Lisinopril: Package Insert and Label Information

LISINOPRIL- lisinopril tablet
REMEDYREPACK INC.

WARNING: FETAL TOXICITY

  • When pregnancy is detected, discontinue lisinopril as soon as possible [see WARNINGS AND PRECAUTIONS ( 5.1)] .
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see WARNINGS AND PRECAUTIONS ( 5.1)] .

1 INDICATIONS AND USAGE

1.1 Hypertension

Lisinopril tablet USP is indicated for the treatment of hypertension in adult patients and pediatric patients 6 years of age and older 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.

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 [see CLINICAL STUDIES ( 14.1)] .

1.2 Heart Failure

Lisinopril tablet USP is indicated to reduce signs and symptoms of systolic heart failure [see CLINICAL STUDIES ( 14.2)] .

1.3 Reduction of Mortality in Acute Myocardial Infarction

Lisinopril tablet USP is indicated for the reduction of mortality in treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blockers [see CLINICAL STUDIES ( 14.3)].

2 DOSAGE AND ADMINISTRATION

2.1 Hypertension

Initial Therapy in adults: 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. Doses up to 80 mg have been used but do not appear to give greater effect.

Use with Diuretics in Adults

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

The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day.

Pediatric Patients 6 Years of Age and Older with Hypertension

For pediatric patients with glomerular filtration rate > 30 mL/min/1.73m 2 , the recommended starting dose is 0.07 mg per kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg per kg (up to 40 mg) once daily. Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients [see CLINICAL PHARMACOLOGY ( 12.3)] .

Lisinopril tablet USP is not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m 2 [see USE IN SPECIFIC POPULATIONS ( 8.4) and CLINICAL STUDIES ( 14.1)] .

2.2 Heart Failure

The recommended starting dose for lisinopril, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily.

Diuretic dose may need to be adjusted to help minimize hypovolemia, which may contribute to hypotension [see WARNINGS AND PRECAUTIONS ( 5.4), and DRUG INTERACTIONS ( 7.1)] . The appearance of hypotension after the initial dose of lisinopril does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

2.3 Reduction of Mortality in Acute Myocardial Infarction

In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give lisinopril tablets USP 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for at least six weeks.

Initiate therapy with 2.5 mg in patients with a low systolic blood pressure (≤ 120 mmHg and > 100 mm Hg) during the first 3 days after the infarct [see WARNINGS AND PRECAUTIONS ( 5.4)] . 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 should be withdrawn.

2.4 Dose in Patients with Renal Impairment

No dose adjustment of lisinopril is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of lisinopril to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2.5 mg. Up titrate as tolerated to a maximum of 40 mg daily. For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily [see USE IN SPECIFIC POPULATIONS ( 8.7) and CLINICAL PHARMACOLOGY ( 12.3)] .

3 DOSAGE FORMS AND STRENGTHS

2.5 mg tablet is a white to off-white, round, biconvex, uncoated tablet with “LUPIN” debossed on one side and “2.5” on other side.

5 mg tablet is a pink coloured, round, biconvex, uncoated tablet with “5” debossed on one side and breakline on other side.

10 mg tablet is a pink coloured, round, biconvex, uncoated tablet with “LUPIN” debossed on one side and “10” on other side.

20 mg tablet is a pink coloured, round, biconvex, uncoated tablet with “LUPIN” debossed on one side and “20” on other side.

30 mg tablet is a red coloured, round, biconvex, uncoated tablet with “LUPIN” debossed on one side and “30” on other side.

40 mg tablet is a yellow coloured, round, biconvex, uncoated tablet with “LUPIN” debossed on one side and “40” on other side.

4 CONTRAINDICATIONS

Lisinopril is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Lisinopril tablet USP within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see WARNINGS and PRECAUTIONS ( 5.2)].

Lisinopril is contraindicated in patients with:

  • a history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme inhibitor
  • hereditary or idiopathic angioedema

Do not co-administer aliskiren with lisinopril in patients with diabetes [see DRUG INTERACTIONS ( 7.4)].

5 WARNINGS AND PRECAUTIONS

5.1 Fetal Toxicity

Lisinopril can cause fetal harm when administered to a pregnant woman. 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 [see USE IN SPECIFIC POPULATIONS ( 8.1)] .

5.2 Angioedema and Anaphylactoid Reactions

Patients taking concomitant mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema. [see DRUG INTERACTIONS ( 7.7, 7.8)].

Angioedema

Head and Neck Angioedema:

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, have occurred in patients treated with angiotensin converting enzyme inhibitors, including lisinopril, at any time during treatment. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Lisinopril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor [see CONTRAINDICATIONS ( 4)]. ACE inhibitors have been associated with a higher rate of angioedema in black than in non-black patients.

Intestinal Angioedema:

Intestinal angioedema has occurred 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. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.

Anaphylactoid Reactions

Anaphylactoid Reactions During Desensitization:

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.

Anaphylactoid Reactions During Dialysis :

Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes 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.

5.3 Impaired Renal Function

Monitor renal function periodically in patients treated with lisinopril. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on lisinopril. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril [see ADVERSE REACTIONS ( 6.1), DRUG INTERACTIONS ( 7.4)] .

5.4 Hypotension

Lisinopril can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology.

In these patients, lisinopril 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. Avoid use of lisinopril in patients who are hemodynamically unstable after acute MI.

Symptomatic hypotension is also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy.

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.

5.5 Hyperkalemia

Serum potassium should be monitored periodically in patients receiving lisinopril. Drugs that inhibit the renin angiotensin system can cause hyperkalemia. 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 [see DRUG INTERACTIONS ( 7.1)] .

5.6 Hepatic Failure

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 treatment.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Hypertension

In clinical trials in patients with hypertension treated with lisinopril, 5.7% of patients on lisinopril discontinued with adverse reactions.

The following adverse reactions (events 2% greater on lisinopril than on placebo) were observed with lisinopril alone: headache (by 3.8%), dizziness (by 3.5%), cough (by 2.5%).

Heart Failure

In patients with systolic heart failure treated with lisinopril for up to four years, 11% discontinued therapy with adverse reactions. 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 adverse reactions (events 2% greater on lisinopril than on placebo) were observed with lisinopril: hypotension (by 3.8%), chest pain (by 2.1%).

In the two-dose ATLAS trial [see CLINICAL STUDIES ( 14.2)] in heart failure patients, withdrawals due to adverse reactions were not different between the low and high groups, either in total number of discontinuation (17 to 18%) or in rare specific reactions (< 1%). The following adverse reactions, mostly related to ACE inhibition, were reported more commonly in the high dose group:

Table 1 Dose-related Adverse Drug Reactions: ATLAS trial
High Dose ( n = 1568 ) Low Dose ( n = 1596 )
Dizziness 19% 12%
Hypotension 11% 7%
Creatinine increased 10% 7%
Hyperkalemia 6% 4%
Syncope 7% 5%

Acute Myocardial Infarction

Patients treated with lisinopril had a higher incidence of hypotension (by 5.3%) and renal dysfunction (by 1.3%) compared with patients not taking lisinopril.

Other clinical adverse reactions occurring in 1 % or higher of patients with hypertension or heart failure treated with lisinopril in controlled clinical trials and do not appear in other sections of labeling are listed below:

Body as a whole:

Fatigue, asthenia, orthostatic effects.

Digestive:

Pancreatitis, constipation, flatulence, dry mouth, diarrhea.

Hematologic:

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

Endocrine:

Diabetes mellitus, inappropriate antidiuretic hormone secretion.

Metabolic:

Gout.

Skin:

Urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, cutaneous pseudolymphoma, toxic epidermal necrolysis, Stevens-Johnson syndrome, and pruritus.

Special Senses:

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

Urogenital:

Impotence.

Miscellaneous:

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

Clinical Laboratory Test Findings

Serum Potassium:

In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in 2.2% and 4.8% of lisinopril-treated patients with hypertension and heart failure, respectively [see WARNINGS AND PRECAUTIONS ( 5.5)] .

Creatinine, Blood Urea Nitrogen:

Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with hypertension treated with lisinopril alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis [see WARNINGS AND PRECAUTIONS ( 5.4)] . Reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased.

Patients with acute myocardial infarction in the GISSI-3 trial treated with lisinopril had a higher (2.4% versus 1.1% in placebo) 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).

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.

Page 1 of 3 1 2 3

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2021. All Rights Reserved.