Enalapril

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Enalapril on Prescriptsy

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Enalapril is a prescription-only medicine belonging to a class of drugs called angiotensin-converting enzyme (ACE) inhibitors.

It is widely used in the United Kingdom to treat high blood pressure (hypertension), heart failure and diabetic nephropathy (kidney disease caused by diabetes).

Enalapril works by blocking the enzyme responsible for producing angiotensin II, a hormone that causes blood vessels to narrow and promotes salt and water retention.

By inhibiting this process, enalapril relaxes blood vessels, lowers blood pressure and reduces the workload on the heart.

It is available as tablets in strengths of 2.5 mg, 5 mg, 10 mg and 20 mg.

The branded version is Innovace, though generic enalapril is now widely prescribed.

High blood pressure is one of the most common cardiovascular conditions in the UK, affecting approximately one in three adults.

It is a leading risk factor for stroke, heart attack, heart failure and chronic kidney disease.

In most cases, hypertension produces no symptoms, which is why it is often called the "silent killer".

Treatment aims to reduce blood pressure to target levels recommended by NICE (typically below 140/90 mmHg in clinic or below 135/85 mmHg on home monitoring for adults under 80), thereby reducing the long-term risk of cardiovascular events.

This page provides a comprehensive clinical overview of enalapril, including how it works, dosing guidance, expected benefits, potential side effects, important safety warnings and how to obtain a prescription in the United Kingdom.

Important safety information about enalapril

Before reading further, note the following essential safety points about enalapril.

• Enalapril is a prescription-only medicine (POM) and must be used under medical supervision.
• Do not take enalapril if you are pregnant or planning to become pregnant. ACE inhibitors can cause serious harm to the developing baby.
• Seek immediate medical help (call 999) if you develop swelling of the face, lips, tongue or throat (angioedema) while taking enalapril.
• Tell your prescriber about all other medicines you take, especially potassium supplements, potassium-sparing diuretics, NSAIDs or lithium.
• Your kidney function and potassium levels should be checked before and during treatment.

Understanding hypertension and cardiovascular risk

Blood pressure is the force exerted by circulating blood against the walls of the arteries.

It is recorded as two numbers: systolic pressure (when the heart contracts) over diastolic pressure (when the heart relaxes).

Persistent elevation of blood pressure damages the arterial walls, accelerates atherosclerosis and increases the risk of stroke, myocardial infarction, heart failure, peripheral arterial disease and chronic kidney disease.

In the UK, NICE guideline NG136 recommends diagnosing hypertension using ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) to confirm sustained elevation before starting treatment.

Risk factors for hypertension include age, family history, obesity, excessive salt intake, sedentary lifestyle, excessive alcohol consumption, smoking and stress.

While lifestyle modifications (dietary changes, increased physical activity, reducing alcohol and salt intake, weight management) are the foundation of blood pressure management, most patients with established hypertension will require at least one antihypertensive medicine.

NICE recommends ACE inhibitors (such as enalapril) as first-line treatment for hypertension in patients under 55 years who are not of Black African or African-Caribbean origin.

For those over 55, or of Black African or African-Caribbean origin, a calcium channel blocker (such as amlodipine) is preferred first-line, with an ACE inhibitor added at step 2 if blood pressure remains above target.

How enalapril works: mechanism of action

Enalapril maleate is an oral prodrug with limited pharmacological activity. After absorption from the gastrointestinal tract, it is rapidly hydrolysed in the liver to its active metabolite, enalaprilat.

Enalaprilat is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), also known as kininase II.

ACE plays a central role in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure, fluid balance and electrolyte homeostasis.

When the kidneys detect reduced perfusion, they release renin, an enzyme that converts angiotensinogen (produced by the liver) into angiotensin I.

ACE then converts angiotensin I into angiotensin II, the most potent naturally occurring vasoconstrictor.

Angiotensin II also stimulates the adrenal cortex to secrete aldosterone, which promotes sodium and water reabsorption in the kidneys, further increasing blood volume and blood pressure.

By blocking ACE, enalaprilat reduces circulating angiotensin II levels, leading to vasodilation, reduced aldosterone secretion, and decreased sodium and water retention.

The net effect is a lowering of peripheral vascular resistance and blood pressure.

ACE is also responsible for the degradation of bradykinin, a vasodilatory peptide. By inhibiting ACE, enalapril increases bradykinin levels, which contributes to vasodilation and blood pressure reduction.

However, elevated bradykinin is also thought to be responsible for the dry cough and, rarely, angioedema associated with ACE inhibitors.

Clinical evidence and UK prescribing guidance

Enalapril has been available in the UK since the mid-1980s and is one of the most extensively studied ACE inhibitors.

The landmark CONSENSUS trial (1987) demonstrated that enalapril reduced mortality by 40% at 6 months in patients with severe heart failure (NYHA class IV).

The subsequent SOLVD trials confirmed mortality and hospitalisation benefits in patients with mild to moderate heart failure and in those with asymptomatic left ventricular dysfunction.

These studies established ACE inhibitors as a cornerstone of heart failure management.

In hypertension, multiple large randomised trials and meta-analyses have demonstrated that ACE inhibitors reduce the risk of stroke, myocardial infarction, heart failure and cardiovascular death.

NICE guideline NG136 recommends ACE inhibitors as step 1 treatment for most hypertensive patients under 55 (or as step 2 in combination with a calcium channel blocker for patients who did not start on an ACE inhibitor first-line).

For diabetic nephropathy, ACE inhibitors have a specific renoprotective effect beyond their blood-pressure-lowering action.

By reducing intraglomerular pressure and decreasing proteinuria, enalapril slows the progression of diabetic kidney disease.

NICE guideline NG28 recommends offering an ACE inhibitor (or ARB if not tolerated) to all people with diabetes and an albumin-to-creatinine ratio (ACR) of 3 mg/mmol or more, regardless of blood pressure.

The British National Formulary (BNF) lists enalapril for hypertension, symptomatic heart failure and prevention of symptomatic heart failure in patients with asymptomatic left ventricular dysfunction.

It is available as a single-ingredient product and is also found in combination tablets with the diuretic hydrochlorothiazide (branded as Innozide).

Enalapril compared with other ACE inhibitors and ARBs

Several ACE inhibitors are available in the UK, including ramipril, lisinopril, perindopril and captopril. All share the same mechanism of action and produce broadly similar clinical effects.

The choice between them depends on dosing convenience, tolerability, clinical trial evidence for specific conditions, cost and prescriber preference.

Ramipril is the most commonly prescribed ACE inhibitor in the UK, supported by the HOPE trial data in cardiovascular risk reduction.

Enalapril has the strongest evidence base in heart failure (from CONSENSUS and SOLVD) and remains widely used for this indication.

Angiotensin II receptor blockers (ARBs) such as losartan, candesartan and valsartan block the angiotensin II receptor directly rather than inhibiting the enzyme that produces it.

ARBs do not affect bradykinin metabolism and are therefore much less likely to cause cough or angioedema.

They are used as an alternative to ACE inhibitors in patients who develop intolerable cough.

Combining an ACE inhibitor with an ARB (dual RAAS blockade) is generally not recommended due to an increased risk of hypotension, hyperkalaemia and renal impairment without additional cardiovascular benefit.

Dosage and administration

Enalapril is taken by mouth as a tablet, usually once daily (or twice daily in heart failure at higher doses). The tablets should be swallowed whole with water and can be taken with or without food.

Hypertension

The initial dose is 5 mg once daily.

For patients at higher risk of first-dose hypotension (elderly patients, those on diuretics, those with renal impairment or hyponatraemia), the starting dose should be 2.5 mg once daily.

The dose is titrated at intervals of 2 to 4 weeks based on blood pressure response.

The usual maintenance dose is 10 mg to 20 mg once daily, with a maximum of 40 mg per day given in one or two divided doses.

Heart failure

Treatment begins at 2.5 mg once daily under close medical supervision.

The dose is increased gradually, typically doubling every 2 to 4 weeks, to a target of 10 mg to 20 mg twice daily as tolerated.

Blood pressure, renal function and serum potassium must be monitored at each dose increment.

Symptomatic hypotension may occur during titration and is managed by reducing or temporarily stopping concomitant diuretics where possible.

Diabetic nephropathy

The dose range is 10 mg to 20 mg once daily, adjusted according to renal function and blood pressure response. Patients with significant renal impairment require lower starting doses (see the renal impairment guidance in the dosage information above).

Missed doses

If you miss a dose, take it as soon as you remember. If it is almost time for the next dose, skip the missed dose. Do not take a double dose to compensate.

Side effects of enalapril

Common side effects

The most characteristic side effect is a dry, persistent, tickling cough, which affects approximately 5 to 15% of patients.

This is a class effect of all ACE inhibitors and is caused by accumulation of bradykinin in the airways. The cough is not harmful but can be distressing.

It usually resolves within 1 to 4 weeks of stopping enalapril.

Other common side effects include dizziness (particularly after the first dose or dose increases), headache, fatigue, nausea and diarrhoea. Taste disturbance (dysgeusia) has been reported uncommonly.

Hypotension

A drop in blood pressure (hypotension) may occur after the first dose, especially in patients who are volume-depleted, on diuretics, or have heart failure.

Symptoms include lightheadedness, dizziness and, rarely, fainting. This is usually transient and can be minimised by starting at a low dose and taking the first dose at bedtime.

Effects on kidney function and potassium

Enalapril may cause a modest rise in serum creatinine and a reduction in GFR, particularly in patients with pre-existing renal impairment, bilateral renal artery stenosis, or concurrent NSAID use.

A rise in creatinine of up to 30% from baseline is generally acceptable and does not require stopping the drug.

Hyperkalaemia (raised potassium) is more likely in patients with chronic kidney disease, diabetes, or those taking potassium-sparing diuretics or potassium supplements. Regular blood monitoring is essential.

Angioedema

Angioedema is a rare but potentially life-threatening side effect, occurring in approximately 0.1 to 0.5% of patients.

It presents as rapid swelling of the face, lips, tongue, throat or, less commonly, the intestines (causing abdominal pain).

It is more common in Black patients and in those with a previous history of angioedema.

If you develop swelling of the face, lips, tongue or throat, stop enalapril immediately and call 999.

Angioedema can occur at any time during treatment, including after years of uneventful use.

When to seek urgent medical advice

Call 999 or attend A&E if you develop swelling of the face, lips, tongue or throat, difficulty breathing or swallowing, or severe dizziness with collapse.

Contact your GP or NHS 111 for a persistent cough, dizziness, signs of infection (fever, sore throat), unexplained bruising or bleeding, or any symptom that concerns you.

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

Warnings and precautions

Pregnancy and breastfeeding

Enalapril must not be used during pregnancy. ACE inhibitors taken during the second and third trimesters can cause foetal renal failure, oligohydramnios, skull ossification defects, hypotension and death.

First-trimester exposure may also carry risk. If you discover you are pregnant while taking enalapril, stop it immediately and seek urgent medical advice.

Enalapril should not be used while breastfeeding, as small amounts of the active metabolite are excreted in breast milk.

Contraindications

Enalapril is contraindicated in patients with a history of angioedema associated with previous ACE inhibitor therapy, hereditary or idiopathic angioedema, severe bilateral renal artery stenosis, and hypersensitivity to enalapril or any excipient.

It must not be used concurrently with sacubitril/valsartan (Entresto); a washout period of at least 36 hours is required when switching between these medicines.

It must not be combined with aliskiren in patients with diabetes or moderate to severe renal impairment.

Drug interactions

Important interactions include potassium-sparing diuretics and potassium supplements (increased risk of hyperkalaemia), NSAIDs including COX-2 inhibitors (reduced antihypertensive effect and increased renal risk), lithium (increased lithium levels requiring monitoring), other antihypertensives (additive blood pressure lowering), and mTOR inhibitors such as temsirolimus and everolimus (increased risk of angioedema).

Gold injections (sodium aurothiomalate) may rarely cause nitritoid reactions (facial flushing, nausea, hypotension) when used with ACE inhibitors.

Monitoring requirements

Before starting enalapril, your prescriber should check blood pressure, renal function (serum creatinine, eGFR) and serum electrolytes (especially potassium).

These tests should be repeated within 1 to 2 weeks of starting treatment and after each dose increase. Once stable, monitoring at least once a year is recommended.

More frequent monitoring is needed in patients with renal impairment, heart failure, diabetes, or those on concomitant medicines that affect potassium.

How to get enalapril in the UK

Enalapril is a prescription-only medicine.

Your GP can prescribe it following a cardiovascular risk assessment, blood pressure measurement (confirmed by ABPM or HBPM as recommended by NICE), blood tests and review of your medical history.

Authorised online prescribers registered with the General Pharmaceutical Council (GPhC) and Care Quality Commission (CQC) can also prescribe enalapril after a structured clinical consultation.

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

Living with hypertension: practical advice alongside enalapril

Medicines like enalapril are most effective when combined with healthy lifestyle habits.

Reducing dietary salt to less than 6 g per day (approximately one teaspoon), eating a balanced diet rich in fruit, vegetables, whole grains and low-fat dairy (the DASH diet pattern), maintaining a healthy weight, taking regular physical activity (at least 150 minutes of moderate-intensity exercise per week), limiting alcohol to no more than 14 units per week and not smoking all contribute to better blood pressure control and lower cardiovascular risk.

Home blood pressure monitoring can help you and your GP track your response to treatment.

Target readings on home monitoring are typically below 135/85 mmHg for adults under 80.

When to seek medical advice

Contact your GP or NHS 111 if you experience troublesome side effects, a persistent cough, dizziness on standing, or any new or worsening symptoms.

Seek emergency care (call 999 or attend A&E) if you develop swelling of the face, lips, tongue or throat, difficulty breathing, chest pain, sudden weakness on one side of the body (possible stroke), or any symptoms of a severe allergic reaction.

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

Sources

• Enalapril Maleate Tablets, Summary of Product Characteristics (EMC)
• Enalapril maleate, British National Formulary (BNF)
• NICE NG136: Hypertension in adults: diagnosis and management
• NICE NG106: Chronic heart failure in adults: diagnosis and management
• Enalapril, NHS
• MHRA Yellow Card Scheme