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Lisinopril

Lisinopril

Pronunciation Class: Angiotensin-Converting Enzyme 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

Brands: Prinivil, Prinzide, Zestoretic, Zestril

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Warning(s)

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 2 3 4 74 75 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue lisinopril as soon as possible.1 2 3 4 75

Introduction

Non-sulfhydryl ACE inhibitor.1 2 3 4 5

Uses for Lisinopril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 4 5 12 34

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.55

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.55

CHF

Management of symptomatic CHF, usually in conjunction with cardiac glycosides and diuretics.1 2

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.1 2 27 Usually initiated within 24 hours of MI.1 2 27

Diabetic Nephropathy

A first-line agent in the treatment of diabetic nephropathy† in hypertensive patients with type 2 diabetes mellitus.59 60

Lisinopril Dosage and Administration

General

Hypertension

  • Lisinopril/hydrochlorothiazide fixed combinations should not be used for initial treatment of hypertension.3 4

Administration

Oral Administration

Administer orally once daily without regard to meals.1 2 3 4 Administer as extemporaneously prepared oral suspension in patients unable to swallow tablets.67 69

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.1 2 67 69 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.1 2 67 69 Shake suspension before dispensing each dose.1 2 67 69

Dosage

Pediatric Patients

Hypertension
Oral

Children ≥6 years of age: Initially, 0.07 mg/kg (up to 5 mg) once daily.1 2 67 68 69 Adjust dosage until the desired BP goal is achieved (up to maximum dosage of 0.61 mg/kg or 40 mg daily).1 2 67 68 69

Adults

Hypertension
Oral

Initially, 10 mg once daily as monotherapy.1 2 55 Adjust dosage to achieve BP control.13

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating lisinopril.1 2 3 4 May cautiously resume diuretic therapy if BP not controlled adequately with lisinopril alone.1 2 3 4 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.1 2 3 4

Usual dosage: 10–40 mg once daily.1 2 55

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.1 2 12

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.3 4 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.3 4

Can switch to the fixed-combination preparation if stable dosages of lisinopril or hydrochlorothiazide have been achieved.3

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.3 4

CHF
Oral

Initially, 2.5–5 mg daily.1 43 Monitor closely (especially patients with systolic BP <100 mg Hg) until BP has stabilized.1 To minimize risk of hypotension, reduce diuretic dosage, if possible.1

Usual dosage: 5–40 mg once daily.1 2 13 14

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.1 2 Recommended maintenance dosage: 10 mg daily for 6 weeks.1 2

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).1 2

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.1 2

If prolonged hypotension (SBP <90 mm Hg lasting >1 hour) occurs, discontinue lisinopril.1 2

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Children ≥6 years of age: Maximum 0.61 mg/kg or 40 mg daily.67 68 69

Adults

Hypertension
Oral

Dosages up to 80 mg daily have been used, but no additional benefit observed.1 2

Dosage of lisinopril/hydrochlorothiazide fixed combination generally should not exceed lisinopril 80 mg and hydrochlorothiazide 50 mg daily.3

Special Populations

Renal Impairment

Hypertension

Initially, 5 mg once daily in adults with Clcr 10–30 mL/minute or 2.5 mg once daily in adults with Clcr <10 mL/minute (usually on hemodialysis).1 2 Titrate until BP is controlled or to maximum of 40 mg daily.1 2 Manufacturers do not recommend use in hypertensive pediatric patients with Clcr <30 mL/minute per 1.73 m2.67 69

Lisinopril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment.3

CHF

Initially, 2.5 mg once daily in CHF patients with moderate to severe renal impairment (Clcr ≤30 mL/minute or Scr >3 mg/dL) under close medical supervision.1 2

AMI

Use with caution in AMI patients with Scr >2 mg/dL.1 2 If renal impairment (Scr >3 mg/dL or a doubling of baseline Scr) occurs during lisinopril therapy, consider discontinuing therapy.1 2

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.1 2

Geriatric Patients

Generally titrate dosage carefully, initiate therapy at the low end of the dosage range.1 2 3

Cautions for Lisinopril

Contraindications

  • Known hypersensitivity (e.g., history of angioedema) to lisinopril or another ACE inhibitor.1 2 3 4 History of hereditary or idiopathic angioedema.1 3 4

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, sometimes associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death.1 2 3 4 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.1 2 Risk of marked hypotension in patients with CHF.1 2

Potential for excessive hypotension to result in MI or stroke in patients with AMI1 2 or ischemic cardiovascular or cerebrovascular disease.1 2 3 4 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.1 2

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.1 2

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.1 2 May minimize potential for hypotension by withholding diuretic therapy, reducing diuretic dosage, and/or increasing sodium intake prior to initiation of lisinopril.1 2 (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.1 2

If excessive hypotension occurs, immediately place patient in a supine position and, if necessary, administer IV infusion of sodium chloride 0.9%.1 2 Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion).1 2 If symptomatic hypotension develops, dosage reduction or discontinuance of lisinopril or diuretic may be necessary.1 2

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.1 2 3 4 Data insufficient to rule out similar incidence of leukopenia, neutropenia, or agranulocytosis with lisinopril.1 2 3 4 67 69

Consider monitoring leukocyte counts in patients with collagen vascular disease and renal disease.1 2

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.1 2 3 4

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.1 2 3 4

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.1 2 3 4 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.75

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.74 75

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.75 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.76 77

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; if associated with laryngeal edema, may be fatal.1 2 3 4 67 69 Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.1 2 3 4 Antihistamines and corticosteroids may not provide sufficient relief; prolonged observation may be necessary.1 2 3 Use caution in patients with history of angioedema unrelated to ACE inhibitor therapy.1 2 3 4

Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.1 2 3 67 68 69 Manifestations include abdominal pain (with or without nausea or vomiting).1 2 3 67 68 69 Consider intestinal angioedema in the differential diagnosis of patients receiving ACE inhibitors and presenting with abdominal pain.1 2 3 67 68 69

Sudden and potentially life-threatening anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing dialysis with high-flux membranes (e.g., AN69).1 67 69 If anaphylactoid reactions occur, immediately stop dialysis and initiate aggressive therapy (symptoms not relieved by antihistamines).1 67 69 Consider using a different type of dialysis membrane or a different class of antihypertensive agent.1 67 69

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption.1 2 3 4

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.1 2 3 4

Not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitors.1 2 3 4

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).1 2 3 4

Renal Effects

Transient increases in BUN and Scr possible; more likely to occur in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.1 2 3 4 Possible increases in BUN and Scr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ACE inhibitor and/or diuretic.1 2 3 4

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe CHF.1 2 3 4

Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis.1 2 Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.1 2

In patients with AMI who develop renal impairment (Scr >3 mg/dL or a doubling of baseline Scr), consider discontinuing therapy.1 2

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).1 2 3 4 (See Specific Drugs under Interactions.)

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.1 2 3 4

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.3 4

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).1 2 3 4 (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.1 2 3 4 Discontinue nursing or the drug.1 2 3 4

Pediatric Use

Safety and efficacy not established in children <6 years of age or in those with Clcr <30 mL/minute per 1.73 m2.1 2 67 68 69

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.1 2 3 (See Geriatric Patients under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Renal Impairment

Deterioration of renal function may occur in susceptible patients.1 (See Renal Effects under Cautions.)

Increased lisinopril concentrations, particularly in patients with GFR <30 mL/minute.1 Initial dosage adjustment recommended in patients with severe renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Lisinopril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment.3

Blacks

BP reduction may be smaller in black patients compared with nonblack patients;1 2 3 4 29 30 53 54 70 71 however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic.12 29 31 32 34 Use in combination with a diuretic.12 34

Higher incidence of angioedema reported with ACE inhibitors in blacks compared with other races.33 54 67 69

Common Adverse Effects

Patients with hypertension: Headache, dizziness, cough, fatigue, diarrhea, upper respiratory tract infection, nausea.1 2 3 4 With fixed combination preparation, muscle cramps, asthenia, orthostatic effects, paresthesia.1 2 3 4

Patients with CHF: Dizziness, hypotension, headache, diarrhea, chest pain, nausea, abdominal pain, rash, upper respiratory tract infection.1 2

Patients with AMI: Hypotension, renal dysfunction.1 2

Interactions for Lisinopril

Specific Drugs

Drug

Interaction

Comments

Digoxin

Interaction unlikely1 2

Diuretics

Increased hypotensive effect1 2 3 4

If possible, discontinue diuretic before initiating lisinopril1 2 3 4 (See Dosage under Dosage and Administration)

Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)

Enhanced hyperkalemic effect1 2 3 4

Use with caution; monitor serum potassium concentrations frequently.1 2 3 4 Concomitant therapy generally not recommended in patients with CHF1 2

Nitrates (nitroglycerin)

Clinically important interaction not observed1 2

NSAIAs

Possible decreased antihypertensive response to lisinopril1 2 3 4 (slightly decreased response observed with concomitant indomethacin)1 2

Potential for acute reduction of renal function in patients with impaired renal function1 3 4

Lithium

Increased serum lithium concentrations; possible toxicity1 2 3 4

Monitor serum lithium concentrations frequently1

Potassium supplements or potassium-containing salt substitutes

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1

Lisinopril Pharmacokinetics

Absorption

Bioavailability

About 25% of oral dose is absorbed.1 2 Absolute bioavailability is about 16% in patients with CHF.1 2

Peak plasma concentrations achieved within 7 hours; time to reach peak plasma concentrations slightly delayed in patients with AMI.1 2

Onset

Following a single oral dose, antihypertensive effects are observed within 1 hour, with peak BP reduction at 6 hours.1 2

During chronic therapy, maximum antihypertensive effect is achieved after 2–4 weeks.1 2

Duration

Antihypertensive effect of a single dose persists for about 24 hours; effect at 24 hours substantially smaller than at 6 hours after dosing.1 2

Food

Food does not affect absorption.1 2

Distribution

Extent

Crosses the blood-brain barrier poorly.1 2

Crosses the placenta and is distributed into milk in rats.1 2

Plasma Protein Binding

Not bound to serum proteins other than ACE.1 2

Elimination

Metabolism

Not metabolized.1 2

Elimination Route

Eliminated principally in urine as unchanged drug.1 2

Removed by hemodialysis.1 2

Half-life

12 hours.1 2

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.1 2

In geriatric patients, peak plasma concentrations and AUCs increased (i.e., may be doubled).1 2

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.1 2 67 69

Tablets

Conventional tablets: 15–30°C.1 2 Protect from moisture, freezing, and excessive heat.1 2

Fixed combination tablets: 15–30°C.3 Protect from excessive light and moisture.3

Actions

  • Suppresses the renin-angiotensin-aldosterone system.1 2 3 4

Advice to Patients

  • Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.1 2 3 4 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.1 2 3 4

  • Importance of reporting signs of infection (e.g., sore throat, fever).1 2
  • Risk of hypotension.1 2 3 4 Importance of informing clinicians promptly if lightheadedness or fainting occurs.1 2
  • Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.1 2
  • Risks of use during pregnancy.1 2 3 4 (See Boxed Warning)
  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).1 2
  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2
  • Importance of advising patients of other important precautionary information.1 2 (See Cautions.)

Preparations

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

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

Lisinopril
Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

2.5 mg*

Zestril

AstraZeneca

5 mg*

Prinivil

Merck

Zestril

AstraZeneca

10 mg*

Prinivil

Merck

Zestril

AstraZeneca

20 mg*

Prinivil

Merck

Zestril

AstraZeneca

30 mg*

Zestril

AstraZeneca

40 mg*

Prinivil

Merck

Zestril

AstraZeneca

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

Lisinopril Combinations
Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg with Hydrochlorothiazide 12.5 mg*

Prinzide

Merck

Zestoretic

AstraZeneca

20 mg with Hydrochlorothiazide 12.5 mg*

Prinzide

Merck

Zestoretic

AstraZeneca

20 mg with Hydrochlorothiazide 25 mg*

Prinzide

Merck

Zestoretic

AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lisinopril 10MG Tablets (LUPIN PHARMACEUTICALS): 30/$13.99 or 90/$32.97

Lisinopril 2.5MG Tablets (LUPIN PHARMACEUTICALS): 30/$12.99 or 60/$23.98

Lisinopril 20MG Tablets (LUPIN PHARMACEUTICALS): 30/$14.99 or 90/$33.97

Lisinopril 30MG Tablets (SANDOZ): 30/$20.99 or 90/$56.97

Lisinopril 40MG Tablets (LUPIN PHARMACEUTICALS): 30/$17.99 or 90/$39.97

Lisinopril 5MG Tablets (LUPIN PHARMACEUTICALS): 30/$14.89 or 60/$17.98

Lisinopril-Hydrochlorothiazide 10-12.5MG Tablets (LUPIN PHARMACEUTICALS): 30/$23.99 or 60/$39.98

Lisinopril-Hydrochlorothiazide 20-12.5MG Tablets (LUPIN PHARMACEUTICALS): 30/$21.99 or 90/$59.97

Lisinopril-Hydrochlorothiazide 20-25MG Tablets (LUPIN PHARMACEUTICALS): 30/$21.99 or 90/$59.97

Prinivil 10MG Tablets (MERCK SHARP &amp; DOHME): 60/$75.99 or 180/$205.96

Prinivil 20MG Tablets (MERCK SHARP &amp; DOHME): 30/$45.99 or 90/$119.97

Prinivil 5MG Tablets (MERCK SHARP &amp; DOHME): 90/$102.98 or 180/$195.96

Prinzide 10-12.5MG Tablets (MERCK SHARP &amp; DOHME): 30/$46.99 or 90/$125.96

Zestoretic 10-12.5MG Tablets (ASTRAZENECA): 30/$56.78 or 90/$147.40

Zestoretic 20-12.5MG Tablets (ASTRAZENECA): 30/$60.05 or 90/$163.77

Zestril 10MG Tablets (ASTRAZENECA): 30/$55.11 or 90/$143.27

Zestril 2.5MG Tablets (ASTRAZENECA): 30/$37.99 or 90/$91.97

Zestril 20MG Tablets (ASTRAZENECA): 30/$52.99 or 90/$149.97

Zestril 30MG Tablets (ASTRAZENECA): 30/$71.99 or 90/$199.98

Zestril 5MG Tablets (ASTRAZENECA): 30/$50.99 or 90/$129.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug’s actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions April 1, 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.

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36. American College of Obstetricians and Gynecologists. ACOG technical bulletin No. 219: hypertension in pregnancy. 1996 Jan.

37. Hanssens M, Keirse MJ, Van Assche FA. Fetal and neonatal effects of treatment with angiotensin-converting enzyme inhibitors in pregnancy. Obstet Gynecol. 1991; 78:128-35. [IDIS 284531] [PubMed 2047053]

38. Brent Rl, Beckman D. Angiotensin-converting enzyme inhibitors, an embryopathic class of drugs with unique properties: information for clinical teratology counselors. Teratology. 1991; 43:543-6. [PubMed 1882342]

39. Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. Obstet Gynecol. 1992; 80:429-32. [IDIS 300973] [PubMed 1495700]

40. Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med. 1996; 335:257-65. [IDIS 369138] [PubMed 8657243]

41. Barr M, Cohen MM. ACE inhibitor fetopathy and hypocalvaria: the kidney-skull connection. Teratology. 1991; 44:485-95. [PubMed 1771591]

42. US Food and Drug Administration. Dangers of ACE inhibitors during pregnancy. FDA Med Bull. 1992; 22:2.

43. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9A-38A.

44. Packer M, Poole-Wilson PA, Armstrong PW et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation. 1999; 100:2312-8. [IDIS 440440] [PubMed 10587334]

45. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999; 341:709-17. [IDIS 431313] [PubMed 10471456]

46. Weber KT. Aldosterone and spironolactone in heart failure. N Engl J Med. 1999; 341:753-4. [IDIS 431314] [PubMed 10471464]

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51. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

52. Hunt SA, Baker DW, Chin MH et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure).

53. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-42. [IDIS 490723] [PubMed 12479770]

54. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2022; 288:2981-97.

55. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (Also published in JAMA. 2003; 289.

56. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.

57. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.

58. Novartis. Diovan (valsartan) tablets prescribing information. East Hanover, NJ; 2002 Aug.

59. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25:134-47. [IDIS 479088] [PubMed 11772914]

60. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl 1):S33-43.

61. American Diabetes Association. Clinical Practice Recommendations 2002. Position Statement. Diabetic nephropathy. Diabetes Care. 2002; 25(Suppl 1):S85-9.

62. Lewis EJ, Hunsicker LG, Bain RP et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993; 329:1456-62. [IDIS 321612] [PubMed 8413456]

63. Remuzzi G. Slowing the progression of diabetic nephropathy. N Engl J Med. 1993; 329:1496-7. [PubMed 8413463]

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65. Viberti G, Mogensen CE, Groop LC et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994; 271:275-9. [IDIS 324307] [PubMed 8295285]

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69. Merck & Co., Inc. Prinivil (lisinopril) tablets prescribing information. Whitehouse Station, NJ; 2003 Apr.

70. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:1595-607. [IDIS 531054] [PubMed 15811979]

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77. US Food and Drug Administration. Dangers of ACE inhibitors during pregnancy. FDA Med Bull. 1992; 22:2.

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Lisinopril

Lisinopril

Dosage Form: tablet

Lisinopril Tablets USP

Rx only

WARNING: FETAL TOXICITY

See full prescribing information for complete boxed warning.

When pregnancy is detected, discontinue Lisinopril as soon as possible.
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS, Fetal Toxicity.

Lisinopril Description

Lisinopril is an oral long-acting angiotensin converting enzyme inhibitor. Lisinopril, a synthetic peptide derivative, is chemically described as (S)-1-[N2-(1-carboxy-3- phenylpropyl)-L-lysyl]-L-proline dihydrate. Its empirical formula is C21H31N3O5 • 2H2O and its structural formula is:

Lisinopril is a white to off-white, crystalline powder, with a molecular weight of 441.53. It is soluble in water and sparingly soluble in methanol and practically insoluble in ethanol.

Lisinopril tablets USP is supplied as 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg and 40 mg tablets for oral administration.

Inactive Ingredients:

2.5 mg tablets – calcium phosphate, magnesium stearate, mannitol, starch.

5 mg, 10 mg and 30 mg tablets – calcium phosphate, magnesium stearate, mannitol, red iron oxide, starch.

20 mg tablets – calcium phosphate, magnesium stearate, mannitol, red iron oxide, starch, yellow iron oxide.

40 mg tablets – calcium phosphate, magnesium stearate, mannitol, starch, yellow iron oxide.

Lisinopril – Clinical Pharmacology

Mechanism of Action

Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of Lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. In hypertensive patients with normal renal function treated with Lisinopril alone for up to 24 weeks, the mean increase in serum potassium was approximately 0.1 mEq/L; however, approximately 15% of patients had increases greater than 0.5 mEq/L and approximately 6% had a decrease greater than 0.5 mEq/L. In the same study, patients treated with Lisinopril and hydrochlorothiazide for up to 24 weeks had a mean decrease in serum potassium of 0.1 mEq/L; approximately 4% of patients had increases greater than 0.5 mEq/L and approximately 12% had a decrease greater than 0.5 mEq/L (see PRECAUTIONS). Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Lisinopril remains to be elucidated.

While the mechanism through which Lisinopril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, Lisinopril is antihypertensive even in patients with low-renin hypertension. Although Lisinopril was antihypertensive in all races studied, Black hypertensive patients (usually a low-renin hypertensive population) had a smaller average response to monotherapy than non-Black patients.

Concomitant administration of Lisinopril and hydrochlorothiazide further reduced blood pressure in Black and non-Black patients and any racial differences in blood pressure response were no longer evident.

Pharmacokinetics and Metabolism

Adult Patients: Following oral administration of Lisinopril, peak serum concentrations of Lisinopril occur within about 7 hours, although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. Declining serum concentrations exhibit a prolonged terminal phase which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose.

Lisinopril does not appear to be bound to other serum proteins. Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine. Based on urinary recovery, the mean extent of absorption of Lisinopril is approximately 25%, with large intersubject variability (6% to 60%) at all doses tested (5 mg to 80 mg). Lisinopril absorption is not influenced by the presence of food in the gastrointestinal tract. The absolute bioavailability of Lisinopril is reduced to 16% in patients with stable NYHA Class II-IV congestive heart failure, and the volume of distribution appears to be slightly smaller than that in normal subjects. The oral bioavailability of Lisinopril in patients with acute myocardial infarction is similar to that in healthy volunteers.

Upon multiple dosing, Lisinopril exhibits an effective half-life of accumulation of 12 hours. Impaired renal function decreases elimination of Lisinopril, which is excreted principally through the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 mL/min. Above this glomerular filtration rate, the elimination half-life is little changed. With greater impairment, however, peak and trough Lisinopril levels increase, time to peak concentration increases and time to attain steady state is prolonged. Older patients, on average, have (approximately doubled) higher blood levels and area under the plasma concentration time curve (AUC) than younger patients (see DOSAGE AND ADMINISTRATION). Lisinopril can be removed by hemodialysis.

Studies in rats indicate that Lisinopril crosses the blood-brain barrier poorly. Multiple doses of Lisinopril in rats do not result in accumulation in any tissues. Milk of lactating rats contains radioactivity following administration of 14C Lisinopril. By whole body autoradiography, radioactivity was found in the placenta following administration of labeled drug to pregnant rats, but none was found in the fetuses.

Pediatric Patients: The pharmacokinetics of Lisinopril were studied in 29 pediatric hypertensive patients between 6 years and 16 years with glomerular filtration rate > 30 mL/min/1.73 m2. After doses of 0.1 mg/kg to 0.2 mg/kg, steady state peak plasma concentrations of Lisinopril occurred within 6 hours and the extent of absorption based on urinary recovery was about 28%. These values are similar to those obtained previously in adults. The typical value of Lisinopril oral clearance (systemic clearance/absolute bioavailability) in a child weighing 30 kg is 10 L/h, which increases in proportion to renal function.

Pharmacodynamics and Clinical Effects

Hypertension 

Adult Patients

Administration of Lisinopril to patients with hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia. Symptomatic postural hypotension is usually not observed although it can occur and should be anticipated in volume and/or salt-depleted patients (see WARNINGS). When given together with thiazide-type diuretics, the blood pressure lowering effects of the two drugs are approximately additive.

In most patients studied, onset of antihypertensive activity was seen at one hour after oral administration of an individual dose of Lisinopril, with peak reduction of blood pressure achieved by 6 hours. Although an antihypertensive effect was observed 24 hours after dosing with recommended single daily doses, the effect was more consistent and the mean effect was considerably larger in some studies with doses of 20 mg or more than with lower doses; however, at all doses studied, the mean antihypertensive effect was substantially smaller 24 hours after dosing than it was 6 hours after dosing.

In some patients achievement of optimal blood pressure reduction may require two to four weeks of therapy.

The antihypertensive effects of Lisinopril are maintained during long-term therapy. Abrupt withdrawal of Lisinopril has not been associated with a rapid increase in blood pressure, or a significant increase in blood pressure compared to pretreatment levels.

Two dose-response studies utilizing a once-daily regimen were conducted in 438 mild to moderate hypertensive patients not on a diuretic. Blood pressure was measured 24 hours after dosing. An antihypertensive effect of Lisinopril was seen with 5 mg in some patients. However, in both studies blood pressure reduction occurred sooner and was greater in patients treated with 10 mg, 20 mg or 80 mg of Lisinopril. In controlled clinical studies, Lisinopril 20 mg to 80 mg has been compared in patients with mild to moderate hypertension to hydrochlorothiazide 12.5 mg to 50 mg and with atenolol 50 mg to 200 mg; and in patients with moderate to severe hypertension to metoprolol 100 mg to 200 mg. It was superior to hydrochlorothiazide in effects on systolic and diastolic pressure in a population that was 3/4 Caucasian. Lisinopril was approximately equivalent to atenolol and metoprolol in effects on diastolic blood pressure, and had somewhat greater effects on systolic blood pressure.

Lisinopril had similar effectiveness and adverse effects in younger and older (> 65 years) patients. It was less effective in Blacks than in Caucasians.

In hemodynamic studies in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with little or no change in cardiac output and in heart rate. In a study in nine hypertensive patients, following administration of Lisinopril, there was an increase in mean renal blood flow that was not significant. Data from several small studies are inconsistent with respect to the effect of Lisinopril on glomerular filtration rate in hypertensive patients with normal renal function, but suggest that changes, if any, are not large.

In patients with renovascular hypertension Lisinopril has been shown to be well tolerated and effective in controlling blood pressure (see PRECAUTIONS).

Pediatric Patients

In a clinical study involving 115 hypertensive pediatric patients 6 to 16 years of age, patients who weighed < 50 kg received either 0.625 mg, 2.5 mg or 20 mg of Lisinopril daily and patients who weighed ≥ 50 kg received either 1.25 mg, 5 mg or 40 mg of Lisinopril daily. At the end of 2 weeks, Lisinopril administered once daily lowered trough blood pressure in a dose-dependent manner with consistent antihypertensive efficacy demonstrated at doses > 1.25 mg (0.02 mg/kg). This effect was confirmed in a withdrawal phase, where the diastolic pressure rose by about 9 mmHg more in patients randomized to placebo than it did in patients who were randomized to remain on the middle and high doses of Lisinopril. The dose-dependent antihypertensive effect of Lisinopril was consistent across several demographic subgroups: age, Tanner stage, gender, and race. In this study, Lisinopril was generally well-tolerated.

In the above pediatric studies, Lisinopril was given either as tablets or in a suspension for those children and infants who were unable to swallow tablets or who required a lower dose than is available in tablet form (see DOSAGE AND ADMINISTRATION, Preparation of Suspension (for 200 mL of a 1.0 mg/mL suspension)).

Heart Failure During baseline-controlled clinical trials, in patients receiving digitalis and diuretics, single doses of Lisinopril resulted in decreases in pulmonary capillary wedge pressure, systemic vascular resistance and blood pressure accompanied by an increase in cardiac output and no change in heart rate.

In two placebo controlled, 12-week clinical studies using doses of Lisinopril up to 20 mg, Lisinopril as adjunctive therapy to digitalis and diuretics improved the following signs and symptoms due to congestive heart failure: edema, rales, paroxysmal nocturnal dyspnea and jugular venous distention. In one of the studies, beneficial response was also noted for: orthopnea, presence of third heart sound and the number of patients classified as NYHA Class III and IV. Exercise tolerance was also improved in this study. The once-daily dosing for the treatment of congestive heart failure was the only dosage regimen used during clinical trial development and was determined by the measurement of hemodynamic response. A large (over 3,000 patients) survival study, the ATLAS Trial, comparing 2.5 mg and 35 mg of Lisinopril in patients with heart failure, showed that the higher dose of Lisinopril had outcomes at least as favorable as the lower dose.

Acute Myocardial Infarction The Gruppo Italiano per lo Studio della Sopravvienza nell’Infarto Miocardico (GISSI-3) study was a multicenter, controlled, randomized, unblinded clinical trial conducted in 19,394 patients with acute myocardial infarction admitted to a coronary care unit. It was designed to examine the effects of short-term (6 week) treatment with Lisinopril, nitrates, their combination, or no therapy on short-term (6 week) mortality and on long-term death and markedly impaired cardiac function. Patients presenting within 24 hours of the onset of symptoms who were hemodynamically stable were randomized, in a 2 x 2 factorial design, to six weeks of either 1) Lisinopril alone (n=4,841), 2) nitrates alone (n=4,869), 3) Lisinopril plus nitrates (n=4,841), or 4) open control (n=4,843). All patients received routine therapies, including thrombolytics (72%), aspirin (84%), and a beta-blocker (31%), as appropriate, normally utilized in acute myocardial infarction (MI) patients.

The protocol excluded patients with hypotension (systolic blood pressure ≤100 mmHg), severe heart failure, cardiogenic shock, and renal dysfunction (serum creatinine >2 mg/dL and/or proteinuria > 500 mg/24 h). Doses of Lisinopril were adjusted as necessary according to protocol (see DOSAGE AND ADMINISTRATION).

Study treatment was withdrawn at six weeks except where clinical conditions indicated continuation of treatment.

The primary outcomes of the trial were the overall mortality at 6 weeks and a combined end point at 6 months after the myocardial infarction, consisting of the number of patients who died, had late (day 4) clinical congestive heart failure, or had extensive left ventricular damage defined as ejection fraction ≤ 35% or an akinetic-dyskinetic [A-D] score ≥ 45%. Patients receiving Lisinopril (n=9,646), alone or with nitrates, had an 11% lower risk of death (2p [two-tailed] = 0.04) compared to patients receiving no Lisinopril (n=9,672) (6.4% vs. 7.2%, respectively) at six weeks. Although patients randomized to receive Lisinopril for up to six weeks also fared numerically better on the combined end point at 6 months, the open nature of the assessment of heart failure, substantial loss to follow-up echocardiography, and substantial excess use of Lisinopril between 6 weeks and 6 months in the group randomized to 6 weeks of Lisinopril, preclude any conclusion about this end point.

Patients with acute myocardial infarction, treated with Lisinopril, had a higher (9.0% versus 3.7%) incidence of persistent hypotension (systolic blood pressure < 90 mmHg for more than 1 hour) and renal dysfunction (2.4% versus 1.1%) in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration). See ADVERSE REACTIONS, Acute Myocardial Infarction.

Indications and Usage for Lisinopril

Hypertension 

Lisinopril tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including Lisinopril.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Lisinopril tablets USP may be administered alone or with other antihypertensive agents.

Heart Failure

Lisinopril tablets USP are indicated as adjunctive therapy in the management of heart failure in patients who are not responding adequately to diuretics and digitalis.

Acute Myocardial Infarction

Lisinopril tablets USP are indicated for the treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction, to improve survival. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blockers.

In using Lisinopril tablets USP, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that Lisinopril tablets USP does not have a similar risk (see WARNINGS).

In considering the use of Lisinopril tablets USP, it should be noted that in controlled clinical trials ACE inhibitors have an effect on blood pressure that is less in Black patients than in non-Blacks. In addition, ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients (see WARNINGS, Anaphylactoid and Possibly Related Reactions).

Contraindications

Lisinopril is contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an angiotensin-converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema.

Warnings

Anaphylactoid and Possibly Related Reactions

Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including Lisinopril) may be subject to a variety of adverse reactions, some of them serious.

Head and Neck Angioedema Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors, including Lisinopril. This may occur at any time during treatment. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients. Lisinopril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, fatalities have been reported due to angioedema associated with laryngeal edema or tongue edema. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and/or measures necessary to ensure a patent airway should be promptly provided (see ADVERSE REACTIONS).

Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also INDICATIONS AND USAGE and CONTRAINDICATIONS).

Anaphylactoid Reactions During Desensitization Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

Anaphylactoid Reactions During Membrane Exposure Sudden and potentially life-threatening anaphylactoid reactions have been reported in some patients dialyzed with high-flux membranes (e.g., AN69®1) and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

1AN69 is a registered trademark of HOSPAL Ltd.

Hypotension 

Excessive hypotension is rare in patients with uncomplicated hypertension treated with Lisinopril alone.

Patients with heart failure given Lisinopril commonly have some reduction in blood pressure, with peak blood pressure reduction occurring 6 to 8 hours post dose. Evidence from the two-dose ATLAS trial suggested that incidence of hypotension may increase with dose of Lisinopril in heart failure patients. Discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed; caution should be observed when initiating therapy (see DOSAGE AND ADMINISTRATION).

Patients at risk of excessive hypotension, sometimes associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death, include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, hyponatremia, high dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, renal dialysis, or severe volume and/or salt depletion of any etiology. It may be advisable to eliminate the diuretic (except in patients with heart failure), reduce the diuretic dose or increase salt intake cautiously before initiating therapy with Lisinopril in patients at risk for excessive hypotension who are able to tolerate such adjustments (see PRECAUTIONS, Drug Interactions and ADVERSE REACTIONS).

Patients with acute myocardial infarction in the GISSI-3 trial had a higher (9.0% versus 3.7%) incidence of persistent hypotension (systolic blood pressure <90 mmHg for more than 1 hour) when treated with Lisinopril. Treatment with Lisinopril must not be initiated in acute myocardial infarction patients at risk of further serious hemodynamic deterioration after treatment with a vasodilator (e.g., systolic blood pressure of 100 mmHg or lower) or cardiogenic shock.

In patients at risk of excessive hypotension, therapy should be started under very close medical supervision and such patients should be followed closely for the first two weeks of treatment and whenever the dose of Lisinopril and/or diuretic is increased. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease, or in patients with acute myocardial infarction, in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

If excessive hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses of Lisinopril which usually can be given without difficulty once the blood pressure has stabilized. If symptomatic hypotension develops, a dose reduction or discontinuation of Lisinopril or concomitant diuretic may be necessary.

Leukopenia/Neutropenia/Agranulocytosis

Another angiotensin-converting enzyme inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression, rarely in uncomplicated patients but more frequently in patients with renal impairment especially if they also have a collagen vascular disease. Available data from clinical trials of Lisinopril are insufficient to show that Lisinopril does not cause agranulocytosis at similar rates. Marketing experience has revealed rare cases of leukopenia/neutropenia and bone marrow depression in which a causal relationship to Lisinopril cannot be excluded. Periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease should be considered.

Hepatic Failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Fetal Toxicity

Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Lisinopril as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Lisinopril, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Lisinopril for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use).

No teratogenic effects of Lisinopril were seen in studies of pregnant rats, mice, and rabbits. On a mg/kg basis, the doses used were up to 625 times (in mice), 188 times (in rats), and 0.6 times (in rabbits) the maximum recommended human dose.

Precautions

General

Aortic Stenosis/Hypertrophic Cardiomyopathy As with all vasodilators, Lisinopril should be given with caution to patients with obstruction in the outflow tract of the left ventricle.

Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors, including Lisinopril, may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death.

In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur. Experience with another angiotensin-converting enzyme inhibitor suggests that these increases are usually reversible upon discontinuation of Lisinopril and/or diuretic therapy. In such patients, renal function should be monitored during the first few weeks of therapy.

Some patients with hypertension or heart failure with no apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when Lisinopril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or Lisinopril may be required.

Patients with acute myocardial infarction in the GISSI-3 trial treated with Lisinopril had a higher (2.4% versus 1.1%) incidence of renal dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration). In acute myocardial infarction, treatment with Lisinopril should be initiated with caution in patients with evidence of renal dysfunction, defined as serum creatinine concentration exceeding 2 mg/dL. If renal dysfunction develops during treatment with Lisinopril (serum creatinine concentration exceeding 3 mg/dL or a doubling from the pre-treatment value) then the physician should consider withdrawal of Lisinopril.

Evaluation of patients with hypertension, heart failure, or myocardial infarction should always include assessment of renal function (see DOSAGE AND ADMINISTRATION).

Hyperkalemia In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in approximately 2.2% of hypertensive patients and 4.8% of patients with heart failure. In most cases these were isolated values which resolved despite continued therapy. Hyperkalemia was a cause of discontinuation of therapy in approximately 0.1% of hypertensive patients; 0.6% of patients with heart failure and 0.1% of patients with myocardial infarction. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes. Hyperkalemia can cause serious, sometimes fatal, arrhythmias. Lisinopril should be used cautiously, if at all, with these agents and with frequent monitoring of serum potassium (see PRECAUTIONS,Drug InteractionsDrug Interactions) .

Cough Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, almost always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Surgery/Anesthesia In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Lisinopril may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Information for Patients

Angioedema Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin-converting enzyme inhibitors, including Lisinopril. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to take no more drug until they have consulted with the prescribing physician.

Symptomatic Hypotension Patients should be cautioned to report lightheadedness especially during the first few days of therapy. If actual syncope occurs, the patient should be told to discontinue the drug until they have consulted with the prescribing physician. All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with their physician.

Hyperkalemia Patients should be told not to use salt substitutes containing potassium without consulting their physician.

Hypoglycemia Diabetic patients treated with oral antidiabetic agents or insulin starting an ACE inhibitor should be told to closely monitor for hypoglycemia, especially during the first month of combined use (see PRECAUTIONS, Drug Interactions).

Leukopenia/Neutropenia Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which may be a sign of leukopenia/neutropenia.

Pregnancy Female patients of childbearing age should be told about the consequences of exposure to Lisinopril during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

NOTE: As with many other drugs, certain advice to patients being treated with Lisinopril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

Drug Interactions

Hypotension – Patients on Diuretic Therapy Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Lisinopril. The possibility of hypotensive effects with Lisinopril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with Lisinopril. If it is necessary to continue the diuretic, initiate therapy with Lisinopril at a dose of 5 mg daily, and provide close medical supervision after the initial dose until blood pressure has stabilized (see WARNINGS, and DOSAGE AND ADMINISTRATION). When a diuretic is added to the therapy of a patient receiving Lisinopril, an additional antihypertensive effect is usually observed. Studies with ACE inhibitors in combination with diuretics indicate that the dose of the ACE inhibitor can be reduced when it is given with a diuretic (see DOSAGE AND ADMINISTRATION).

Antidiabetics Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia. This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment. In diabetic patients treated with oral antidiabetic agents or insulin, glycemic control should be closely monitored for hypoglycemia, especially during the first month of treatment with an ACE inhibitor.

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including Lisinopril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Lisinopril and NSAID therapy.

The antihypertensive effect of ACE inhibitors, including Lisinopril, may be attenuated by NSAIDs.

Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on Lisinopril and other agents that affect the RAS.

Do not co-administer aliskiren with Lisinopril in patients with diabetes. Avoid use of aliskiren with Lisinopril in patients with renal impairment (GFR < 60 ml/min).

Other Agents Lisinopril has been used concomitantly with nitrates and/or digoxin without evidence of clinically significant adverse interactions. This included post myocardial infarction patients who were receiving intravenous or transdermal nitroglycerin. No clinically important pharmacokinetic interactions occurred when Lisinopril was used concomitantly with propranolol or hydrochlorothiazide. The presence of food in the stomach does not alter the bioavailability of Lisinopril.

Agents Increasing Serum Potassium Lisinopril attenuates potassium loss caused by thiazide-type diuretics. Use of Lisinopril with potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium. Potassium-sparing agents should generally not be used in patients with heart failure who are receiving Lisinopril.

Lithium Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. Lithium toxicity was usually reversible upon discontinuation of lithium and the ACE inhibitor. It is recommended that serum lithium levels be monitored frequently if Lisinopril is administered concomitantly with lithium.

Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Lisinopril.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no evidence of a tumorigenic effect when Lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg/kg/day (about 56 or 9 times2 the maximum recommended daily human dose, based on body weight and body surface area, respectively). There was no evidence of carcinogenicity when Lisinopril was administered for 92 weeks to (male and female) mice at doses up to 135 mg/kg/day (about 84 times2 the maximum recommended daily human dose). This dose was 6.8 times the maximum human dose based on body surface area in mice.

Lisinopril was not mutagenic in the Ames microbial mutagen test with or without metabolic activation. It was also negative in a forward mutation assay using Chinese hamster lung cells. Lisinopril did not produce single strand DNA breaks in an in vitro alkaline elution rat hepatocyte assay. In addition, Lisinopril did not produce increases in chromosomal aberrations in an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow.

There were no adverse effects on reproductive performance in male and female rats treated with up to 300 mg/kg/day of Lisinopril. This dose is 188 times and 30 times the maximum human dose when based on mg/kg and mg/m2, respectively.

2Calculations assume a human weight of 50 kg and human body surface area of 1.62 m2.

Nursing Mothers

Milk of lactating rats contains radioactivity following administration of 14C Lisinopril. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ACE inhibitors, a decision should be made whether to discontinue nursing or discontinue Lisinopril, taking into account the importance of the drug to the mother.

Pediatric Use

Neonates with a history of in utero exposure to Lisinopril:

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Lisinopril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion, although there is no experience with the latter procedure.

Antihypertensive effects of Lisinopril have been established in hypertensive pediatric patients aged 6 to 16 years.

There are no data on the effect of Lisinopril on blood pressure in pediatric patients under the age 6 or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2 (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism and Pharmacodynamics and Clinical Effects, and DOSAGE AND ADMINISTRATION).

Geriatric Use

Clinical studies of Lisinopril in patients with hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience in this population has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

In the ATLAS trial of Lisinopril in patients with congestive heart failure, 1,596 (50%) were 65 and over, while 437 (14%) were 75 and over. In a clinical study of Lisinopril in patients with myocardial infarctions 4,413 (47%) were 65 and over, while 1,656 (18%) were 75 and over. In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients, and other reported clinical experiences have not identified differences in responses between the elderly and younger patients (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Heart Failure and CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Acute Myocardial Infarction).

Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Pharmacokinetic studies indicate that maximum blood levels and area under the plasma concentration time curve (AUC) are doubled in older patients (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Evaluation of patients with hypertension, congestive heart failure, or myocardial infarction should always include assessment of renal function (see DOSAGE AND ADMINISTRATION).

Adverse Reactions

Lisinopril has been found to be generally well tolerated in controlled clinical trials involving 1,969 patients with hypertension or heart failure. For the most part, adverse experiences were mild and transient.

Hypertension

In clinical trials in patients with hypertension treated with Lisinopril, discontinuation of therapy due to clinical adverse experiences occurred in 5.7% of patients. The overall frequency of adverse experiences could not be related to total daily dosage within the recommended therapeutic dosage range.

For adverse experiences occurring in greater than 1% of patients with hypertension treated with Lisinopril or Lisinopril plus hydrochlorothiazide in controlled clinical trials, and more frequently with Lisinopril and/or Lisinopril plus hydrochlorothiazide than placebo, comparative incidence data are listed in the table below:

Percent of Patients in Controlled Studies
 

Lisinopril

(n=1,349)

Incidence

(discontinuation)

Lisinopril/

Hydrochlorothiazide

(n=629)

Incidence

(discontinuation)

 

Placebo

(n=207)

Incidence

(discontinuation)

Body as a Whole

Fatigue

2.5 (0.3)

4.0 (0.5)

1.0 (0.0)

Asthenia

1.3 (0.5)

2.1 (0.2)

1.0 (0.0)

Orthostatic

Effects

1.2 (0.0)

3.5 (0.2)

1.0 (0.0)

Cardiovascular

Hypotension

1.2 (0.5)

1.6 (0.5)

0.5 (0.5)

Digestive

Diarrhea

2.7 (0.2)

2.7 (0.3)

2.4 (0.0)

Nausea

2.0 (0.4)

2.5 (0.2)

2.4 (0.0)

Vomiting

1.1 (0.2)

1.4 (0.1)

0.5 (0.0)

Dyspepsia

0.9 (0.0)

1.9 (0.0)

0.0 (0.0)

Musculoskeletal

Muscle Cramps

0.5 (0.0)

2.9 (0.8)

0.5 (0.0)

Nervous/Psychiatric

Headache

5.7 (0.2)

4.5 (0.5)

1.9 (0.0)

Dizziness

5.4 (0.4)

9.2 (1.0)

1.9 (0.0)

Paresthesia

0.8 (0.1)

2.1 (0.2)

0.0 (0.0)

Decreased Libido

0.4 (0.1)

1.3 (0.1)

0.0 (0.0)

Vertigo

0.2 (0.1)

1.1 (0.2)

0.0 (0.0)

Respiratory

Cough

3.5 (0.7)

4.6 (0.8)

1.0 (0.0)

Upper Respiratory

Infection

2.1 (0.1)

2.7 (0.1)

0.0 (0.0)

Common Cold

1.1 (0.1)

1.3 (0.1)

0.0 (0.0)

Nasal Congestion

0.4 (0.1)

1.3 (0.1)

0.0 (0.0)

Influenza

0.3 (0.1)

1.1 (0.1)

0.0 (0.0)

Skin

Rash

1.3 (0.4)

1.6 (0.2)

0.5 (0.5)

Urogenital

Impotence

1.0 (0.4)

1.6 (0.5)

0.0 (0.0)

Chest pain and back pain were also seen, but were more common on placebo than Lisinopril.

Heart Failure

In patients with heart failure treated with Lisinopril for up to four years, discontinuation of therapy due to clinical adverse experiences occurred in 11.0% of patients. In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with Lisinopril for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks.

The following table lists those adverse experiences which occurred in greater than 1% of patients with heart failure treated with Lisinopril or placebo for up to 12 weeks in controlled clinical trials, and more frequently on Lisinopril than placebo.

Controlled Trials

Lisinopril

(n=407)

Incidence

(discontinuation)

12 weeks

Placebo

(n=155)

Incidence

(discontinuation)

12 weeks

Body as a Whole

Chest Pain

3.4 (0.2)

1.3 (0.0)

Abdominal Pain

2.2 (0.7)

1.9 (0.0)

Cardiovascular

Hypotension

4.4 (1.7)

0.6 (0.6)

Digestive

Diarrhea

3.7 (0.5)

1.9 (0.0)

Nervous/Psychiatric

Dizziness

11.8 (1.2)

4.5 (1.3)

Headache

4.4 (0.2)

3.9 (0.0)

Respiratory

Upper Respiratory

Infection

1.5 (0.0)

1.3 (0.0)

Skin

Rash

1.7 (0.5)

0.6 (0.6)

Also observed at >1% with Lisinopril but more frequent or as frequent on placebo than Lisinopril in controlled trials were asthenia, angina pectoris, nausea, dyspnea, cough, and pruritus.

Worsening of heart failure, anorexia, increased salivation, muscle cramps, back pain, myalgia, depression, chest sound abnormalities, and pulmonary edema were also seen in controlled clinical trials, but were more common on placebo than Lisinopril.

In the two-dose ATLAS trial in heart failure patients, withdrawals due to adverse events were not different between the low and high groups, either in total number of discontinuation (17% to 18%) or in rare specific events (<1%). The following adverse events, mostly related to ACE inhibition, were reported more commonly in the high dose group:

*
NPN = non-protein nitrogen
% of Patients

Events

High Dose (N=1,568)

Low Dose

(N=1,596)

Dizziness

18.9

12.1

Hypotension

10.8

6.7

Creatinine Increased

9.9

7.0

Hyperkalemia

6.4

3.5

NPN* Increased

9.2

6.5

Syncope

7.0

5.1

Acute Myocardial Infarction

In the GISSI-3 trial, in patients treated with Lisinopril for six weeks following acute myocardial infarction, discontinuation of therapy occurred in 17.6% of patients.

Patients treated with Lisinopril had a significantly higher incidence of hypotension and renal dysfunction compared with patients not taking Lisinopril.

In the GISSI-3 trial, hypotension (9.7%), renal dysfunction (2.0%), cough (0.5%), post infarction angina (0.3%), skin rash and generalized edema (0.01%), and angioedema (0.01%) resulted in withdrawal of treatment. In elderly patients treated with Lisinopril, discontinuation due to renal dysfunction was 4.2%.

Other clinical adverse experiences occurring in 0.3% to 1.0% of patients with hypertension or heart failure treated with Lisinopril in controlled clinical trials and rarer, serious, possibly drug-related events reported in uncontrolled studies or marketing experience are listed below, and within each category are in order of decreasing severity:

Body as a Whole:Anaphylactoid reactions (see WARNINGS, Anaphylactoid and Possibly Related Reactions), syncope, orthostatic effects, chest discomfort, pain, pelvic pain, flank pain, edema, facial edema, virus infection, fever, chills, malaise.

Cardiovascular:Cardiac arrest; myocardial infarction or cerebrovascular accident possibly secondary to excessive hypotension in high risk patients (see WARNINGS, Hypotension ); pulmonary embolism and infarction, arrhythmias (including ventricular tachycardia, atrial tachycardia, atrial fibrillation, bradycardia and premature ventricular contractions), palpitations, transient ischemic attacks, paroxysmal nocturnal dyspnea, orthostatic hypotension, decreased blood pressure, peripheral edema, vasculitis.

Digestive:Pancreatitis, hepatitis (hepatocellular or cholestatic jaundice) (see WARNINGS, Hepatic Failure), vomiting, gastritis, dyspepsia, heartburn, gastrointestinal cramps, constipation, flatulence, dry mouth.

Hematologic:Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia and thrombocytopenia.

Endocrine:Diabetes mellitus, inappropriate antidiuretic hormone secretion.

Metabolic:Weight loss, dehydration, fluid overload, gout, weight gain. Cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin have been reported in post-marketing experience (see PRECAUTIONS, Drug Interactions).

Musculoskeletal:Arthritis, arthralgia, neck pain, hip pain, low back pain, joint pain, leg pain, knee pain, shoulder pain, arm pain, lumbago.

Nervous System/Psychiatric:Stroke, ataxia, memory impairment, tremor, peripheral neuropathy (e.g., dysesthesia), spasm, paresthesia, confusion, insomnia, somnolence, hypersomnia, irritability, nervousness and mood alterations (including depressive symptoms).

Respiratory System:Malignant lung neoplasms, hemoptysis, pulmonary infiltrates, bronchospasm, asthma, pleural effusion, pneumonia, eosinophilic pneumonitis, bronchitis, wheezing, orthopnea, painful respiration, epistaxis, laryngitis, sinusitis, pharyngeal pain, pharyngitis, rhinitis, rhinorrhea.

Skin:Urticaria, alopecia, herpes zoster, photosensitivity, skin lesions, skin infections, pemphigus, erythema, flushing, diaphoresis, cutaneous pseudolymphoma, psoriasis. Other severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens-Johnson Syndrome; causal relationship has not been established.

Special Senses:Visual loss, diplopia, blurred vision, tinnitus, photophobia, taste disturbances, olfactory disturbance.

Urogenital System:Acute renal failure, oliguria, anuria, uremia, progressive azotemia, renal dysfunction (see PRECAUTIONS and DOSAGE AND ADMINISTRATION), pyelonephritis, dysuria, urinary tract infection, breast pain.

Miscellaneous:A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia and leukocytosis. Rash, photosensitivity or other dermatological manifestations may occur alone or in combination with these symptoms.

Angioedema:Angioedema has been reported in patients receiving Lisinopril with an incidence higher in Black than in non-Black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with Lisinopril should be discontinued and appropriate therapy instituted immediately (see WARNINGS).

In rare cases, intestinal angioedema has been reported in post marketing experience.

Hypotension:In hypertensive patients, hypotension occurred in 1.2% and syncope occurred in 0.1% of patients with an incidence higher in Black than in non-Black patients. Hypotension or syncope was a cause of discontinuation of therapy in 0.5% of hypertensive patients. In patients with heart failure, hypotension occurred in 5.3% and syncope occurred in 1.8% of patients. These adverse experiences were possibly dose-related (see above data from ATLAS Trial) and caused discontinuation of therapy in 1.8% of these patients in the symptomatic trials. In patients treated with Lisinopril for six weeks after acute myocardial infarction, hypotension (systolic blood pressure ≤100 mmHg) resulted in discontinuation of therapy in 9.7% of the patients (see WARNINGS).

Cough:See PRECAUTIONS,Cough.

Pediatric Patients:No relevant differences between the adverse experience profile for pediatric patients and that previously reported for adult patients were identified.

Clinical Laboratory Test Findings

Serum Electrolytes Hyperkalemia (see PRECAUTIONS), hyponatremia.

Creatinine, Blood Urea Nitrogen Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2.0% of patients with essential hypertension treated with Lisinopril alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis (see PRECAUTIONS). Reversible minor increases in blood urea nitrogen and serum creatinine were observed in approximately 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased.

Hemoglobin and Hematocrit Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.4 g% and 1.3 vol%, respectively) occurred frequently in patients treated with Lisinopril but were rarely of clinical importance in patients without some other cause of anemia. In clinical trials, less than 0.1% of patients discontinued therapy due to anemia. Hemolytic anemia has been reported; a causal relationship to Lisinopril cannot be excluded.

Liver Function Tests Rarely, elevations of liver enzymes and/or serum bilirubin have occurred (see WARNINGS, Hepatic Failure).

In hypertensive patients, 2.0% discontinued therapy due to laboratory adverse experiences, principally elevations in blood urea nitrogen (0.6%), serum creatinine (0.5%) and serum potassium (0.4%).

In the heart failure trials, 3.4% of patients discontinued therapy due to laboratory adverse experiences; 1.8% due to elevations in blood urea nitrogen and/or creatinine and 0.6% due to elevations in serum potassium.

In the myocardial infarction trial, 2.0% of patients receiving Lisinopril discontinued therapy due to renal dysfunction (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration); less than 1.0% of patients discontinued therapy due to other laboratory adverse experiences: 0.1% with hyperkalemia and less than 0.1% with hepatic enzyme alterations.

Overdosage

Following a single oral dose of 20 g/kg no lethality occurred in rats, and death occurred in one of 20 mice receiving the same dose. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution.

Lisinopril can be removed by hemodialysis (see WARNINGS, Anaphylactoid Reactions During Membrane Exposure).

Lisinopril Dosage and Administration

Hypertension

Initial Therapy In patients with uncomplicated essential hypertension not on diuretic therapy, the recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 mg to 40 mg per day administered in a single daily dose. The antihypertensive effect may diminish toward the end of the dosing interval regardless of the administered dose, but most commonly with a dose of 10 mg daily. This can be evaluated by measuring blood pressure just prior to dosing to determine whether satisfactory control is being maintained for 24 hours. If it is not, an increase in dose should be considered. Doses up to 80 mg have been used but do not appear to give greater effect. If blood pressure is not controlled with Lisinopril tablets alone, a low dose of a diuretic may be added. Hydrochlorothiazide, 12.5 mg has been shown to provide an additive effect. After the addition of a diuretic, it may be possible to reduce the dose of Lisinopril tablets.

Diuretic Treated Patients In hypertensive patients who are currently being treated with a diuretic, symptomatic hypotension may occur occasionally following the initial dose of Lisinopril tablets. The diuretic should be discontinued, if possible, for two to three days before beginning therapy with Lisinopril tablets to reduce the likelihood of hypotension (see WARNINGS). The dosage of Lisinopril tablets should be adjusted according to blood pressure response. If the patient’s blood pressure is not controlled with Lisinopril tablets alone, diuretic therapy may be resumed as described above.

If the diuretic cannot be discontinued, an initial dose of 5 mg should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS and PRECAUTIONS, Drug Interactions).

Concomitant administration of Lisinopril tablets with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics may lead to increases of serum potassium (see PRECAUTIONS).

Dosage Adjustment in Renal Impairment The usual dose of Lisinopril tablets (10 mg) is recommended for patients with creatinine clearance >30 mL/min (serum creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance ≥10 mL/min ≤30 mL/min (serum creatinine ≥3 mg/dL), the first dose is 5 mg once daily. For patients with creatinine clearance <10 mL/min (usually on hemodialysis) the recommended initial dose is 2.5 mg. The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.

*
See WARNINGS, Anaphylactoid Reactions During Membrane Exposure.
Dosage or dosing interval should be adjusted depending on the blood pressure response.
Renal Status

Creatinine

Clearance

mL/min

Initial

Dose

mg/day

Normal Renal Function

to Mild Impairment

>30

10

Moderate to Severe

Impairment

≥10 ≤30

5

Dialysis Patients*

<10

2.5†

Heart Failure

Lisinopril tablets are indicated as adjunctive therapy with diuretics and (usually) digitalis. The recommended starting dose is 5 mg once a day. When initiating treatment with Lisinopril in patients with heart failure, the initial dose should be administered under medical observation, especially in those patients with low blood pressure (systolic blood pressure below 100 mmHg). The mean peak blood pressure lowering occurs six to eight hours after dosing. Observation should continue until blood pressure is stable. The concomitant diuretic dose should be reduced, if possible, to help minimize hypovolemia which may contribute to hypotension (see WARNINGS and PRECAUTIONS, Drug Interactions). The appearance of hypotension after the initial dose of Lisinopril tablets does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

The usual effective dosage range is 5 mg to 40 mg per day administered as a single daily dose. The dose of Lisinopril tablets can be increased by increments of no greater than 10 mg, at intervals of no less than 2 weeks to the highest tolerated dose, up to a maximum of 40 mg daily. Dose adjustment should be based on the clinical response of individual patients.

Dosage Adjustment in Patients with Heart Failure and Renal Impairment or Hyponatremia  In patients with heart failure who have hyponatremia (serum sodium <130 mEq/L) or moderate to severe renal impairment (creatinine clearance ≤30 mL/min or serum creatinine >3 mg/dL), therapy with Lisinopril tablets should be initiated at a dose of 2.5 mg once a day under close medical supervision (see WARNINGS and PRECAUTIONS, Drug Interactions).

Acute Myocardial Infarction

In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, the first dose of Lisinopril tablets is 5 mg given orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg of Lisinopril tablets once daily. Dosing should continue for six weeks. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin, and beta-blockers.

Patients with a low systolic blood pressure (≤120 mmHg) when treatment is started or during the first 3 days after the infarct should be given a lower 2.5 mg oral dose of Lisinopril tablets (see WARNINGS). If hypotension occurs (systolic blood pressure ≤100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure <90 mmHg for more than 1 hour) Lisinopril tablets should be withdrawn. For patients who develop symptoms of heart failure, see DOSAGE AND ADMINISTRATION, Heart Failure.

Dosage Adjustment in Patients with Myocardial Infarction with Renal Impairment In acute myocardial infarction, treatment with Lisinopril tablets should be initiated with caution in patients with evidence of renal dysfunction, defined as serum creatinine concentration exceeding 2 mg/dL. No evaluation of dosing adjustments in myocardial infarction patients with severe renal impairment has been performed.

Use in Elderly

In general, the clinical response was similar in younger and older patients given similar doses of Lisinopril tablets. Pharmacokinetic studies, however indicate that maximum blood levels and area under the plasma concentration time curve (AUC) are doubled in older patients, so that dosage adjustments should be made with particular caution.

Pediatric Hypertensive Patients ≥ 6 Years of Age

The usual recommended starting dose is 0.07 mg/kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response. Doses above 0.61 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism and Pharmacodynamics and Clinical Effects).

Lisinopril tablets are not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2 (see CLINICALPHARMACOLOGY, Pharmacokinetics and Metabolism and Pharmacodynamics and Clinical Effects and  PRECAUTIONSPRECAUTIONS).

Preparation of Suspension (for 200 mL of a 1.0 mg/mL suspension)

Add 10 mL of Purified Water USP to a polyethylene terephthalate (PET) bottle containing ten 20 mg tablets of Lisinopril and shake for at least one minute. Add 30 mL of Bicitra®3 diluent and 160 mL of Ora-Sweet SF™4to the concentrate in the PET bottle and gently shake for several seconds to disperse the ingredients. The suspension should be stored at or below 25°C (77°F) and can be stored for up to four weeks. Shake the suspension before each use.

3 Registered trademark of Alza Corporation

4 Trademark of Paddock Laboratories, Inc.

How is Lisinopril Supplied

Lisinopril Tablets USP, for oral administration, are available as:

2.5 mg: White, oval, biconvex, uncoated tablets debossed “E  25” on one side and plain on the other side and supplied as:

NDC 0185-0025-01 bottles of 100

NDC 0185-0025-10 bottles of 1000

5 mg: Pink, oval, biconvex, uncoated tablets debossed “ 54” on one side and bisected on the other side and supplied as:

NDC 0185-5400-01 bottles of 100

NDC 0185-5400-10 bottles of 1000

10 mg: Pink, oval, biconvex, uncoated tablets debossed “ 101” on one side and plain on the other side and supplied as:

NDC 0185-0101-01 bottles of 100

NDC 0185-0101-10 bottles of 1000

NDC 0185-0101-33 bottles of 3000

20 mg: Peach, oval, biconvex, uncoated tablets debossed “ 102” on one side and plain on the other side and supplied as:

NDC 0185-0102-01 bottles of 100

NDC 0185-0102-10 bottles of 1000

NDC 0185-0102-33 bottles of 3000

30 mg: Red, oval, biconvex, uncoated tablets debossed “E  103” on one side and plain on the other side and supplied as:

NDC 0185-0103-01 bottles of 100

NDC 0185-0103-10 bottles of 1000

40 mg: Yellow, oval, biconvex, uncoated tablets debossed “ 104” on one side and plain on the other side and supplied as:

NDC 0185-0104-01 bottles of 100

NDC 0185-0104-10 bottles of 1000

Storage

Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Protect from moisture, freezing and excessive heat. Dispense in a tight container.

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Sandoz Inc.

Princeton, NJ 08540

OS7708

Rev. 12/12

MF0025REV12/12

Lisinopril Tablets USP, 2.5 mg x 100 Tablets – Label

NDC 0185-0025-01

Lisinopril Tablets USP

2.5 mg

Rx only

100 Tablets

Sandoz

Lisinopril Tablets USP, 5 mg x 100 Tablets – Label

NDC 0185-5400-01

Lisinopril Tablets USP

5 mg

Rx only

100 Tablets

Sandoz

Lisinopril Tablets USP, 10 mg x 100 Tablets – Label

NDC 0185-0101-01

Lisinopril Tablets USP

10 mg

Rx only

100 Tablets

Sandoz

Lisinopril Tablets USP, 20 mg x 100 Tablets – Label

NDC 0185-0102-01

Lisinopril Tablets USP

20 mg

Rx only

100 Tablets

Sandoz

Lisinopril Tablets USP, 30 mg x 100 Tablets – Label

NDC 0185-0103-01

Lisinopril Tablets USP

30 mg

Rx only

100 Tablets

Sandoz

Lisinopril Tablets USP, 40 mg x 100 Tablets – Label

NDC 0185-0104-01

Lisinopril Tablets USP

40 mg

Rx only

100 Tablets

Sandoz

Lisinopril 

Lisinopril tablet

Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0185-0025
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Lisinopril (Lisinopril ANHYDROUS) Lisinopril 2.5 mg
Inactive Ingredients
Ingredient Name Strength
CALCIUM PHOSPHATE  
MAGNESIUM STEARATE  
MANNITOL  
STARCH, CORN  
Product Characteristics
Color WHITE Score no score
Shape OVAL Size 8mm
Flavor Imprint Code E25
Contains         
Packaging
# Item Code Package Description
1 NDC:0185-0025-10 1000 TABLET in 1 BOTTLE
2 NDC:0185-0025-01 100 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075994 07/01/2002
Lisinopril 

Lisinopril tablet

Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0185-5400
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Lisinopril (Lisinopril ANHYDROUS) Lisinopril 5 mg
Inactive Ingredients
Ingredient Name Strength
CALCIUM PHOSPHATE  
MAGNESIUM STEARATE  
MANNITOL  
FERRIC OXIDE RED  
STARCH, CORN  
Product Characteristics
Color PINK Score 2 pieces
Shape OVAL Size 8mm
Flavor Imprint Code E54
Contains         
Packaging
# Item Code Package Description
1 NDC:0185-5400-10 1000 TABLET in 1 BOTTLE
2 NDC:0185-5400-01 100 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075994 07/01/2002
Lisinopril 

Lisinopril tablet

Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0185-0101
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Lisinopril (Lisinopril ANHYDROUS) Lisinopril 10 mg
Inactive Ingredients
Ingredient Name Strength
CALCIUM PHOSPHATE  
MAGNESIUM STEARATE  
MANNITOL  
STARCH, CORN  
Product Characteristics
Color PINK Score 2 pieces
Shape OVAL Size 10mm
Flavor Imprint Code E101
Contains         
Packaging
# Item Code Package Description
1 NDC:0185-0101-01 100 TABLET in 1 BOTTLE
2 NDC:0185-0101-10 1000 TABLET in 1 BOTTLE
3 NDC:0185-0101-33 3000 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075994 07/01/2002
Lisinopril 

Lisinopril tablet

Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0185-0102
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Lisinopril (Lisinopril ANHYDROUS) Lisinopril 20 mg
Inactive Ingredients
Ingredient Name Strength
CALCIUM PHOSPHATE  
MAGNESIUM STEARATE  
MANNITOL  
FERRIC OXIDE RED  
STARCH, CORN  
FERRIC OXIDE YELLOW  
Product Characteristics
Color ORANGE Score 2 pieces
Shape OVAL Size 10mm
Flavor Imprint Code E102
Contains         
Packaging
# Item Code Package Description
1 NDC:0185-0102-01 100 TABLET in 1 BOTTLE
2 NDC:0185-0102-10 1000 TABLET in 1 BOTTLE
3 NDC:0185-0102-33 3000 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075994 07/01/2002
Lisinopril 

Lisinopril tablet

Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0185-0103
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Lisinopril (Lisinopril ANHYDROUS) Lisinopril 30 mg
Inactive Ingredients
Ingredient Name Strength
CALCIUM PHOSPHATE  
MAGNESIUM STEARATE  
MANNITOL  
FERRIC OXIDE RED  
STARCH, CORN  
Product Characteristics
Color RED Score 2 pieces
Shape OVAL Size 10mm
Flavor Imprint Code E103
Contains         
Packaging
# Item Code Package Description
1 NDC:0185-0103-10 1000 TABLET in 1 BOTTLE
2 NDC:0185-0103-01 100 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075994 07/01/2002
Lisinopril 

Lisinopril tablet

Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0185-0104
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Lisinopril (Lisinopril ANHYDROUS) Lisinopril 40 mg
Inactive Ingredients
Ingredient Name Strength
CALCIUM PHOSPHATE  
MAGNESIUM STEARATE  
MANNITOL  
STARCH, CORN  
FERRIC OXIDE YELLOW  
Product Characteristics
Color YELLOW Score 2 pieces
Shape OVAL Size 10mm
Flavor Imprint Code E104
Contains         
Packaging
# Item Code Package Description
1 NDC:0185-0104-01 100 TABLET in 1 BOTTLE
2 NDC:0185-0104-10 1000 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075994 07/01/2002
Labeler - Eon Labs, Inc. (012656273)

Revised: 01/2013   Eon Labs, Inc.

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Lisinopril

Lisinopril

Pronunciation Pronunciation: lye-SIN-oh-pril

Class: ACE inhibitor

For ProfessionalsSide EffectsDosageInteractionsMore…

Trade Names

Prinivil

– Tablets 10 mg

– Tablets 20 mg

Zestril

– Tablets 2.5 mg

– Tablets 5 mg

– Tablets 10 mg

– Tablets 20 mg

– Tablets 30 mg

– Tablets 40 mg

Apo-Lisinopril (Canada)

Pharmacology

Competitively inhibits angiotensin-converting enzyme; prevents angiotensin I conversion to angiotensin II, a potent vasoconstrictor that also stimulates aldosterone secretion. Results in decrease in sodium and fluid retention, decrease in BP, and increase in diuresis.

Pharmacokinetics

Absorption

T max is about 7 h.

Distribution

Does not appear to be bound to other serum proteins.

Metabolism

Does not undergo metabolism.

Elimination

The t ½ is 12 h. Excreted via the kidney; excreted unchanged entirely in the urine. Lisinopril can be removed by hemodialysis.

Onset

1 h.

Peak

6 h.

Duration

24 h.

Special Populations

Renal Function Impairment

Decreased elimination when glomerular filtration rate is 30 mL/min or less.

Race

Black patients with hypertension had a smaller response to monotherapy of ACE inhibitor.

CHF (New York Heart Association class II through IV) Bioavailability decreases about 16% and Vd is slightly smaller.

Indications and Usage

Treatment of hypertension; treatment of heart failure not responding to diuretics and digitalis; treatment of acute MI within 24 h in hemodynamically stable patients.

Unlabeled Uses

Migraine prophylaxis.

Contraindications

Hypersensitivity to ACE inhibitors; hereditary or idiopathic angioedema.

Dosage and Administration

CHF

Adults Initial dose PO 5 mg every day with diuretics and digitalis; reduce concomitant diuretic dose, if possible, to minimize hypovolemia.

Dose adjustment for hyponatremia (serum sodium less than 130 mEq/L) or moderate to severe renal function impairment (CrCl 30 mL/min or less or serum creatinine greater than 3 mg/dL) PO Start with 2.5 mg once daily.

Usual dose PO 5 to 40 mg once daily.

Hypertension

Adults PO

Initial dose 10 mg once daily. If a diuretic is coadministered, start with lisinopril 5 mg (under medical supervision) for at least 2 h and until BP has stabilized for at least 1 additional h.

Maintenance 20 to 40 mg/day; may add diuretic if needed and decrease lisinopril dose.

Renal function impairment Moderate to severe function impairment (CrCl 10 mL/min or more to 30 mL/min or less) 5 mg/day as initial dose.

Dialysis (CrCl less than 10 mL/min) 2.5 mg/day as initial dose.

Children (6 yr of age and older) PO Start with 0.07 mg/kg every day (up to 5 mg). Adjust dose according to BP response. Doses above 0.61 mg/kg (or in excess of 40 mg) have not been studied. Not recommended in children with glomerular filtration rate less than 30 mL/min per 1.73 m 2 .

MI

Adults Initial dose PO 5 mg, then 5 mg after 24 h, then 10 mg after 48 h.

Dose adjustment PO In patients with low systolic BP (120 mm Hg or less) or when treatment is started during the first 3 days after infarct, administer 2.5 mg. If hypotension occurs (systolic BP 100 mm Hg or less) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic BP less than 90 mm Hg for more than 1 h), discontinue treatment.

Maintenance PO 10 mg/day for 6 wk. Patients should receive, as appropriate, the standard recommended treatments, such as thrombolytics, aspirin, and beta-blockers.

Renal function impairment (CrCl exceeding 2 mg/dL) Use with caution.

General Advice

  • Give prescribed dose without regard to meals. Administer with food if GI upset occurs.
  • Preparation of suspension: Add 10 mL of purified water to a polyethylene terephthalate bottle containing ten 20 mg tablets of lisinopril and shake for at least 1 minute. Add 30 mL of Bacitra diluent and 160 mL of OraSweet SF and shake gently for several seconds.

Storage/Stability

Tablets Store tablets at 68° to 77°F. Protect from moisture, freezing, and excessive heat.

Suspension Store suspension at controlled room temperature (below 77°F). Discard any unused suspension after 28 days.

Drug Interactions

Antacids Lisinopril bioavailability may be decreased. Separate administration times by 1 to 2 h.

Antidiabetic agents Risk of hypoglycemia may be increased.

Capsaicin Cough may be exacerbated.

Digoxin May increase or decrease plasma digoxin levels.

Diuretics Excessive decrease in blood pressure may occur.

Gold therapy (eg, aurothiomalate) Nitritoid reactions, including facial flushing, nausea, vomiting, and hypotension, may occur.

Indomethacin, salicylates (eg, aspirin) Reduced hypotensive effects, especially in low-renin or volume-dependent hypertensive patients.

Lithium Increased lithium levels and symptoms of lithium toxicity.

NSAIDs Increased risk of renal function impairment.

Phenothiazines May increase pharmacological effect of lisinopril.

Potassium-sparing diuretics, potassium preparations May increase serum potassium levels.

Laboratory Test Interactions

False elevation of liver enzymes or serum bilirubin may occur.

Adverse Reactions

Cardiovascular

Hypotension (10%); orthostatic effects (1%); cardiac arrest, cerebral vascular accident, MI.

CNS

Dizziness (12%); headache (6%); fatigue (3%); stroke.

Dermatologic

Rash (2%); Stevens-Johnson syndrome, toxic epidermal necrolysis.

EENT

Visual loss.

GI

Diarrhea (4%); nausea (2%); vomiting (1%).

Genitourinary

Renal function impairment (2%); impotence (1%); acute renal failure, anuria, oliguria, progressive azotemia, uremia.

Hematologic

Bone marrow depression; hemolytic anemia; leukopenia/neutropenia; thrombocytopenia.

Hepatic

Hepatocellular or cholestatic jaundice.

Metabolic

Hyperkalemia.

Respiratory

Cough (4%); upper respiratory tract infections (2%); common cold (1%); malignant lung neoplasm.

Miscellaneous

Chest pain (3%); abdominal pain (2%); asthenia (1%); anaphylactoid reactions; angioedema; symptom complex that includes a positive antinuclear antibody, elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, and leukocytosis.

Precautions

Warnings

Pregnancy When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.

Monitor

Frequently monitor serum potassium in patients with risk factors for hyperkalemia (eg, renal insufficiency, diabetes mellitus, concomitant use of potassium supplements).

Pregnancy

Category D (second and third trimester); Category C (first trimester). Can cause injury or death to fetus if used during the second or third trimester.

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 6 yr of age.

Elderly

Use with caution, usually starting at the low end of the dosage range because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Renal Function

Reduce dose and give less frequently. In renal function impairment, stable elevations in BUN and serum creatinine may occur because of inadequate renal perfusion; monitor renal function during first few weeks of therapy and adjust dosage carefully, especially if glomerular filtration rate is less than 30 mL/min.

Angioedema

Use with extreme caution in patients with hereditary angioedema. Angioedema of the face, extremities, lips, tongue, glottis, larynx, and intestine has been reported in patients treated with ACE inhibitors.

Aortic stenosis/hypertrophic cardiomyopathy

As with other vasodilators, use lisinopril with caution in patients with obstruction in the outflow tract of the left ventricle.

Hepatic failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.

Hypotension/First-dose effect

Significant decreases in BP may occur after first dose, especially in severely salt- or volume-depleted patients or those with heart failure. Minimize risk by discontinuing diuretics, decreasing dose, or increasing salt intake approximately 1 wk prior to initiating drug.

Neutropenia and agranulocytosis

May occur; risk appears greater in patients with renal function impairment, heart failure, or immunosuppression.

Surgery/Anesthesia

Risk of hypotension may be increased.

Overdosage

Symptoms

Hypotension.

Patient Information

  • Advise patient to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
  • Advise patient or caregiver to shake suspension well before measuring dose and administer prescribed dose using dosing cup, spoon, or syringe.
  • Advise patient to try to take each dose at about the same time each day.
  • Inform hypertensive patient that drug controls, but does not cure, hypertension and to continue taking drug as prescribed even when BP is not elevated.
  • Instruct patient to continue taking other medications for the condition as prescribed by health care provider.
  • Instruct patient in BP and pulse measurement skills.
  • Advise patient to monitor and record BP and pulse at home and to inform health care provider should abnormal measurements be noted. Also advise patient to take record of BP and pulse to each follow-up visit.
  • Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patient to lie or sit down if experiencing dizziness or light-headedness when standing.
  • Emphasize to hypertensive patient the importance of other modalities on BP control: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
  • Emphasize to heart failure patient the importance of other modalities that can help control heart failure symptoms: weight control, progressive exercise program, smoking cessation, and moderate intake of alcohol and salt.
  • Advise heart failure patient to weigh daily, keep a record of daily weights, and notify health care provider if rapid weight gain (eg, 5 pounds in 1 wk) is noted or if edema or shortness of breath is getting worse.
  • Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in light-headedness or fainting.
  • Advise patient that medication may cause dizziness or light-headedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Caution patient to avoid unnecessary exposure to ultraviolet (UV) light (eg, sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
  • Instruct patient to stop taking drug and immediately report any of these symptoms to health care provider: chest pains; difficulty breathing; fainting; fever; irregular heartbeat; sore throat; swelling of the face, lips, eyelids, or tongue; or swelling of the hands or feet.
  • Instruct patient to inform health care provider if a persistent cough develops while taking this medication.
  • Caution patient not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, or dietary supplements unless advised by health care provider.

Copyright © 2009 Wolters Kluwer Health.

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lisinopril

lisinopril

Pronunciation Generic Name: lisinopril (lyse IN oh pril)

Brand Name: Prinivil, Zestril

OverviewSide EffectsDosageInteractionsFor ProfessionalsMore…

What is lisinopril?

Lisinopril is in a group of drugs called ACE inhibitors. ACE stands for angiotensin converting enzyme.

Lisinopril is used to treat high blood pressure (hypertension), congestive heart failure, and to improve survival after a heart attack.

Lisinopril may also be used for purposes not listed in this medication guide.

What is the most important information I should know about lisinopril?

Do not use lisinopril if you are pregnant. It could harm the unborn baby. Stop using this medication and tell your doctor right away if you become pregnant.

Drinking alcohol can further lower your blood pressure and may increase certain side effects of lisinopril.

Do not use salt substitutes or potassium supplements while taking lisinopril, unless your doctor has told you to.

Vomiting, diarrhea, or heavy sweating can cause you to become dehydrated. This can lead to very low blood pressure, electrolyte disorders, or kidney failure while you are taking lisinopril. Drink plenty of water each day while you are taking this medication.

What should I discuss with my healthcare provider before taking lisinopril?

Do not use this medication if you are allergic to lisinopril or to any other ACE inhibitor, such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).

To make sure you can safely take lisinopril, tell your doctor if you have any of these other conditions:

  • kidney disease (or if you are on dialysis);

  • liver disease;
  • heart disease or congestive heart failure;
  • diabetes; or
  • a connective tissue disease such as Marfan syndrome, Sjogren’s syndrome, lupus, scleroderma, or rheumatoid arthritis.

If you have diabetes or kidney disease, you may not be able to take lisinopril if you are also taking aliskiren (Tekturna, Tekamlo, Valturna, Amturnide).

FDA pregnancy category D. Do not use lisinopril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Lisinopril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking lisinopril.

It is not known whether lisinopril passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take lisinopril?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Take each dose with a full glass of water.

Lisinopril can be taken with or without food.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low salt diet, or taking diuretics (water pills). Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

Your blood pressure will need to be checked often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using lisinopril. You may need to stop using the medicine for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture and heat.

See also: Lisinopril dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include feeling extremely dizzy or light-headed, or fainting.

What should I avoid while taking lisinopril?

Drinking alcohol can further lower your blood pressure and may increase certain side effects of lisinopril.

Do not use salt substitutes or potassium supplements while taking lisinopril, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Lisinopril side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain, difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • feeling like you might pass out;

  • urinating less than usual or not at all;
  • swelling, rapid weight gain;
  • fever, chills, body aches, flu symptoms;
  • tired feeling, muscle weakness, and pounding or uneven heartbeats;
  • psoriasis (raised, silvery flaking of the skin);
  • chest pain; or
  • high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling);

Less serious side effects may include:

  • cough;

  • dizziness, drowsiness, headache;
  • depressed mood;
  • nausea, vomiting, diarrhea, upset stomach; or
  • mild skin itching or rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

See also: lisinopril side effects (in more detail)

Lisinopril Dosing Information

Usual Adult Dose for Hypertension:

Initial dose: 10 mg orally once a day, in patients not receiving a diuretic.

Maintenance dose: 20 to 40 mg orally once a day.

Some patients appear to have a further response to 80 mg, but experience with this dose is limited.

Usual Adult Dose for Congestive Heart Failure:

Initial dose: 5 mg orally once a day (If on diuretic, the diuretic dose should be reduced).

Maintenance dose: 5 to 20 mg orally once a day.

Usual Adult Dose for Myocardial Infarction:

Initial dose: 5 mg orally (within 24 hours of the onset of acute myocardial infarction).

Subsequent doses: 5 mg orally after 24 hours.

10 mg orally after 48 hours.

Maintenance dose: 10 mg orally once a day. Dosing should continue for six weeks.

Patients with a low systolic blood pressure (<=120 mm Hg) when treatment is started or during the first 3 days after the infarct should be given a lower 2.5 mg oral dose of lisinopril. If hypotension occurs (systolic blood pressure <=100 mm Hg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure <90 mm Hg for more than 1 hour), lisinopril should be withdrawn.

Usual Adult Dose for Diabetic Nephropathy:

Initial dose: 10 to 20 mg orally once a day.

Maintenance dose: 20 to 40 mg orally once a day.

Dosage may be titrated upward every 3 days.

Usual Geriatric Dose for Hypertension:

Initial dose: 2.5 to 5 mg orally once a day.

Maintenance dose: Dosages should be increased at 2.5 to 5 mg/day increments at 1 to 2 week intervals.

Maximum dose: 40 mg/day.

Usual Pediatric Dose for Hypertension:

Pediatric patients greater than or equal to 6 years of age:

Initial dose: 0.07 mg/kg once daily (Maximum initial dose is 5 mg once daily)

Maintenance dose: Dosage should be adjusted according to blood pressure response at 1 to 2 week intervals.

Maximum dose: Doses above 0.61 mg/kg or greater than 40 mg have not been studied in pediatric patients.

What other drugs will affect lisinopril?

Tell your doctor about all other medicines you use, especially:

  • any other blood pressure medications;

  • gold injections to treat arthritis;
  • lithium (Lithobid, Eskalith);
  • a potassium supplement such as K-Dur, Klor-Con;
  • salt substitutes that contain potassium;
  • insulin or diabetes medication you take by mouth;
  • aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others; or
  • a diuretic (water pill).

This list is not complete and other drugs may interact with lisinopril. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Next Page → Side Effects

More lisinopril resources

  • Side Effects
  • Recommended Dosage
  • Pregnancy Warnings
  • Drug Images
  • Drug Interactions
  • Support Group
  • 185 Reviews - Add your own review/rating
  • lisinopril Advanced Consumer (Micromedex) – Includes Dosage Information
  • lisinopril MedFacts Consumer Leaflet (Wolters Kluwer)
  • Lisinopril Professional Patient Advice (Wolters Kluwer)
  • Lisinopril Prescribing Information (FDA)
  • Lisinopril Monograph (AHFS DI)
  • Lisinopril
  • Prinivil Prescribing Information (FDA)
  • Prinivil Consumer Overview
  • Zestril Prescribing Information (FDA)
  • Zestril Consumer Overview

Compare lisinopril with other medications

  • Alport Syndrome
  • Coronary Artery Disease
  • Diabetic Kidney Disease
  • Heart Attack
  • Heart Failure
  • High Blood Pressure
  • Migraine Prevention

Where can I get more information?

  • Your pharmacist can provide more information about lisinopril.

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Lisinopril

Lisinopril

Pronunciation Generic Name: lisinopril (lye-SIN-oh-pril)

Brand Name: Examples include Prinivil and Zestril

Lisinopril may cause injury or death to the fetus if taken during pregnancy. If you think you may be pregnant, contact your doctor right away. If you are planning to become pregnant, talk with your doctor about other treatment options.

OverviewSide EffectsDosageInteractionsFor ProfessionalsMore…

Lisinopril is used for:

Treating high blood pressure alone or with other medicines. It is used along with other medicines to manage heart failure or improve survival after a heart attack. It may also be used for other conditions as determined by your doctor.

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor. It works by relaxing blood vessels. This helps to lower blood pressure.

Do NOT use lisinopril if:

  • you are allergic to any ingredient in lisinopril
  • you have a history of angioedema (swelling of the hands, face, lips, eyes, throat, or tongue; difficulty swallowing or breathing; or hoarseness), including angioedema caused by treatment with an ACE inhibitor
  • you are pregnant
  • the patient is a CHILD with severe kidney problems
  • you are also taking aliskiren and you have either diabetes or kidney problems

Contact your doctor or health care provider right away if any of these apply to you.

Before using lisinopril:

Some medical conditions may interact with lisinopril. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

  • if you are pregnant, planning to become pregnant, or are breast-feeding
  • if you are able to become pregnant
  • if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
  • if you have allergies to medicines (including other ACE inhibitors, such as ramipril), foods, or other substances
  • if you have a history of heart problems (eg, heart failure, aortic stenosis), blood vessel problems, blood flow problems, bone marrow problems, diabetes, liver problems, or kidney problems (eg, renal artery stenosis)
  • if you have a history of stroke, recent heart attack, or kidney transplant
  • if you have an autoimmune disease (eg, rheumatoid arthritis, lupus, scleroderma)
  • if you are dehydrated or have low blood volume
  • if you have high blood potassium levels, low blood sodium levels, or are on a low-salt (sodium) diet
  • if you are on dialysis, or are scheduled to have surgery or receive anesthesia
  • if you are receiving treatments to reduce sensitivity to bee or wasp stings
  • if you are taking another medicine to treat high blood pressure

Some MEDICINES MAY INTERACT with lisinopril. Tell your health care provider if you are taking any other medicines, especially any of the following:

  • Dextran sulfate or diuretics (eg, furosemide, hydrochlorothiazide) because they may increase the risk of lisinopril’s side effects, such as low blood pressure
  • Everolimus or sirolimus because the risk of angioedema may be increased
  • Aliskiren or angiotensin II receptor blockers (eg, valsartan) because the risk of certain side effects (eg, kidney problems, high blood potassium levels, low blood pressure) may be increased
  • Eplerenone, potassium-sparing diuretics (eg, amiloride, spironolactone, triamterene), potassium supplements, or trimethoprim because the risk of high blood potassium levels may be increased
  • Insulin or other oral diabetes medicines (eg, glyburide, metformin) because the risk of low blood sugar may be increased
  • Certain gold-containing medicines (eg, sodium aurothiomalate) because flushing, nausea, vomiting, and low blood pressure may occur
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen, indomethacin, celecoxib) because they may decrease lisinopril’s effectiveness and the risk of kidney problems may be increased
  • Lithium or thiopurines (eg, azathioprine) because the risk of their side effects may be increased by lisinopril

This may not be a complete list of all interactions that may occur. Ask your health care provider if lisinopril may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use lisinopril:

Use lisinopril as directed by your doctor. Check the label on the medicine for exact dosing instructions.

  • Take lisinopril by mouth with or without food.
  • Taking lisinopril at the same time each day will help you remember to take it.
  • Drink plenty of fluids while taking lisinopril. Not drinking enough fluids or excessive sweating, diarrhea, or vomiting can lead to light-headedness or fainting.
  • Continue to take lisinopril even if you feel well. Do not miss any doses.
  • If you miss a dose of lisinopril, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use lisinopril.

Important safety information:

  • Lisinopril may cause dizziness, light-headedness, or fainting. These effects may be worse if you take it with alcohol or certain medicines. Use lisinopril with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.
  • Lisinopril may cause a serious side effect called angioedema. The risk may be higher in black patients. Contact your doctor at once if you develop swelling of the hands, face, lips, eyes, throat, or tongue; difficulty swallowing or breathing; or hoarseness.
  • Lisinopril may not work as well in black patients. Contact your doctor if your symptoms do not improve or if they become worse.
  • It may take 2 to 4 weeks to get the full benefit from lisinopril. Do not stop using lisinopril or change your dose of lisinopril without checking with your doctor.
  • Lisinopril may cause a dry, unproductive cough. If caused by lisinopril, this symptom usually stops after treatment with lisinopril is stopped.
  • Dehydration, excessive sweating, vomiting, or diarrhea may increase the risk of low blood pressure. Contact your health care provider at once if any of these occur.
  • Lisinopril may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to lisinopril. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.
  • Rarely, lisinopril may lower the ability of your body to fight infection. This risk may be greater if you have certain other health problems (eg, kidney problems, collagen vascular disease). Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.
  • Check with your doctor before you use a salt substitute or a product that has potassium in it.
  • Tell your doctor or dentist that you take lisinopril before you receive any medical or dental care, emergency care, or surgery.
  • Patients who take medicine for high blood pressure often feel tired or run down for a few weeks after starting treatment. Be sure to take your medicine even if you may not feel “normal.” Tell your doctor if you develop any new symptoms.
  • If you have high blood pressure, do not use nonprescription products that contain stimulants. These products may include diet pills or cold medicines. Contact your doctor if you have any questions or concerns.
  • Diabetes patients – Lisinopril may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.
  • Lab tests, including blood pressure, blood electrolyte levels, heart function, or kidney or liver function, may be performed while you use lisinopril. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.
  • Use lisinopril with caution in the ELDERLY; they may be more sensitive to its effects.
  • Lisinopril should be used with extreme caution in CHILDREN younger than 6 years old; safety and effectiveness in these children have not been confirmed.
  • PREGNANCY AND BREAST-FEEDING: Lisinopril may cause birth defects or fetal death if you take it while you are pregnant. If you think you may be pregnant, contact your doctor right away. It is not known if lisinopril is found in breast milk. Do not breast-feed while taking lisinopril.

Possible side effects of lisinopril:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Cough; diarrhea; dizziness; headache; tiredness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the hands, eyes, mouth, face, lips, or tongue; hoarseness); chest pain; decreased urination; fast, slow, or irregular heartbeat; shortness of breath; stomach pain (with or without nausea or vomiting); symptoms of infection (eg, fever, chills, persistent sore throat); symptoms of liver problems (eg, dark urine, loss of appetite, pale stools, yellowing of the skin or eyes); symptoms of low blood pressure (eg, fainting, severe dizziness, light-headedness).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fainting; severe dizziness or light-headedness.

Proper storage of lisinopril: Store lisinopril at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Do not freeze. Store away from heat, moisture, and light. Do not store in the bathroom. Keep lisinopril out of the reach of children and away from pets.

General information:

  • If you have any questions about lisinopril, please talk with your doctor, pharmacist, or other health care provider.
  • Lisinopril is to be used only by the patient for whom it is prescribed. Do not share it with other people.
  • If your symptoms do not improve or if they become worse, check with your doctor.
  • Check with your pharmacist about how to dispose of unused medicine.

This information should not be used to decide whether or not to take lisinopril or any other medicine. Only your health care provider has the knowledge and training to decide which medicines are right for you. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about lisinopril. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to lisinopril. This information is not specific medical advice and does not replace information you receive from your health care provider. You must talk with your healthcare provider for complete information about the risks and benefits of using lisinopril.

Issue Date: March 6, 2013 Database Edition 13.1.1.003 Copyright © 2013 Wolters Kluwer Health, Inc.

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