
go back to reference Ganetsky M, Babu KM, Salhanick SD, Brown RS, Boyer EW. Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant. J Med Toxicol. 2011;7(4):281–7.CrossRefPubMedPubMedCentral Ganetsky M, Babu KM, Salhanick SD, Brown RS, Boyer EW. Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant. J Med Toxicol. 2011;7(4):281–7.CrossRefPubMedPubMedCentral
2.
go back to reference Perzborn E, Roehrig S, Straub A, Kubitza D, Misselwitz F. The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor. Nat Rev Drug Discov. 2011;10(1):61–75.CrossRefPubMed Perzborn E, Roehrig S, Straub A, Kubitza D, Misselwitz F. The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor. Nat Rev Drug Discov. 2011;10(1):61–75.CrossRefPubMed
3.
go back to reference Keating GM. Apixaban: a review of its use for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Drugs. 2013;73(8):825–43.CrossRefPubMed Keating GM. Apixaban: a review of its use for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Drugs. 2013;73(8):825–43.CrossRefPubMed
4.
go back to reference Anon. Edoxaban tosylate. Am J Cardiovasc Drugs. 2011;11(2):129–35. Anon. Edoxaban tosylate. Am J Cardiovasc Drugs. 2011;11(2):129–35.
5.
go back to reference Finch A, Pillans P. P-glycoprotein and its role in drug-drug interactions. Aust Prescr. 2014;37:137–9.CrossRef Finch A, Pillans P. P-glycoprotein and its role in drug-drug interactions. Aust Prescr. 2014;37:137–9.CrossRef
6.
go back to reference Nutescu E, Chuatrisorn I, Hellenbart E. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J Thromb Thrombolysis. 2011;31(3):326–43.CrossRefPubMed Nutescu E, Chuatrisorn I, Hellenbart E. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J Thromb Thrombolysis. 2011;31(3):326–43.CrossRefPubMed
7.
go back to reference Nielsen D, Skovsgaard T. P-glycoprotein as multidrug transporter: a critical review of current multidrug resistant cell lines. Biochim Biophys Acta. 1992;1139(3):169–83.CrossRefPubMed Nielsen D, Skovsgaard T. P-glycoprotein as multidrug transporter: a critical review of current multidrug resistant cell lines. Biochim Biophys Acta. 1992;1139(3):169–83.CrossRefPubMed
8.
go back to reference Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomics to mechanism. Oncogene. 2003;22(47):7468–85.CrossRefPubMed Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomics to mechanism. Oncogene. 2003;22(47):7468–85.CrossRefPubMed
9.
go back to reference Lippi G, Favaloro EJ, Mattiuzzi C. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring? Semin Thromb Hemost. 2014;40(7):756–65.CrossRefPubMed Lippi G, Favaloro EJ, Mattiuzzi C. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring? Semin Thromb Hemost. 2014;40(7):756–65.CrossRefPubMed
11.
go back to reference Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76(3):455–66.CrossRefPubMedPubMedCentral Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76(3):455–66.CrossRefPubMedPubMedCentral
12.
go back to reference Zhang D, He K, Herbst JJ, Kolb J, Shou W, Wang L, et al. Characterization of efflux transporters involved in distribution and disposition of apixaban. Drug Metab Dispos. 2013;41(4):827–35.CrossRefPubMed Zhang D, He K, Herbst JJ, Kolb J, Shou W, Wang L, et al. Characterization of efflux transporters involved in distribution and disposition of apixaban. Drug Metab Dispos. 2013;41(4):827–35.CrossRefPubMed
14.
go back to reference Spinler S. The pharmacology and therapeutic use of dabigatran etexilate. J Clin Pharmacol. 2013;53(1):1–13. Spinler S. The pharmacology and therapeutic use of dabigatran etexilate. J Clin Pharmacol. 2013;53(1):1–13.
15.
go back to reference Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.CrossRefPubMed Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.CrossRefPubMed
16.
go back to reference Hennessy M, Kelleher D, Spiers JP, Barry M, Kavanagh P, Back D, et al. St Johns wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol. 2002;53(1):75–82.CrossRefPubMedPubMedCentral Hennessy M, Kelleher D, Spiers JP, Barry M, Kavanagh P, Back D, et al. St Johns wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol. 2002;53(1):75–82.CrossRefPubMedPubMedCentral
17.
go back to reference Rahimi R, Abdollahi M. An update on the ability of St. John’s wort to affect the metabolism of other drugs. Expert Opin Drug Metab Toxicol. 2012;8(6):691–708.CrossRefPubMed Rahimi R, Abdollahi M. An update on the ability of St. John’s wort to affect the metabolism of other drugs. Expert Opin Drug Metab Toxicol. 2012;8(6):691–708.CrossRefPubMed
18.
go back to reference Stangier J, Stahle H, Rathgen K, Roth W, Reseski K, Kornicke T. Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin. J Clin Pharmacol. 2012;52(2):243–50.CrossRefPubMed Stangier J, Stahle H, Rathgen K, Roth W, Reseski K, Kornicke T. Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin. J Clin Pharmacol. 2012;52(2):243–50.CrossRefPubMed
22.
go back to reference Davidson BL, Verheijen S, Lensing AW, Gebel M, Brighton TA, Lyons RM, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947–53.CrossRefPubMed Davidson BL, Verheijen S, Lensing AW, Gebel M, Brighton TA, Lyons RM, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947–53.CrossRefPubMed
23.
go back to reference Caldeira D, Barra M, Ferreira A, Rocha A, Augusto A, Pinto FJ, et al. Systematic review with meta-analysis: the risk of major gastrointestinal bleeding with non-vitamin K antagonist oral anticoagulants. Aliment Pharmacol Ther. 2015;42(11–12):1239–49.CrossRefPubMed Caldeira D, Barra M, Ferreira A, Rocha A, Augusto A, Pinto FJ, et al. Systematic review with meta-analysis: the risk of major gastrointestinal bleeding with non-vitamin K antagonist oral anticoagulants. Aliment Pharmacol Ther. 2015;42(11–12):1239–49.CrossRefPubMed
Metadata
Title
Drug Interactions of Direct-Acting Oral Anticoagulants
Authors
John Leonard Fitzgerald
Laurence Guy Howes
Publication date
01-09-2016
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 9/2016
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.1007/s40264-016-0443-8

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