Brand names: Qbrelis, Zestril
Drug class: Angiotensin-Converting Enzyme Inhibitors

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

ACE inhibitor.

Uses for Lisinopril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents). FDA-labeled for use in adults and pediatric patients ≥6 years of age.

ACE inhibitors recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics. While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.

Heart Failure

Management of heart failure as adjunctive therapy in patients with inadequate response to diuretics and a cardiac glycoside.

Current guidelines from the American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) recommend that asymptomatic patients with stage B pre-heart failure and reduced left ventricular ejection fraction (LVEF) ≤40% be treated with an ACE inhibitor and a β-adrenergic blocker to reduce mortality and prevent symptomatic heart failure. In patients with symptomatic heart failure with reduced ejection fraction (HFrEF; LVEF ≤40%, stage C symptomatic HF), AHA/ACC/HFSA recommends treatment with an angiotensin receptor-neprilysin inhibitor (ARNI), an evidence-based beta-adrenergic blocker, sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a mineralocorticoid antagonist. These 4 key medication classes should be initiated and titrated as soon as possible in newly diagnosed patients with stage C HFrEF.

Although ACE inhibitors have shown clear benefits in patients with HFrEF, ARNIs are preferred for renin-angiotensin-aldosterone (RAA) inhibition because of improved morbidity and mortality. ACE inhibitors and angiotensin II receptor antagonists should only be considered when ARNIs are contraindicated, inaccessible, or poorly tolerated.

Mortality Reduction After Acute MI

Used in conjunction with standard therapies (e.g., thrombolytic agents, aspirin, β-adrenergic blockers) to improve survival in hemodynamically stable patients with acute MI.

Expert guidelines recommend initiation of an ACE inhibitor within the first 24 hours of acute MI in patients with an anterior infarction, heart failure, or ejection fraction ≤40% who do not have any contraindications (e.g., hypotension, shock, renal dysfunction). Use with caution (and with gradual upward titration) during initial postinfarction period because of the possibility of hypotension or renal dysfunction.

Continue therapy indefinitely in patients with left ventricular dysfunction or other compelling indications (e.g., hypertension, diabetes mellitus, CKD).

Diabetic Nephropathy

Recommended agent in the management of patients with diabetes mellitus and persistent albuminuria^{† [off-label]} who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.

Migraine Prevention

Has been used for migraine prevention^{† [off-label]} .

Lisinopril Dosage and Administration

General

Patient Monitoring

• Monitor renal function periodically.

• Monitor serum potassium periodically.

• Monitor for jaundice or signs of hepatic failure during therapy.

• Monitor patients at increased risk of hypotension closely for the first 2 weeks of lisinopril therapy and with dosage increases of lisinopril and/or any concomitant diuretics.

• Monitor for angioedema; if angioedema occurs, monitor patients until complete and sustained resolution of signs and symptoms.

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) includes Zestril (lisinopril), Zegerid (omeprazole/sodium bicarbonate), Zetia (ezetimibe), and Zyprexa (olanzapine) on the ISMP List of Confused Drug Names, and recommends using special safeguards to ensure the accuracy of prescriptions for these drugs.

Other General Considerations

• May administer with other antihypertensive agents.

• Blood pressure control should be part of a comprehensive cardiovascular risk management plan, including (as appropriate) lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.

Administration

Oral Administration

Administer orally as tablets or oral solution.

Food does not alter bioavailability.

Commercially available in fixed-combination tablets containing lisinopril and hydrochlorothiazide (Zestoretic); see full prescribing information for administration of this combination product.

Dosage

Pediatric Patients

Hypertension

Oral

Children ≥6 years of age with GFR >30 mL/minute per 1.73 m²: Initially, 0.07 mg/kg (up to 5 mg) once daily. Adjust dosage according to blood pressure up to a maximum of 0.61 mg/kg (up to 40 mg) once daily. Safety and efficacy of doses exceeding 0.61 mg/kg (or in excess of 40 mg) not established.

Adults

Hypertension

Oral

Patients not receiving a diuretic: 10 mg once daily initially.

Patients receiving a diuretic: 5 mg once daily initially.

Adjust dosage based on blood pressure response.

Usual maintenance dosage: Manufacturer states 20–40 mg once daily. Some experts state 10–40 mg once daily.

If blood pressure not adequately controlled with lisinopril alone, low dosage of a diuretic (e.g., hydrochlorothiazide 12.5 mg) may be added. After addition of a diuretic, may be possible to reduce lisinopril dosage.

Heart Failure

Oral

5 mg once daily initially, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure.

In patients with hyponatremia (serum sodium concentration <130 mEq/L): 2.5 mg once daily initially.

Increase dosage as tolerated to maximum of 40 mg once daily.

Heart failure with reduced ejection fraction: Initial lisinopril dosage of 2.5—5 mg once daily, with target dosage of 20—40 mg once daily, as part of guideline-directed medical therapy.

Adjunctive diuretic dosage may require adjustment to minimize hypovolemia, which may contribute to hypotension. Hypotension occurring after initial dose of lisinopril does not preclude subsequent dosage titration, provided hypotension has been managed effectively.

Mortality Reduction After Acute MI

Oral

Initiate 5 mg within 24 hours of onset of MI, followed by 5 mg 24 hours after initial dose, 10 mg 48 hours after initial dose, and then 10 mg daily.

Recommended maintenance dosage: 10 mg daily for 6 weeks.

If low blood pressure during the first 3 days post-MI, initiate at lower dose (i.e., 2.5 mg).

If hypotension (systolic blood pressure <100 mm Hg) occurs, reduce maintenance dosage to 5 mg daily; may temporarily reduce further to 2.5 mg daily if needed.

If prolonged hypotension (systolic blood pressure <90 mm Hg lasting >1 hour) occurs, discontinue lisinopril.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

Cl_cr >30 mL/minute: no dosage adjustment necessary.

Adults with Cl_cr10-30 mL/minute: reduce initial dosage to half of usual recommended dosage (i.e., 5 mg once daily in patients with hypertension, and 2.5 mg once daily in patients with systolic heart failure or acute MI). Uptitrate as tolerated to maximum of 40 mg daily.

Adults with Cl_cr <10 mL/minute or on hemodialysis: recommended initial dosage is 2.5 mg once daily.

In pediatric patients, lisinopril not recommended in those with GFR <30 mL/minute per 1.73 m².

Geriatric Patients

No specific dosage recommendations.

Cautions for Lisinopril

Contraindications

• History of angioedema or hypersensitivity related to previous ACE inhibitor treatment.

• Hereditary or idiopathic angioedema.

• Concomitant use of lisinopril and aliskiren in patients with diabetes mellitus.

• Use in combination with a neprilysin inhibitor (e.g., sacubitril); do not administer lisinopril within 36 hours of switching to or from sacubitril/valsartan.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Can cause fetal harm (see Boxed Warning). Use during second and third trimesters of pregnancy decreases fetal renal function and increases fetal/neonatal morbidity and mortality. Oligohydramnios caused by medications that act on the renin-angiotensin system (RAS) can cause fetal lung hypoplasia, skeletal deformations (including skull hypoplasia), anuria, hypotension, renal failure, and death.

Discontinue as soon as possible when pregnancy detected. In the rare case that no appropriate alternative therapy exists, apprise the mother of potential risk to the fetus.

If lisinopril is taken during pregnancy, perform serial ultrasound examinations to assess intra-amniotic environment. Oligohydramnios may not appear until after fetus has sustained irreversible injury.

Closely observe neonates exposed to lisinopril in utero for signs of hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required.

Other Warnings and Precautions

Angioedema and Anaphylactoid Reactions

Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx, including some fatal reactions, reported; can occur at any time during treatment. Patients with head and neck angioedema involving the tongue, glottis, or larynx likely to experience airway obstruction, especially those with a history of airway surgery.

If angioedema occurs, discontinue lisinopril immediately; provide appropriate therapy and monitoring until complete and sustained resolution of signs and symptoms.

Use contraindicated in patients with history of angioedema or hypersensitivity related to previous ACE inhibitor therapy.

Patients with history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving ACE inhibitor. Additionally, patients taking a concomitant mammalian target of rapamycin (mTOR) inhibitor (e.g., temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor (e.g., sacubitril) with lisinopril may be at increased risk.

Intestinal angioedema reported. Manifestations included abdominal pain (with or without nausea or vomiting); resolved after discontinuance of ACE inhibitor.

Life-threatening anaphylactoid reactions reported in 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.

Sudden and potentially life-threatening anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing dialysis with high-flux membranes. In these patients, immediately stop dialysis and initiate aggressive therapy. Consider using a different type of dialysis membrane or a different class of antihypertensive agent.

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption.

Impaired Renal Function

Changes in renal function (including acute renal failure) may occur. Patients whose renal function may depend in part on RAS activity (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-MI, or volume depletion) may be at increased risk of developing acute renal failure.

Consider withholding or discontinuing lisinopril in patients who develop a clinically important decrease in renal function during treatment.

Monitor renal function periodically.

Hypotension

Possible symptomatic hypotension, sometimes associated with oliguria, progressive azotemia, acute renal failure, or death. Risk increased in patients with heart failure with systolic blood pressure <100 mm Hg, hyponatremia, high-dose or recent intensive diuretic therapy, recent increase in diuretic dose, dialysis, or severe volume and/or salt depletion of any etiology. In these patients, initiate therapy under close medical supervision; monitor closely for first 2 weeks of lisinopril therapy and after dosage increases of lisinopril or any concomitant diuretic.

Avoid use in patients who are hemodynamically unstable after acute MI. Symptomatic hypotension can also occur in patients with severe aortic stenosis or hypertrophic cardiomyopathy.

In patients undergoing major surgery or anesthesia with drugs that produce hypotension, lisinopril may inhibit angiotensin II formation secondary to compensatory renin release. If hypotension occurs due to this mechanism, correct hypotension by volume expansion.

Hyperkalemia

Possible hyperkalemia, especially in patients with renal insufficiency or diabetes mellitus or those receiving drugs that can increase serum potassium concentration (e.g., potassium- sparing diuretics, potassium supplements, potassium-containing salt substitutes).

Monitor serum potassium periodically.

Hepatic Failure

Clinical syndrome manifested initially by cholestatic jaundice or hepatitis with progression to fulminant hepatic necrosis (occasionally fatal) reported with ACE inhibitors. Mechanism not understood. If jaundice or marked elevation of liver enzymes occurs, discontinue lisinopril and monitor patient.

Use of Fixed Combinations

When the fixed combination of lisinopril and hydrochlorothiazide is used, the cautions, precautions, contraindications, and drug interactions associated with both medications must be considered. Consult the full prescribing information for the fixed combination preparation for specific information.

Specific Populations

Pregnancy

Can cause fetal harm when administered to pregnant females.

Use during second and third trimesters of pregnancy decreases fetal renal function and increases fetal/neonatal morbidity and mortality. Oligohydramnios caused by medications that act on RAS can cause fetal lung hypoplasia, skeletal deformations (including skull hypoplasia), anuria, hypotension, renal failure, and death.

Discontinue lisinopril as soon as possible when pregnancy detected. In rare case that no appropriate alternative exists, apprise mother of potential hazard to fetus.

Perform serial ultrasound examinations to assess intra-amniotic environment. Fetal testing may be appropriate based on week of pregnancy; however, oligohydramnios may not manifest until after fetus has sustained irreversible injury. Closely observe neonates exposed to lisinopril in utero for hypotension, oliguria, and hyperkalemia; if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required to reverse hypotension and substitute for disordered renal function.

Hypertension in pregnancy associated with maternal and embryofetal risks (pre-eclampsia, gestational diabetes, premature delivery, delivery complications, fetal intrauterine growth restriction, fetal intrauterine death). Monitor pregnant females with hypertension carefully and manage accordingly.

Lactation

Distributed into milk in rats; not known whether distributed into milk in humans. Effects on breast-fed infant or on milk production also unknown.

Advise women not to breast-feed during treatment with lisinopril.

Pediatric Use

Safety and efficacy established in pediatric patients 6—16 years of age for treatment of hypertension. No important differences observed in adverse reaction profile between pediatric and adult patients.

Safety and efficacy not established in children <6 years of age or in those with GFR <30 mL/minute per 1.73 m².

Geriatric Use

More patients ≥75 years of age discontinued lisinopril because of renal dysfunction compared to patients <75 years of age in a clinical study. No other differences in safety or effectiveness observed between geriatric and younger patients; however, greater sensitivity of some older individuals cannot be excluded.

Hepatic Impairment

No specific dosage recommendations for patients with hepatic impairment. Cholestatic jaundice and hepatic failure may occur during treatment with lisinopril.

Renal Impairment

Changes in renal function may occur. Impaired renal function decreases lisinopril elimination (clinically important only when GFR <30 mL/minute). Dosage adjustment required in patients undergoing hemodialysis or whose Cl_cr ≤30 mL/minute.

In patients with renal impairment (GFR <30 mL/minute), peak and trough lisinopril levels increase, time to peak plasma concentration increases, and time to attain steady state is prolonged; in patients with GFR ≥30 mL/minute, elimination half-life is minimally altered. Lisinopril removed by hemodialysis.

Black Patients

Less effective in reducing blood pressure in Black patients compared with non-Black patients. Higher incidence of angioedema reported with ACE inhibitors in Black patients compared with non-Black patients.

Common Adverse Effects

Adverse effects (>2%) in patients receiving lisinopril for management of hypertension: headache, dizziness, and cough.

Adverse effects (>2%) in patients receiving lisinopril for management of heart failure: hypotension and chest pain.

Adverse effects (>2%) in patients receiving lisinopril for management of acute MI: hypotension.

Drug Interactions

Drugs Increasing Serum Potassium

Additive hyperkalemic effect may occur with concomitant use of lisinopril and potassium-sparing diuretics, potassium supplements, or other medications that can increase serum potassium.

Do not use lisinopril with potassium supplements or salt substitutes containing potassium without consulting a clinician.

Monitor potassium levels frequently if concomitant use of lisinopril and potassium-sparing diuretics indicated.

Specific Drugs

Lisinopril Pharmacokinetics

Absorption

Bioavailability

Mean extent of absorption approximately 25%, with considerable intersubject variability (6—60%) at all doses tested (5—80 mg).

Absolute bioavailability reduced to 16% in patients with heart failure.

Oral bioavailability in patients with acute MI similar to that in healthy volunteers.

Peak plasma concentrations achieved within 7 hours of administration of lisinopril tablets; time to reach peak plasma concentrations slightly delayed in patients with acute MI.

Onset

Following a single oral dose, antihypertensive effects observed within 1 hour, with peak blood pressure reduction at 6 hours.

Duration

Antihypertensive effect of a single dose persists for about 24 hours; effect at 24 hours substantially smaller than at 6 hours after dosing.

Food

Food does not alter bioavailability of lisinopril tablets.

Distribution

Extent

Crosses the blood-brain barrier poorly based on studies in rats.

Distributed into milk in rats.

Plasma Protein Binding

Does not appear to bind to serum proteins.

Elimination

Metabolism

Not metabolized.

Elimination Route

Eliminated entirely in urine as unchanged drug.

Removed by hemodialysis.

Half-life

12 hours.

Stability

Storage

Oral

Solution

20—25°C. Store in tight container. Protect from freezing and excessive heat.

Tablets

20—25°C. Protect from moisture, freezing, and excessive heat. Dispense in a tight container.

Actions

• Inhibits ACE (bradykinase, kininase II); inhibition of ACE results in decreased plasma angiotensin II which leads to reduced vasopressor activity and decreased aldosterone secretion.

• Suppression of the renin-angiotensin-aldosterone system primarily responsible for beneficial effects observed in hypertension and heart failure.

• Inhibition of ACE also leads to increased bradykinin levels.

Advice to Patients

• Advise patients of the risk of angioedema (including laryngeal edema), anaphylactoid, and other sensitivity reactions and the importance of discontinuing lisinopril and reporting suggestive manifestations (e.g., edema of face, eyes, lips, or tongue; swallowing or breathing with difficulty) to a clinician.

• Advise patients of the risk of hypotension (e.g., lightheadedness, syncope), especially during initial therapy and with volume depletion secondary to excessive perspiration or dehydration, vomiting, or diarrhea. Inform patients of the importance of adequate fluid intake. If syncope occurs, advise patients to discontinue lisinopril until consultation with the prescribing clinician.

• Advise patients to contact their clinician promptly if manifestations of infection or neutropenia (e.g., sore throat, fever) develop.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal products, as well as any concomitant illnesses.

• Advise patients of the risk of hyperkalemia. Advise patients to avoid use of potassium supplements or salt substitutes containing potassium without consultation with a clinician.

• Advise patients of the risk of hypoglycemia in patients receiving concomitant therapy with insulin or oral antidiabetic agents. Inform patients of the importance of closely monitoring blood glucose concentrations, especially during the first month of combined use.

• Advise females to inform their clinician immediately if they are or plan to become pregnant. Advise pregnant women and females of reproductive potential of the potential hazard to a fetus.

• Advise women not to breast-feed during treatment with lisinopril.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

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