Perindopril arginine and amlodipine besylate for hypertension: a safety evaluation

ABSTRACT

Introduction: Controlling blood pressure is a global health priority; single-pill antihypertensive combinations may improve adherence, persistence, and outcomes.

Areas covered: A novel combination of perindopril arginine and amlodipine besylate was recently approved. A systematic review of the literature revealed its most common adverse effects as: peripheral edema (depending on the dose of amlodipine, but attenuated by perindopril), cough, dizziness and hypotension. Dose-dependent hyperkalemia, impairment of renal function (especially in renovascular hypertension), angioedema, and teratogenicity were derived from experience with other ACE-inhibitors.

Expert opinion: Substantial clinical trial experience with amlodipine or perindopril suggests that these two agents effectively lower blood pressure, and can reduce the risk of major adverse cardiovascular events, as in the Anglo-Scandinavian Cardiac Outcomes Trial. The incidence of adverse effects reported in clinical trials is lower than expected, likely due to exclusion of subjects previously exposed to its components; the nature of open-label, uncontrolled observational studies; and difficulty in recognizing and measuring cough and pedal edema. This new formulation of perindopril arginine protects its ethyl ester, without requiring physical separation from amlodipine in a single tablet, and is less hygroscopic than perindopril erbumine. These and other attributes may make this combination an attractive addition to the antihypertensive armamentarium.

KEYWORDS:

• Angiotensin converting-enzyme inhibitor
• calcium antagonist
• clinical trials

Box 1. Drug summary box.

Declaration of interest

WJ Elliott has received research support or grants from Pharmaceutical Manufacturers’ Association Foundation, Smith, Kline & French Laboratories, Hoechst Marion Roussel, Inc, Glaxo Inc, SmithKline Beecham Inc G. D. Searle & Co, Boehringer-Ingleheim, National Institutes of Health, American Heart Association—Chicago, Abbott Laboratories, Pfizer Inc, Bristol-Myers Squibb, Knoll Pharmaceuticals, Merck Human Health, Sankyo Pharmaceuticals, Wyeth-Ayerst, Astra Merck,Novartis Pharmaceuticals Corporation, Omron Healthcare, AstraZeneca, LP, Mylan Laboratories, Forest Research Institute. He has also served as a consultant for Smith, Kline & French Laboratories, National Heart Lung and Blood Institute, G.D. Searle & Co., Curative Technologies, Agency for Health Care Policy & Research, Bristol-Myers Squibb, Pfizer, AstraZeneca, LP, Biovail Pharmaceuticals, Kos Pharmaceuticals, KV Pharmaceutical, Accu-Break Pharmaceuticals, Boehringer-Ingelheim, Takeda Pharmaceuticals, North America. Abbott Laboratories, Astra Merck, Astra Pharmaceuticals, L.P, Astra USA, AstraZeneca L.P, Bayer Pharmaceuticals Co, Biovail Pharmaceuticals, Bristol-Myers Squibb Company, Bristol-Myers Squibb/Sanofi Partnership, Ciba-Geigy, CibaGeneva Pharmaceuticals, Daiichi-Sankyo Pharmaceuticals, E.R. Squibb & Sons, Forest Laboratories, G. D. Searle & Co, Glaxo, Hoechst-Marion-Roussel, ICI Pharma, Key Pharmaceuticals, Knoll Pharmaceuticals, Kos Pharmaceuticals, Marion Merrell-Dow, Merck Human Health, Merck, Sharp & Dohme, Monstanto, Neurex, Novartis Pharmaceuticals Corp, Parke-Davis, Pharmacia, Pfizer, Procter & Gamble, Sandoz, Sankyo Pharmaceuticals, Sanofi-aventis, Schwarz Pharmaceuticals, Syntex, Solvay Pharmaceuticals, Takeda Pharmaceuticals, The Upjohn Company, Unimed Pharmaceuticals, Wyeth-Ayerst and Zeneca. Other Financial or Material Support from Entities not already listed: Lederle Laboratories, Forest Pharmaceuticals, E.R. Lilly, Rhône-Poulenc Rorer, sanofi~synthélabo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper has not been funded.