ENALAPRILAT
Clinical safety rating: avoid
Contraindicated (not allowed)
Enalaprilat is an angiotensin-converting enzyme (ACE) inhibitor that blocks the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion, leading to decreased blood pressure and cardiac workload.
| Metabolism | Enalaprilat is minimally metabolized; it is the active metabolite of enalapril. No significant hepatic metabolism. |
| Excretion | Renal: 60-80% unchanged; biliary/fecal: minimal (<10%) |
| Half-life | Terminal half-life: 35 hours (prolonged in renal impairment; accumulates with CrCl <30 mL/min) |
| Protein binding | 50-60% (primarily albumin, minimal binding to other proteins) |
| Volume of Distribution | ~0.7 L/kg (large, indicates extensive tissue distribution; does not cross blood-brain barrier well) |
| Bioavailability | IV: 100% (given as active drug); oral: N/A (enalaprilat is not orally administered; enalapril oral bioavailability ~60%) |
| Onset of Action | IV: 5-15 minutes; oral: N/A (prodrug enalapril, requires hepatic activation) |
| Duration of Action | 24 hours; dose-dependent, sustained effect in heart failure and hypertension |
| Molecular Weight | 348.39 |
1.25 mg IV over 5 minutes every 6 hours; may increase to 5 mg IV every 6 hours if needed.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-60 mL/min: 0.625 mg IV every 6 hours; GFR <30 mL/min (including dialysis): 0.625 mg IV every 6 hours, titrate cautiously. |
| Liver impairment | No specific dose adjustment recommended; monitor for hypotension and hyperkalemia. |
| Pediatric use | Children ≥1 month: 5-10 mcg/kg/dose IV every 8-12 hours, max 1.25 mg/dose. |
| Geriatric use | Initiate at 0.625 mg IV every 6 hours; titrate slowly due to increased risk of hypotension and renal impairment. |
| 1st trimester | Contraindicated: associated with fetal renal dysfunction, oligohydramnios, skull ossification defects, and fetal death. Risk of teratogenicity is low but potential for severe adverse effects exists. |
| 2nd trimester | Contraindicated: increased risk of fetal renal impairment, oligohydramnios, pulmonary hypoplasia, and neonatal hypotension. ACE inhibitors cause fetal and neonatal morbidity and mortality. |
| 3rd trimester | Contraindicated: same risks as second trimester; use of ACE inhibitors during the second and third trimesters is associated with oligohydramnios, fetal renal dysfunction, skull hypoplasia, and neonatal hypotension and renal failure. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| Placental transfer | Enalaprilat crosses the placenta in humans. Fetal drug levels are similar to maternal levels. It is associated with adverse fetal and neonatal effects including oligohydramnios and renal dysfunction. |
| Breastfeeding |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
Hypersensitivity to enalaprilat or any ACE inhibitorHistory of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaConcomitant use with aliskiren in patients with diabetes mellitusPregnancy (second and third trimesters)
| Precautions | Angioedema, Hypotension, Renal impairment, Hyperkalemia, Cough |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, potatoes, spinach, salt substitutes) due to risk of hyperkalemia. Avoid alcohol as it may potentiate hypotension. |
Loading safety data…
| Enalaprilat is excreted into human breast milk, but concentrations are low (approximately 1% of maternal dose). No adverse effects reported in nursing infants. Caution is advised, especially in preterm infants or those with renal impairment, due to potential for hypotension and renal dysfunction. |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | First trimester: Association with congenital malformations (cardiac, CNS) based on retrospective data; second and third trimesters: Known fetal toxicity including oligohydramnios, fetal hypotension, renal failure, skull hypoplasia, and death due to renin-angiotensin system blockade. |
| Fetal Monitoring | Fetal ultrasound for amniotic fluid volume and renal function in second/third trimesters; maternal blood pressure, renal function, serum potassium, and urine protein. Monitor for signs of oligohydramnios or fetal distress. |
| Fertility Effects | No significant adverse effects on human fertility reported; animal studies show no impairment of fertility at clinically relevant doses. |
| Clinical Pearls | Enalaprilat is the active metabolite of enalapril and is administered intravenously for hypertensive emergencies. Onset of action is within 15 minutes with peak effect at 1-4 hours. Monitor blood pressure closely, especially in volume-depleted patients. Do not use in pregnancy (category D). Adjust dose in renal impairment (CrCl <30 mL/min: reduce initial dose to 0.625 mg). |
| Patient Advice | This medication is given intravenously to rapidly lower blood pressure. · Report any symptoms of low blood pressure such as dizziness, lightheadedness, or fainting. · Tell your doctor if you become pregnant or plan to become pregnant; this drug can harm the unborn baby. · Avoid salt substitutes containing potassium unless directed by your doctor. · Stay hydrated, but follow your doctor's instructions regarding fluid intake. |