ENALAPRIL MALEATE

Main information

  • Trade name:
  • ENALAPRIL MALEATE- enalapril maleate tablet
  • Composition:
  • ENALAPRIL MALEATE 20 mg
  • Administration route:
  • ORAL
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ENALAPRIL MALEATE- enalapril maleate tablet
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • Enalapril maleate is indicated for the treatment of hypertension. Enalapril maleate is effective alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. The blood pressure lowering effects of enalapril maleate and thiazides are approximately additive. Enalapril maleate is indicated for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis. In these patients enalapril maleate improves symptoms, increases survival, and decreases the frequency of hospitalization (see CLINICAL PHARMACOLOGY, Heart Failure, Mortality Trials for details and limitations of survival trials). In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction ≤35 percent), enalapril maleate decreases the rate of development of overt heart failure and decreases the incidence of hospitalization for heart failure (see CLINICAL PHARMACOLOGY, Heart Failure, Mortality Trials for details and limitations of survival trial
  • Product summary:
  • 5mg White, round flat-faced beveled edged, compressed tablets with W 924 on one side and breakline on the other side. NDC: 60760-0227-30 bottle of 30 20mg Light Beige, round flat-faced beveled edged, compressed tablets with 926 on one side, plain on the other side. NDC: 60760-0226-30 BOTTLE OF 30 Store below 30°C (86°F) and avoid transient temperatures above 50°C (122°F). Keep container tightly closed. Protect from moisture. Dispense in a tight container as per USP, if product package is subdivided. ** Registered trademark of Alza Corporation. *** Trademark of Paddock Laboratories, Inc. Manufactured by: Wockhardt Limited, Mumbai, India. Distributed by: Wockhardt USA LLC. 20 Waterview Blvd. Parsippany, NJ 07054 USA. Rev.111213

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 60760-226-30, 60760-227-30
  • Last update:
  • 27-05-2019

Summary of Product characteristics: dosage, interactions, side effects

ENALAPRIL MALEATE- enalapril maleate tablet

St Marys Medical Park Pharmacy

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ENALAPRIL MALEATE TABLETS, USP

Rx only

WARNING: FETAL TOXICITY

See full prescribing information for complete boxed warning.

When pregnancy is detected, discontinue enalapril maleate 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

DESCRIPTION

Enalapril maleate is the maleate salt of enalapril, the ethyl ester of a long-acting angiotensin converting

enzyme inhibitor, enalaprilat. Enalapril maleate is chemically described as (S)-1-[ N-[1-

(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline, ( Z)-2-butenedioate salt (1:1). Its molecular

formula is, C

C

, and its structural formula is:

Enalapril maleate is a white to off-white, crystalline powder with a molecular weight of 492.53. It is

sparingly soluble in water, soluble in ethanol, and freely soluble in methanol.

Enalapril is a pro-drug; following oral administration, it is bioactivated by hydrolysis of the ethyl ester

to enalaprilat, which is the active angiotensin converting enzyme inhibitor.

Enalapril maleate is supplied as 2.5 mg, 5 mg, 10 mg, and 20 mg tablets for oral administration. In

addition to the active ingredient enalapril maleate, each tablet contains the following inactive

ingredients: hypromellose, anhydrous lactose, corn starch, stearic acid and talc. The 10 mg and 20 mg

tablets also contain iron oxides.

CLINICAL PHARMACOLOGY

Mechanism of Action

Enalapril, after hydrolysis to enalaprilat, 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 enalapril 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. Although the latter decrease is small, it results in small increases of serum

potassium. In hypertensive patients treated with enalapril alone for up to 48 weeks, mean increases in

serum potassium of approximately 0.2 mEq/L were observed. In patients treated with enalapril plus a

thiazide diuretic, there was essentially no change in serum potassium (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 enalapril remains to

be elucidated.

While the mechanism through which enalapril lowers blood pressure is believed to be primarily

suppression of the renin-angiotensin- aldosterone system, enalapril is antihypertensive even in patients

with low-renin hypertension. Although enalapril was antihypertensive in all races studied, black

hypertensive patients (usually a low-renin hypertensive population) had a smaller average response to

enalapril monotherapy than non-black patients.

Pharmacokinetics and Metabolism

Following oral administration of enalapril maleate, peak serum concentrations of enalapril occur within

about one hour. Based on urinary recovery, the extent of absorption of enalapril is approximately 60

percent. Enalapril absorption is not influenced by the presence of food in the gastrointestinal tract.

Following absorption, enalapril is hydrolyzed to enalaprilat, which is a more potent angiotensin

converting enzyme inhibitor than enalapril; enalaprilat is poorly absorbed when administered orally.

Peak serum concentrations of enalaprilat occur three to four hours after an oral dose of enalapril

maleate. Excretion of enalapril is primarily renal. Approximately 94 percent of the dose is recovered in

the urine and feces as enalaprilat or enalapril. The principal components in urine are enalaprilat,

accounting for about 40 percent of the dose, and intact enalapril. There is no evidence of metabolites of

enalapril, other than enalaprilat.

The serum concentration profile of enalaprilat exhibits a prolonged terminal phase, apparently

representing a small fraction of the administered dose that has been bound to ACE. The amount bound

does not increase with dose, indicating a saturable site of binding. The effective half-life for

accumulation of enalaprilat following multiple doses of enalapril maleate is 11 hours. The disposition

of enalapril and enalaprilat in patients with renal insufficiency is similar to that in patients with normal

renal function until the glomerular filtration rate is 30 mL/min or less. With glomerular filtration rate

≤30 mL/min, peak and trough enalaprilat levels increase, time to peak concentration increases and time to

steady state may be delayed. The effective half-life of enalaprilat following multiple doses of enalapril

maleate is prolonged at this level of renal insufficiency (see DOSAGE AND ADMINISTRATION).

Enalaprilat is dialyzable at the rate of 62 mL/min.

Studies in dogs indicate that enalapril crosses the blood-brain barrier poorly, if at all; enalaprilat does

not enter the brain. Multiple doses of enalapril maleate in rats do not result in accumulation in any

tissues. Milk of lactating rats contains radioactivity following administration of

C-enalapril maleate.

Radioactivity was found to cross the placenta following administration of labeled drug to pregnant

hamsters.

Pharmacodynamics and Clinical Effects

Hypertension

Administration of enalapril to patients with hypertension of severity ranging from mild to severe results

in a reduction of both supine and standing blood pressure usually with no orthostatic component.

Symptomatic postural hypotension is therefore infrequent, although it might be anticipated in volume-

depleted patients (see WARNINGS).

In most patients studied, after oral administration of a single dose of enalapril, onset of antihypertensive

activity was seen at one hour with peak reduction of blood pressure achieved by four to six hours.

At recommended doses, antihypertensive effects have been maintained for at least 24 hours. In some

patients the effects may diminish toward the end of the dosing interval (see DOSAGE AND

ADMINISTRATION).

In some patients achievement of optimal blood pressure reduction may require several weeks of

therapy.

The antihypertensive effects of enalapril have continued during long term therapy. Abrupt withdrawal

of enalapril has not been associated with a rapid increase in blood pressure.

In hemodynamic studies in patients with essential hypertension, blood pressure reduction was

accompanied by a reduction in peripheral arterial resistance with an increase in cardiac output and little

or no change in heart rate. Following administration of enalapril, there is an increase in renal blood

flow; glomerular filtration rate is usually unchanged. The effects appear to be similar in patients with

renovascular hypertension.

When given together with thiazide-type diuretics, the blood pressure lowering effects of enalapril are

approximately additive.

In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients

receiving enalapril. In this study there was no evidence of a blunting of the antihypertensive action of

enalapril (see PRECAUTIONS, Drug Interactions).

Heart Failure

In trials in patients treated with digitalis and diuretics, treatment with enalapril resulted in decreased

systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure and heart size, and

increased cardiac output and exercise tolerance. Heart rate was unchanged or slightly reduced, and

mean ejection fraction was unchanged or increased. There was a beneficial effect on severity of heart

failure as measured by the New York Heart Association (NYHA) classification and on symptoms of

dyspnea and fatigue. Hemodynamic effects were observed after the first dose, and appeared to be

maintained in uncontrolled studies lasting as long as four months. Effects on exercise tolerance, heart

size, and severity and symptoms of heart failure were observed in placebo-controlled studies lasting

from eight weeks to over one year.

Heart Failure, Mortality Trials

In a multicenter, placebo-controlled clinical trial, 2,569 patients with all degrees of symptomatic heart

failure and ejection fraction ≤35 percent were randomized to placebo or enalapril and followed for up

to 55 months (Solvd-Treatment). Use of enalapril was associated with an 11 percent reduction in all-

cause mortality and a 30 percent reduction in hospitalization for heart failure. Diseases that excluded

patients from enrollment in the study included severe stable angina (>2 attacks/day), hemodynamically

significant valvular or outflow tract obstruction, renal failure (creatinine >2.5 mg/dL), cerebral vascular

disease (e.g., significant carotid artery disease), advanced pulmonary disease, malignancies, active

myocarditis and constrictive pericarditis. The mortality benefit associated with enalapril does not

appear to depend upon digitalis being present.

A second multicenter trial used the SOLVD protocol for study of asymptomatic or minimally

symptomatic patients. SOLVD-Prevention patients, who had left ventricular ejection fraction ≤35% and

no history of symptomatic heart failure, were randomized to placebo (n=2117) or enalapril (n=2111) and

followed for up to 5 years. The majority of patients in the SOLVD-Prevention trial had a history of

ischemic heart disease. A history of myocardial infarction was present in 80 percent of patients,

current angina pectoris in 34 percent, and a history of hypertension in 37 percent. No statistically

significant mortality effect was demonstrated in this population. Enalapril-treated subjects had 32%

fewer first hospitalizations for heart failure, and 32% fewer total heart failure hospitalizations.

Compared to placebo, 32 percent fewer patients receiving enalapril developed symptoms of overt heart

failure. Hospitalizations for cardiovascular reasons were also reduced. There was an insignificant

reduction in hospitalizations for any cause in the enalapril treatment group (for enalapril vs. placebo,

respectively, 1166 vs. 1201 first hospitalizations, 2649 vs. 2840 total hospitalizations), although the

study was not powered to look for such an effect.

The SOLVD-Prevention trial was not designed to determine whether treatment of asymptomatic patients

with low ejection fraction would be superior, with respect to preventing hospitalization, to closer

follow-up and use of enalapril at the earliest sign of heart failure. However, under the conditions of

follow-up in the SOLVD-Prevention trial (every 4 months at the study clinic; personal physician as

needed), 68% of patients on placebo who were hospitalized for heart failure had no prior symptoms

recorded which would have signaled initiation of treatment.

The SOLVD-Prevention trial was also not designed to show whether enalapril modified the

progression of underlying heart disease.

In another multicenter, placebo-controlled trial (CONSENSUS) limited to patients with NYHA Class IV

congestive heart failure and radiographic evidence of cardiomegaly, use of enalapril was associated

with improved survival. The results are shown in the following table.

SURVIVAL (%)

Six Months

One Year

Enalapril Maleate (n=127)

Placebo (n=126)

Clinical Pharmacology in Pediatric Patients

A multiple dose pharmacokinetic study was conducted in 40 hypertensive male and female pediatric

patients aged 2 months to ≤16 years following daily oral administration of 0.07 to 0.14 mg/kg enalapril

maleate. At steady state, the mean effective half-life for accumulation of enalaprilat was 14 hours and

the mean urinary recovery of total enalapril and enalaprilat in 24 hours was 68% of the administered

dose. Conversion of enalapril to enalaprilat was in the range of 63-76%. The overall results of this

study indicate that the pharmacokinetics of enalapril in hypertensive children aged 2 months to ≤16 years

are consistent across the studied age groups and consistent with pharmacokinetic historic data in healthy

adults.

In a clinical study involving 110 hypertensive pediatric patients 6 to 16 years of age, patients who

weighed <50 kg received either 0.625, 2.5 or 20 mg of enalapril daily and patients who weighed ≥50 kg

received either 1.25, 5, or 40 mg of enalapril daily. Enalapril administration once daily lowered trough

blood pressure in a dose-dependent manner. The dose-dependent antihypertensive efficacy of enalapril

was consistent across all subgroups (age, Tanner stage, gender, race). However, the lowest doses

studied, 0.625 mg and 1.25 mg, corresponding to an average of 0.02 mg/kg once daily, did not appear to

offer consistent antihypertensive efficacy. In this study, enalapril maleate was generally well tolerated.

In the above pediatric studies, enalapril maleate was given as tablets of enalapril maleate and for those

children and infants who were unable to swallow tablets or who required a lower dose than is available

in tablet form, enalapril was administered in a suspension formulation (see Preparation of Suspension

under DOSAGE AND ADMINISTRATION).

INDICATIONS AND USAGE

Hypertens ion

Enalapril maleate is indicated for the treatment of hypertension.

Enalapril maleate is effective alone or in combination with other antihypertensive agents, especially

thiazide-type diuretics. The blood pressure lowering effects of enalapril maleate and thiazides are

approximately additive.

Heart Failure

Enalapril maleate is indicated for the treatment of symptomatic congestive heart failure, usually in

combination with diuretics and digitalis. In these patients enalapril maleate improves symptoms,

increases survival, and decreases the frequency of hospitalization (see CLINICAL

PHARMACOLOGY, Heart Failure, Mortality Trials for details and limitations of survival trials).

Asymptomatic Left Ventricular Dysfunction

In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction ≤35

percent), enalapril maleate decreases the rate of development of overt heart failure and decreases the

incidence of hospitalization for heart failure (see CLINICAL PHARMACOLOGY, Heart Failure,

Mortality Trials for details and limitations of survival trials).

In using enalapril maleate 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 enalapril maleate does not

have a similar risk (see WARNINGS).

In considering use of enalapril maleate 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, it

should be noted that black patients receiving ACE inhibitors have been reported to have a higher

incidence of angioedema compared to non-blacks (see WARNINGS, Head and Neck Angioedema).

CONTRAINDICATIONS

Enalapril maleate 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.

Do not co-administer aliskiren with enalapril maleate in patients with diabetes (see PRECAUTIONS,

Drug Interactions).

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 enalapril

maleate) 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 enalapril maleate. This may occur at

any time during treatment. In such cases enalapril maleate should be promptly discontinued and

appropriate therapy and monitoring should be provided until complete and sustained resolution of signs

and symptoms has occurred. In instances where swelling has been confined to the face and lips the

condition has generally resolved without treatment, although antihistamines have been useful in

relieving symptoms. Angioedema associated with laryngeal edema may be fatal. 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

Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated

concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients

undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Hypotens ion

Excessive hypotension is rare in uncomplicated hypertensive patients treated with enalapril maleate

alone. Patients with heart failure given enalapril maleate commonly have some reduction in blood

pressure, especially with the first dose, but discontinuation of therapy for 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 for

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, 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 enalapril maleate in patients at risk for excessive

hypotension who are able to tolerate such adjustments (see PRECAUTIONS, Drug Interactions and

ADVERSE REACTIONS). In patients at risk for 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 enalapril and/or diuretic is increased. Similar

considerations may apply to patients with ischemic heart or cerebrovascular disease, 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 enalapril maleate, which usually can be given without difficulty

once the blood pressure has stabilized. If symptomatic hypotension develops, a dose reduction or

discontinuation of enalapril maleate or concomitant diuretic may be necessary.

Neutropenia/Agranulocytos is

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 enalapril are insufficient to show that enalapril does not cause agranulocytosis at similar rates.

Marketing experience has revealed cases of neutropenia or agranulocytosis in which a causal

relationship to enalapril 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 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 enalapril maleate tablets 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 enalapril maleate tablets, 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 enalapril maleate tablets for hypotension, oliguria, and

hyperkalemia [see PRECAUTIONS, Pediatric use].

No teratogenic effects of enalapril were seen in studies of pregnant rats and rabbits. On a body surface

area basis, the doses used were 57 times and 12 times, respectively, the maximum recommended human

daily dose (MRHDD).

PRECAUTIONS

General

Aortic Stenosis/Hypertrophic Cardiomyopathy:

As with all vasodilators, enalapril 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 heart failure whose renal function may

depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin

converting enzyme inhibitors, including enalapril maleate, may be associated with oliguria and/or

progressive azotemia and rarely with acute renal failure and/or death [see PRECAUTIONS, Drug

Interaction].

In clinical studies in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in

blood urea nitrogen and serum creatinine were observed in 20 percent of patients. These increases

were almost always reversible upon discontinuation of enalapril 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 and serum creatinine, usually minor and transient, especially

when enalapril maleate 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 enalapril maleate may be required.

Evaluation of patients with hypertension or heart failure should always include assessment of

renal function (s ee DOSAGE AND ADMINISTRATION).

Hyperkalemia:

Elevated serum potassium (greater than 5.7 mEq/L) was observed in approximately one percent of

hypertensive patients in clinical trials. In most cases these were isolated values which resolved despite

continued therapy. Hyperkalemia was a cause of discontinuation of therapy in 0.28 percent of

hypertensive patients. In clinical trials in heart failure, hyperkalemia was observed in 3.8 percent of

patients but was not a cause for discontinuation.

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, which should be used cautiously, if at all, with enalapril maleate (see Drug Interactions).

Cough:

Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive

cough has been reported with all ACE inhibitors, 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,

enalapril 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 enalapril. 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.

Hypotension:

Patients should be cautioned to report light headedness, especially during the first few days of therapy.

If actual syncope occurs, the patients 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 the physician.

Hyperkalemia:

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

physician.

Neutropenia:

Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which may

be a sign of neutropenia.

Pregnancy:

Female patients of childbearing age should be told about the consequences of exposure to enalapril

maleate tablets 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 enalapril 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

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 enalapril maleate tablets and other agents that affect the RAS.

Do not co-administer aliskiren with enalapril maleate in patients with diabetes. Avoid use of aliskiren

with enalapril maleate in patients with renal impairment (GFR <60 ml/min).

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

enalapril. The possibility of hypotensive effects with enalapril can be minimized by either discontinuing

the diuretic or increasing the salt intake prior to initiation of treatment with enalapril. If it is necessary to

continue the diuretic, provide close medical supervision after the initial dose for at least two hours and

until blood pressure has stabilized for at least an additional hour (see WARNINGS and DOSAGE AND

ADMINISTRATION).

Agents Causing Renin Release:

The antihypertensive effect of enalapril maleate is augmented by antihypertensive agents that cause

renin release (e.g., diuretics).

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 enalapril, may result in deterioration of renal function, including possible acute

renal failure. These effects are usually reversible. Monitor renal function periodically in patients

receiving enalapril and NSAID therapy.

In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients

receiving enalapril maleate. In this study there was no evidence of a blunting of the antihypertensive

action of enalapril maleate. However, reports suggest that NSAIDs may diminish the antihypertensive

effect of ACE inhibitors.

Other Cardiovascular Agents:

Enalapril maleate has been used concomitantly with beta adrenergic-blocking agents, methyldopa,

nitrates, calcium-blocking agents, hydralazine, prazosin and digoxin without evidence of clinically

significant adverse interactions.

Agents Increasing Serum Potassium:

Enalapril maleate attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing

diuretics (e.g., Spironolactone, 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 receiving enalapril maleate.

Lithium:

Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause

elimination of sodium, including ACE inhibitors. A few cases of lithium toxicity have been reported in

patients receiving concomitant enalapril maleate and lithium and were reversible upon discontinuation of

both drugs. It is recommended that serum lithium levels be monitored frequently if enalapril 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 enalapril maleate.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no evidence of a tumorigenic effect when enalapril was administered for 106 weeks to male

and female rats at doses up to 90 mg/kg/day or for 94 weeks to male and female mice at doses up to 90

and 180 mg/kg/day, respectively. These doses are 26 times (in rats and female mice) and 13 times (in

male mice) the maximum recommended human daily dose (MRHDD) when compared on a body surface

area basis.

Neither enalapril maleate nor the active diacid was mutagenic in the Ames microbial mutagen test with

or without metabolic activation. Enalapril was also negative in the following genotoxicity studies: rec-

assay, reverse mutation assay with E. coli, sister chromatid exchange with cultured mammalian cells, and

the micronucleus test with mice, as well as in an in vivo cytogenic study using mouse bone marrow.

There were no adverse effects on reproductive performance of male and female rats treated with up to

90 mg/kg/day of enalapril (26 times the MRHDD when compared on a body surface area basis).

Pregnancy

Nursing Mothers

Enalapril and enalaprilat have been detected in human breast milk. Because of the potential for serious

adverse reactions in nursing infants from enalapril, a decision should be made whether to discontinue

nursing or to discontinue enalapril maleate, taking into account the importance of the drug to the mother.

Pediatric Use

Neonates with a history of in utero exposure to enalapril maleate

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. Enalapril, 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 enalapril maleate have been established in hypertensive pediatric patients

age 1 month to 16 years. Use of enalapril maleate in these age groups is supported by evidence from

adequate and well-controlled studies of enalapril maleate in pediatric and adult patients as well as by

published literature in pediatric patients (see CLINICAL PHARMACOLOGY, Clinical

Pharmacology in Pediatric Patients and DOSAGE AND ADMINISTRATION).

Enalapril maleate is not recommended in neonates and in pediatric patients with glomerular filtration rate

<30 mL/min/1.73 m

, as no data are available.

ADVERSE REACTIONS

Enalapril maleate has been evaluated for safety in more than 10,000 patients, including over 1000

patients treated for one year or more. Enalapril maleate has been found to be generally well tolerated in

controlled clinical trials involving 2987 patients.

For the most part, adverse experiences were mild and transient in nature. In clinical trials,

discontinuation of therapy due to clinical adverse experiences was required in 3.3 percent of patients

with hypertension and in 5.7 percent of patients with heart failure. The frequency of adverse

experiences was not related to total daily dosage within the usual dosage ranges. In patients with

hypertension the overall percentage of patients treated with enalapril maleate reporting adverse

experiences was comparable to placebo.

HYPERTENSION

Adverse experiences occurring in greater than one percent of patients with hypertension treated with

enalapril maleate in controlled clinical trials are shown below. In patients treated with enalapril maleate,

the maximum duration of therapy was three years; in placebo treated patients the maximum duration of

therapy was 12 weeks.

Enalapril Maleate

(n=2314)

Incidence

(discontinuation)

Placebo

(n=230)

Incidence

Body As A Whole

Fatigue

3.0 (<0.1)

Orthostatic Effects

1.2 (<0.1)

Asthenia

1.1 (0.1)

Digestive

Diarrhea

1.4 (<0.1)

Nausea

1.4 (0.2)

Nervous/Psychiatric

Headache

5.2 (0.3)

Dizziness

4.3 (0.4)

Respiratory

Cough

1.3 (0.1)

Skin

Rash

1.4 (0.4)

HEART FAILURE

Adverse experiences occurring in greater than one percent of patients with heart failure treated with

enalapril maleate are shown below. The incidences represent the experiences from both controlled and

uncontrolled clinical trials (maximum duration of therapy was approximately one year). In the placebo

treated patients, the incidences reported are from the controlled trials (maximum duration of therapy is

12 weeks). The percentage of patients with severe heart failure (NYHA Class IV) was 29 percent and

43 percent for patients treated with enalapril maleate and placebo, respectively.

Enalapril Maleate

(n=673)

Placebo

(n=339)

Incidence

(discontinuation)

Incidence

Body As A Whole

Orthostatic Effects

2.2 (0.1)

Syncope

2.2 (0.1)

Chest Pain

2.1 (0.0)

Fatigue

1.8 (0.0)

Abdominal Pain

1.6 (0.4)

Asthenia

1.6 (0.1)

Cardiovascular

Hypotension

6.7 (1.9)

Orthostatic Hypotension

1.6 (0.1)

Angina Pectoris

1.5 (0.1)

Myocardial Infarction

1.2 (0.3)

Digestive

Diarrhea

2.1 (0.1)

Nausea

1.3 (0.1)

Vomiting

1.3 (0.0)

Nervous/Psychiatric

Dizziness

7.9 (0.6)

Headache

1.8 (0.1)

Vertigo

1.6 (0.1)

Respiratory

Cough

2.2 (0.0)

Bronchitis

1.3 (0.0)

Dyspnea

1.3 (0.1)

Pneumonia

1.0 (0.0)

Skin

Rash

1.3 (0.0)

Urogenital

Urinary Tract Infection

1.3 (0.0)

Other serious clinical adverse experiences occurring since the drug was marketed or adverse

experiences occurring in 0.5 to 1.0 percent of patients with hypertension or heart failure in clinical

trials 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 ).

Cardiovascular: Cardiac arrest; myocardial infarction or cerebrovascular accident, possibly secondary

to excessive hypotension in high risk patients (see WARNINGS, Hypotension); pulmonary embolism

and infarction; pulmonary edema; rhythm disturbances including atrial tachycardia and bradycardia; atrial

fibrillation; palpitation, Raynaud's phenomenon.

Digestive: Ileus, pancreatitis, hepatic failure, hepatitis (hepatocellular [proven on rechallenge] or

cholestatic jaundice) (see WARNINGS, Hepatic Failure), melena, anorexia, dyspepsia, constipation,

glossitis, stomatitis, dry mouth.

Hematologic: Rare cases of neutropenia, thrombocytopenia and bone marrow depression.

Musculoskeletal: Muscle cramps.

Nervous/Psychiatric: Depression, confusion, ataxia, somnolence, insomnia, nervousness, peripheral

neuropathy (e.g., paresthesia, dysesthesia), dream abnormality.

Respiratory: Bronchospasm, rhinorrhea, sore throat and hoarseness, asthma, upper respiratory infection,

pulmonary infiltrates, eosinophilic pneumonitis.

Skin: Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, pemphigus, herpes

zoster, erythema multiforme, urticaria, pruritus, alopecia, flushing, diaphoresis, photosensitivity.

Special Senses: Blurred vision, taste alteration, anosmia, tinnitus, conjunctivitis, dry eyes, tearing.

Urogenital: Renal failure, oliguria, renal dysfunction (see PRECAUTIONS and DOSAGE AND

ADMINISTRATION), flank pain, gynecomastia, impotence.

Miscellaneous: A symptom complex has been reported which may include some or all of the following:

a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia/myositis, fever,

serositis, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash and other dermatologic

manifestations.

Angioedema: Angioedema has been reported in patients receiving enalapril maleate 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 enalapril

maleate should be discontinued and appropriate therapy instituted immediately (see WARNINGS).

Hypotension: In the hypertensive patients, hypotension occurred in 0.9 percent and syncope occurred in

0.5 percent of patients following the initial dose or during extended therapy. Hypotension or syncope

was a cause for discontinuation of Therapy in 0.1 percent of hypertensive patients. In heart failure

patients, hypotension occurred in 6.7 percent and syncope occurred in 2.2 percent of patients.

Hypotension or syncope was a cause for discontinuation of therapy in 1.9 percent of patients with heart

failure (see WARNINGS).

Cough: See PRECAUTIONS, Cough.

Pediatric Patients

The adverse experience profile for pediatric patients appears to be similar to that seen in adult patients.

Clinical Laboratory Test Findings

Serum Electrolytes:

Hyperkalemia (see PRECAUTIONS), hyponatremia.

Creatinine, Blood Urea Nitrogen:

In controlled clinical trials minor increases in blood urea nitrogen and serum creatinine, reversible upon

discontinuation of therapy, were observed in about 0.2 percent of patients with essential hypertension

treated with enalapril maleate alone. Increases are more likely to occur in patients receiving concomitant

diuretics or in patients with renal artery stenosis (see PRECAUTIONS). In patients with heart failure

who were also receiving diuretics with or without digitalis, increases in blood urea nitrogen or serum

creatinine, usually reversible upon discontinuation of enalapril maleate and/or other concomitant

diuretic therapy, were observed in about 11 percent of patients. Increases in blood urea nitrogen or

creatinine were a cause for discontinuation in 1.2 percent of patients.

Hematology:

Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g percent and 1.0

vol percent, respectively) occur frequently in either hypertension or congestive heart failure patients

treated with enalapril maleate but are rarely of clinical importance unless another cause of anemia

coexists. In clinical trials, less than 0.1 percent of patients discontinued therapy due to anemia.

Hemolytic anemia, including cases of hemolysis in patients with G-6-PD deficiency, has been reported;

a causal relationship to enalapril cannot be excluded.

Liver Function Tests

Elevations of liver enzymes and/or serum bilirubin have occurred (see WARNINGS, Hepatic Failure).

OVERDOSAGE

Limited data are available in regard to overdosage in humans.

Single oral doses of enalapril above 1,000 mg/kg and ≥1,775 mg/kg were associated with lethality in

mice and rats, respectively.

The most likely manifestation of overdosage would be hypotension, for which the usual treatment

would be intravenous infusion of normal saline solution.

Enalaprilat may be removed from general circulation by hemodialysis and has been removed from

neonatal circulation by peritoneal dialysis (see WARNINGS, Anaphylactoid reactions during

membrane exposure).

DOSAGE AND ADMINISTRATION

Hypertens ion

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally may

occur following the initial dose of enalapril maleate tablets. The diuretic should, if possible, be

discontinued for two to three days before beginning therapy with enalapril maleate tablets to reduce the

likelihood of hypotension (see WARNINGS). If the patient's blood pressure is not controlled with

enalapril maleate tablets alone, diuretic therapy may be resumed.

If the diuretic cannot be discontinued an initial dose of 2.5 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).

The recommended initial dose in patients not on diuretics is 5 mg once a day. Dosage should be adjusted

according to blood pressure response. The usual dosage range is 10 to 40 mg per day administered in a

single dose or two divided doses. In some patients treated once daily, the antihypertensive effect may

diminish toward the end of the dosing interval. In such patients, an increase in dosage or twice daily

administration should be considered. If blood pressure is not controlled with enalapril maleate tablets

alone, a diuretic may be added.

Concomitant administration of enalapril maleate tablets with potassium supplements, potassium salt

substitutes, or potassium-sparing diuretics may lead to increases of serum potassium (see

PRECAUTIONS).

Dosage Adjustment in Hypertensive Patients with Renal Impairment

The usual dose of enalapril is recommended for patients with a creatinine clearance >30 mL/min (serum

creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance ≤30 mL/min (serum

creatinine ≥3 mg/dL), the first dose is 2.5 mg once daily. 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 on nondialysis days should be adjusted depending on the blood pressure response.

Renal Status

Creatinine-

Clearance

mL/min

Initial Dose

mg/day

Normal Renal Function

>80 mL/min

5 mg

Mild Impairment

≤80 >30 mL/min

5 mg

Moderate to Severe Impairment

≤30 mL/min

2.5 mg

Dialysis Patients*

2.5 mg on dialysis days

Heart Failure

Enalapril maleate tablets are indicated for the treatment of symptomatic heart failure, usually in

combination with diuretics and digitalis. In the placebo-controlled studies that demonstrated improved

survival, patients were titrated as tolerated up to 40 mg, administered in two divided doses.

The recommended initial dose is 2.5 mg. The recommended dosing range is 2.5 to 20 mg given twice a

day. Doses should be titrated upward, as tolerated, over a period of a few days or weeks. The maximum

daily dose administered in clinical trials was 40 mg in divided doses.

After the initial dose of enalapril maleate tablets, the patient should be observed 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). If possible, the dose of any concomitant

diuretic should be reduced which may diminish the likelihood of hypotension. The appearance of

hypotension after the initial dose of enalapril maleate tablets does not preclude subsequent careful dose

titration with the drug, following effective management of the hypotension.

Asymptomatic Left Ventricular Dysfunction

In the trial that demonstrated efficacy, patients were started on 2.5 mg twice daily and were titrated as

tolerated to the targeted daily dose of 20 mg (in divided doses).

After the initial dose of enalapril maleate tablets, the patient should be observed 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). If possible, the dose of any concomitant

diuretic should be reduced which may diminish the likelihood of hypotension. The appearance of

hypotension after the initial dose of enalapril maleate tablets does not preclude subsequent careful dose

titration with the drug, following effective management of the hypotension.

Dosage Adjustment in Patients with Heart Failure and Renal Impairment or Hyponatremia

In patients with heart failure who have hyponatremia (serum sodium less than 130 mEq/L) or with serum

creatinine greater than 1.6 mg/dL, therapy should be initiated at 2.5 mg daily under close medical

supervision (see DOSAGE AND ADMINISTRATION, Heart Failure, WARNINGS and

PRECAUTIONS, Drug Interactions). The dose may be increased to 2.5 mg b.i.d., then 5 mg b.i.d. and

higher as needed, usually at intervals of four days or more if at the time of dosage adjustment there is

not excessive hypotension or significant deterioration of renal function. The maximum daily dose is 40

Pediatric Hypertensive Patients

The usual recommended starting dose is 0.08 mg/kg (up to 5 mg) once daily. Dosage should be adjusted

according to blood pressure response. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been

studied in pediatric patients (see CLINICAL PHARMACOLOGY, Clinical Pharmacology in

Pediatric Patients).

Enalapril maleate is not recommended in neonates and in pediatric patients with glomerular filtration rate

<30 mL/ min/1.73 m

, as no data are available.

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

Add 50 mL of Bicitra

to a polyethylene terephthalate (PET) bottle containing ten 20 mg tablets of

enalapril maleate and shake for at least 2 minutes. Let concentrate stand for 60-minutes. Following the

60-minute hold time, shake the concentrate for an additional minute. Add 150 mL of Ora-Sweet SF

to the concentrate in the PET bottle and shake the suspension to disperse the ingredients.

The suspension should be refrigerated at 2-8°C (36-46°F) and can be stored for up to 30 days. Shake

the suspension before each use.

HOW SUPPLIED

5mg White, round flat-faced beveled edged, compressed tablets with W 924 on one side and breakline

on the other side.

NDC: 60760-0227-30 bottle of 30

20mg Light Beige, round flat-faced beveled edged, compressed tablets with 926 on one side, plain on

the other side.

NDC: 60760-0226-30 BOTTLE OF 30

Storage

Store below 30°C (86°F) and avoid transient temperatures above 50°C (122°F). Keep container tightly

closed. Protect from moisture.

Dispense in a tight container as per USP, if product package is subdivided.

Registered trademark of Alza Corporation.

Trademark of Paddock Laboratories, Inc.

Manufactured by:

Wockhardt Limited,

Mumbai, India.

Distributed by:

Wockhardt USA LLC.

20 Waterview Blvd.

Parsippany, NJ 07054

USA.

Rev.111213

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

®**

TM***

ENALAPRIL MALEATE

enalapril maleate tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 0 76 0 -226 (NDC:6 46 79 -9 26 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

ENALAPRIL MALEATE (UNII: 9 O25354EPJ) (ENALAPRILAT ANHYDROUS - UNII:Q50 8 Q118 JM)

ENALAPRIL MALEATE 20 mg

Inactive Ingredients

Ingredient Name

Stre ng th

ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)

ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)

HYPRO MELLO SE 2 9 10 ( 6 MPA.S) (UNII: 0 WZ8 WG20 P6 )

STARCH, CO RN (UNII: O8 232NY3SJ)

STEARIC ACID (UNII: 4ELV7Z6 5AP)

TALC (UNII: 7SEV7J4R1U)

Product Characteristics

Color

bro wn (Light Beige)

S core

no sco re

S hap e

ROUND (ro und flat-faced beveled edged)

S iz e

8 mm

Flavor

Imprint Code

W;9 26

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:6 0 76 0 -226 -

30 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 4/21/20 14

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 7548 3

0 4/21/20 14

ENALAPRIL MALEATE

enalapril maleate tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 0 76 0 -227(NDC:6 46 79 -9 24)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

ENALAPRIL MALEATE (UNII: 9 O25354EPJ) (ENALAPRILAT ANHYDROUS - UNII:Q50 8 Q118 JM)

ENALAPRIL MALEATE 5 mg

Inactive Ingredients

Ingredient Name

Stre ng th

ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)

HYPRO MELLO SE 2 9 10 ( 6 MPA.S) (UNII: 0 WZ8 WG20 P6 )

STARCH, CO RN (UNII: O8 232NY3SJ)

STEARIC ACID (UNII: 4ELV7Z6 5AP)

TALC (UNII: 7SEV7J4R1U)

St Marys Medical Park Pharmacy

Product Characteristics

Color

white (White)

S core

2 pieces

S hap e

ROUND (ro und flat-faced beveled edged)

S iz e

8 mm

Flavor

Imprint Code

W;9 24

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:6 0 76 0 -227-

30 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 4/21/20 14

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 7548 3

0 4/21/20 14

Labeler -

St Marys Medical Park Pharmacy (063050751)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

St Marys Medical Park Pharmacy

0 6 30 50 751

relabel(6 0 76 0 -227, 6 0 76 0 -226 ) , repack(6 0 76 0 -227, 6 0 76 0 -226 )

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Wo ckhardt Limited

6 76 257570

manufacture(6 0 76 0 -227, 6 0 76 0 -226 )

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Wo ckhardt Limited

9 16 48 9 9 53

manufacture(6 0 76 0 -227, 6 0 76 0 -226 )

Revised: 11/2018