Lisinopril

What Is Lisinopril and What Is It Used For?

Lisinopril is an ACE inhibitor (angiotensin-converting enzyme inhibitor) that relaxes and widens blood vessels, lowering blood pressure and reducing the workload on the heart. It is prescribed to treat high blood pressure (hypertension), heart failure, short-term recovery after a heart attack, and kidney disease in patients with type 2 diabetes and hypertension.

Lisinopril belongs to a group of medicines known as ACE inhibitors. It works by blocking the angiotensin-converting enzyme (ACE), which normally converts angiotensin I into angiotensin II – a powerful vasoconstrictor (a substance that narrows blood vessels). By preventing the formation of angiotensin II, lisinopril causes blood vessels to relax and dilate, reducing peripheral vascular resistance and lowering blood pressure. It also decreases the release of aldosterone, a hormone that causes the body to retain sodium and water, further contributing to blood pressure reduction.

In patients with high blood pressure (hypertension), lisinopril reduces the resistance in blood vessels, allowing blood to flow more easily. This reduction in blood pressure decreases the long-term strain on the heart, blood vessels, kidneys, and brain, helping to prevent serious complications including heart attack, stroke, kidney failure, and heart failure. The European Society of Cardiology (ESC), the American Heart Association (AHA), and the National Institute for Health and Care Excellence (NICE) all recommend ACE inhibitors as first-line treatment for hypertension, particularly in younger patients and those with diabetes or chronic kidney disease.

In patients with heart failure, the heart is unable to pump blood efficiently enough to meet the body's needs. Lisinopril reduces the workload on the failing heart by lowering blood pressure and reducing fluid retention. Large clinical trials, including the ATLAS trial, have demonstrated that ACE inhibitors improve symptoms, reduce hospitalisations, and extend survival in patients with heart failure. Lisinopril is typically used in combination with other heart failure medications, including beta-blockers, diuretics, and mineralocorticoid receptor antagonists.

Lisinopril is also used for short-term treatment after a heart attack (myocardial infarction). When started within 24 hours of a heart attack, ACE inhibitors help prevent adverse remodelling of the heart muscle and reduce the risk of subsequent heart failure and death. The landmark GISSI-3 trial demonstrated significant survival benefits with early lisinopril use after acute myocardial infarction.

In patients with type 2 diabetes and hypertension, lisinopril provides an additional benefit of protecting the kidneys. ACE inhibitors reduce pressure within the tiny blood vessels of the kidneys (the glomeruli), slowing the progression of diabetic nephropathy. This makes lisinopril a particularly valuable choice for patients who have both high blood pressure and diabetes, as it treats the blood pressure while simultaneously offering renal protection.

What Should You Know Before Taking Lisinopril?

Before starting lisinopril, inform your doctor about all your medical conditions, especially any history of angioedema, kidney disease, liver disease, diabetes, or if you are pregnant or breastfeeding. Lisinopril is strictly contraindicated in pregnancy and in patients with a history of ACE inhibitor-related angioedema.

Contraindications

You should not take lisinopril if any of the following apply to you:

• Allergy to lisinopril or any other ACE inhibitor – symptoms of allergic reaction may include rash, itching, swelling, or difficulty breathing
• History of angioedema related to previous ACE inhibitor treatment – angioedema is a sudden swelling beneath the skin (similar to hives) that can affect the face, lips, tongue, throat, arms, or legs. This can be life-threatening if the airway is involved
• Hereditary or idiopathic angioedema – if you have a personal or family history of angioedema unrelated to ACE inhibitors, this medicine could trigger an episode
• Pregnancy, especially in the second and third trimesters – ACE inhibitors can cause serious birth defects, kidney damage, low amniotic fluid, and foetal death. Lisinopril should also be avoided in early pregnancy when possible
• Concurrent use with sacubitril/valsartan (Entresto) – this combination significantly increases the risk of angioedema. You must wait at least 36 hours after stopping sacubitril/valsartan before starting lisinopril, and vice versa
• Concurrent use with aliskiren in patients with diabetes or moderate-to-severe kidney impairment – dual blockade of the renin-angiotensin system increases the risk of hypotension, hyperkalaemia, and acute kidney injury

Warnings and Precautions

Talk to your doctor or pharmacist before taking lisinopril if you have or have had any of the following conditions:

• Kidney disease or renal artery stenosis (narrowing of the blood vessels supplying the kidneys) – lisinopril is excreted by the kidneys, and impaired kidney function may require dose adjustment. In bilateral renal artery stenosis, ACE inhibitors can cause acute kidney failure
• Liver disease – although lisinopril is not metabolised by the liver, rarely ACE inhibitors have been associated with a syndrome beginning with cholestatic jaundice and progressing to fulminant hepatic necrosis
• Heart valve disease or hypertrophic cardiomyopathy – the blood pressure-lowering effect may be pronounced and require careful monitoring
• Recent heart attack with unstable haemodynamics – careful blood pressure monitoring is essential
• Low blood pressure (hypotension) – particularly common at the start of treatment, in patients taking diuretics, or in those who are dehydrated
• Diabetes – lisinopril may enhance the blood sugar-lowering effect of insulin and oral antidiabetic agents; blood glucose monitoring is recommended
• Connective tissue disease (e.g. systemic lupus erythematosus, scleroderma) – increased risk of neutropenia and agranulocytosis with ACE inhibitors
• Black patients – ACE inhibitors may be less effective at lowering blood pressure in Black patients and carry a higher risk of angioedema in this population. A calcium channel blocker or thiazide diuretic may be preferred as initial therapy
• Patients undergoing dialysis with high-flux membranes or LDL apheresis – anaphylactoid reactions have been reported
• Patients undergoing desensitisation therapy (e.g. for bee or wasp venom allergy) – increased risk of anaphylactoid reactions
• Before surgery or anaesthesia – inform your surgeon, anaesthetist, or dentist that you are taking lisinopril, as the medicine may enhance the hypotensive effects of anaesthetic agents

Pregnancy and Breastfeeding

Lisinopril must not be used during pregnancy. ACE inhibitors taken during the second and third trimesters are known to cause serious developmental toxicity, including reduced kidney function in the foetus, low amniotic fluid (oligohydramnios), skull ossification defects, and in severe cases, neonatal death. Even in early pregnancy, lisinopril should be avoided unless there is no suitable alternative.

If you discover you are pregnant while taking lisinopril, stop the medication immediately and contact your doctor. Your doctor will recommend a safer alternative for blood pressure control during pregnancy, such as labetalol, methyldopa, or nifedipine (extended-release).

Lisinopril is not recommended during breastfeeding, particularly for mothers of premature or newborn infants. If you need to take an ACE inhibitor while breastfeeding, your doctor will assess the benefits against the potential risks to your baby and may recommend an alternative treatment.

Driving and Operating Machinery

Lisinopril can occasionally cause dizziness, lightheadedness, or fatigue, particularly at the start of treatment, after a dose increase, or in combination with other blood pressure-lowering medications. If you experience any of these symptoms, you should not drive or operate machinery until you know how the medicine affects you. These effects are most common during the first few days of treatment and usually improve with continued use.

How Does Lisinopril Interact with Other Drugs?

Lisinopril can interact with several important medications, including potassium supplements, potassium-sparing diuretics, NSAIDs, lithium, aliskiren, and sacubitril/valsartan. These interactions can lead to dangerously high potassium levels, kidney damage, or excessive blood pressure lowering. Always tell your doctor about all medications you are taking.

Unlike many other ACE inhibitors, lisinopril is not significantly metabolised by liver enzymes and does not interact with the cytochrome P450 system. However, it has important pharmacodynamic interactions, particularly with drugs that affect the renin-angiotensin-aldosterone system (RAAS), potassium balance, or kidney function. The following tables summarise the most clinically significant interactions.

Major Interactions

Moderate Interactions

Lisinopril is frequently and safely combined with calcium channel blockers (such as amlodipine) and thiazide diuretics (such as hydrochlorothiazide) as part of an optimised blood pressure treatment regimen. Fixed-dose combinations of lisinopril with hydrochlorothiazide are widely available. However, always inform your doctor about all medications, supplements, and herbal products you are taking, including potassium-containing salt substitutes.

What Is the Correct Dosage of Lisinopril?

The usual starting dose for adults with hypertension is 10 mg once daily, with a maintenance dose of 20 mg daily and a maximum of 80 mg daily. Doses vary significantly depending on the condition being treated. Take the tablet at the same time each day with a glass of water, with or without food.

Always take lisinopril exactly as your doctor has prescribed. Do not change your dose without consulting your doctor first. Lisinopril tablets should be swallowed whole with a glass of water and can be taken with or without food. The tablets can be split in half if your doctor prescribes a half-dose. Take your tablet at approximately the same time each day for consistent blood pressure control.

Adults – High Blood Pressure (Hypertension)

Adults – Heart Failure

Adults – After a Heart Attack

Adults – Diabetic Kidney Disease

Children and Adolescents (6–16 years)

Elderly Patients

Elderly patients may require dose adjustments, particularly if they have impaired kidney function. Your doctor will determine the appropriate dose based on your kidney function tests and blood pressure response. Treatment is typically started at a lower dose with careful monitoring.

Patients with Kidney Impairment

Since lisinopril is excreted entirely by the kidneys, dose reduction is essential in patients with impaired kidney function. Your doctor will calculate the starting dose based on your creatinine clearance and will monitor your kidney function and potassium levels regularly throughout treatment.

Missed Dose

If you forget to take a dose, simply skip it and take your next dose at the usual time. Do not take a double dose to make up for the missed one. If you frequently miss doses, consider setting a daily alarm or taking your tablet at the same time as another daily routine (such as breakfast).

Overdose

What Are the Side Effects of Lisinopril?

The most common side effects of lisinopril include dizziness, headache, dry cough, diarrhoea, vomiting, and low blood pressure when standing up (orthostatic hypotension). The dry cough is a well-known class effect of ACE inhibitors and occurs in approximately 5–10% of patients. Most side effects are mild and manageable.

Like all medicines, lisinopril can cause side effects, although not everybody gets them. Many side effects are dose-related and tend to improve as your body adjusts to the medication. If any side effects become severe, persistent, or troublesome, consult your doctor.

A symptom complex of fever, muscle pain, joint pain, vasculitis (inflammation of blood vessels), elevated ESR, changes in blood values, skin rash, and photosensitivity has been reported. Side effects in children appear to be similar to those seen in adults.

If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor or pharmacist. Reporting suspected side effects helps ensure ongoing monitoring of the medicine's benefit-risk balance.

How Should You Store Lisinopril?

Store lisinopril tablets below 25°C, in the original packaging, out of the reach and sight of children. Do not use after the expiry date printed on the packaging.

Keep the tablets in their original packaging (blister pack or bottle) to protect them from moisture. Store at room temperature, not exceeding 25°C. Check the expiry date (marked "EXP" on the carton or blister) before taking any tablets. The expiry date refers to the last day of the stated month.

Do not flush unused tablets down the toilet or throw them in household waste. Return any unused or expired medication to your pharmacy for safe disposal, which helps protect the environment from pharmaceutical contamination.

What Does Lisinopril Contain?

Each lisinopril tablet contains the active ingredient lisinopril (as lisinopril dihydrate) and several standard pharmaceutical excipients. The 5 mg tablets are white and round, the 10 mg tablets are light pink and round, and the 20 mg tablets are pink and round.

Active Ingredient

The active substance is lisinopril. Each 5 mg tablet contains 5 mg lisinopril (as lisinopril dihydrate). Each 10 mg tablet contains 10 mg lisinopril (as lisinopril dihydrate). Each 20 mg tablet contains 20 mg lisinopril (as lisinopril dihydrate).

Inactive Ingredients (Excipients)

The other ingredients are: mannitol, calcium hydrogen phosphate dihydrate, pregelatinised maize starch, croscarmellose sodium, and magnesium stearate. The 10 mg and 20 mg tablets also contain iron oxide pigments (E172) for colouring. These are standard pharmaceutical excipients used to ensure proper tablet formation, disintegration, and absorption.

Sodium Content

This medicine contains less than 1 mmol (23 mg) sodium per tablet, meaning it is essentially "sodium-free". This is relevant for patients on a sodium-restricted diet.

Tablet Appearance and Packaging

5 mg tablets: White, round, flat, uncoated, 8 mm tablet with a score line on both sides.

10 mg tablets: Light pink, round, uncoated, biconvex, 7 mm tablet with a score line.

20 mg tablets: Pink, round, uncoated, biconvex, 9 mm tablet with a score line.

Available in PVC/Al blister packs and/or white HDPE bottles with PP caps and silica gel desiccant: 14, 28, 30, 50, 98, and 100 tablets. Not all pack sizes may be marketed in your country.

How Does Lisinopril Work in the Body?

Lisinopril works by inhibiting the angiotensin-converting enzyme (ACE), which prevents the formation of angiotensin II – a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and lower blood pressure. It also increases bradykinin levels, which further promotes vasodilation but is responsible for the characteristic dry cough.

The renin-angiotensin-aldosterone system (RAAS) is one of the body's most important mechanisms for regulating blood pressure and fluid balance. When blood pressure drops or the kidneys detect reduced blood flow, the kidneys release an enzyme called renin. Renin converts angiotensinogen (produced by the liver) into angiotensin I, which is then converted to angiotensin II by ACE, primarily in the lungs. Angiotensin II is a very powerful vasoconstrictor that raises blood pressure by narrowing blood vessels and stimulating the release of aldosterone from the adrenal glands, which causes the kidneys to retain sodium and water.

Lisinopril blocks the ACE enzyme, preventing the conversion of angiotensin I to angiotensin II. The result is twofold: blood vessels relax and dilate (vasodilation), and the kidneys excrete more sodium and water (due to reduced aldosterone). Together, these effects significantly lower blood pressure. In addition, by blocking ACE, lisinopril increases levels of bradykinin, a peptide that promotes vasodilation and has anti-inflammatory properties. However, accumulated bradykinin in the airways is responsible for the characteristic dry cough that affects approximately 5–10% of ACE inhibitor users.

Beyond blood pressure reduction, lisinopril has several protective effects on target organs. In the heart, it reduces afterload (the resistance the heart pumps against), improving cardiac output in patients with heart failure. It also inhibits pathological remodelling of the heart muscle after a heart attack. In the kidneys, lisinopril preferentially dilates the efferent (outgoing) arteriole of the glomerulus, reducing intraglomerular pressure and thereby slowing the progression of diabetic nephropathy and proteinuria.

Pharmacokinetic Profile

After oral administration, lisinopril is absorbed from the gastrointestinal tract with a bioavailability of approximately 25% (range 6–60%), which is not significantly affected by food. Peak plasma concentrations are reached approximately 6–8 hours after dosing. Importantly, lisinopril is the only ACE inhibitor that is not a prodrug and not metabolised by the liver – it is active in its unchanged form and is excreted entirely by the kidneys. This makes it a good choice for patients with liver impairment but means that dose adjustment is necessary in patients with kidney disease.

The effective half-life is approximately 12 hours, which allows once-daily dosing. Steady-state plasma concentrations are achieved after 2–3 days of continuous daily dosing. Lisinopril does not bind significantly to plasma proteins other than ACE itself. The onset of antihypertensive action occurs within 1–2 hours, with peak effect at 6–8 hours, and the effect is maintained for at least 24 hours.

Frequently Asked Questions About Lisinopril