Enalapril Maleate — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5 mg/kg	q12h or q24h	Duration: Long-term (chronic) Notes: Dose may be increased up to 1-2 mg/kg/day if needed. For heart failure, start at 0.5 mg/kg q12h. For proteinuria, use 0.5 mg/kg q12h.
Cat	PO	0.25-0.5 mg/kg	q24h or q12h	Duration: Long-term (chronic) Notes: Start at 0.25 mg/kg q24h, may increase to 0.5 mg/kg q12h if needed. Monitor renal function and potassium.
Horse	PO	0.5-1 mg/kg	q12h	Duration: Variable Notes: Limited data; use with caution. Monitor blood pressure and renal function.
Cattle	PO	Not established	Not established	Duration: Not established Notes: Not recommended for food animals due to lack of withdrawal times and efficacy data.
Small Ruminants	PO	Not established	Not established	Duration: Not established Notes: Not recommended for food animals.
Rabbit	PO	0.5-1 mg/kg	q12h	Duration: Variable Notes: Use with caution; monitor renal function.
Bird/Poultry	PO	Not established	Not established	Duration: Not established Notes: Not recommended for food animals.
Exotic/Other	PO	Variable	Variable	Duration: Variable Notes: Dose based on extrapolation; consult specialist.

Clinical Indications & Species Uses

General Indications

Heart failure
Hypertension
Proteinuric chronic kidney disease

Dog (Canine)

Heart failure (congestive heart failure, mitral regurgitation, dilated cardiomyopathy)
Hypertension (systemic)
Chronic kidney disease (proteinuria, to slow progression)

Cat (Feline)

Heart failure (hypertrophic cardiomyopathy, restrictive cardiomyopathy)
Hypertension (systemic)
Chronic kidney disease (proteinuria)

Pharmacology & Mechanism of Action

Drug Class: ACE inhibitor | Pharmacological Group: Angiotensin-Converting Enzyme Inhibitor

Mechanism of Action: Enalapril is a prodrug that is hydrolyzed in the liver to enalaprilat, which competitively inhibits angiotensin-converting enzyme (ACE). This enzyme converts angiotensin I to the potent vasoconstrictor angiotensin II. Inhibition of ACE leads to decreased plasma angiotensin II levels, resulting in vasodilation, reduced aldosterone secretion, decreased sodium and water retention, and reduced preload and afterload. It also increases bradykinin levels, contributing to vasodilatory effects. In the kidney, it causes efferent arteriolar dilation, which reduces glomerular filtration pressure and proteinuria in chronic kidney disease.

Pharmacodynamics: Enalapril produces a dose-dependent reduction in blood pressure in hypertensive animals. In heart failure, it improves cardiac output, reduces pulmonary capillary wedge pressure, and decreases systemic vascular resistance. It also attenuates adverse cardiac remodeling and slows progression of chronic kidney disease by reducing intraglomerular hypertension and proteinuria. The onset of action after oral administration is usually within 1-2 hours, with peak effects at 4-6 hours. The duration of effect is approximately 12-24 hours depending on species.

⚡ Pharmacokinetics Summary

Absorption: Enalapril is well absorbed after oral administration in most species. In dogs, bioavailability is approximately 60-70% (with food reducing absorption). In cats, bioavailability is about 50-60%. It is a prodrug and is rapidly hydrolyzed to the active form enalaprilat, primarily in the liver.

Distribution: Enalaprilat is widely distributed, with low protein binding (approximately 50-60% in dogs). It penetrates tissues, including the heart, kidneys, and vasculature. It does not cross the blood-brain barrier significantly. In lactating animals, it is excreted into milk in small amounts.

Metabolism: Enalapril is extensively metabolized in the liver to enalaprilat via ester hydrolysis. Enalaprilat is not further metabolized to any significant extent.

Excretion: Enalaprilat is primarily excreted by the kidneys via glomerular filtration and tubular secretion. In dogs, approximately 60-70% of the dose is excreted in urine, with the remainder in feces. In animals with renal impairment, elimination is prolonged, and dose adjustments may be necessary.

Half-Life: Dog: 1-2 hours (enalaprilat: 2-4 hours); Cat: 1-2 hours (enalaprilat: 2-3 hours); Horse: 1-2 hours (enalaprilat: 2-4 hours).

Bioavailability: Dog: 60-70% (oral); Cat: 50-60% (oral); Horse: 30-40% (oral).

Protein Binding: Enalaprilat: approximately 50-60% in dogs and cats.

Available Formulations & Strengths

Oral Tablet 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg (PO)

Oral Solution (compounded) Various (PO)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to enalapril or other ACE inhibitors
History of angioedema related to ACE inhibitor therapy
Concurrent use with aliskiren (in humans; not relevant in animals)
Severe renal artery stenosis (bilateral or unilateral in a solitary kidney)
Hypotension or shock
Pregnancy (especially in the second and third trimester) - risk of fetal toxicity

Warnings & Clinical Precautions:

Use with caution in animals with renal impairment; monitor renal function and serum potassium.
May cause hypotension, especially in volume-depleted animals; correct dehydration before starting therapy.
Monitor for signs of hyperkalemia, especially in animals with renal disease or those receiving potassium-sparing diuretics.
Use with caution in animals with congestive heart failure; adjust diuretic dose as needed.
In animals with chronic kidney disease, a transient increase in serum creatinine may occur; if stable, continue therapy.
Safety in pregnant or lactating animals has not been established; use only if clearly needed.
Do not use in animals with a history of ACE inhibitor-induced angioedema.
In food animals, withdrawal times are not established; do not use in animals intended for food.

Adverse Effects & Reactions

Common:

Hypotension
Weakness
Lethargy
Gastrointestinal upset (vomiting, diarrhea)
Decreased appetite

Serious / Severe:

Acute renal failure (especially in volume-depleted animals)
Hyperkalemia
Angioedema (rare but serious)
Severe hypotension
Bone marrow suppression (rare)

Rare:

Cough (reported in humans, rare in animals)
Hepatotoxicity
Pancreatitis
Dermatologic reactions

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Potassium-sparing diuretics (spironolactone, triamterene)	Increased risk of hyperkalemia	High
Potassium supplements	Increased risk of hyperkalemia	High
NSAIDs (e.g., carprofen, meloxicam)	Reduced antihypertensive effect; increased risk of renal dysfunction	Moderate
Diuretics (furosemide)	Additive hypotension; risk of volume depletion and renal impairment	Moderate
Other vasodilators (e.g., hydralazine, amlodipine)	Additive hypotensive effects	Moderate
Anesthetics	Enhanced hypotensive effects	Moderate
Lithium	Increased lithium levels and toxicity	High

Overdose & Toxicity Management

Signs of Toxicity:

Severe hypotension
Weakness
Collapse
Bradycardia
Renal failure
Hyperkalemia
Lethargy

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids (0.9% NaCl) to correct hypotension and maintain renal perfusion. Monitor blood pressure, ECG, renal function, and serum electrolytes. In severe cases, administer angiotensin II (if available) or vasopressors (e.g., norepinephrine). Treat hyperkalemia with calcium gluconate, sodium bicarbonate, glucose/insulin, or beta-agonists as needed. Hemodialysis may be considered in severe cases.

Food Animal Withdrawal Times

Not approved for use in food animals. Withdrawal times have not been established. Do not use in animals intended for food.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).

Handling & Special Conditions: Protect from moisture. Keep container tightly closed. Compounded oral solutions should be stored according to compounding pharmacy instructions, typically refrigerated.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs (Enacard) for the management of heart failure. Not approved for cats or other species, but commonly used extra-label.

Extra-Label (Off-Label) Use: In the US, enalapril is approved for dogs (Enacard) for heart failure. Use in other species or for other indications is extra-label and must comply with AMDUCA regulations. For food animals, extra-label use is prohibited if no withdrawal times are established and if there is a risk of violative residues.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Enalapril is a commonly used ACE inhibitor in veterinary medicine, primarily for heart failure and proteinuric kidney disease. It is generally well-tolerated, but monitoring of renal function and electrolytes is essential, especially during the first weeks of therapy. In dogs with heart failure, it is often used in combination with furosemide and pimobendan. In cats, it is used for hypertension and chronic kidney disease, but amlodipine is often preferred for hypertension. Enalapril should be started at a low dose and titrated upward based on response. It may take 2-4 weeks to see full effects on proteinuria. Always ensure adequate hydration before starting therapy to avoid acute renal decompensation. In animals with renal disease, a mild increase in creatinine is acceptable if it stabilizes. Do not use in pregnant animals due to risk of fetal toxicity. For compounding, note that enalapril is unstable in aqueous solutions; use appropriate vehicles and storage conditions.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)