High Blood Pressure / Hypertension

Perindopril

By Cardiologist on September 10th, 2010

(British Approved Name, US Adopted Name, rINN)

Drug Nomenclature

Perindopril Erbumine

(British Approved Name Modified, US Adopted Name, rINNM)

Drug Nomenclature

Pharmacopoeias. In Europe.

European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Perindopril tert-Butylamine; Perindopnl Erbumine British Pharmacopoeia, 2008:). A white or almost white, slightly hygroscopic, crystalline powder. It exhibits polymorphism. Freely soluble in water and in alcohol; soluble or sparingly soluble in dichloromethane. Store in airtight containers.

Adverse Effects, Treatment, and Precautions

As for ACE inhibitors.

In a postmarketing surveillance study of 47 351 patients receiving perindopril for hypertension, no unexpected adverse effects were reported and serious reactions were rare; 1587 (6.3%) women and 782 (3.5%) men withdrew from therapy due to adverse effects.

Although a study of perindopril use in patients with stable chronic heart failure reported no significant first-dose hypotension, there has been a case report of ischaemic stroke, possibly associated with hypotension, after a single dose of perindopril in a patient with post-infarction heart failure. Standard precautions as for other ACE inhibitors should be followed when starting perindopril therapy.

Interactions

As for ACE inhibitors.

Pharmacokinetics

Perindopril acts as a prodrug of the diacid perindoprilat, its active form. After oral doses perindopril is rapidly absorbed with a bioavailability of about 65 to 75%. It is extensively metabolised, mainly in the liver, to perindoprilat and inactive metabolites including glucuronides. The presence of food is reported to reduce the conversion of perindopril to perindoprilat. Peak plasma concentrations of perindoprilat are achieved 3 to 4 hours after an oral dose of perindopril. Perindoprilat is about 10 to 20% bound to plasma proteins. Perindopril is excreted predominantly in the urine, as unchanged drug, as perindoprilat, and as other metabolites. The elimination of perindoprilat is biphasic with a distribution half-life of about 5 hours and an elimination half-life of 25 to 30 hours or longer, the latter half-life probably representing strong binding to angiotensin-converting enzyme. The excretion of perindoprilat is decreased in renal impairment. Both perindopril and perindoprilat are removed by dialysis.

Uses and Administration

Perindopril is an ACE inhibitor. It is used in the treatment of hypertension and heart failure. It is also used to reduce the risk of cardiovascular events in patients with stable ischaemic heart disease (see Cardiovascular Risk Reduction). Perindopril is converted in the body into its active metabolite perindoprilat. ACE inhibition is reported to occur within 1 hour of a dose, to be at a maximum at about 4 to 8 hours, and to be maintained for 24 hours. Perindopril is given orally as the erbumine salt and should be taken before food. In some countries perindopril is also available as the arginine salt; 5 mg of perindopril arginine is equivalent to about 4 mg of perindopril erbumine.

In the treatment of hypertension perindopril is given in an initial dose of 4 mg of the erbumine or 5 mg of the arginine salt once daily. Since there may be a precipitous fall in blood pressure in some patients when starting therapy with an ACE inhibitor, the first dose should preferably be given at bedtime. Hypotension is particularly likely in patients with renovascular hypertension, volume depletion, heart failure, or severe hypertension and in such patients the initial dose may be halved to 2 or 2.5 mg respectively once daily. Patients taking diuretics should have the diuretic withdrawn 2 or 3 days before perindopril is started and resumed later if required; if this is not possible, the initial dose may be halved similarly. The same lower initial dose may also be used in the elderly. The dose of perindopril may be increased according to response to a maximum of 8 mg of the erbumine or 10 mg of the arginine salt daily. In the United States of America (USA) a maximum dose of 16 mg of perindopril erbumine daily is allowed in uncomplicated hypertension.

In the management of heart failure, severe first-dose hypotension on introduction of an ACE inhibitor is common in patients on loop diuretics, but their temporary withdrawal may cause rebound pulmonary oedema. Thus treatment should be initiated with a low dose under close medical supervision. Perindopril is given in an initial dose of 2 mg of the erbumine or 2.5 mg of the arginine salt in the morning. The usual maintenance dose is 4 mg or 5 mg respectively daily. In the management of patients with ischaemic heart disease perindopril is given in an initial dose of 4 mg (erbumine) or 5 mg (arginine) once daily for 2 weeks, then titrated up to a maintenance dose of 8 or 10 mg respectively once daily if tolerated. Elderly patients should be started on 2 or 2.5 mg once daily for the first week.

Dosage should be reduced in patients with impaired renal function (see below).

Administration in renal impairment. The dose of perindopril should be reduced in patients with renal impairment. UK licensed product information recommends the following doses:

• creatinine clearance (CC) between 30 and 60 mL/minute: 2 mg of the erbumine or 2.5 mg of the arginine salt daily

• CC between 15 and 30 mL/minute: 2 mg (erbumine) or 2.5 mg (arginine) on alternate days

• CC less than 15 mL/minute: 2 mg (erbumine) or 2.5 mg (arginine) on dialysis days.

Preparations

Proprietary Preparations

Argentina: Coverene;

Australia: Coversyl; Perindo;

Austria: Coversum;

Belgium: Coversyl;

Brazil: Coversyl;

Canada: Coversyl;

Chile: Coversyl;

Czech Republic: Apo-Perindo; Cordesyl; Covedaspen; Covemarin; Covemedal; Covepet; Coverdosyn; Coverdyne; Coverex; Coversidin; Coversyspes; Covethanar; Prenessa; Prestarium; Prestarium Neo; Prexanil; Pricoron;

Denmark: Coversyl;

Finland: Coversyl;

France: Coversyl;

Germany: Coversum;

Greece: Coversyl;

Hong Kong: Acertil;

Hungary: Armix; Coverex; Perindan; Prenessa;

India: Coversyl; Perigard

Indonesia: Prexum;

Ireland: Coversyl;

Italy: Coversyl; Procaptan;

Japan: Coversyl;

Malaysia: Covapril; Coversyl; Perinace;

Mexico: Coversyl;

The Netherlands: Coverex; Coversyl;

New Zealand: Coversyl;

Philippines: Coversyl;

Poland: Coverex; Irpax; Prenessa; Prestarium;

Portugal: Coversyl; Ostion; Prexum;

Russia: Prestarium;

South Africa: Coversyl; Prexum;

Singapore: Coversyl;

Spain: Coversyl;

Switzerland: Coversum;

Thailand: Coversyl;

Turkey: Coversyl;

United Kingdom (UK): Coversyl;

United States of America (US and USA): Aceon;

Venezuela: Coversyl.

Multi-ingredient

Argentina: Bipreterax; Preterax;

Australia: Coversyl Plus;

Austria: Predonium; Preterax;

Belgium: Bi Preterax; Coversyl Plus; Preterax;

Brazil: Coversyl Plus;

Canada: Coversyl Plus; Preterax;

Czech Republic: Noliprel Prenewel; Prestarium Combi; Prestarium Neo Combi;

Denmark: Coversyl Comp;

Finland: Coversyl Comp;

France: Bipreterax; Preterax;

Germany: Coversum Combi; Preterax;

Greece: Preterax;

Hong Kong: Predonium;

Hungary: Armix Komb; Armix Prekomb; Co-Prenessa; Coverex Komb; Coverex Prekomb; Noliprel †; Noriplex †;

India: Coversyl Plus; Perigard D; Perigard DF;

Ireland: Bipreterax; Coversyl Plus; Preterax;

Italy: Prelectal; Preterax;

Malaysia: Coversyl Plus;

Mexico: Preterax;

The Netherlands: Coversyl Plus; Predonium; Preterax;

New Zealand: Coversyl Plus; Predonium;

Philippines: Bi-Preterax; Preterax;

Poland: Noliprel; Prestarium Plus;

Portugal: Bi Predonium; Bi Preterax; Predonium; Preterax;

Russia: Noliprel;

South Africa: Bipreterax; Coversyl Plus; Preterax; Prexum Plus;

Singapore: Coversyl Plus; Preterax;

Spain: Bipredonium †; Bipreterax; Preterax;

Switzerland: Coversum Combi; Preterax;

Turkey: Coversyl Plus; Preterax;

United Kingdom (UK): Coversyl Plus;

Venezuela: Bipreterax; Preterax.

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