LD₅₀ and Overdose

Oral LD₅₀ in rats is 2973 mg/kg.MSDS Lethality was observed with single oral doses of enalapril above 1000 mg/kg in mice and greater than or equal to 1775 mg/kg in rats. Serum enalaprilat levels 100- and 200-fold higher than usually seen after therapeutic doses have been reported after ingestion of 300 mg and 440 mg of enalapril, respectively.^L6586 While there is limited data about enalapril overdose in humans, overdosage may result in marked hypotension and stupor based on the pharmacological properties of the drug. Most common adverse effects of enalapril include cough, hypotension, stupor, headache, dizziness and fatigue. If hypotension is seen, usual treatment of intravenous infusion of normal saline solution is recommended. Enalaprilat may be removed from systemic circulation with the use of hemodialysis. It has been removed from neonatal circulation by peritoneal dialysis.label

Nonclinical toxicology

Maternal and fetal toxicity occudred in some rabbits treated with enalapril at doses of 1 mg/kg/day or more. There was no fetotoxicity, expressed as a decrease in average fetal weight, or teratogenicity in rats treated with enalapril at doses up to 200 mg/kg/day, which is about 333 times the maximum human dose.^L6586 In mice and rats receiving enalapril at doses ranging from 90 to 180 mg/kg/day, there was no evidence of a tumorigenic effect. Neither enalapril or its active metabolite were shown to be mutagenic or genotoxic in in vitro and in vivo studies. There were no adverse effects on reproductive performance of male and female rats treated with up to 90 mg/kg/day of enalapril. label

Use in special populations

Caution is warranted in patients who are concurrently using another ACE inhibitors with enalapril, as there have been incidences of agranulocytosis with the use of captopril, which is another ACE inhibitor. This adverse event may be particularly significant in patients with renal impairment or collagen vascular disease.label As enalapril and enalaprilat were shown to be secreted in human milk in trace amounts, the use of enalaprilat in nursing women is not recommended.^L6586 Significant fetal transfer occurs with enalapril and enalaprilat thus the use of the drug in pregnant women should be strongly avoided. Caution is advised when enalapril is used in patients who are elderly or with renal impairment, as dosage adjustments may be appropriate. The antihypertensive effect of angiotensin converting enzyme inhibitors is generally lower in individuals of African descent, usually a low-renin hypertensive population.label