ENALAPRIL MALEATE- enalapril maleate tablet 
REMEDYREPACK INC.

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USE IN PREGNANCY

When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus.When pregnancy is detected, enalapril maleate tablets should be discontinued as soon as possible. (See WARNINGS: Fetal/Neonatal Morbidity and Mortality.)

CONTRAINDICATIONS

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

WARNINGS

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, may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death.

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% 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 preexisting renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when enalapril has been given concomitantly with a diuretic. This is more likely to occur in patients with preexisting renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or enalapril may be required

Evaluation of patients with hypertension or heart failure should always include assessment of renal function. (See DOSAGE AND ADMINISTRATION.

Hyperkalemia

Elevated serum potassium (greater than 5.7 mEq/L) was observed in approximately 1% 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% of hypertensive patients. In clinical trials in heart failure, hyperkalemia was observed in 3.8% 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. (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 lightheadedness, 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 ACE inhibitors. 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 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

Hypotensionon 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 2 hours and until blood pressure has stabilized for at least an additional hour. (See

WARNINGSand DOSAGE AND ADMINISTRATION.)

Agents Causing Renin Release

The antihypertensive effect of enalapril is augmented by antihypertensive agents that cause renin release (e.g., diuretics).

Non-Steroidal Anti-Inflammatory Agents

In some patients with compromised renal function who are being treated with non-steroidal anti-inflammatory drugs, the coadministration of enalapril may result in a further deterioration of renal function. These effects are usually reversible.

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. However, reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.

Other Cardiovascular Agents

Enalapril 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 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

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 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.

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.

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

Pregnancy Categories C (first trimester) and D (second and third trimesters)

WARNINGS: Fetal/Neonatal Morbidity an Mortality.

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, taking into account the importance of the drug to the mother.

Pediatric Use

Antihypertensive effects of enalapril have been established in hypertensive pediatric patients age 1 month to 16 years. Use of enalapril in these age groups is supported by evidence from adequate and well controlled studies of enalapril in pediatric and adult patients as well as by published literature in pediatric patients (see

CLINICAL PHARMACOLOGY: Clinical Pharmacology in Pediatric Patientsand DOSAGE AND ADMINISTRATION).

Enalapril is not recommended in neonates and in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m2, as no data are available.

OVERDOSAGE

ADVERSE REACTIONS

DOSAGE & ADMINISTRATION

Hypertension

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 2 to 3 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 2 hours and until blood pressure has stabilized for at least an additional hour. (See

WARNINGSand 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 mg 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 maleate tablets is recommended for patients with a creatinine clearance > 30 mL/min (serum creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance30 mL/min (serum creatinine3 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.

*

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/min5 mgMild Impairment80 > 30 mL/min5 mgModerate to Severe Impairment30 mL/min2.5 mgDialysis 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 mg 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 2 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 2 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 4 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 mg.

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 tablets are not recommended in neonates and in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2, as no data are available.

Preparation of Suspension (for 200 mL of a 1 mg/mL suspension)

Add 50 mL of Bicitra

1to 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 2to the concentrate in the PET bottle and shake the suspension to disperse the ingredients. The suspension should be refrigerated at 2to 8(36to 46and can be stored for up to 30 days. Shake the suspension before each use.

2

Trademark of Paddock Laboratories, Inc.

HOW SUPPLIED

STORAGE AND HANDLING

Store at 20 to 25 C (68 to 77 F).[See USP Controlled Room Temperature.]

Protect from moisture.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION

DRUG: Enalapril Maleate

GENERIC: ENALAPRIL MALEATE

DOSAGE: TABLET

ADMINSTRATION: ORAL

NDC: 52125-164-02

STRENGTH:5 mg

COLOR: white

SHAPE: ROUND

SCORE: Two even pieces

SIZE: 8 mm

IMPRINT: 30

QTY: 30

MM2

MM3

ENALAPRIL MALEATE 
enalapril maleate tablet
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:52125-164(NDC:0378-1052)
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
ENALAPRIL MALEATE (UNII: 9O25354EPJ) (ENALAPRILAT ANHYDROUS - UNII:Q508Q118JM) ENALAPRIL MALEATE5 mg
Inactive Ingredients
Ingredient NameStrength
ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
MALEIC ACID (UNII: 91XW058U2C)  
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
STARCH, CORN (UNII: O8232NY3SJ)  
SODIUM LAURYL SULFATE (UNII: 368GB5141J)  
Product Characteristics
ColorwhiteScore2 pieces
ShapeROUND (TABLET) Size8mm
FlavorImprint Code M;E16
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:52125-164-0230 in 1 BLISTER PACK; Type 0: Not a Combination Product08/21/201201/27/2017
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA07548008/21/201201/27/2017
Labeler - REMEDYREPACK INC. (829572556)

Revised: 1/2017
 
REMEDYREPACK INC.