Generic Name: lisinopril

Brand Names: Prinivil, Zestril

Uses

Hypertension

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

One of several preferred initial therapies in hypertensive patients with heart failure, post-MI, high coronary disease risk, diabetes mellitus, chronic renal failure, and/or cerebrovascular disease.

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.

CHF

Management of symptomatic CHF, usually in conjunction with cardiac glycosides and diuretics.

AMI

Used in conjunction with thrombolytic agents, aspirin, and/or β-adrenergic blocking agents to improve survival in patients with AMI who are hemodynamically stable. Usually initiated within 24 hours of MI.

Diabetic Nephropathy

A first-line agent in the treatment of diabetic nephropathy† in hypertensive patients with type 2 diabetes mellitus.

Dosage and Administration

General

Hypertension

• Lisinopril/hydrochlorothiazide fixed combinations should not be used for initial treatment of hypertension.

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

Pediatric Patients

Hypertension

Oral

Children ≥6 years of age: Initially, 0.07 mg/kg (up to 5 mg) once daily. Adjust dosage until the desired BP goal is achieved (up to maximum dosage of 0.61 mg/kg or 40 mg daily).

Adults

Hypertension

Oral

Initially, 10 mg once daily as monotherapy. Adjust dosage to achieve BP control.

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, increase sodium intake and 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 dosage: 10–40 mg once daily.

If effectiveness diminishes toward end of dosing interval in patients treated once daily (particularly likely with daily dosage of 10 mg), consider increasing dosage or administering drug in 2 divided doses.

Lisinopril/Hydrochlorothiazide Combination Therapy

Oral

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.

CHF

Oral

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

Usual dosage: 5–40 mg once daily.

AMI

Oral

5 mg within 24 hours post-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 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 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.

CHF

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

AMI

Use with caution in AMI 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.

Volume- and/or Salt-depleted Patients

CHF

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

Geriatric Patients

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

Cautions

Contraindications

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

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, sometimes associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death. Patients at particular risk include those with CHF with BP <100 mm Hg, intensive diuretic therapy or recent increase in diuretic dose, dialysis, or severe volume and/or salt depletion of any etiology. Risk of marked hypotension in patients with CHF.

Potential for excessive hypotension to result in MI or stroke in patients with AMI or ischemic cardiovascular or cerebrovascular disease. Do not use in patients with AMI 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.

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

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 by withholding diuretic therapy, reducing diuretic dosage, and/or 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 CHF.

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 AMI 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.

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.

Blacks

BP reduction may be smaller in black patients compared with nonblack patients; however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic. Use in combination with a diuretic.

Higher incidence of angioedema reported with ACE inhibitors in blacks 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 CHF: Dizziness, hypotension, headache, diarrhea, chest pain, nausea, abdominal pain, rash, upper respiratory tract infection.

Patients with AMI: Hypotension, renal dysfunction.

Interactions

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

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

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

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.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions April 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.