ENALAPRILAT- enalaprilat injection, solution
Hospira, Inc.
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, Enalaprilat Injection, USP should be discontinued as soon as possible.
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 molecular formula is C18 H24 N2 O5 � 2H2 O
Enalaprilat is a white to off-white, crystalline powder with a molecular weight of 384.43. It is sparingly soluble in methanol and slightly soluble in water.
Each milliliter contains 1.25 mg enalaprilat (anhydrous equivalent); sodium chloride to adjust tonicity; benzyl alcohol, 9 mg, added as a preservative. May contain sodium hydroxide for pH adjustment.
CLINICAL PHARMACOLOGY
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.
Mechanism of Action
Intravenous enalaprilat, or oral enalapril, after hydrolysis to enalaprilat, inhibits 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. 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.
INDICATIONS AND USAGE
Enalaprilat Injection is indicated for the treatment of hypertension when oral therapy is not practical.
Enalaprilat Injection 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, 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 does not have a similar risk. (See WARNINGS.)
In considering use of Enalaprilat Injection, 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
DOSAGE AND ADMINISTRATION
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 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 has not been administered for periods longer than 48 hours. In other studies, patients have received enalaprilat injection for as long as seven days.
The dose for patients being converted to enalaprilat injection 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 Enalapril Maleate Tablets is 5 mg once a day with subsequent dosage adjustments as necessary.
Patients on Diuretic Therapy
For patients on diuretic therapy the recommended starting dose for hypertension is 0.625 mg administered intravenously over a five minute period; also see below, Patients at Risk of Excessive Hypotension . 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, although most of the effect is usually apparent within the first hour. If after one hour there is an inadequate clinical response, the 0.625 mg dose may be repeated. Additional doses of 1.25 mg may be administered at six hour intervals.
For conversion from intravenous to oral therapy, the recommended initial dose of Enalapril Maleate Tablets for patients who have responded to 0.625 mg of enalaprilat every six hours is 2.5 mg once a day with subsequent dosage adjustment as necessary
