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Assessment of Drug Interaction Potential between LCZ696, an Angiotensin Receptor Neprilysin Inhibitor, and Digoxin or Warfa rin | OMICS International | Abstract
ISSN: 2167-065X

Clinical Pharmacology & Biopharmaceutics
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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: [email protected]
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.

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