Continuing Education Activity

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 requires intravenous administration. It inhibits angiotensin I to angiotensin II conversion via competitive inhibition of angiotensin-converting enzyme (ACE). This activity will highlight the mechanism of action, adverse event profile, pharmacology, monitoring, and relevant interactions of enalaprilat, pertinent for members of the interprofessional team in the treatment of patients with conditions where this agent is indicated.


  • Review the mechanism of action of enalaprilat and its conversion to enalapril.
  • Discuss the indications and contraindication for enalaprilat therapy.
  • Review the adverse event profile for enalaprilat.
  • Review interprofessional team strategies for improving care coordination and communication to advance enalaprilat and improve outcomes in hypertensive care.


Enalaprilat injection is used in the management of hypertension when oral therapy is not practical.[1]

Mechanism of Action

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).[2] 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.[3] ACE breaks down bradykinin, a peptide that causes vasodilation. ACE inhibitors impede the breakdown of bradykinin, resulting in vasodilation and a bradykinin cough.[4]


For Heart Failure:

  • Avoid administration in patients with unstable heart failure or acute myocardial infarction

For Hypertension:

  • Intravenous (IV): 1.25 mg/dose given over 5 minutes every 6 hours. A clinical response typically occurs within 15 minutes.
  • Concomitant diuretic therapy: start with 0.625 mg IV over 5 minutes.
    • If the effect is inadequate after 1 hour: repeat the dose and administer 1.25 mg at 6-hour intervals
    • If the effect is adequate after 1 hour: administer 0.625 mg IV every 6 hours
  • Conversion from IV enalaprilat to enalapril:
    • No concomitant diuretic therapy: initiate enalapril 5 mg once daily
    • Concomitant diuretic therapy: initiate enalapril 2.5 mg once daily and titrate as needed

For Renal Impairment:

  • Creatinine Clearance (CrCl) > 30 mL/minute: No dosage adjustment necessary
  • CrCl = 30 mL/minute: initiate 0.625 mg; if after 1 hour clinical response is unsatisfactory, repeat and then administer 1.25 mg every 6 hours
  • Intermittent hemodialysis (IHD): 20 to 50% dialyzable (moderate)
    • Initial: 0.625 mg IV over 5 to 60 minutes
  • Conversion from IV enalaprilat to enalapril:
    • CrCl > 30 mL/minute: initiate enalapril 5 mg once daily
    • CrCl = 30 mL/minute: initiate enalapril 2.5 mg once daily

Enalaprilat administration should be via 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 patients undergoing intensive diuresis, an increase in diuretic dose, or renal dialysis.[5]

Adverse Effects

  • Hypotension (2-5%) is the most common manifestation of overdose, but the incidence of excessive hypotension remains relatively rare. Incidence increases with use in severely salt or volume-depleted persons such as patients treated with diuretics or patients on dialysis. Before initiating therapy with enalaprilat, consider eliminating or reducing the diuretic dose. In the event of hypotension, place the patient in the supine position and infuse IV normal saline.
  • Headache (3%)
  • Nausea (1%)
  • Myocardial infarction (< 1%)
  • Cough (< 1%)
  • Constipation (< 1%)
  • Rash (< 1%)
  • Fever (< 1%)
  • Hypersensitivity reactions or anaphylactoid reactions

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.[6] If pregnancy is detected, discontinue enalaprilat should as soon as possible. Enalaprilat is also detectable in human breast milk, which creates a potential for adverse events in nursing infants.[7] The safety and effectiveness of enalaprilat use in children have not been established.[8] In elderly patients, dose selection should be modest and initiated at a low dose. Enalaprilat undergoes substantial excretion 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 occur 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.[9] 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 is correctable by volume expansion.[10]


  • Hypersensitivity to enalapril, enalaprilat or any component of the formulation
  • Patients with a history of angioedema resulting from previous treatment with an ACE inhibitor
  • Idiopathic or hereditary angioedema
  • Concomitant aliskiren use in patients with diabetes mellitus


Monitoring parameters include blood pressure, BUN, serum creatinine, and potassium. Blood pressure needs close monitored with first dose administration or change in dose. If the patient has collagen vascular disease or renal impairment, complete blood count with differential is also a periodic monitoring requirement. Each patient should have an assessment for the presence of potential interactions with other medications that may impact their fluid balance or cardiac status. Monitoring for anaphylactic reactions, hypovolemia, angioedema, and postural hypotension is also necessary.[5]


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.[11] 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.[12] If angioedema occurs, immediately discontinue enalaprilat and initiate appropriate therapy with antihistamines and monitoring as necessary. 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 the result of the inhibition of the degradation of bradykinin and generally resolves within 1 to 4 weeks after discontinuation.[4] Symptomatic hypotension, including syncope, can occur with ACE inhibitor therapy. Close monitoring and correction of volume depletion are necessary before initiating treatment. If hypotension occurs, consider reducing the enalaprilat dose, but do not abruptly discontinue therapy.

Enhancing Healthcare Team Outcomes

Enalaprilat is a widely used drug in the ICU for the management of hypertension. It is often prescribed by nurse practitioners, intensivists, cardiologists, and internists. The drug is effective with a rapid onset of action. However, nurses need to monitor the patient as hypotension can develop quickly. It is preferable to have an arterial line for continuous monitoring of the blood pressure while using enalaprilat.

Article Details

Article Author

Francheska Marte

Article Author

Graham Dersnah

Article Editor:

Manouchkathe Cassagnol


11/4/2020 1:42:34 AM

PubMed Link:




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