LISINOPRIL TABLETS, USP, Rx only

/LISINOPRIL TABLETS, USP, Rx only
LISINOPRIL TABLETS, USP, Rx only2018-09-06T09:12:40+00:00

Prescription Drug Name:

LISINOPRIL TABLETS, USP, Rx only

ID:

65d4f363-5958-40be-e053-2991aa0a0239

Code:

34391-3

DESCRIPTION


id: 65d4f363-5912-40be-e053-2991aa0a0239
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Lisinopril is an oral long-acting angiotensin converting enzyme inhibitor. Lisinopril, a synthetic peptide derivative, is chemically described as (S)-1-[
N
2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate. Its empirical formula is C
21H
31N
3O
5• 2H
2O 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 is supplied as 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg and 40 mg tablets for oral administration.

CONTRAINDICATIONS


id: 65d4f363-5915-40be-e053-2991aa0a0239
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Lisinopril tablet 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.

ADVERSE REACTIONS


id: 65d4f363-5918-40be-e053-2991aa0a0239
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Lisinopril has been found to be generally well tolerated in controlled clinical trials involving 1969 patients with hypertension or heart failure. For the most part, adverse experiences were mild and transient. HypertensionIn 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=1349)

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 (0.00)
Chest pain and back pain were also seen, but were more common on placebo than lisinopril. Heart FailureIn 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:
% of Patients

Events

 High Dose

(N=1568)

 Low Dose

(N=1596)

 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 InfarctionIn 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


id: 65d4f363-5919-40be-e053-2991aa0a0239
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

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 ).

HOW SUPPLIED


id: 65d522dd-68a9-8513-e053-2991aa0ad5ef
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Lisinopril Tablets 5 mg are white, capsule shaped, convex, bisected tablets, debossed “42/10” on one side and “V” on the reverse side; and supplied as follows: NDC 60760-266-30 BOTTLES OF 30 60760-266-90 BOTTLES OF 90

PRINCIPAL DISPLAY PANEL


id: 65d4f363-5920-40be-e053-2991aa0a0239
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4