Scientific Online Resource System

Heart - Lung (Varna)

Drug-drug interactions with the new oral anticoagulants

Virginia Tzankova, Veselin Petrov

Abstract

Drug-drug interactions (DDI) and adverse drug effects (ADR) have received much attention because many patients are being hospitalized or remain hospitalized longer than necessary. The use of multiple drugs (8-12 on average in hospitalized patients) is common in a number of therapeutic regimens. Anticoagulant drugs are among the most commonly implicated medications that cause ADR in hospitalized patients and medication errors involving anticoagulant drugs remain common. Elderly and cardiac patients represent populations at particularly high risk for suffering anticoagulant-associated ARD and drug interactions.


We review clinically significant pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs) with the new oral anticoagulants, including dabigatran, rivaroxaban, and apixaban. The main pharmacokinetic drug interactions are focused on drugs affecting the permeability glycoprotein (P-gp) efflux transporter protein and/or cytochrome P- 450 enzymes. Awareness of drugs that are involved in drug-drug interactions and especially those that alter the function of the P-gp efflux transporter protein and CYP enzymes and provide adverse effects should enable clinicians to anticipate and avoid potential DDIs involving the anticoagulants.


Full Text


References

Alexander, JH, Lopes RD, James S, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med, 2011;365:699-708.

Bauer KA. Reversal of antithrombotic agents. Am J Hematol, 2012;87(Suppl 1):S119-S126.

Eliquis (apixaban) [Prescribing information]. Princeton, NJ: Bristol Myers Squibb, Pfizer Inc; December 2012.

Gulseth MP, Wittkowsky AK, Fanikos J, et al. Dabigatran etexilate in clinical practice: confronting challenges to improve safety and effectiveness. Pharmacotherapy, 2011;31:1232-1249.

http://www.xareltohcp.com/sites/default/files/pdf/medication_guide#zoom=100.

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf

http://bidocs.boehringeringelheim.com/BIWebAccess/ViewServlet.ser?docBase =renetnt&folderPath=/Prescribing Information/PIs/Pradaxa/Patient Info/PradaxaMedGuide.

Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation, 2011;123:1436-1450.

Kaatz S, Kouides PA, Garcia DA et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol, 2012;87(1):S141-S145.

Kubitza D, Becka M, Mueck W, et al. Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban - an oral, direct Factor Xa inhibitor - are not affected by aspirin. J Clin Pharmacol, 2006;46:981-990.

Leucuta SE, Vlase L. Pharmacokinetics and metabolic drug interactions. Curr Clin Pharmacol, 2006;1:5-20.

Lip G, Larsen T, Skjoth F, et al. Indirect comparisons of new oral anticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation. J Am Coll Cardiol, 2012;60:738-746.

Mendell J, Lee F, Chen S, et al. The effects of the antiplatelet agents, aspirin and naproxen,on pharmacokinetics and pharmacodynamics of the anticoagulant edoxaban, a direct factor Xa inhibitor. J Cardiovasc Pharmacol, 2013;62:212-221.

Nutescu E, Chuatrisorn I, Hellenbart E. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J Thromb Thrombolysis, 2011;31:326-343.

Perez A, Eraso L, Merli G. Implications of new anticoagulants in primary practice. Int J ClinPract, 2013;67:139-156.

Pisters R, Lane D, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest, 2010;138:1093-1100.

Poulsen B, Grove E, Husted S. New oral anticoagulants: a review of the literature with particular emphasis on patients with impaired renal function. Drugs, 2012;72:1739-1753.

Pradaxa (dabigatran etexilate) [Prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; April 2013.

Schulman S, Kearon C, Kakkar AK et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med, 2013;368:709-718.

Xarelto (rivaroxaban) [Prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; March 2013.




DOI: http://dx.doi.org/10.14748/hl.v20i1-2.1485

Refbacks

Font Size


|