Lack of drug–drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and warfarin in healthy volunteers. Issue 4 (22nd November 2012)

• Record Type: Journal Article
• Authors: Macha, S.; Rose, P.; Mattheus, M.; Pinnetti, S.; Woerle, H. J.
• Is Part Of: Diabetes, obesity & metabolism. Volume 15:Issue 4(2013:Apr.)
• Page Start: 316
• Page End: 323
• Publication Date: 2012-11-22
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12028
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dom12028-sec-0001" sec-type="section"> <title>Aim</title> <p>To investigate potential drug–drug interactions between empagliflozin and warfarin.</p> </sec> <sec id="dom12028-sec-0002" sec-type="section"> <title>Methods</title> <p>Healthy subjects (n = 18) received empagliflozin 25 mg qd for 5 days (treatment A), followed by empagliflozin 25 mg qd for 7 days (days 6–12) with a single 25 mg dose of warfarin on day 6 (treatment B), and a single 25 mg dose of warfarin alone (treatment C), in an open‐label, crossover study. Subjects received treatments in sequence AB_C or C_AB with a washout period of ≥14 days between AB and C or C and AB.</p> </sec> <sec id="dom12028-sec-0003" sec-type="section"> <title>Results</title> <p>Warfarin had no effect on empagliflozin area under concentration‐time curve or maximum plasma concentration at steady‐state (AUC<sub>τ, ss</sub> or C<sub>max, ss</sub>): geometric mean ratios (GMRs) (90% confidence intervals [CI]) were 100.89% (96.86, 105.10) and 100.64% (89.79, 112.80), respectively. Empagliflozin had no effect on AUC from 0 h to infinity (AUC<sub>0–∞</sub>) or C<sub>max</sub> for <italic>R</italic>‐ or <italic>S</italic>‐warfarin (GMRs [90% CI] for AUC<sub>0–∞</sub>: 98.49% [95.29, 101.80] and 95.88% [93.40, 98.43], respectively; C<sub>max</sub>: 97.89% [91.12, 105.15] and 98.88% [91.84, 106.47], respectively). Empagliflozin had no clinically relevant effects on warfarin's anticoagulant activity (international normalised ratio [INR]) (GMR [95% CI] for peak INR: 0.87 [0.73, 1.04]; area under the effect‐time curve from 0 to 168 h: 0.88 [0.79, 0.98]. No drug‐related adverse events were reported for empagliflozin after monotherapy or combined administration. The combination of empagliflozin and warfarin was well tolerated.</p> </sec> <sec id="dom12028-sec-0004" sec-type="section"> <title>Conclusions</title> <p>No drug–drug interactions were observed between empagliflozin and warfarin, indicating that empagliflozin and warfarin can be co‐administered without dosage adjustments of either drug.</p> </sec> </abstract>