Perindopril is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

used to treat

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), 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. Long-term high bl ...

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, or stable

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

. As a long-acting

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...

, it works by relaxing

blood vessels The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...

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 per ...

. As a

prodrug A prodrug is a 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 used to improve how the drug ...

, perindopril is hydrolyzed 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 Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

(trade names include Coversyl, Coversum) or perindopril erbumine (Aceon). Both forms are therapeutically equivalent and interchangeable, but the dose prescribed to achieve the same effect differs between the two forms. It is also often combined with another medication, sometimes in the same tablet (see #Combinations below).

Medical uses

Perindopril shares the indications of ACE inhibitors as a class, including essential

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), 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. Long-term high bl ...

, stable

(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 blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

and/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 reva ...

), treatment of symptomatic

, 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 causes 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 kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

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 A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

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. The ...

, 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 heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...

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 high blood pressure and coronary artery disease. It is taken by mouth. Common side effects include swelling, feeling tired, ab ...

and perindopril (trade names Viacoram, AceryCal etc.). The study of more than 19 000 patients world-wide 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 and the outcomes of the ASCOT-BLA trial paved the way for further research into combination therapy and newer agents.

Contraindications

*Children *

Pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

Lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...

*Situations where a patient has a history of hypersensitivity *

Kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

Precautions

*Assess

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

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 arteries supplying the kidneys. When functioning properly this hormonal axis regulates blood pressure. Due to lo ...

*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 is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

. 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 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...

. *Combination with

neuroleptic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...

s or imipramine-type drugs may increase the blood pressure lowering effect. Serum

lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid el ...

concentrations may rise during lithium therapy.

Side effects

Side effects are mild, usually at the start of treatment; they include: *Cough *Fatigue *Weakness/

Asthenia Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

*Headache *Disturbances of mood and/or sleep Less often *Taste impairment *

Epigastric In anatomy, the epigastrium (or epigastric region) is the upper central region of the abdomen. It is located between the costal margins and the subcostal plane. Pain may be referred to the epigastrium from damage to structures derived from the fo ...

discomfort *Nausea *Abdominal pain *Rash Reversible increases in blood

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important r ...

and

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...

may be observed.

Proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...

has occurred in some patients. Rarely, angioneurotic

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

and decreases in

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

, red cells, and

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

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 Perindopril/indapamide (marketed as Preterax, Coversyl Plus and Noliprel) is a combination medication which contains perindopril (an ACE inhibitor) and indapamide (a thiazide-like diuretic) both of which are used for the treatment of essential ...

, containing 4 mg of perindopril combined with 1.25 mg

, 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 metolaz ...

. 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 Perindopril/indapamide (marketed as Preterax, Coversyl Plus and Noliprel) is a combination medication which contains perindopril (an ACE inhibitor) and indapamide (a thiazide-like diuretic) both of which are used for the treatment of essential ...

, 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

, a calcium channel antagonist, has been confirmed in a prospective, observational multicenter trial of 1,250 hypertensive patients.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): 135-4
Link text
/ref> A preparation of the two drugs is available commercially as Coveram.

Society and culture

Trade names

Perindopril is available under the following brand names among others:

Marketing

On 9 July 2014, the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

imposed fines of €427,700,000 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 5 companies which produce generics due to Servier's abuse of their dominant market position, in breach of

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...

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.

References

External links

* {{Commons category-inline ACE inhibitors Carboxamides Enantiopure drugs Ethyl esters Indoles Laboratoires Servier Prodrugs