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Hindi Research Article
Assessment of Drug Interaction Potential between LCZ696, an Angiotensin Receptor Neprilysin Inhibitor, and Digoxin or Warfa rin
| Surya Ayalasomayajula1*, Pierre Jordaan, MBChB2, Parasar Pal3, Priyamvada Chandra1, Diego Albrecht2, Thomas Langenickel2, Iris Rajman2and Gangadhar Sunkara1 | |
| 1DMPK, Novartis Institutes for BioMedical Research (NIBR), East Hanover, NJ, USA | |
| 2Translational Medicine, Novartis Institutes for BioMedical Research (NIBR), Basel, Switzerland | |
| 3Biostatistical Sciences, IDFR, Novartis Healthcare Pvt Ltd, Hyderabad, Telangana, India | |
| Corresponding Author : | Surya Ayalasomayajula Novartis Institutes for BioMedical Research (NIBR), DMPK One Health Plaza 438/3413, East Hanover, NJ 07936, USA Tel: +1-862-778-0217 E-mail: surya.ayalasomayajula@novartis.com. |
| Received: October 01, 2015; Accepted: October 08, 2015; Published: October 14, 2015 | |
| Citation: Ayalasomayajula S, Jordaan P, MBChB, Pal P, Chandra P, Albrecht D et al. (2015) Assessment of Drug Interaction Potential between LCZ696, an Angiotensin Receptor Neprilysin Inhibitor, and Digoxin or Warfarin. Clin Pharmacol Biopharm 4:147. doi:10.4172/2167-065X.1000147 | |
| Copyright: © 2015 Ayalasomayajula S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
Abstract
LCZ696 (sacubitril/valsartan) is a first-in-class angiotensin receptor neprilysin inhibitor that simultaneously inhibits neprilysin and blocks the angiotensin II receptor. LCZ696 has been recently approved for treatment of HF and likely be co-administered with digoxin or warfarin. The drug interaction potential between LCZ696 and digoxin or warfarin was evaluated because of their potentially shared metabolic/elimination pathways. Two separate drug-drug interaction studies were conducted in healthy subjects: LCZ696 200 mg twice daily was co-administered with digoxin 0.25 mg once daily (n=24) and warfarin 25 mg single dose (n=26), respectively. The pharmacokinetic profiles of the LCZ696 analytes (sacubitril, LBQ657 and valsartan), digoxin and R- and S-warfarin, the pharmacodynamic effects of warfarin and the safety and tolerability of the investigational drugs were assessed. The geometric mean ratio (GMR) and 90%confidence interval (90% CI) for Cmax and AUCs of R- and S-warfarin, digoxin, and pharmacologically active LCZ696 analytes were within the bioequivalence range of 0.8-1.25 when co-administered. The GMR and 90% CI of warfarin pharmacodynamics effects were also within 0.8-1.25 range when co-administered with LCZ696. LCZ696 was generally safe and welltolerated when administered alone or in combination with digoxin/warfarin. No drug-drug interaction was observed upon co-administration of LCZ696 with digoxin/warfarin in healthy subjects.
