Perindopril

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Perindopril on Prescriptsy

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Perindopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat hypertension (high blood pressure), stable coronary artery disease, and symptomatic heart failure.

It is one of the most widely prescribed ACE inhibitors in the United Kingdom and is available as tablets in two salt forms: perindopril erbumine (tert-butylamine salt) in strengths of 2 mg, 4 mg, and 8 mg, and perindopril arginine in strengths of 2.5 mg, 5 mg, and 10 mg.

Perindopril is a prescription-only medicine (POM).

This page provides a detailed clinical guide to perindopril, including how it works, dosage instructions, side effects, safety warnings, and how to obtain it in the United Kingdom.

Important safety information about perindopril

Before reading further, please note these essential safety points.

• Perindopril is contraindicated in pregnancy. Women of childbearing potential must use effective contraception.
• Stop perindopril and call 999 immediately if you develop swelling of the face, lips, tongue, or throat (angioedema).
• Kidney function and potassium levels must be checked before starting and monitored during treatment.
• Do not take perindopril with potassium supplements or potassium-sparing diuretics without medical supervision.
• Do not combine perindopril with sacubitril/valsartan (Entresto) without a 36-hour washout period.

Understanding high blood pressure and cardiovascular risk

Hypertension is one of the most significant modifiable risk factors for cardiovascular disease, stroke, heart failure, chronic kidney disease, and vascular dementia.

In the UK, approximately one in three adults has high blood pressure, though many are undiagnosed because the condition is usually asymptomatic.

The NHS Health Check programme aims to identify undiagnosed hypertension in adults aged 40 to 74.

NICE guideline NG136 (Hypertension in adults, 2019) defines hypertension as a clinic blood pressure consistently at or above 140/90 mmHg, confirmed by ambulatory or home monitoring.

Untreated hypertension causes progressive damage to the arteries, heart, brain, kidneys, and eyes.

Lowering blood pressure with medication significantly reduces the risk of stroke by approximately 30% to 40% and the risk of heart attack by approximately 20% to 25%.

ACE inhibitors are recommended as first-line treatment for hypertension in patients under 55 years of age, and in patients of any age with type 2 diabetes, chronic kidney disease with proteinuria, or heart failure.

For patients aged 55 and over without diabetes or CKD, a calcium channel blocker (such as amlodipine) is usually recommended first.

How perindopril works

The renin-angiotensin-aldosterone system (RAAS) is a hormonal cascade that plays a central role in regulating blood pressure, fluid balance, and electrolyte homeostasis.

When blood pressure or blood volume falls, the kidneys release renin, which converts angiotensinogen (produced by the liver) to angiotensin I.

Angiotensin-converting enzyme (ACE), found predominantly in the lungs, then converts angiotensin I to angiotensin II, a powerful vasoconstrictor.

Angiotensin II also stimulates the release of aldosterone from the adrenal glands, promoting sodium and water retention, and stimulates thirst and vasopressin release.

Perindopril is a prodrug that is converted in the liver to its active metabolite, perindoprilat. Perindoprilat competitively inhibits ACE, blocking the conversion of angiotensin I to angiotensin II.

This results in vasodilation, reduced aldosterone secretion, and a net decrease in blood pressure. ACE is also the enzyme responsible for breaking down bradykinin, a vasodilatory peptide.

By inhibiting ACE, perindopril increases bradykinin levels, which contributes to its blood-pressure-lowering and cardioprotective effects but is also responsible for the characteristic ACE inhibitor cough.

Perindopril has a long duration of action, allowing once-daily dosing.

Peak plasma concentrations of the active metabolite perindoprilat are reached at 3 to 4 hours after oral administration, with a terminal elimination half-life of approximately 17 hours.

This provides consistent 24-hour blood pressure control when taken regularly.

Clinical evidence for perindopril

Perindopril has an extensive evidence base from several landmark clinical trials.

The EUROPA trial (European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease, 2003) enrolled over 12,000 patients with stable coronary artery disease and demonstrated that perindopril 8 mg daily reduced the combined endpoint of cardiovascular death, myocardial infarction, or cardiac arrest by 20% compared with placebo.

This trial led to the licensing of perindopril for stable coronary artery disease.

The PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study, 2001) showed that a regimen of perindopril plus indapamide reduced the risk of recurrent stroke by 43% in patients with a history of stroke or transient ischaemic attack.

The ADVANCE trial demonstrated cardiovascular and renal benefits of perindopril plus indapamide in patients with type 2 diabetes.

The HYVET trial showed that treatment with indapamide with or without perindopril reduced stroke and mortality in patients aged 80 and over with hypertension.

These trials have established perindopril as a well-evidenced ACE inhibitor with proven benefits across multiple cardiovascular conditions, including hypertension, stable coronary disease, post-stroke secondary prevention, and diabetes-related cardiovascular risk reduction.

Perindopril compared with other ACE inhibitors

Several ACE inhibitors are available in the UK, including ramipril, lisinopril, enalapril, and captopril.

All ACE inhibitors share the same mechanism of action, and there is no strong evidence that one is clinically superior to another at equivalent doses.

However, they differ in their pharmacokinetic profiles, dosing frequency, and evidence base for specific indications. Ramipril has strong evidence from the HOPE trial in high-risk cardiovascular patients.

Lisinopril has the advantage of not being a prodrug (it does not require hepatic activation).

Enalapril was the first ACE inhibitor shown to reduce mortality in heart failure (CONSENSUS and SOLVD trials).

Perindopril's key distinguishing feature is its EUROPA trial evidence for stable coronary artery disease.

The choice between ACE inhibitors is often guided by the prescriber's familiarity, the patient's tolerability, the specific clinical indication, and cost. Generic perindopril is widely available in the UK and is cost-effective.

Dosage and administration

For hypertension, the usual starting dose of perindopril erbumine is 4 mg once daily (or 5 mg arginine once daily), taken in the morning.

The dose may be increased after 4 weeks to 8 mg erbumine (10 mg arginine) once daily if blood pressure control is insufficient.

In elderly patients, those with renal impairment, or those with heart failure, a lower starting dose of 2 mg erbumine (2.5 mg arginine) once daily is recommended.

For stable coronary artery disease, the target dose is 8 mg erbumine (10 mg arginine) once daily, reached after an initial two-week period at 4 mg erbumine (5 mg arginine).

For heart failure, perindopril is started at 2 mg erbumine (2.5 mg arginine) once daily and titrated upward gradually.

NICE guideline NG106 recommends titrating ACE inhibitors to the maximum tolerated dose, as higher doses provide greater prognostic benefit.

Uptitration should occur at intervals of at least 2 weeks, with monitoring of blood pressure, renal function, and potassium at each step.

Perindopril erbumine should be taken in the morning before food, as food may reduce absorption of this salt form. Perindopril arginine can be taken with or without food.

Swallow the tablet whole with water. Consistency in timing helps maintain steady blood pressure control throughout the day.

If you miss a dose, take it as soon as you remember. If it is nearly time for your next dose, skip the missed one and continue as usual. Do not double up.

Side effects of perindopril

Common side effects

Persistent dry cough is the most characteristic side effect of ACE inhibitors and affects approximately 5% to 15% of patients.

The cough is typically dry, tickling, and worse at night or when lying down. It is caused by increased bradykinin levels in the lungs.

The cough usually develops within the first few months of treatment and resolves within 1 to 4 weeks of stopping the drug.

If the cough is intolerable, switching to an ARB (such as losartan, candesartan, or valsartan) is recommended, as ARBs do not affect bradykinin metabolism.

Other common side effects include dizziness (especially on standing), headache, fatigue, and gastrointestinal symptoms (nausea, diarrhoea, abdominal pain). Taste disturbance (a metallic or altered taste) may occur. These side effects are usually mild and often improve with continued use.

Hyperkalaemia and renal effects

Raised potassium levels (hyperkalaemia) are a risk with all ACE inhibitors, particularly in patients with renal impairment, diabetes, or concurrent use of potassium-sparing diuretics, potassium supplements, trimethoprim, or NSAIDs.

Potassium levels above 5.5 mmol/L require dose reduction or discontinuation. ACE inhibitors can also cause a rise in serum creatinine.

A small rise (up to 30% above baseline) is acceptable and expected, but a greater rise should prompt investigation for renal artery stenosis, volume depletion, or other causes.

Angioedema

Angioedema is a rare but potentially life-threatening side effect of ACE inhibitors, occurring in approximately 0.1% to 0.7% of patients.

It presents as sudden swelling of the face, lips, tongue, pharynx, or larynx and can cause airway obstruction.

Angioedema is more common in patients of African or Caribbean descent. If angioedema occurs, stop perindopril immediately, call 999, and do not rechallenge with any ACE inhibitor.

An ARB may be cautiously considered as an alternative, although a small cross-reactivity risk exists.

First-dose hypotension

A significant drop in blood pressure may occur after the first dose, particularly in patients who are volume-depleted (those taking high-dose diuretics, on a low-sodium diet, or with dehydration), those with heart failure, or elderly patients.

Consider reducing or temporarily stopping diuretics for 24 to 48 hours before starting perindopril.

The first dose can be taken at bedtime to reduce the impact of any hypotensive episode.

When to seek medical advice

Stop perindopril and call 999 if you develop swelling of the face, lips, tongue, or throat (angioedema), severe dizziness or fainting, or chest pain.

Contact your GP or call NHS 111 for persistent cough, skin rash, unexplained bruising, signs of infection (sore throat, fever), or symptoms suggestive of high potassium (muscle weakness, palpitations).

Report suspected adverse reactions to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk .

Warnings and precautions

Contraindications

Perindopril is contraindicated in patients with a history of angioedema related to any ACE inhibitor, hereditary or idiopathic angioedema, bilateral renal artery stenosis, pregnancy, and hypersensitivity to any ACE inhibitor.

It must not be combined with sacubitril/valsartan without a 36-hour washout period.

Pregnancy and breastfeeding

All ACE inhibitors are contraindicated throughout pregnancy. Use during the second and third trimesters can cause fetal renal failure, oligohydramnios, neonatal hypotension, and skull defects.

First-trimester exposure is associated with a possible increased risk of congenital malformations. Women of childbearing potential must use effective contraception.

If pregnancy is detected, stop perindopril immediately and seek specialist advice. NICE NG133 recommends labetalol, nifedipine, or methyldopa for hypertension in pregnancy.

Perindopril is generally not recommended during breastfeeding.

Monitoring

Check renal function (serum creatinine, eGFR) and electrolytes (potassium) before starting perindopril, 1 to 2 weeks after initiation or dose change, and periodically during treatment.

Full blood count may be monitored in patients with collagen vascular diseases (SLE, scleroderma), as ACE inhibitors may rarely cause neutropenia in these patients.

Drug interactions

Key interactions include potassium-sparing diuretics and potassium supplements (risk of hyperkalaemia), NSAIDs (reduced antihypertensive effect, increased renal risk), lithium (increased lithium levels), aliskiren (contraindicated in combination in patients with diabetes or renal impairment), sacubitril/valsartan (risk of angioedema), and co-trimoxazole or trimethoprim (risk of hyperkalaemia).

Discuss all current medicines with your prescriber.

Lifestyle and blood pressure management

Medication is one component of a comprehensive approach to cardiovascular risk reduction.

NICE NG136 recommends lifestyle modifications alongside antihypertensive treatment: reducing salt intake to less than 6 g per day, maintaining a healthy weight, taking regular aerobic exercise (at least 150 minutes per week), limiting alcohol to 14 units or fewer per week, eating a balanced diet rich in fruit, vegetables, whole grains, and oily fish, managing stress, and stopping smoking.

These measures can reduce systolic blood pressure by 5 to 15 mmHg and reduce overall cardiovascular risk.

How to get perindopril in the UK

Perindopril is available on NHS prescription from your GP, cardiologist, or specialist. Generic perindopril tablets are widely available and cost-effective.

The standard NHS prescription charge in England is 9.90 pounds per item; prescriptions are free in Scotland, Wales, and Northern Ireland.

Sources

• Perindopril Erbumine Tablets, Summary of Product Characteristics (EMC)
• Perindopril erbumine, British National Formulary (BNF)
• NICE NG136: Hypertension in adults
• NICE NG106: Chronic heart failure in adults
• High blood pressure (hypertension), NHS
• MHRA Yellow Card Scheme