Perindopril is a
medication
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
used to treat
high blood pressure
Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...
,
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood.
Although symptoms vary based on which side of the heart is affected, HF ...
, or stable
coronary artery disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
.
As a long-acting
ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...
, perindopril works by inhibiting production of the
vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...
hormone
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
,
angiotensin
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...
, thereby relaxing
blood vessels
Blood vessels are the tubular structures of a circulatory system that transport blood throughout many animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste an ...
, increasing
urine
Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
output, and decreasing
blood volume
Blood volume (volemia) is the volume of blood ( blood cells and plasma) in the circulatory system of any individual.
Humans
A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood p ...
, leading to a reduction of blood pressure. It also increases blood
renin
Renin ( etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin-angiotensin-aldosterone system (RAAS)—also known as the reni ...
activity and decreases
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...
secretion, causing
increased urine production and
excretion of sodium.
[
As a ]prodrug
A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...
, perindopril is hydrolyzed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysi ...
in the liver to its active metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
, perindoprilat. It was patented in 1980 and approved for medical use in 1988.
Perindopril is taken in the form of perindopril arginine/amlodipine or perindopril erbumine.[ Both forms are therapeutically equivalent and interchangeable,][ but the dose prescribed to achieve the same effect may differ between the two forms.][
Perindopril should not be used during pregnancy, as it may harm the fetus.][ Some people may have ]allergic reaction
Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...
s to perindopril, while common side-effects may include cough,
headache, dizziness, diarrhea
Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
, or upset stomach.[
In Australia during 2023-24, it was the fourth-most prescribed drug.]
Medical uses
Perindopril shares the indications of ACE inhibitors as a class, including essential hypertension
Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
, stable coronary artery disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
(reduction of risk of cardiac events in patients with a history of myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
or revascularization
In medical and surgical therapy, revascularization is the restoration of perfusion to a body part or organ that has had ischemia. It is typically accomplished by surgical means. Vascular bypass and angioplasty are the two primary means of r ...
), treatment of symptomatic coronary artery disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
or heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood.
Although symptoms vary based on which side of the heart is affected, HF ...
, and diabetic nephropathy
Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading cause of chronic kidney disease (CKD) and end-stage renal disease ...
.
Combination therapy
With indapamide
In combination with indapamide
Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril (an ACE inhibitor antihypertensive) are available. The thiazide-like diuretics ...
, perindopril has been shown to significantly reduce the progression of chronic kidney disease
Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...
and renal complications in patients with type 2 diabetes. In addition, the Perindopril pROtection aGainst REcurrent Stroke Study (''PROGRESS'') found that whilst perindopril monotherapy demonstrated no significant benefit in reducing recurrent strokes when compared to placebo, the addition of low dose indapamide to perindopril therapy was associated with larger reductions in both blood pressure lowering and recurrent stroke risk in patients with pre-existing cerebrovascular disease
Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. Th ...
, irrespective of their blood pressure. There is evidence to support the use of perindopril and indapamide combination over perindopril monotherapy to prevent strokes and improve mortality in patients with a history of stroke, transient ischaemic attack or other cardiovascular disease.
With amlodipine
The Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (''ASCOT-BLA'') was a 2005 landmark trial that compared the effects of the established therapy of the combination of atenolol
Atenolol is a beta blocker medication primarily used to treat high blood pressure and angina, heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality rate, mortality in those with the condi ...
and bendroflumethiazide
Bendroflumethiazide, formerly bendrofluazide, trade name Aprinox, is a thiazide diuretic used to treat hypertension.
Bendroflumethiazide is a thiazide diuretic which works by inhibiting sodium reabsorption at the beginning of the distal convolut ...
to the new drug combination of amlodipine
Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat hypertension, high blood pressure, coronary artery disease (CAD) and variant angina (also called Prinzmetal angina or coronary ar ...
and perindopril (trade names ''Viacoram'', ''AceryCal''). The study of more than 19,000 patients worldwide was terminated earlier than anticipated because it clearly demonstrated a statistically significant improvement in mortality and cardiovascular outcomes with the newer treatment. The combination of amlodipine and perindopril remains in the current treatment guidelines for hypertension.[
]
Warning and adverse effects
Perindopril may cause death or birth defect
A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth de ...
s of a fetus if taken by the mother during pregnancy.[ It is poisonous in children and is not prescribed for them.][
It may cause allergic reactions, and may have ]adverse effect
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...
s in people with heart, liver or kidney problems.[
]
Precautions
*Assess kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
function before and during treatment where appropriate.[
*]Renovascular hypertension
Renovascular hypertension is a condition in which high blood pressure is caused by the kidneys' hormonal response to narrowing of the renal arteries, arteries supplying the kidneys. When functioning properly this hormonal axis regulates blood pres ...
*Surgery/anesthesia
*An analysis on the PROGRESS trial showed that perindopril has key benefits in reducing cardiovascular events by 30% in patients with chronic kidney disease defined as a CrCl <60ml/min. A 2016 and 2017 meta-analysis review looking at ACE inhibitors demonstrated a reduction in cardiovascular events but also slowed the decline of renal failure by 39% when compared to placebo. These studies included patients with moderate to severe kidney disease and those on dialysis.
*Its renoprotective benefits of decreasing blood pressure and removing filtration pressure is highlighted in a 2016 review. ACE inhibitor can result in an initial increase of serum creatinine, but mostly returns to baseline in a few weeks in majority of patients. It has been suggested that increased monitoring, especially in advanced kidney failure, will minimise any related risk and improve long-term benefits.
*Use cautiously in patients with sodium or volume depletion due to potential excessive hypotensive effects of renin-angiotensin blockade causing symptomatic hypotension
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
. Careful monitoring or short-term dose reduction of diuretics prior to commencing perindopril is recommended to prevent this potential effect. A diuretic may later be given in combination if necessary; potassium-sparing diuretics are not recommended in combination with perindopril due to the risk of hyperkalaemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occ ...
.
*Combination with neuroleptic
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizoph ...
s or imipramine-type drugs may increase the blood pressure lowering effect. Serum lithium
Lithium (from , , ) is a chemical element; it has chemical symbol, symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard temperature and pressure, standard conditions, it is the least dense metal and the ...
concentrations may rise during lithium therapy.
Side effects
Usually mild at the start of treatment, side effects may include cough, fatigue, headache, nausea, or upset stomach, among other minor effects.[
]
Composition
Each tablet contains 2, 4, or 8 mg of the tert-butylamine salt of perindopril.[ Perindopril is also available under the ]trade name
A trade name, trading name, or business name is a pseudonym used by companies that do not operate under their registered company name. The term for this type of alternative name is fictitious business name. Registering the fictitious name with ...
'' Coversyl Plus'', containing 4 mg of perindopril combined with 1.25 mg indapamide
Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril (an ACE inhibitor antihypertensive) are available. The thiazide-like diuretics ...
, a thiazide-like diuretic
A thiazide-like diuretic is a sulfonamide diuretic that has similar physiological properties to a thiazide diuretic, but does not have the chemical properties of a thiazide, lacking the benzothiadiazine molecular structure. Examples include metola ...
.[
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
Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat hypertension, high blood pressure, coronary artery disease (CAD) and variant angina (also called Prinzmetal angina or coronary ar ...
, a calcium channel antagonist, is used.[
]
Society and culture
Brand names
Perindopril is available under the following brand names among others:[
]
Marketing
In July 2014, the European Commission
The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...
imposed fines of on Laboratoires Servier
Servier Laboratories (French: Laboratoires Servier, often abbreviated to Servier) is an international pharmaceutical company governed by a non-profit foundation, with its headquarters in France (Suresnes).
The consolidated turnover for the 2018 ...
and five companies which produce generics due to Servier's abuse of their dominant market position, in breach of European Union Competition law. Servier's strategy included acquiring the principal source of generic production of perindopril and entering into several pay-for-delay agreements with potential generic competitors.
References
Further reading
*
*
*
*
External links
{{Angiotensin receptor modulators
ACE inhibitors
Alpha-Amino acids
Carboxamides
Enantiopure drugs
Ethyl esters
Indoles
Laboratoires Servier
Prodrugs
Propyl compounds
Secondary amino acids