VASOTEC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VASOTEC (VASOTEC).

How it works

Enalaprilat, the active metabolite of enalapril, competitively inhibits angiotensin-converting enzyme (ACE), preventing conversion of angiotensin I to angiotensin II. This reduces vasoconstriction, aldosterone secretion, and sodium reabsorption, leading to decreased blood pressure and afterload.

What the body does with it

Metabolism	Enalapril is a prodrug that is hydrolyzed in the liver to its active metabolite enalaprilat. Minor metabolism by esterases. Enalaprilat is not further metabolized.
Excretion	Renal: 60-70% as enalaprilat; fecal: 20-30% as enalaprilat; biliary: minor (<10%).
Half-life	Terminal half-life of enalaprilat is 35-38 hours, with multiple-dose half-life ~11 hours due to prolonged terminal phase; clinical context: once-daily dosing achieves steady-state in 3-4 days.
Protein binding	Enalaprilat: 50-60% bound to plasma proteins; enalapril: <60% bound.
Volume of Distribution	Enalapril: 0.5 L/kg; enalaprilat: 0.2-0.3 L/kg; clinically reflects distribution into extracellular fluid.
Bioavailability	Oral enalapril: 60% (approximately; absorbed as prodrug, hydrolyzed to enalaprilat); IV: 100% (as enalaprilat).
Onset of Action	Oral: 1 hour (peak effect 4-6 hours); IV: within 15 minutes (peak effect 1-4 hours).
Duration of Action	Oral: 24 hours (antihypertensive effect); clinical notes: dose-dependent; longer duration with higher doses or renal impairment.

Classification & Brands

Dosing & administration

2.5 to 10 mg orally twice daily; initial dose 5 mg once daily; titrate based on blood pressure response; maximum 40 mg/day.

Dosage form	TABLET
Renal impairment	For CrCl 30-80 mL/min: initial dose 2.5 mg/day; for CrCl 10-30 mL/min: initial dose 2.5 mg/day; for CrCl <10 mL/min: initial dose 2.5 mg on dialysis days.
Liver impairment	No specific Child-Pugh based adjustments; use with caution and consider lower initial doses in patients with hepatic impairment.
Pediatric use	Children ≥1 month: initial 0.08 mg/kg/day up to 5 mg; titrate to 0.58 mg/kg/day; maximum 40 mg/day.
Geriatric use	Initial dose 2.5 mg/day, titrate slowly; monitor renal function and blood pressure closely due to increased sensitivity and risk of hypotension.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VASOTEC (VASOTEC).

Breastfeeding	Enalapril is excreted into breast milk in low concentrations. The milk-to-plasma ratio is approximately 0.1. Due to potential for adverse effects in the nursing infant (e.g., hypotension, renal impairment), caution is advised, especially in preterm or neonates. Alternative agents are preferred.
Teratogenic Risk	First trimester: limited human data, but animal studies suggest no major teratogenic risk. Second and third trimesters: known to cause fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal hypotension, anuria, and renal failure. Risk increases with gestational age.

Warnings & precautions

■ FDA Black Box Warning

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, discontinue VASOTEC as soon as possible.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to enalapril or any ACE inhibitor","History of angioedema related to previous ACE inhibitor therapy","Hereditary or idiopathic angioedema","Concomitant use with aliskiren in patients with diabetes","Pregnancy (second and third trimesters)"]

Clinical Precautions

Precautions

["Angioedema: risk increased with history of angioedema or concurrent use with mTOR inhibitors or neprilysin inhibitors.","Hypotension: especially in volume-depleted patients or those with heart failure.","Renal impairment: monitor renal function; may worsen renal function, especially in bilateral renal artery stenosis.","Hyperkalemia: risk increased with renal impairment, diabetes, or concurrent use of potassium-sparing diuretics or supplements.","Cough: persistent, dry cough due to bradykinin accumulation.","Hepatic impairment: rare hepatic toxicity."]

Clinical Tips & Counseling

Drug interactions

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VASOTEC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VASOTEC (VASOTEC).

How it works

What the body does with it

Metabolism	Enalapril is a prodrug that is hydrolyzed in the liver to its active metabolite enalaprilat. Minor metabolism by esterases. Enalaprilat is not further metabolized.
Excretion	Renal: 60-70% as enalaprilat; fecal: 20-30% as enalaprilat; biliary: minor (<10%).
Half-life	Terminal half-life of enalaprilat is 35-38 hours, with multiple-dose half-life ~11 hours due to prolonged terminal phase; clinical context: once-daily dosing achieves steady-state in 3-4 days.
Protein binding	Enalaprilat: 50-60% bound to plasma proteins; enalapril: <60% bound.
Volume of Distribution	Enalapril: 0.5 L/kg; enalaprilat: 0.2-0.3 L/kg; clinically reflects distribution into extracellular fluid.
Bioavailability	Oral enalapril: 60% (approximately; absorbed as prodrug, hydrolyzed to enalaprilat); IV: 100% (as enalaprilat).
Onset of Action	Oral: 1 hour (peak effect 4-6 hours); IV: within 15 minutes (peak effect 1-4 hours).
Duration of Action	Oral: 24 hours (antihypertensive effect); clinical notes: dose-dependent; longer duration with higher doses or renal impairment.

Classification & Brands

Dosing & administration

2.5 to 10 mg orally twice daily; initial dose 5 mg once daily; titrate based on blood pressure response; maximum 40 mg/day.

Dosage form	TABLET
Renal impairment	For CrCl 30-80 mL/min: initial dose 2.5 mg/day; for CrCl 10-30 mL/min: initial dose 2.5 mg/day; for CrCl <10 mL/min: initial dose 2.5 mg on dialysis days.
Liver impairment	No specific Child-Pugh based adjustments; use with caution and consider lower initial doses in patients with hepatic impairment.
Pediatric use	Children ≥1 month: initial 0.08 mg/kg/day up to 5 mg; titrate to 0.58 mg/kg/day; maximum 40 mg/day.
Geriatric use	Initial dose 2.5 mg/day, titrate slowly; monitor renal function and blood pressure closely due to increased sensitivity and risk of hypotension.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VASOTEC (VASOTEC).

Breastfeeding	Enalapril is excreted into breast milk in low concentrations. The milk-to-plasma ratio is approximately 0.1. Due to potential for adverse effects in the nursing infant (e.g., hypotension, renal impairment), caution is advised, especially in preterm or neonates. Alternative agents are preferred.
Teratogenic Risk	First trimester: limited human data, but animal studies suggest no major teratogenic risk. Second and third trimesters: known to cause fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal hypotension, anuria, and renal failure. Risk increases with gestational age.