title: Lack of drug-drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and warfarin in healthy volunteers.
abstract: OBJECTIVE
  To investigate potential drug-drug interactions between empagliflozin and warfarin.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Pharmacokinetics and Pharmacodynamics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. sreeraj.macha@boehringer-ingelheim.com
authors.forename: S
authors.initials: S
authors.lastname: Macha
authors.forename: P
authors.initials: P
authors.lastname: Rose
authors.forename: M
authors.initials: M
authors.lastname: Mattheus
authors.forename: S
authors.initials: S
authors.lastname: Pinnetti
authors.forename: H J
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D005960:Glucosides / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014859:Warfarin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014859:Warfarin; C570240:empagliflozin