Brand names: Prinivil, Zestril
Drug class: Angiotensin-Converting Enzyme Inhibitors
- ACE Inhibitors
VA class: CV800
Chemical name: (S)-1-[N2-[(S-1- Carboxy-3-phenylpropyl]-l-lysyl-l-proline dihydrate
Molecular formula: C₂₁H₃₁N₃O₅•2H₂O
CAS number: 83915-83-7

Medically reviewed by Drugs.com on Oct 26, 2023. Written by ASHP.

Introduction

Non-sulfhydryl ACE inhibitor.

Uses for Lisinopril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).

ACE inhibitors are 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.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension. (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient’s BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the current ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommends initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in patients with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors. However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.

Heart Failure

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

Some evidence indicates that therapy with an ACE inhibitor may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.

Mortality Reduction After Acute MI

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

Expert guidelines recommend initiation of an oral ACE inhibitor within the first 24 hours of acute MI in patients with an anterior infarct, 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

A 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.

Related/similar drugs

amlodipine, metoprolol, aspirin, losartan, furosemide, carvedilol, hydrochlorothiazide

Lisinopril Dosage and Administration

General

BP Monitoring and Treatment Goals

• Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

• If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

• If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic). Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.

Administration

Oral Administration

Administer orally once daily without regard to meals. Administer as extemporaneously prepared oral suspension in patients unable to swallow tablets.

Reconstitution

Preparation of extemporaneous suspension containing lisinopril 1 mg/mL: Add 10 mL of purified water USP to a polyethylene terephthalate (PET) bottle containing ten 20-mg lisinopril tablets; shake contents for ≥1 minute. Add 30 mL of sodium citrate dihydrate (Bicitra) and 160 mL of syrup (Ora-Sweet SF) to the PET bottle; gently shake for several seconds to disperse ingredients. Shake suspension before dispensing each dose.

Dosage

May minimize risk of hypotension in patients currently receiving diuretic therapy by discontinuing the diuretic, reducing diuretic dosage, or cautiously increasing salt intake before initiating lisinopril. If diuretic cannot be discontinued, initiate lisinopril in adults at dosage of 5 mg daily under close medical supervision until BP has stabilized. (See Hypotension under Cautions and see the individual dosage sections in Dosage and Administration. )

Pediatric Patients

Hypertension

Oral

Children ≥6 years of age: Initially, 0.07 mg/kg (up to 5 mg) once daily. Some experts state that dosage may be increased every 2–4 weeks until BP controlled, maximum dosage (0.61 mg/kg or 40 mg daily) reached, or adverse effects occur.

Adults

Hypertension

Lisinopril Therapy

Oral

Manufacturer recommends initial dosage of 10 mg once daily in patients not receiving a diuretic. Adjust dosage based on BP response.

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating lisinopril. May cautiously resume diuretic therapy if BP not controlled adequately with lisinopril alone. If diuretic cannot be discontinued, initiate lisinopril at 5 mg daily under close medical supervision for at least 2 hours and until BP has stabilized for at least an additional hour.

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

If effectiveness diminishes toward end of dosing interval (particularly likely with daily dosage of 10 mg), consider increasing dosage.

Lisinopril/Hydrochlorothiazide Fixed-combination Therapy

Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.

If BP is not adequately controlled by monotherapy with lisinopril or hydrochlorothiazide, can switch to the fixed-combination preparation containing lisinopril 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, lisinopril 20 mg and hydrochlorothiazide 12.5 mg. Adjust dosage of either or both drugs according to patient’s response; however, dosage of hydrochlorothiazide should not be increased for about 2–3 weeks after initiation of therapy.

Can switch to the fixed-combination preparation if stable dosages of lisinopril or hydrochlorothiazide have been achieved.

If BP is controlled by monotherapy with hydrochlorothiazide 25 mg daily but potassium loss is problematic, can switch to fixed-combination preparation containing lisinopril 10 mg and hydrochlorothiazide 12.5 mg.

Heart Failure

Oral

Initially, 2.5–5 mg once daily. Monitor closely (especially patients with SBP <80–100 mg Hg) until BP has stabilized. To minimize risk of hypotension, reduce diuretic dosage, if possible.

Initially, 2.5 mg once daily in heart failure patients with hyponatremia (serum sodium concentration <130 mEq/L) under close medical supervision.

Usual dosage: 5–40 mg once daily.

Mortality Reduction After Acute MI

Oral

Manufacturers recommend 5 mg within 24 hours of the 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.

Other experts recommend 2.5–5 mg daily (initiated within 24 hours after MI) titrated to 10 mg daily or higher.

If low SBP (≤120 mm Hg) observed when lisinopril therapy is initiated or during the first 3 days post-MI, give lower dose (i.e., 2.5 mg).

If hypotension (SBP <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 (SBP <90 mm Hg lasting >1 hour) occurs, discontinue lisinopril.

Prescribing Limits

Pediatric Patients

Hypertension

Oral

Children ≥6 years of age: Maximum 0.61 mg/kg or 40 mg daily.

Adults

Hypertension

Oral

Dosages up to 80 mg daily have been used, but no additional benefit observed.

Dosage of lisinopril/hydrochlorothiazide fixed combination generally should not exceed lisinopril 80 mg and hydrochlorothiazide 50 mg daily.

Special Populations

Renal Impairment

Hypertension

Initially, 5 mg once daily in adults with Cl_cr 10–30 mL/minute or 2.5 mg once daily in adults with Cl_cr <10 mL/minute (usually on hemodialysis). Titrate dosage until BP is controlled or to maximum of 40 mg daily. Manufacturers do not recommend use in hypertensive pediatric patients with Cl_cr <30 mL/minute per 1.73 m².

Lisinopril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment.

Heart Failure

Initially, 2.5 mg once daily in heart failure patients with moderate to severe renal impairment (Cl_cr ≤30 mL/minute or S_cr >3 mg/dL) under close medical supervision.

Mortality Reduction After Acute MI

Use with caution in MI patients with S_cr >2 mg/dL. If renal impairment (S_cr >3 mg/dL or a doubling of baseline S_cr) occurs during lisinopril therapy, consider discontinuing therapy.

Geriatric Patients

Generally titrate dosage carefully, initiate therapy at the low end of the dosage range.

Cautions for Lisinopril

Contraindications

• Known hypersensitivity (e.g., history of angioedema) to lisinopril or another ACE inhibitor. History of hereditary or idiopathic angioedema.

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

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, sometimes associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death. Risk of marked hypotension in patients with heart failure with SBP <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.

Potential for excessive hypotension to result in MI or stroke in patients with acute MI or ischemic cardiovascular or cerebrovascular disease. Do not use in patients with acute MI at risk of further serious hemodynamic deterioration following treatment with a vasodilator (e.g., those with SBP ≤100 mm Hg) or in those with cardiogenic shock.

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions. May minimize potential for hypotension in patients at risk for excessive hypotension by withholding diuretic therapy (except in patients with heart failure), reducing diuretic dosage, and/or cautiously increasing sodium intake prior to initiation of lisinopril. (See Dosage under Dosage and Administration.)

In patients at risk of excessive hypotension, initiate therapy under close medical supervision; monitor closely for first 2 weeks following initiation of lisinopril or any increase in lisinopril or diuretic dosage.

If excessive hypotension occurs, immediately place patient in a supine position and, if necessary, administer IV infusion of sodium chloride 0.9%. Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion). If symptomatic hypotension develops, dosage reduction or discontinuance of lisinopril or diuretic may be necessary.

Hematologic Effects

Neutropenia and agranulocytosis reported with captopril; risk appears to depend principally on presence of renal impairment and/or presence of collagen vascular disease. Data insufficient to rule out similar incidence of leukopenia, neutropenia, or agranulocytosis with lisinopril.

Consider monitoring leukocyte counts in patients with collagen vascular disease and renal disease.

Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy. (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving. Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; if associated with laryngeal edema, may be fatal. Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx. Antihistamines and corticosteroids may not provide sufficient relief; prolonged observation may be necessary. Use caution in patients with history of angioedema unrelated to ACE inhibitor therapy.

Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain. Manifestations include abdominal pain (with or without nausea or vomiting). Consider intestinal angioedema in the differential diagnosis of patients receiving ACE inhibitors and presenting with abdominal pain.

Sudden and potentially life-threatening anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing dialysis with high-flux membranes (e.g., AN69). If anaphylactoid reactions occur, immediately stop dialysis and initiate aggressive therapy (symptoms not relieved by antihistamines). 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.

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

Not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitors.

General Precautions

Aortic Stenosis/Hypertrophic Cardiomyopathy

Use with caution in patients with obstruction in the outflow tract of the left ventricle (e.g., aortic stenosis, hypertrophic cardiomyopathy).

Renal Effects

Transient increases in BUN and S_cr possible; more likely to occur in patients with preexisting renal impairment or those receiving concomitant diuretic therapy. Possible increases in BUN and S_cr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ACE inhibitor and/or diuretic.

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe heart failure.

Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis. Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.

In patients with acute MI who develop renal impairment (S_cr >3 mg/dL or a doubling of baseline S_cr), consider discontinuing therapy.

Hyperkalemia

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

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.

Surgery/Anesthesia

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters). (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Distributed into milk in rats; not known whether lisinopril is distributed into milk in humans. Discontinue nursing or the drug.

Pediatric Use

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

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults; however, use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly. (See Geriatric Patients under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Renal Impairment

Deterioration of renal function may occur in susceptible patients. (See Renal Effects under Cautions.)

Increased lisinopril concentrations, particularly in patients with GFR <30 mL/minute. Initial dosage adjustment recommended in patients with severe renal impairment. (See Renal Impairment under Dosage and Administration.)

Lisinopril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment.

Black Patients

BP reduction may be smaller in black patients compared with nonblack patients. (See Hypertension under Uses.)

Higher incidence of angioedema reported with ACE inhibitors in black patients compared with other races.

Common Adverse Effects

Patients with hypertension: Headache, dizziness, cough, fatigue, diarrhea, upper respiratory tract infection, nausea. With fixed combination preparation, muscle cramps, asthenia, orthostatic effects, paresthesia.

Patients with heart failure: Dizziness, hypotension, headache, diarrhea, chest pain, nausea, abdominal pain, rash, upper respiratory tract infection.

Patients with acute MI: Hypotension, renal dysfunction.

Drug Interactions

Specific Drugs

Lisinopril Pharmacokinetics

Absorption

Bioavailability

About 25% of oral dose is absorbed. Absolute bioavailability is about 16% in patients with heart failure.

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

Onset

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

During chronic therapy, maximum antihypertensive effect is achieved after 2–4 weeks.

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 affect absorption.

Distribution

Extent

Crosses the blood-brain barrier poorly.

Crosses the placenta and is distributed into milk in rats.

Plasma Protein Binding

Not bound to serum proteins other than ACE.

Elimination

Metabolism

Not metabolized.

Elimination Route

Eliminated principally in urine as unchanged drug.

Removed by hemodialysis.

Half-life

12 hours.

Special Populations

In patients with renal impairment (GFR <30 mL/minute), clearance is decreased, plasma concentrations increased; in patients with GFR ≥30 mL/minute, elimination half-life is minimally altered.

In geriatric patients, peak plasma concentrations and AUCs increased (i.e., may be doubled).

Stability

Storage

Oral

Extemporaneous Suspension

1-mg/mL preparation of lisinopril tablets in syrup (Ora-Sweet SF) (see Oral Administration under Dosage and Administration): Stable up to 4 weeks at ≤25°C.

Tablets

Conventional tablets: 15–30°C. Protect from moisture, freezing, and excessive heat.

Fixed combination tablets: 15–30°C. Protect from excessive light and moisture.

Actions

• Suppresses the renin-angiotensin-aldosterone system.

Advice to Patients

• Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions. Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.

• Importance of reporting signs of infection (e.g., sore throat, fever).

• Risk of hypotension. Importance of informing clinicians promptly if lightheadedness or fainting occurs.

• Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.

• Risks of use during pregnancy. (See Boxed Warning.)

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of advising patients of other important precautionary information. (See Cautions.)

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

• Does lisinopril cause weight gain?
• What is the strength of Qbrelis (lisinopril) oral solution?
• How long after taking 5 mg lisinopril will my blood pressure drop down?
• Can I just stop taking lisinopril?
• Do ACE inhibitors make COVID-19 worse?

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