Lisinopril

REMEDYREPACK INC.

FULL PRESCRIBING INFORMATION: CONTENTS*

• BOXED WARNING
• WARNINGS
• LISINOPRIL DESCRIPTION
• INACTIVE INGREDIENT
• CLINICAL PHARMACOLOGY
• MECHANISM OF ACTION
• PRECAUTIONS
• PHARMACOKINETICS
• PHARMACODYNAMICS
• CLINICAL STUDIES
• LISINOPRIL ADVERSE REACTIONS
• LISINOPRIL CONTRAINDICATIONS
• DRUG INTERACTIONS
• TERATOGENIC EFFECTS
• INFORMATION FOR PATIENTS
• NURSING MOTHERS
• PEDIATRIC USE
• GERIATRIC USE
• OVERDOSAGE
• WARNINGS AND PRECAUTIONS
• HOW SUPPLIED
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

WARNINGS

LISINOPRIL DESCRIPTION

INACTIVE INGREDIENT

Inactive ingredients: colloidal silicon dioxide, dibasic calcium phosphate, FDandC Blue No 2 Aluminum Lake (10mg only), FDandC Yellow No 5 Aluminum Lake (20 mg, 30 mg, and 40 mg, only), magnesium stearate, mannitol, pregelatinized starch.

CLINICAL PHARMACOLOGY

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 percent 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 4percent 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 reninangiotensin-
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.

MECHANISM OF ACTION

PRECAUTIONS

PHARMACOKINETICS

PHARMACODYNAMICS

CLINICAL STUDIES

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 (50percent) were 65 and over, while 437 (14percent) were
75 and over. In a clinical study of lisinopril in patients with myocardial infarctions 4,413 (47percent) were 65 and over, while 1,656
(18percent) 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 has 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).
This product contains FD andC Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain
susceptible persons. Although the overall incidence of FD andC Yellow No.5 (tartrazine) sensitivity in the general population is low, it is
frequently seen in patients who also have aspirin hypersensitivity.

LISINOPRIL ADVERSE REACTIONS

LISINOPRIL CONTRAINDICATIONS

DRUG INTERACTIONS

TERATOGENIC EFFECTS

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.

INFORMATION FOR PATIENTS

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 second- and third-trimester exposure to
ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE inhibitor
exposure that has been limited to the first trimester. These 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.

NURSING MOTHERS

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

PEDIATRIC USE

Pediatric Use: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 withglomerular filtration rate < 30 mL/min/1.73 m2. (See CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism andPharmacodynamics and Clinical Effects, and DOSAGE AND ADMINISTRATION.)

GERIATRIC USE

OVERDOSAGE

OVERDOSAGEFollowing 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 ofnormal saline solution.Lisinopril can be removed by hemodialysis. (See WARNINGS, Anaphylactoid Reactions During Membrane Exposure.) page 12 of 13 DOSAGE AND ADMINISTRATIONHypertensionInitial Therapy: In patients with uncomplicated essential hypertension not on diuretic therapy, the recommended initial dose is 10mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 to 40 mg per dayadministered in a single daily dose. The antihypertensive effect may diminish toward the end of the dosing interval regardless ofthe administered dose, but most commonly with a dose of 10 mg daily. This can be evaluated by measuring blood pressure justprior to dosing to determine whether satisfactory control is being maintained for 24 hours. If it is not, an increase in dose shouldbe considered. Doses up to 80 mg have been used but do not appear to give greater effect. If blood pressure is not controlled withlisinopril 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.Diuretic Treated Patients: In hypertensive patients who are currently being treated with a diuretic, symptomatic hypotension mayoccur occasionally following the initial dose of lisinopril. The diuretic should be discontinued, if possible, for two to three days beforebeginning therapy with lisinopril tablet to reduce the likelihood of hypotension. (See WARNINGS.) The dosage of lisinopril shouldbe adjusted according to blood pressure response. If the patient's blood pressure is not controlled with lisinopril alone, diuretic therapymay 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 untilblood pressure has stabilized for at least an additional hour.

WARNINGS AND PRECAUTIONS

HOW SUPPLIED

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL