Enalaprilat
Also known as: Enalapril diacid, Enalaprilat, Enalaprilate, MK-422, Vasotec IV
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Summary
Enalaprilat is the active, intravenously administered dipeptide metabolite of the oral ACE inhibitor enalapril. It belongs to the RAAS‑acting peptide family and is approved for use in hypertensive emergencies, acute heart‑failure states, and as an after‑load reducer in critical care. The compound is delivered by IV infusion and is employed when rapid blood‑pressure control is required, especially in patients at risk of cerebral hypoperfusion.
Mechanism of Action
Enalaprilat binds to the active site of angiotensin‑converting enzyme (ACE), blocking the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. This inhibition reduces systemic vascular resistance, lowers aldosterone secretion, and promotes vasodilation of cerebral and peripheral vessels. The resulting decrease in after‑load and blood pressure can improve cardiac output in acute heart‑failure settings and lessen the risk of cerebral hypotensive episodes in hypertensive emergencies.
What the Research Shows
A 1995 review of hypertensive emergencies highlighted enalaprilat’s cerebral vasodilatory properties, suggesting benefit for patients with impaired cerebral circulation. A 2025 narrative review of sympathetic crashing acute pulmonary edema (SCAPE) listed enalaprilat as an option for patients with normal renal function and resistant hypertension when other vasodilators are insufficient. Pediatric data are sparse: a 2021 systematic review identified three pharmacokinetic studies showing age‑related increases in enalaprilat exposure and markedly higher exposure in neonates, while a 2020 review emphasized the paucity of robust efficacy and safety data in children, especially those under 20 days old. Overall, evidence supports enalaprilat’s role in acute IV blood‑pressure control in adults, but pediatric evidence remains limited.
Reported Benefits
Enalaprilat provides rapid, controllable blood‑pressure reduction via ACE inhibition, making it useful in hypertensive emergencies and acute heart‑failure where after‑load reduction is critical. Its cerebral vasodilatory effect may protect against hypoperfusion in patients with compromised cerebral circulation. In SCAPE, it serves as an additional vasodilator when nitroglycerin or calcium‑channel blockers are inadequate, and it can be administered to patients with normal renal function without the need for oral dosing.
Limitations of the Evidence
Clinical data for enalaprilat are largely derived from reviews and limited pediatric pharmacokinetic studies rather than large randomized trials. Evidence in children, especially neonates and infants with heart failure, is scarce and sometimes conflicting. The drug’s use is confined to intravenous administration, restricting its applicability to settings with IV access. Comparative efficacy versus other IV antihypertensives (e.g., nitroprusside, nicardipine) is not well quantified in the cited literature.
Safety Considerations
As an ACE inhibitor, enalaprilat can cause hypotension, especially in volume‑depleted patients, and may precipitate renal dysfunction or hyperkalaemia in those with impaired renal function. Cerebral vasodilation may lead to hypotensive episodes in patients with compromised cerebral blood flow. Class‑related adverse effects such as cough, angioedema, and elevated bradykinin are possible, though specific rates are not detailed in the abstracts. Caution is advised in patients with renal insufficiency or a history of angioedema.
How It Is Administered
Enalaprilat is administered intravenously, typically as a short‑term infusion in acute care settings. Dosing regimens are tailored to the clinical scenario (e.g., hypertensive emergency, acute pulmonary edema) and patient renal function, but specific protocols are not provided in the cited sources. The formulation is supplied for IV use only.
Routes of Administration
Goals & Uses
- Heart failureCardiovascularHigh
- Acute renal protectionRenalModerate
- HypertensionCardiovascularHigh
- Reduction of proteinuria in renal diseaseRenalModerate
- Hypertensive emergency/urgency managementCardiovascularHigh
- Heart failure management (acute)CardiovascularModerate
- Blood pressure control in hospitalized patientsCardiovascularHigh
Contraindications
- History of angioedema related to ACE inhibitorsImmunologicHigh
- Hereditary or idiopathic angioedemaImmunologic/AllergicHigh
- Hypersensitivity to enalaprilat or any ACE inhibitorHypersensitivityHigh
- PregnancyPopulationHighPotential fetal risk or insufficient safety data
- Pregnancy (2nd and 3rd trimester)ObstetricHigh
- Concomitant use with sacubitril/valsartanDrug InteractionHigh
- History of ACE inhibitor-induced angioedemaImmunologic/AllergicHigh
- Bilateral renal artery stenosisVascular/RenalHigh
- Severe bilateral renal artery stenosisRenalHigh
Adverse Effects
- Injection site reactionsLocalUncommon
- CoughRespiratoryCommonPersistent or episodic cough
- Acute kidney injuryRenalUncommonSudden decline in kidney function
- HypotensionCardiovascularCommonLow blood pressure
- Renal impairmentRenalUncommon
- Headache / dizzinessNeurologicalCommon
- HyperkalemiaElectrolyte ImbalanceCommon
- AngioedemaImmunologicRare
Drug Interactions
- Non‑steroidal anti‑inflammatory drugs (NSAIDs)Moderate
- Potassium-sparing diuretics / potassium supplementsModerate
- Diuretics (loop/thiazide)Moderate
- Sacubitril/valsartan (Entresto)High
- Potassium‑sparing diuretics (e.g., spironolactone)Moderate
- AliskirenHigh
- NSAIDsModerateMay increase renal risk in susceptible patients
- LithiumHigh
Population Constraints
- PregnancyReproductive SafetyAbsolute
- Bilateral renal artery stenosis or single functioning kidney with renal artery stenosisRenalAbsolute
- Renal impairmentOrgan ImpairmentRelative
- Pediatric patientsAgeRelative
- Elderly patientsAgeRelative
- Pregnant womenReproductiveAbsolute
- Neonates and infants (premature/newborn)PediatricAbsolute
- Severe renal impairment (eGFR <30 mL/min)RenalRelative
Regulatory Status
- European UnionApprovedApproved: Hypertensive emergencies, Heart failureApproved for IV use; same indications as US
- United StatesApprovedApproved: Acute hypertension, Acute decompensated heart failureIV formulation (Enalaprilat) approved; oral enalapril is the prodrug
- United KingdomApprovedApproved: Hypertensive emergencies, Acute heart failureAvailable under prescription as Enalaprilat injection
Not orally bioavailable; approved for intravenous use only in most jurisdictions.
Evidence & Sources
- Journal ArticleModerateAbdelwahab W, Frishman W, Landau A1995-01-01T00:00:00.000000Z
- Journal ArticleModerateLong B, Brady WJ, Gottlieb M2025-01-01T00:00:00.000000Z
- Journal ArticleModerateLangtry HD, Markham A1997-01-01T00:00:00.000000Z
- Journal ArticleHighFaisal M, et al.2021-01-01T00:00:00.000000Z
- Journal ArticleModerateSmeets NJL, et al.2020-01-01T00:00:00.000000Z
Frequently Asked Questions
When is enalaprilat preferred over other IV antihypertensives?
Enalaprilat may be chosen in hypertensive emergencies where cerebral vasodilation is desired or when patients have normal renal function and are resistant to agents such as nitroglycerin or calcium‑channel blockers, as noted in emergency‑medicine reviews.
Can enalaprilat be used in children?
Enalaprilat is approved for pediatric hypertension, but pharmacokinetic data are limited, especially in infants under 20 days. The literature calls for more studies before routine use in young children with heart failure can be recommended.
What are the main safety concerns with IV enalaprilat?
Key concerns include rapid hypotension, potential worsening of renal function, hyperkalaemia, and cerebral hypotensive episodes in patients with impaired cerebral circulation. As with all ACE inhibitors, angioedema and cough may also occur.
How does enalaprilat work to lower blood pressure?
It inhibits angiotensin‑converting enzyme, preventing formation of angiotensin II, which reduces vasoconstriction and aldosterone‑mediated sodium retention, leading to vasodilation and lower systemic vascular resistance.
Is enalaprilat available for oral use?
No. Enalaprilat is formulated only for intravenous administration; the oral ACE inhibitor enalapril is the pro‑drug that is converted to enalaprilat in the body.
What is Enalaprilat?
Enalaprilat is the active, intravenously administered dipeptide metabolite of the oral ACE inhibitor enalapril. It belongs to the RAAS‑acting peptide family and is approved for use in hypertensive emergencies, acute heart‑failure states, and as an after‑load reducer in critical care. The compound is delivered by IV infusion and is employed when rapid blood‑pressure control is required, especially in patients at risk of cerebral hypoperfusion.
What is Enalaprilat used for?
Enalaprilat is educationally associated with: Heart failure, Acute renal protection, Hypertension, Reduction of proteinuria in renal disease, Hypertensive emergency/urgency management, Heart failure management (acute), Blood pressure control in hospitalized patients. Educational only — not medical advice.
How is Enalaprilat administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Enalaprilat?
Reported adverse effects include: Injection site reactions, Cough, Acute kidney injury, Hypotension, Renal impairment, Headache / dizziness, Hyperkalemia, Angioedema. This list is not exhaustive — consult a qualified clinician.
Who should avoid Enalaprilat?
Recorded contraindications: History of angioedema related to ACE inhibitors, Hereditary or idiopathic angioedema, Hypersensitivity to enalaprilat or any ACE inhibitor, Pregnancy, Pregnancy (2nd and 3rd trimester), Concomitant use with sacubitril/valsartan, History of ACE inhibitor-induced angioedema, Bilateral renal artery stenosis, Severe bilateral renal artery stenosis. Consult a qualified clinician before use.