Benazepril Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.25-0.5 mg/kg	q24h	Duration: Chronic Notes: Dose may be increased up to 1 mg/kg q24h if needed. For heart failure, start at 0.25 mg/kg q24h and titrate as tolerated.
Cat	PO	0.5-1 mg/kg	q24h	Duration: Chronic Notes: For CKD and proteinuria, start at 0.5 mg/kg q24h; may increase to 1 mg/kg q24h if needed.
Horse	PO	0.5-1 mg/kg	q12-24h	Duration: Variable Notes: Limited data; use with caution and monitor blood pressure.
Rabbit	PO	0.5-1 mg/kg	q24h	Duration: Chronic Notes: Anecdotal; monitor renal function and blood pressure.

Clinical Indications & Species Uses

General Indications

Treatment of hypertension
Management of chronic heart failure
Reduction of proteinuria in chronic kidney disease

Dog (Canine)

Heart failure (congestive heart failure, mitral regurgitation, dilated cardiomyopathy)
Chronic kidney disease (proteinuric nephropathy)
Hypertension (systemic)

Cat (Feline)

Chronic kidney disease (proteinuric nephropathy)
Hypertension (systemic)
Heart failure (less common)

Horse (Equine)

Hypertension (rarely used)
Heart failure (rarely used)

Rabbit & Small Mammals

Hypertension (rarely used)
Chronic kidney disease (anecdotal)

Exotic & Other Species

Hypertension (in some exotic species, anecdotal)

Pharmacology & Mechanism of Action

Drug Class: ACE inhibitor | Pharmacological Group: Angiotensin-converting enzyme inhibitor

Mechanism of Action: Benazepril is a prodrug that is hydrolyzed in the liver to its active metabolite, benazeprilat, which inhibits angiotensin-converting enzyme (ACE). ACE converts angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone release. By inhibiting ACE, benazepril reduces angiotensin II levels, leading to vasodilation, decreased aldosterone secretion, and reduced sodium and water retention. This results in decreased blood pressure, reduced preload and afterload, and improved cardiac output. Additionally, benazepril reduces glomerular capillary pressure and proteinuria by dilating efferent arterioles, which is beneficial in chronic kidney disease.

Pharmacodynamics: Benazepril produces dose-dependent inhibition of ACE activity, leading to decreased plasma angiotensin II and aldosterone concentrations. It reduces systemic vascular resistance and blood pressure without causing reflex tachycardia. In the kidney, it increases renal blood flow and glomerular filtration rate, and reduces proteinuria. In heart failure, it improves cardiac output and exercise tolerance, and reduces cardiac remodeling. The effects are more pronounced in animals with activated renin-angiotensin-aldosterone system (RAAS), such as those with heart failure or renal disease.

⚡ Pharmacokinetics Summary

Absorption: Benazepril is rapidly absorbed after oral administration in dogs, cats, and horses. In dogs, bioavailability is about 50-60% due to first-pass metabolism. Food may slightly reduce the rate but not the extent of absorption. In cats, bioavailability is approximately 50%.

Distribution: Benazepril and benazeprilat are extensively distributed to tissues. Benazeprilat is highly protein-bound (approximately 90-95% in dogs and cats). It crosses the placenta and is excreted in milk in small amounts.

Metabolism: Benazepril is hydrolyzed by hepatic esterases to the active metabolite benazeprilat. Benazeprilat is not further metabolized to any significant extent.

Excretion: Benazepril and benazeprilat are excreted primarily via the biliary route in dogs and cats, with a smaller proportion excreted renally. In horses, renal excretion is more significant. In animals with hepatic impairment, metabolism may be reduced, but biliary excretion provides an alternative route.

Half-Life: In dogs, the terminal half-life of benazeprilat is approximately 10-14 hours. In cats, it is about 10-12 hours. In horses, the half-life is shorter, around 2-4 hours.

Bioavailability: Oral bioavailability of benazepril is about 50-60% in dogs and cats, and approximately 50% in horses.

Protein Binding: Benazeprilat is approximately 90-95% protein-bound in dogs and cats.

Available Formulations & Strengths

Oral Tablet 2.5 mg, 5 mg, 10 mg, 20 mg, 40 mg (PO)

Oral Solution (compounded) Various (PO)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to benazepril or other ACE inhibitors
History of angioedema associated with ACE inhibitor use
Concurrent use with aliskiren (in humans; not relevant in animals)
Severe hypotension or cardiogenic shock
Pregnancy (especially in the second and third trimester) due to risk of fetal renal damage
Bilateral renal artery stenosis (rare in animals)

Warnings & Clinical Precautions:

Use with caution in animals with renal insufficiency; monitor renal function and potassium levels.
May cause hypotension, especially in volume-depleted animals; correct dehydration before starting therapy.
In animals with heart failure, monitor for worsening renal function and hyperkalemia.
Use with caution in animals with hepatic impairment, as benazepril is a prodrug requiring hepatic activation.
Safety in pregnant or lactating animals has not been fully established; use only when clearly needed.
In food animals, withdrawal times must be observed; extra-label use is regulated by AMDUCA.

Adverse Effects & Reactions

Common:

Hypotension
Fatigue
Dizziness
Gastrointestinal upset (vomiting, diarrhea)
Cough (rare in animals)

Serious / Severe:

Acute renal failure (especially in dehydrated animals)
Hyperkalemia
Angioedema (rare)
Severe hypotension
Neutropenia (rare)

Rare:

Hepatotoxicity
Pancreatitis
Alopecia
Pruritus

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Potassium-sparing diuretics (e.g., spironolactone, triamterene)	Increased risk of hyperkalemia	High
Nonsteroidal anti-inflammatory drugs (NSAIDs)	Reduced antihypertensive effect and increased risk of renal dysfunction	Moderate
Diuretics (e.g., furosemide)	Additive hypotensive effect; may cause excessive blood pressure reduction	Moderate
Other antihypertensives (e.g., amlodipine)	Additive hypotensive effect	Moderate
Potassium supplements	Increased risk of hyperkalemia	High
Lithium	Increased lithium levels and toxicity	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe hypotension
Dizziness
Syncope
Renal failure
Hyperkalemia
Bradycardia

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and animal is stable. Administer activated charcoal to reduce absorption. Provide intravenous fluids to maintain blood pressure and renal perfusion. Monitor blood pressure, renal function, and electrolytes. In severe cases, administer angiotensin II (if available) or vasopressors such as norepinephrine. Treat hyperkalemia with calcium gluconate, insulin/glucose, or sodium bicarbonate as needed.

Food Animal Withdrawal Times

Benazepril is not approved for use in food animals. In the US, extra-label use in food animals is prohibited under AMDUCA if an approved drug exists for the indication. If used in food animals, a prolonged withdrawal period should be considered, but no official withdrawal times are established.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F)

Handling & Special Conditions: Protect from moisture. Keep in a tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats (e.g., Fortekor, Lotensin).

Extra-Label (Off-Label) Use: In the US, benazepril is approved for use in dogs and cats. Extra-label use in other species is permitted under AMDUCA, but requires a valid veterinarian-client-patient relationship and must not result in violative residues in food animals. For food animals, extra-label use is prohibited if an approved drug is available for the same indication.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Benazepril is a widely used ACE inhibitor in veterinary medicine, primarily for the management of heart failure and chronic kidney disease with proteinuria. It is preferred over enalapril in some cases due to its dual route of excretion (biliary and renal), which may be advantageous in animals with renal impairment. Clinical monitoring should include blood pressure, renal function (BUN, creatinine), and serum potassium levels, especially during the first weeks of therapy. In dogs with heart failure, benazepril is often used in combination with furosemide and pimobendan. In cats with CKD, it helps reduce proteinuria and slow disease progression. The drug is generally well-tolerated, but hypotension and hyperkalemia are potential concerns. Dosage adjustments may be necessary in animals with severe renal or hepatic disease. Always follow label instructions and consult current veterinary guidelines.

References & Literature

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