Enalapril side effects: a detailed patient guide

Enalapril is one of the most widely prescribed ACE inhibitors in the UK. Like all medicines in this class, it has a well-characterised side effect profile.

Very common (more than 1 in 10 people):

• Dizziness: particularly common when treatment is first started or the dose is increased. This is due to the blood pressure lowering effect and usually improves within the first few days
• Blurred vision: related to blood pressure changes, typically transient

Common (1 in 10 to 1 in 100 people):

• Dry cough: the hallmark side effect of ACE inhibitors. It is caused by accumulation of bradykinin in the lungs. The cough is typically dry, tickly and persistent, often worse at night
• Headache: usually mild and self-limiting
• Fatigue and asthenia: feeling tired or weak, particularly during the initial weeks
• Nausea: may be reduced by taking enalapril with food
• Diarrhoea: usually mild
• Hypotension: low blood pressure, especially with the first dose or in volume-depleted patients
• Rash: mild skin rashes occur in some patients

The BNF notes that most ACE inhibitor side effects are dose-related and often improve with continued use or dose adjustment.

If side effects are troublesome, speak to your prescriber before making any changes to your medication.

The dry cough associated with enalapril and other ACE inhibitors deserves special attention, as it is the most common reason patients switch to an alternative medicine.

Why does enalapril cause a cough?

ACE (angiotensin-converting enzyme) is involved in the breakdown of bradykinin, a peptide that causes blood vessel dilation and can irritate the airways. When ACE is inhibited by enalapril:

• Bradykinin accumulates in the lungs
• Substance P levels increase
• Prostaglandin production is enhanced
• Together, these cause irritation of the airway sensory nerves, triggering a dry cough

Key facts about the ACE inhibitor cough:

• Affects approximately 10 to 15% of patients
• More common in women than men
• More common in people of African or Caribbean heritage
• Usually develops within 1 to 6 months of starting treatment, though it can appear at any time
• The cough is characteristically dry, tickly, non-productive and often worse at night or when lying down
• It resolves within 1 to 4 weeks of stopping the medicine

Management options:

• If the cough is mild and the blood pressure benefit is significant, some patients choose to continue
• If the cough is troublesome, the usual approach is to switch to an angiotensin receptor blocker (ARB) such as losartan or candesartan, which provides similar cardiovascular benefits without causing cough
• Over-the-counter cough remedies are generally not effective for ACE inhibitor cough

Although rare, some side effects of enalapril are serious and require immediate medical attention.

Angioedema:

This is the most dangerous side effect of ACE inhibitors. It involves rapid swelling of the face, lips, tongue, throat or intestines. Symptoms can include:

• Swelling of the face and lips
• Difficulty breathing or swallowing
• Abdominal pain (intestinal angioedema)

Angioedema occurs in approximately 0.1 to 0.7% of patients and is more common in people of African or Caribbean heritage.

It can occur at any point during treatment, even after years of stable use. Call 999 immediately if you experience swelling of the face or throat.

Hyperkalaemia (high potassium):

Enalapril reduces aldosterone secretion, which can lead to potassium retention. High potassium levels can cause:

• Muscle weakness
• Irregular heartbeat
• Fatigue

Risk is increased in patients with kidney disease, diabetes, or those taking potassium supplements or potassium-sparing diuretics. Regular blood tests are essential.

Renal impairment:

Enalapril can worsen kidney function, particularly in patients with bilateral renal artery stenosis or pre-existing kidney disease.

The BNF recommends checking kidney function (including eGFR and potassium) before starting, 1 to 2 weeks after, and at each dose change.

Neutropenia and agranulocytosis:

Very rarely, enalapril can suppress white blood cell production. Report unexplained infections, fever or sore throat.

A significant drop in blood pressure after the first dose of enalapril (first-dose hypotension) is a well-known effect that can cause dizziness, lightheadedness or fainting.

Who is most at risk:

• Patients taking diuretics (especially high-dose loop diuretics)
• Those who are dehydrated or volume-depleted
• Patients with heart failure (where the renin-angiotensin system is highly activated)
• Elderly patients
• Those on a low-sodium diet

How to minimise the risk:

• Start with a low dose: the BNF recommends an initial dose of 5 mg daily (or 2.5 mg in heart failure or if on diuretics)
• Take the first dose at bedtime: lying down reduces the impact of any blood pressure drop
• Withhold or reduce diuretics for 24 to 48 hours before starting enalapril, if clinically appropriate
• Stay hydrated: ensure adequate fluid intake in the days before starting
• Rise slowly from sitting or lying positions, especially during the first few days

After the first few doses:

First-dose hypotension typically settles within a few days as the body adjusts. If dizziness persists beyond the first week, the dose may need adjustment.

Regular blood pressure monitoring, both sitting and standing, is advisable during the titration phase.

Regular monitoring is an important part of safe enalapril treatment. The BNF and NICE guidelines set out what should be checked and when.

Recommended monitoring:

• Blood pressure: at every review, including lying and standing measurements to check for postural hypotension
• Renal function (eGFR, creatinine): before starting, 1 to 2 weeks after starting or after each dose increase, then annually
• Electrolytes (especially potassium): at the same intervals as renal function
• Full blood count: if the patient develops signs of infection or illness

What to do about common side effects:

• Dry cough: if troublesome, discuss switching to an ARB with your GP
• Dizziness: often settles. Ensure adequate fluid intake and rise slowly from sitting
• Fatigue: may improve with time. If persistent, review the dose
• Nausea: take enalapril with food

Lifestyle measures that complement enalapril:

• Maintain a healthy diet low in salt
• Regular physical activity (aim for 150 minutes per week)
• Achieve and maintain a healthy weight
• Limit alcohol intake
• Stop smoking if applicable

When to contact your GP or NHS 111:

• Persistent dizziness or fainting
• New or worsening cough
• Signs of angioedema (facial or throat swelling)
• Signs of infection (fever, sore throat)
• Muscle weakness or palpitations (possible hyperkalaemia)