lisinopril
ACE inhibitor· Brands: Zestril, Prinivil, QbrelisPO
Mechanism of action
Lisinopril inhibits angiotensin-converting enzyme (ACE), thereby preventing the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This reduces aldosterone secretion, leading to vasodilation, decreased peripheral resistance, and reduced blood pressure. It also decreases the degradation of bradykinin, which may contribute to its effects and adverse reactions.
Pharmacokinetics
Lisinopril is well absorbed orally, with an absolute bioavailability of about 25-30%. Unlike other ACE inhibitors, it is not a prodrug and is active as administered. Peak plasma concentrations occur within 6-8 hours, and the effective half-life is approximately 12 hours. Lisinopril is not metabolized to any significant extent and is excreted unchanged in the urine. In renal impairment, clearance is reduced requiring dose adjustment.
Indications & dosing
Hypertension
Initiate at 10 mg once daily; adjust according to response, usual range 10-40 mg.
- adult · PO: 10–40 mg once daily · Initiate at 10 mg once daily; adjust according to response, usual range 10-40 mg.
Heart failure
Start at 2.5 mg once daily, titrate as tolerated; usual maintenance 5-35 mg.
- adult · PO: 2.5–35 mg once daily · Start at 2.5 mg once daily, titrate as tolerated; usual maintenance 5-35 mg.
Acute myocardial infarction
Give 5 mg within 24 hours of symptom onset, then 5 mg after 24 hours, then 10 mg after 48 hours; maintenance 10 mg once daily.
- adult · PO: 5–10 mg once daily · Give 5 mg within 24 hours of symptom onset, then 5 mg after 24 hours, then 10 mg after 48 hours; maintenance 10 mg once daily.
Diabetic nephropathy
Used in hypertensive patients with diabetic nephropathy to slow progression.
- adult · PO: 10–20 mg once daily · Used in hypertensive patients with diabetic nephropathy to slow progression.
Contraindications & precautions
- Pregnancy · ACE inhibitors can cause fetal renal damage, oligohydramnios and neonatal renal failure. Discontinue immediately if pregnancy is suspected.
- History of angioedema related to ACE inhibitors or hereditary/idiopathic angioedema · Risk of severe, potentially fatal angioedema recurs on rechallenge.
- Bilateral renal artery stenosis · High risk of acute renal failure; use only with specialist supervision and close monitoring of renal function.
- Concomitant use of aliskiren in patients with diabetes mellitus · Increased risk of hyperkalaemia and renal impairment.
- Monitor renal function and serum potassium before and during treatment, especially in patients with renal impairment, diabetes or taking potassium-sparing diuretics.
- Reduce initial dose in patients with renal impairment, volume depletion or those on diuretics to minimise risk of profound first-dose hypotension.
- Avoid in pregnancy, discontinue immediately if pregnancy is suspected.
- Caution with concurrent use of NSAIDs, aliskiren or potassium supplements due to increased risk of renal impairment and hyperkalaemia.
- Caution in aortic stenosis or hypertrophic cardiomyopathy, as reducing afterload may worsen coronary perfusion.
- Consider stopping ACE inhibitor therapy before surgery if hypotension risk is of concern.
Adverse effects
- Dry, persistent cough
- Hypotension, especially first doseserious
- Dizziness, headache
- Hyperkalaemiaserious
- Renal impairmentserious
- Angioedemaserious
Interactions
- spironolactonemajorUse together with caution. Monitor serum potassium and creatinine at baseline, within 1-2 weeks after starting or changing doses, and then periodically. Avoid in patients with significant renal impairment or baseline potassium above 5.0 mmol/L. Consider alternative antihypertensive or renin-angiotensin system blocker, or use lower doses.
- potassium chloridemajorAvoid routine co-prescription unless there is documented hypokalaemia and the patient is closely monitored. If combined, measure serum potassium before initiation, within 1 week, and regularly thereafter. Adjust or stop potassium supplementation as needed. Monitor renal function and for signs of hyperkalaemia. Consider alternatives to potassium supplementation, such as dietary changes or potassium-sparing diuretics, with caution.
- trimethoprimmajorAvoid empiric combination in high-risk patients. If co-prescription is necessary, check baseline serum potassium and renal function, recheck within 1–2 weeks after starting therapy, and periodically thereafter. Advise patients to avoid potassium supplements and salt substitutes. If hyperkalaemia develops, stop the offending drug(s), treat accordingly, and consider switching trimethoprim to an alternative antibiotic (e.g. nitrofurantoin for uncomplicated UTI) where clinically appropriate.
- ibuprofenmajorAvoid routine co-prescription, especially in patients at increased risk. If unavoidable, use the lowest effective dose of ibuprofen for the shortest duration. Monitor blood pressure and serum creatinine, and potassium at baseline and within 1 to 2 weeks after starting or changing therapy. Consider alternative analgesics such as paracetamol or opioids, which have less effect on renal function and blood pressure.
- diclofenacmajorMonitor blood pressure and renal function (serum creatinine and potassium) at baseline and within 1 to 2 weeks of starting or changing doses. Consider using a non-NSAID analgesic if possible. If an NSAID is necessary, use the lowest effective dose for the shortest duration. Avoid in patients with chronic kidney disease or dehydration. Adjust lisinopril dose as needed.
- naproxenmoderatePrescribers should avoid this combination if possible, especially in high-risk patients. If co-administration is necessary, use the lowest effective NSAID dose for the shortest duration, and consider substitution with paracetamol or another non-NSAID analgesic. Monitor serum creatinine, estimated GFR, blood pressure, and serum potassium at baseline, within one week of starting the combination, and thereafter as clinically indicated. Advise patients to maintain adequate hydration and report symptoms such as oedema, reduced urine output, or weakness.
- lithiummajorAvoid co-prescription where possible. If an ACE inhibitor is necessary, consider an alternative antihypertensive. If combined, use the lowest effective doses, monitor serum lithium levels and renal function at baseline, after any dose change, and at least weekly for the first few weeks, then less frequently. Patients should be advised to seek immediate medical attention if symptoms of lithium toxicity occur.
Renal & hepatic adjustment
- eGFR 10–30: Initial dose 2.5 mg once daily; titrate to response. Maximum dose 40 mg once daily.
- eGFR 0–10: Initial dose 2.5 mg once daily; titrate cautiously. Maximum dose 40 mg once daily.
Monitoring, pregnancy & toxicity
- Blood pressure · At baseline, after dose changes, and regularly
- Serum potassium · At baseline, after dose changes, and within 1-2 weeks of starting or dose increase
- Renal function (serum creatinine, eGFR) · At baseline, after dose changes, and at least every 3 months
- Signs of angioedema · At each visit
- Pregnancy: Lisinopril is contraindicated in pregnancy. It can cause fetal and neonatal morbidity and death when used in the second and third trimesters. Discontinue as soon as pregnancy is detected.
- Toxicity: Hypotension · Supportive measures: place patient supine, IV fluids, vasopressors if necessary
- Toxicity: Hyperkalaemia · Discontinue lisinopril, treat with IV calcium gluconate, insulin/glucose, and diuretics if needed
- Toxicity: Angioedema · Airway maintenance, administer epinephrine, antihistamines and corticosteroids as appropriate
- Toxicity: Renal impairment · Withdraw drug, monitor renal function, provide supportive care
Clinical notes
Lisinopril is used for hypertension, heart failure, and to improve survival after myocardial infarction. It also slows the progression of diabetic nephropathy. Common adverse effects include a dry cough, hyperkalemia, and hypotension. Rarely, angioedema can occur and requires urgent management. It is contraindicated in pregnancy. First-dose hypotension may occur, especially in volume-depleted patients. Monitor renal function, potassium, and blood pressure regularly.
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BNF; local formulary