Lack of drug–drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and warfarin in healthy volunteers
- 22 November 2012
- journal article
- Published by Wiley in Diabetes, Obesity and Metabolism
- Vol. 15 (4), 316-323
- https://doi.org/10.1111/dom.12028
Abstract
To investigate potential drug-drug interactions between empagliflozin and warfarin. 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. Warfarin had no effect on empagliflozin area under concentration-time curve or maximum plasma concentration at steady-state (AUC(τ,ss) or C(max,ss)): 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(0-∞)) or C(max) for R- or S-warfarin (GMRs [90% CI] for AUC(0-∞): 98.49% [95.29, 101.80] and 95.88% [93.40, 98.43], respectively; C(max): 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. 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.Keywords
This publication has 21 references indexed in Scilit:
- Type 2 diabetes, glucose homeostasis and incident atrial fibrillation: the Atherosclerosis Risk in Communities studyHeart, 2011
- Platelet Function in Patients with Diabetes Mellitus: From a Theoretical to a Practical PerspectiveInternational Journal of Endocrinology, 2011
- Inflammation and thrombosis in diabetesThrombosis and Haemostasis, 2011
- Dapagliflozin: more than just another oral glucose-lowering agent?Expert Opinion on Investigational Drugs, 2010
- Dapagliflozin Monotherapy in Type 2 Diabetic Patients With Inadequate Glycemic Control by Diet and ExerciseDiabetes Care, 2010
- Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studiesThe Lancet, 2010
- Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trialThe Lancet, 2010
- Glycated haemoglobin and cardiovascular outcomes in people with Type 2 diabetes: a large prospective cohort studyDiabetic Medicine, 2008
- Pharmacology and Management of the Vitamin K AntagonistsChest, 2008
- Association Between Diabetes and Stroke Subtype on Survival and Functional Outcome 3 Months After StrokeStroke, 2003