OBJECTIVE: This study was undertaken to investigate potential drugdrug interactions between the sodium glucose cotransporter 2 inhibitor empagliflozin and simvastatin. MATERIALS AND METHODS: In this open-label, randomized crossover trial, healthy volunteers (median (range) age 36.5 (20 - 50) years) received 3 single-dose treatments: 25 mg empagliflozin (n = 18), 40 mg simvastatin (n = 17), and 25 mg empagliflozin with 40 mg simvastatin (n = 18). RESULTS: Based on standard criteria, simvastatin had no effect on empagliflozin area under the plasma concentration-time curve (AUC(0-∞), adjusted geometric mean ratio (GMR): 102.05; 90% CI: 98.90 - 105.29) or maximum plasma concentration (C(max), GMR: 109.49; 90% CI: 96.91 - 123.69). There were only minor deviations in simvastatin AUC(0-∞) (GMR: 101.26; 90% CI: 80.06 - 128.07) and C(max) (GMR: 97.18; 90% CI: 76.30 - 123.77) when co-administered with empagliflozin. Empagliflozin had no effect on AUC(0-∞) (GMR: 104.87; 90% CI: 90.09 - 122.07) or C(max) (GMR: 97.27; 90% CI: 84.90 - 111.44) of simvastatin acid, the active metabolite of simvastatin. Adverse events (AEs) were reported for 6 subjects on empagliflozin, 4 on simvastatin, and 5 on co-administered treatment. No serious AEs or investigator-defined drug-related AEs were reported. CONCLUSION: No relevant drug-drug interaction was observed, and pharmacokinetic results suggest that no dose adjustments for either drug are necessary when empagliflozin and simvastatin are co-administered. Empagliflozin was well tolerated when administered alone or in combination with simvastatin.
RCT Entities:
OBJECTIVE: This study was undertaken to investigate potential drugdrug interactions between the sodium glucose cotransporter 2 inhibitor empagliflozin and simvastatin. MATERIALS AND METHODS: In this open-label, randomized crossover trial, healthy volunteers (median (range) age 36.5 (20 - 50) years) received 3 single-dose treatments: 25 mg empagliflozin (n = 18), 40 mg simvastatin (n = 17), and 25 mg empagliflozin with 40 mg simvastatin (n = 18). RESULTS: Based on standard criteria, simvastatin had no effect on empagliflozin area under the plasma concentration-time curve (AUC(0-∞), adjusted geometric mean ratio (GMR): 102.05; 90% CI: 98.90 - 105.29) or maximum plasma concentration (C(max), GMR: 109.49; 90% CI: 96.91 - 123.69). There were only minor deviations in simvastatin AUC(0-∞) (GMR: 101.26; 90% CI: 80.06 - 128.07) and C(max) (GMR: 97.18; 90% CI: 76.30 - 123.77) when co-administered with empagliflozin. Empagliflozin had no effect on AUC(0-∞) (GMR: 104.87; 90% CI: 90.09 - 122.07) or C(max) (GMR: 97.27; 90% CI: 84.90 - 111.44) of simvastatin acid, the active metabolite of simvastatin. Adverse events (AEs) were reported for 6 subjects on empagliflozin, 4 on simvastatin, and 5 on co-administered treatment. No serious AEs or investigator-defined drug-related AEs were reported. CONCLUSION: No relevant drug-drug interaction was observed, and pharmacokinetic results suggest that no dose adjustments for either drug are necessary when empagliflozin and simvastatin are co-administered. Empagliflozin was well tolerated when administered alone or in combination with simvastatin.
Authors: Wajd Alkabbani; Ryan Pelletier; Michael A Beazely; Youssef Labib; Breanna Quan; John-Michael Gamble Journal: Drug Saf Date: 2022-03-05 Impact factor: 5.228
Authors: Vikas Kumar Dawra; David L Cutler; Susan Zhou; Rajesh Krishna; Haihong Shi; Yali Liang; Christine Alvey; Anne Hickman; Didier Saur; Steven G Terra; Vaishali Sahasrabudhe Journal: Clin Pharmacol Drug Dev Date: 2018-05-22