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The results of a recently published study suggest that taking the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa) with either simvastatin (Zocor, and others) or lovastatin (Altoprev, and others) increases the risk of major hemorrhage.1
POSSIBLE MECHANISMS — The mechanism for this potential interaction has not been established. Dabigatran etexilate is a substrate of the transporter P-glycoprotein (P-gp); drugs that inhibit P-gp could increase dabigatran serum concentrations and the risk of bleeding.2 In in vitro studies, simvastatin and lovastatin have been shown to inhibit P-gp3; however, limited data from in vivo studies suggest simvastatin and lovastatin have little to no effect on serum concentrations of P-gp substrates such as digoxin.
- T Antoniou et al. Association between statin use and ischemic stroke or major hemorrhage in patients taking dabigatran for atrial fibrillation. CMAJ 2016 Nov 21 (epub).
- Which oral anticoagulant for atrial fibrillation? Med Lett Drugs Ther 2016; 58:45.
- C Chen et al. Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos 2005; 33:537.
- FDA. Center for Drug Evaluation and Research. Juvisync (sitagliptin + simvastatin tablets). Clinical Pharmacology and Biopharmaceutics Review(s). Available at: www.accessdata.fda.gov. Accessed January 19, 2017.
- A Bernsdorf et al. Simvastatin does not influence the intestinal P-glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms. Br J Clin Pharmacol 2006; 61:440.
- W Dieterle et al. Pharmacokinetic interactions of the oral renin inhibitor aliskiren with lovastatin, atenolol, celecoxib and cimetidine. Int J Clin Pharmacol Ther 2005; 43:527.
- F Violi et al. Statins as antithrombotic drugs. Circulation 2013; 127:251.