USE IN PREGNANCY
id: c1c9eb32-4735-44b0-9257-d6094fea64bc
displayName: BOXED WARNING SECTION
FDA Article Code: 34066-1
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, enalaprilat injection, USP should be discontinued as soon as possible. See
WARNINGS,
Fetal/Neonatal Morbidity and Mortality
.
DESCRIPTION
id: e7e39def-e3fb-4d60-912b-1e5a71a3846d
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Enalaprilat injection, USP is a sterile aqueous solution for intravenous administration. Enalaprilat is an angiotensin converting enzyme inhibitor. It is chemically described as (S)-1-[N-(1-carboxy-3-phenylpropyl)-L-alanyl]-L-proline dihydrate. Its empirical formula is C18H24N2O5•2H2O and its structural formula is:
Enalaprilat is a white to off-white, crystalline powder with a molecular weight of 384.42. It is sparingly soluble in methanol and slightly soluble in water.
Each milliliter of enalaprilat injection, USP contains 1.25 mg enalaprilat (anhydrous equivalent); sodium chloride to adjust tonicity; sodium hydroxide to adjust pH; water for injection, q.s.; with benzyl alcohol, 9 mg, added as a preservative.
CLINICAL PHARMACOLOGY
id: 601880e1-2736-404a-936c-4b732d6ceb0f
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
Enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor when administered intravenously, is the active metabolite of the orally administered pro-drug, enalapril maleate. Enalaprilat is poorly absorbed orally.
INDICATIONS AND USAGE
id: 06f1e302-fb78-4520-846b-771df797393d
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Enalaprilat injection, USP is indicated for the treatment of hypertension when oral therapy is not practical.
Enalaprilat injection, USP has been studied with only one other antihypertensive agent, furosemide, which showed approximately additive effects on blood pressure. Enalapril, the pro-drug of enalaprilat, has been used extensively with a variety of other antihypertensive agents, without apparent difficulty except for occasional hypotension.
In using enalaprilat injection, USP, 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 enalaprilat injection, USP does not have a similar risk. (See WARNINGS.)
In considering use of enalaprilat injection, USP, 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,
Angioedema
).
CONTRAINDICATIONS
id: 7bc4ce68-3fbb-4e45-956b-a6b7b0b5d964
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Enalaprilat injection, USP is contraindicated in patients who are hypersensitive to any component of this product and in patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema.
ADVERSE REACTIONS
id: 7bd9e734-2d96-46d2-b878-d5ba2be422c7
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Enalaprila injection, USP has been found to be generally well tolerated in controlled clinical trials involving 349 patients (168 with hypertension, 153 with congestive heart failure and 28 with coronary artery disease). The most frequent clinically significant adverse experience was hypotension (3.4 percent), occurring in eight patients (5.2 percent) with congestive heart failure, three (1.8 percent) with hypertension and one with coronary artery disease. Other adverse experiences occurring in greater than one percent of patients were: headache (2.9 percent) and nausea (1.1 percent).
Adverse experiences occurring in 0.5 to 1.0 percent of patients in controlled clinical trials included: myocardial infarction, fatigue, dizziness, fever, rash and constipation.
Angioedema: Angioedema has been reported in patients receiving enalaprilat, 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 enalaprilat should be discontinued and appropriate therapy instituted immediately (see
WARNINGS
).
Cough: See
PRECAUTIONS,
Cough
.
OVERDOSAGE
id: 1a1ab14c-8501-482b-b912-31ce92e112e0
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
In clinical studies, some hypertensive patients received a maximum dose of 80 mg of enalaprilat intravenously over a fifteen minute period. At this high dose, no adverse effects beyond those as associated with the recommended dosages were observed.
A single intravenous dose of ≤4167 mg/kg of enalaprilat was associated with lethality in female mice. No lethality occurred after an intravenous dose of 3472 mg/kg.
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
id: 0c931d2c-82cf-4760-83ff-803d97caab82
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
FOR INTRAVENOUS ADMINISTRATION ONLY
The dose in hypertension is 1.25 mg every six hours administered intravenously over a five minute period. A clinical response is usually seen within 15 minutes. Peak effects after the first dose may not occur for up to four hours after dosing. The peak effects of the second and subsequent doses may exceed those of the first.
No dosage regimen for enalaprilat injection, USP has been clearly demonstrated to be more effective in treating hypertension than 1.25 mg every six hours. However, in controlled clinical studies in hypertension, doses as high as 5 mg every six hours were well tolerated for up to 36 hours. There has been inadequate experience with doses greater than 20 mg per day.
In studies of patients with hypertension, enalaprilat injection, USP has not been administered for periods longer than 48 hours. In other studies, patients have received enalaprilat injection, USP for as long as seven days.
The dose for patients being converted to enalaprilat injection, USP from oral therapy for hypertension with enalapril maleate is 1.25 mg every six hours. For conversion from intravenous to oral therapy, the recommended initial dose of Tablets VASOTEC (Enalapril Maleate) is 5 mg once a day with subsequent dosage adjustments as necessary.
HOW SUPPLIED
id: 8b5d36d7-f8fb-439f-8069-f48012c75cf5
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Enalaprilat injection, USP, 1.25 mg per mL, is a clear, colorless solution and is supplied in vials containing 1 mL and 2 mL.
NDC 0143-9787-10, 1 mL vials, Carton of 10.
NDC 0143-9786-10, 2 mL vials, Carton of 10
PRINCIPAL DISPLAY PANEL – 1.25 mg Vial
id: 82984b43-d495-47cf-a477-20a39fca5e71
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Enalaprilat Injection, USP
1.25 mg/mL
0143-9787-10
PRINCIPAL DISPLAY PANEL – 2.5 mg Vial
id: 6d663a77-d1b1-44cd-954d-cedeb73b6e8c
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Enalaprilat Injection, USP
2.5 mg/2 mL
0143-9786-10
