Enalaprilat injection is used in the management of hypertension when oral therapy is not practical.
Enalaprilat is the active metabolite of the oral prodrug enalapril maleate. Enalaprilat is poorly absorbed orally and must be administered intravenously. It inhibits angiotensin I to angiotensin II conversion via competitive inhibition of angiotensin-converting enzyme (ACE). This inhibition disrupts the renin-angiotensin-aldosterone system. Angiotensin II binds to AT1 receptors on smooth muscles to produce vasoconstriction and an increase in blood pressure. Additionally, angiotensin II stimulates the adrenal cortex to secrete aldosterone. Aldosterone causes the distal tubules and collecting ducts of the kidneys to reabsorb water and sodium in exchange for potassium, which results in an expansion in extracellular volume and an increase in blood pressure. Inhibition of ACE leads to decreased plasma angiotensin II, leading to vasodilation and decreased aldosterone secretion. Angiotensin II also causes vasoconstriction of the afferent and efferent arterioles of the kidney, exerting a more significant effect on the efferent arterioles. Enalaprilat administration in the presence of hypovolemia can cause renal injury due to inadequate renal perfusion. ACE breaks down bradykinin, a peptide that causes vasodilation. ACE inhibitors impede the breakdown of bradykinin, resulting in vasodilation and a bradykinin cough.
For Heart Failure:
For Renal Impairment:
Enalaprilat should be administered IV push undiluted over at least 5 minutes or as an infusion diluted in up to 50 milliliters of D5W or 0.9% NaCl. Avoid salt substitutes or a potassium-rich diet. A dose no greater than 0.625 mg over 5 minutes should be administered in patients with heart failure or hyponatremia, and in patients undergoing intensive diuresis, an increase in diuretic dose or renal dialysis.
These adverse reactions may also be associated with enalapril because enalapril undergoes biotransformation to enalaprilat.
Warnings and Precautions
Enalaprilat is pregnancy Category C in the first trimester and Category D in the second and third trimesters. All ACE inhibitors can cause injury and even death to the fetus when used in pregnancy during the second and third trimesters. Hypotension, neonatal skull hypoplasia, anuria, and renal failure can also occur with use in pregnancy. If pregnancy is detected, discontinue enalaprilat should as soon as possible. Enalaprilat has also been detected in human breast milk, which creates a potential for adverse events in nursing infants. The safety and effectiveness of enalaprilat use in children have not been established. In elderly patients, dose selection should be modest and initiated at a low dose. Enalaprilat is substantially excreted by the kidney, and the risk of toxic reactions may be higher in elderly patients with impaired renal function. With severe heart failure patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system, ACE inhibitor therapy may be associated with oliguria, progressive azotemia, acute renal failure or death. In the absence of pre-existing renal vascular disease, it is still possible to develop increases in blood urea and serum creatinine. Hyperkalemia or elevated serum potassium greater than 5.7 mEq/L may be observed in some hypertensive patients. Additional risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus and the concomitant use of potassium supplements or potassium-sparing agents. In patients undergoing major surgery or anesthesia with agents that may cause hypotension, enalaprilat may block angiotensin II formation and hypotension may result. This hypotension can be corrected by volume expansion.
Monitoring parameters include blood pressure, BUN, serum creatinine and potassium. Blood pressure should be closely monitored with first dose administration or change in dose. If the patient has collagen vascular disease or renal impairment, complete blood count with differential should be periodically monitored. Each patient should be assessed for potential interactions with other medications that may impact their fluid balance or cardiac status. Monitoring for anaphylactic reactions, hypovolemia, angioedema, and postural hypotension should also be performed.
Cholestatic jaundice progressing to fulminant hepatic necrosis may occur. If a marked elevation of hepatic transaminases or jaundice occurs, then enalaprilat should be discontinued. Following the first dose or at any time during treatment, angioedema can occur. Angioedema of the face, extremities, lips, tongue, glottis or larynx can lead to airway compromise. African Americans may be at an increased risk of developing angioedema. If angioedema occurs, enalaprilat should be immediately discontinued, and appropriate therapy with antihistamines and monitoring should be provided. When the tongue, glottis or larynx is involved, subcutaneous epinephrine 1:1000 may be administered to reverse airway obstruction. A persistent, dry, hacking, nonproductive cough that occurs within the first few months of treatment can also occur with enalaprilat therapy. ACE inhibitor-induced cough is caused by the inhibition of the degradation of bradykinin and generally resolves within 1-4 weeks after discontinuation. Symptomatic hypotension including syncope can occur with ACE inhibitor therapy. Close monitoring and correction of volume depletion are required before initiating treatment. If hypotension occurs, consider reducing the enalaprilat dose, but do not abruptly discontinue therapy.