DESCRIPTION
SPL UNCLASSIFIED SECTION
Product InformationENALAPRIL MALEATE TABLETS, USPRx only
BOXED WARNING SECTION
USE IN PREGNANCYWhen 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 should be discontinued as soon as possible. See WARNINGS, Fetal / Neonatal Morbidity and Mortality.
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 L-Proline,1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]- , (S)-, (Z)-2-butenedioate (1:1). Its molecular formula is, C20H28N2O5·C4H4O4, 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, 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
| Six Months | One Year | |
| Enalapril Maleate (n=127) | 74 | 64 |
| Placebo (n=126) | 56 | 48 |
INDICATIONS AND USAGE
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.
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
| Enalapril Maleate(n=2314)Incidence(discontinuation) | Placebo(n=230)Incidence | |
| Body As A Whole | ||
| Fatigue | 3.0 (less than 0.1) | 2.6 |
| Orthostatic Effets | 1.2 (less than 0.1) | 0.0 |
| Asthenia | 1.1 (0.1) | 0.9 |
| Digestive | ||
| Diarrhea | 1.4 (less than 0.1) | 1.7 |
| Nausea | 1.4 (0.2) | 1.7 |
| Nervous/Psychiatric | ||
| Headache | 5.2 (0.3) | 9.1 |
| Dizziness | 4.3 (0.4) | 4.3 |
| Respiratory | ||
| Cough | 1.3 (0.1) | 0.9 |
| Skin | ||
| Rash | 1.4 (0.4) | 0.4 |
| Enalapril Maleate(n=673)Incidence(discontinuation) | Placebo(n=339)Incidence | |
| Body As A Whole | ||
| Orthostatic Effects | 2.2 (0.1) | 0.3 |
| Syncope | 2.2 (0.1) | 0.9 |
| Chest Pain | 2.1 (0.0) | 2.1 |
| Fatigue | 1.8 (0.0) | 1.8 |
| Abdominal Pain | 1.6 (0.4) | 2.1 |
| Asthenia | 1.6 (0.1) | 0.3 |
| Cardiovascular | ||
| Hypotension | 6.7 (1.9) | 0.6 |
| Orthostatic Hypotension | 1.6 (0.1) | 0.3 |
| Angina Pectoris | 1.5 (0.1) | 1.8 |
| Myocardial Infarction | 1.2 (0.3) | 1.8 |
| Digestive | ||
| Diarrhea | 2.1 (0.1) | 1.2 |
| Nausea | 1.3 (0.1) | 0.6 |
| Vomiting | 1.3 (0.0) | 0.9 |
| Nervous/Psychiatric | ||
| Dizziness | 7.9(0.6) | 0.6 |
| Headache | 1.8 (0.1) | 0.9 |
| Vertigo | 1.6 (0.1) | 1.2 |
| Respiratory | ||
| Cough | 2.2 (0.0) | 0.6 |
| Bronchitis | 1.3 (0.0) | 0.9 |
| Dyspnea | 1.3 (0.1) | 0.4 |
| Pneumonia | 1.0 (0.0) | 2.4 |
| Skin | ||
| Rash | 1.3 (0.0) | 2.4 |
| Urogenital | ||
| Urinary Tract Infection | 1.3 (0.0) | 2.4 |
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
| Renal Status | Creatinine-Clearanceml/min | Initial Dosemg/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† |
HOW SUPPLIED
StorageStore 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 07054USA.Rev.221209Relabeling and Repackaging by:Physicians Total Care, Inc.Tulsa, OK 74146
| Quantity | NDC Number | Strength | Description |
| Bottles of 30Bottles of 60Bottles of 100 | NDC 54868-4332-1NDC 54868-4332-0NDC 54868-4332-2 | 2.5 mg | White, rount flat-faced beveled edged, compressed tablets with W on one side and breakline on the other side. |
| Bottles of 30Bottles of 60Bottles of 90Bottles of 100 | NDC 54868-4357-0NDC 54868-4357-1NDC 54868-4357-3NDC 54868-4357-2 | 5 mg | White, rount flat-faced beveled edged, compressed tablets with W on one side and breakline on the other side. |
| Bottles of 30Bottles of 60Bottles of 90Bottles of 100 | NDC 54868-4358-0NDC 54868-4358-1NDC 54868-4358-3NDC 54868-4358-2 | 10 mg | Light Salmon, round flat-faced beveled edged, compressed tablets with W on one side plain on the other side. |
| Bottles of 30Bottles of 60Bottles of 90Bottles of 100 | NDC 54868-4331-1NDC 54868-4331-2NDC 54868-4331-3NDC 54868-4331-0 | 20 mg | Light Beige, rount flat-faced beveled edged, compressed tablets with W on one side plain on the other side. |