Coadministration of Dabigatran Etexilate and Atorvastatin

Abstract

Results of this randomized, open-label, three-way crossover design study in healthy male and female volunteers showed that atorvastatin had no influence on the pharmacokinetic/pharmacodynamic profile of dabigatran, and vice versa, dabigatran etexilate had no impact on the pharmacokinetic/pharmacodynamic profile of atorvastatin. Both drugs were well tolerated when given alone or in combination.

Association between statin use and ischemic stroke or major hemorrhage in patients taking dabigatran for atrial fibrillation

“…Consequently, a clinically important interaction between dabigatran etexilate and these statins would not be expected; this assertion is supported by findings of a small decrease in dabigatran concentrations with the concomitant use of atorvastatin. 12 Although increased dabigatran absorption might also be expected to improve drug efficacy, previous studies have found a stronger relation between dabigatran concentrations and major hemorrhage than for ischemic events. 13 Another possible explanation for the lack of association between simvastatin or lovastatin and the risk of stroke relates to postabsorption hydrolysis of the lactone form of these drugs to their pharmacologically active hydroxy acid forms, which do not inhibit carboxylesterase.…”

“…However, apart from a small pharmacokinetic study involving healthy volunteers that found that use of atorvastatin reduced systemic dabigatran exposure by 18% without affecting the pharmacodynamic properties of the drug, 12 data are lacking on the potential interaction between statins and dabigatran etexilate in patients with atrial fibrillation. This is important because the safety and efficacy of dabigatran etexilate are related to its plasma concentrations, single-nucleotide polymorphisms in the gene encoding P-glycoprotein are associated with a 12% increase in peak dabigatran concentration per minor allele carried, studies with other P-glycoprotein inhibitors have found increases in dabigatran exposure ranging from 30% to 171%, and the likelihood of concomitant statin use among these patients is high.…”

Dabigatran: An Oral Novel Potent Reversible Nonpeptide Inhibitor of Thrombin

“…No important drug interactions with atorvastatin (CYP3A4) and its metabolites were measured. 18 Likewise, the mean area under the curves and Cmaxs of dabigatran remained unchanged with a single dose of diclofenac (CYP2C9) and were slightly reduced with pantoprazole (CYP2C19).…”

Dabigatran Etexilate

“…Administration of dabigatran with atorvastatin 80 mg/d (CYP3A4), diclofenac 50 mg/d (CYP2C9), or digoxin 0.25 mg/d (p-glycoprotein) was safe and well tolerated without affecting routine coagulation assays. 19,33 …”