VASOTEC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VASOTEC (VASOTEC).
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.
| 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. |
| Molecular Weight | 376.45 |
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. |
| 1st trimester | Risk of teratogenicity, including renal dysplasia and oligohydramnios, especially in second and third trimesters. Use not recommended in first trimester due to potential fetal renal effects. |
| 2nd trimester | Contraindicated: fetal renal damage, oligohydramnios, and neonatal complications. Discontinue immediately if exposure occurs. |
| 3rd trimester | Contraindicated: fetal renal damage, oligohydramnios, neonatal hypotension, and skull hypoplasia. Discontinue immediately if exposure occurs. |
Clinical note
Comprehensive clinical and safety monograph for VASOTEC (VASOTEC).
| Placental transfer | Enalapril crosses the placenta. Fetal exposure is significant, especially in second and third trimesters, leading to fetal renin-angiotensin system suppression. |
| Breastfeeding | Enalapril is excreted into breast milk in very low concentrations. No adverse effects have been reported in breastfed infants. However, caution is advised, especially in preterm or renally impaired infants. |
■ 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.
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaPregnancy (especially second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitusBilateral renal artery stenosisHypersensitivity to enalapril or any ACE inhibitor
| 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. |
| Food/Dietary |
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| Lactation Rating | L2 (Limited data – possibly compatible) |
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), and potassium levels. Serial ultrasound assessments for fetal growth, amniotic fluid volume, and renal anatomy. Fetal monitoring for heart rate and renal function after 20 weeks. |
| Fertility Effects | No direct studies in humans; animal studies show no impairment of fertility. Indirect effects due to maternal hypotension or renal dysfunction may affect uterine perfusion but not fertility per se. |
| Avoid high-potassium foods (e.g., bananas, oranges, tomatoes, spinach, salt substitutes) without medical approval, as ACE inhibitors can increase serum potassium. No other significant food interactions. |
| Clinical Pearls | Monitor serum potassium and renal function within 1-2 weeks after initiation or dose titration. First-dose hypotension is more likely in volume-depleted patients; consider starting with a low dose. Angioedema, though rare, requires immediate discontinuation. Use with caution in renal artery stenosis. ACE inhibitors are teratogenic; discontinue if pregnancy is suspected. |
| Patient Advice | Take exactly as prescribed, usually once or twice daily. · Avoid salt substitutes containing potassium unless directed by your doctor. · Report any swelling of the face, lips, or throat immediately. · May cause dizziness, especially after the first dose; rise slowly from sitting or lying down. · Do not use during pregnancy; notify your doctor if you become pregnant. · Drink adequate fluids unless fluid restricted. |