Perindopril

Perindopril is a long-acting ACE inhibitor used to treat high blood pressure, heart failure, or stable coronary artery disease[1] in form of perindopril arginine (trade names include Coversyl, Coversum) or perindopril erbumine (Aceon). According to the Australian government's Pharmaceutical Benefits Scheme website, based on data provided to the Australian Department of Health and Ageing by the manufacturer, perindopril arginine and perindopril erbumine are therapeutically equivalent and may be interchanged without differences in clinical effect.[2] However, the dose prescribed to achieve the same effect differs due to different molecular weights for the two forms. A prodrug, perindopril is hydrolyzed to its active metabolite, perindoprilat, in the liver.

Perindopril
Clinical data
Trade namesCoversyl, Coversum, Aceon
AHFS/Drugs.comMonograph
Pregnancy
category
  • US: D (Evidence of risk)
    Routes of
    administration    		Oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability24%
    Protein binding20%
    MetabolismRenal
    Elimination half-life1–17 hours for perindoprilat (active metabolite)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.120.843
    Chemical and physical data
    FormulaC19H32N2O5
    Molar mass368.468 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    It was patented in 1980 and approved for medical use in 1988.[3]

    Medical uses

    Perindopril shares the indications of ACE inhibitors as a class, including essential hypertension, stable coronary artery disease (reduction of risk of cardiac events in patients with a history of myocardial infarction and/or revascularization) and treatment of symptomatic heart disease or heart failure. In addition, the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) found that perindopril reduces the risk of stroke in both hypertensive and normotensive individuals with a history of stroke or transient ischemic attack.[4]

    The Anglo-Scandinavian Cardiac Outcomes Trial showed the benefits of taking the two drugs perindopril and amlodipine together. About 9000 British patients aged 40 to 79 were involved in the five-year trial. Half were given the new drug combination; the rest were given traditional drugs. Perindopril and amlodipine were found to be so effective, the trial was stopped early so all patients could receive the combination.[5][6]

    Contraindications
    • Children
    • Pregnancy
    • Lactation
    • Situations where a patient has a history of hypersensitivity
    • Renal failure

    Precautions
    • Assess kidney function before and during treatment where appropriate.
    • Renovascular hypertension
    • Surgery/anesthesia
    • Kidney failure: the dose should be cautiously adjusted in accordance with the creatinine clearance (refer to complete data sheet).
    • Symptomatic low blood pressure is rarely seen, but is more likely in volume-depleted patients, those receiving diuretics, or with the first two doses. In diuretic-treated patients, stop the diuretic three days before starting perindopril. A diuretic may later be given in combination if necessary; potassium-sparing diuretics are not recommended. Combination with neuroleptics or imipramine-type drugs may increase the blood pressure lowering effect. Serum lithium concentrations may rise during lithium therapy.

    Side effects

    Side effects are mild, usually at the start of treatment; they include:

    • Cough
    • Fatigue
    • Weakness/Asthenia
    • Headache
    • Disturbances of mood and/or sleep

    Less often

    • Taste impairment
    • Epigastric discomfort
    • Nausea
    • Abdominal pain
    • Rash

    Reversible increases in blood urea and creatinine may be observed. Proteinuria has occurred in some patients. Rarely, angioneurotic edema and decreases in hemoglobin, red cells, and platelets have been reported.

    Composition

    Each tablet contains 2, 4, or 8 mg of the tert-butylamine salt of perindopril. Perindopril is also available under the trade name Coversyl Plus, containing 4 mg of perindopril combined with 1.25 mg indapamide.

    In Australia, each tablet contains 2.5, 5, or 10 mg of perindopril arginine. Perindopril is also available under the trade name Coversyl Plus, containing 5 mg of perindopril arginine combined with 1.25 mg indapamide and Coversyl Plus LD, containing 2.5 mg of perindopril arginine combined with 0.625 mg indapamide.

    The efficacy and tolerability of a fixed-dose combination of 4 mg perindopril and 5 mg amlodipine, a calcium channel antagonist, has been confirmed in a prospective, observational multicenter trial of 1,250 hypertensive patients.[7] A preparation of the two drugs is available commercially as Coveram.

    Society and culture

    Trade names

    Also, it is available under the brand names:

    • Acertil
    • Actiprex
    • Armix
    • Coverene
    • Coverex
    • Coversum
    • Coversyl
    • Covinace
    • Indapril
    • Perineva
    • Prenessa
    • Prestarium
    • Preterax
    • Prexanil
    • Prexum
    • Procaptan
    • Provinace
    • Pericard
    • Percarnil
    • Perindal
    • Repres

    Marketing

    On 9 July 2014, the European Commission imposed fines of €427,700,000 on Laboratoires Servier and 5 companies which produce generics due to Servier's abuse of their dominant market position, in breach of European Union Competition law. Servier's strategy had included acquiring the principal source of generic production of Perindopril and entering into several pay-for-delay agreements with potential generic competitors.[8]

    References
    1. Royal Australian College of General Practitioners. "Consumer Medicine Information, GenRx Perindopril" (PDF). Clinical Resources, Medicine information for health professionals. Archived from the original (PDF) on 2007-09-01.
    2. Australian Government Department of Health and Ageing (2008). "PBS For Health Professionals". Pharmaceutical Benefits Scheme. Archived from the original on 2008-10-30. Retrieved 2008-09-04.
    3. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 467. ISBN 9783527607495.
    4. PROGRESS Collaborative Group (2001). "Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack". The Lancet. 2001 Sep 29;. 358 (9287): 1033–1041. doi:10.1016/s0140-6736(01)06178-5. PMID 11589932.CS1 maint: extra punctuation (link)
    5. Charlotte Harding (2005). "What you need to know about the new wonder drug cocktail for high blood pressure..." JADN Repository. Retrieved 2007-07-01.
    6. Linda Brookes (2003). "ASCOT: Anglo-Scandinavian Cardiac Outcomes Trial -- Results From The Lipid-Lowering Arm". Medscape Today. Retrieved 2007-07-01.
    7. Bahl VK, Jadhav UM, Thacker HP. Management of Hypertension with the Fixed Combination of Perindopril and Amlodipine in Daily Clinical Practice: Results from the STRONG Prospective, Observational, Multicenter Study. American Journal of Cardiovascular Drugs May 22, 2009; 9 (3): 135-42 Link text
    8. "European Commission - PRESS RELEASES - Press release - Antitrust: Commission fines Servier and five generic companies for curbing entry of cheaper versions of cardiovascular medicine". europa.eu.

    Further reading
    • Bounhoure JP, Bottineau G, Lechat P, et al.. "Value of perindopril in the treatment of chronic congestive heart failure: multicentre double-blind placebo-controlled study." Clin Exp Hypertens. 1989;A11(suppl 2):575-586.
    • Lechat P, Granham SP, Desche P, et al.. "Efficacy and acceptability of perindopril in mild-to-moderate chronic congestive heart failure." Am Heart J. 1993;126:798-806.
    • Morgan T and Anderson A; "Clinical efficacy of perindopril in hypertension." Clin Exp Pharmacol Physiol. 1992;19:61-65.
    • Myers MG; (on behalf of the perindopril multicentre dose-response study group) "A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24h after dosing." Can J Cardiol. 1996;12:1191-1196.
    • "The European trial on reduction of cardiac events with perindopril in stable coronary artery disease investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomized, double-blind, placebo controlled, multicentre trial (the EUROPA study)." The Lancet 2003;362:782-788.
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