Verapamil Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-2 mg/kg	q8h	Duration: As needed for arrhythmia control Notes: Start at low end and titrate to effect. Monitor heart rate and blood pressure.
Dog	IV	0.02-0.05 mg/kg	Slow IV bolus over 2-3 minutes; may repeat once after 10-15 minutes	Duration: Emergency use for SVT Notes: Monitor ECG continuously. Have calcium gluconate and atropine available.
Cat	PO	0.5-1 mg/kg	q8h	Duration: Chronic therapy for HCM or arrhythmias Notes: Use with caution in cats with heart failure. Monitor blood pressure and heart rate.
Cat	IV	0.025-0.05 mg/kg	Slow IV bolus over 2-3 minutes; may repeat once	Duration: Emergency use for SVT Notes: Use with extreme caution; cats are sensitive to negative inotropic effects.
Horse	PO	0.5-1 mg/kg	q8h	Duration: For atrial fibrillation rate control Notes: Limited efficacy; often used as an adjunct to quinidine or other treatments.
Horse	IV	0.025-0.05 mg/kg	Slow IV bolus over 2-3 minutes	Duration: Emergency treatment for SVT Notes: Monitor ECG and blood pressure closely.
Cattle	IV	0.025-0.05 mg/kg	Slow IV bolus	Duration: Emergency treatment for SVT Notes: Not commonly used; use with caution.
Small Ruminants	IV	0.025-0.05 mg/kg	Slow IV bolus	Duration: Emergency treatment for SVT Notes: Not commonly used; use with caution.
Rabbit	PO	0.5-1 mg/kg	q8h	Duration: For arrhythmias Notes: Limited data; use with caution.
Bird/Poultry	PO	0.5-1 mg/kg	q8h	Duration: For arrhythmias Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Supraventricular tachyarrhythmias (SVT, atrial fibrillation, atrial flutter)
Hypertension (adjunctive)
Hypertrophic cardiomyopathy (in cats)

Dog (Canine)

Supraventricular tachycardia (SVT)
Atrial fibrillation (rate control)
Atrial flutter
Hypertension (less common)
Hypertrophic cardiomyopathy (adjunctive therapy)

Cat (Feline)

Hypertrophic cardiomyopathy (HCM) - to slow heart rate and improve diastolic function
Supraventricular tachycardia
Atrial fibrillation (rate control)
Hypertension (less common)

Horse (Equine)

Supraventricular tachycardia
Atrial fibrillation (rate control)
Atrial flutter

Pharmacology & Mechanism of Action

Drug Class: Calcium Channel Blocker (Class IV antiarrhythmic) | Pharmacological Group: Phenylalkylamine calcium channel antagonist

Mechanism of Action: Verapamil inhibits the influx of calcium ions through L-type calcium channels in cardiac and vascular smooth muscle cells. It primarily blocks the slow inward calcium current in the sinoatrial (SA) and atrioventricular (AV) nodes, slowing conduction and prolonging refractoriness. It also causes vasodilation of peripheral arterioles, reducing afterload and myocardial oxygen demand. In vascular smooth muscle, it inhibits calcium-dependent contraction, leading to relaxation.

Pharmacodynamics: Verapamil produces negative chronotropic, dromotropic, and inotropic effects. It slows heart rate, reduces AV nodal conduction velocity, and decreases myocardial contractility. It also causes dose-dependent vasodilation, lowering systemic vascular resistance and arterial blood pressure. In animals, it is used primarily for its antiarrhythmic effects, particularly for supraventricular tachyarrhythmias. It may also have anti-hypertensive and anti-anginal effects, but these are less commonly exploited in veterinary medicine.

⚡ Pharmacokinetics Summary

Absorption: Rapidly and almost completely absorbed after oral administration, but undergoes extensive first-pass hepatic metabolism, resulting in a bioavailability of only 20-35% in most species. Peak plasma concentrations occur within 1-2 hours after oral dosing. Food may increase the rate of absorption.

Distribution: Widely distributed throughout the body. It crosses the blood-brain barrier and placenta, and is distributed into milk. Protein binding is approximately 90% in most species. Volume of distribution is large, indicating extensive tissue binding.

Metabolism: Extensively metabolized in the liver via cytochrome P450 enzymes (primarily CYP3A4) to several metabolites, including norverapamil, which has about 20% of the parent drug's activity. First-pass metabolism is significant, reducing oral bioavailability.

Excretion: Excreted primarily in the urine as metabolites (up to 70%), with about 16% excreted in feces. Less than 5% is excreted unchanged. Elimination is delayed in animals with hepatic or renal impairment.

Half-Life: Dog: 2-4 hours (oral), 1-2 hours (IV); Cat: 1-2 hours; Horse: 1-2 hours; Cattle: 1-2 hours (estimated).

Bioavailability: Oral: 20-35% due to first-pass metabolism; IV: 100%.

Protein Binding: Approximately 90% in most species.

Available Formulations & Strengths

Oral Tablet 40 mg, 80 mg, 120 mg (PO)

Extended-release Tablet 120 mg, 180 mg, 240 mg (PO)

Injectable Solution 2.5 mg/mL (2 mL ampule) (IV)

Contraindications & Clinical Warnings

Contraindications:

Severe hypotension or cardiogenic shock
Second- or third-degree AV block without a functioning pacemaker
Sick sinus syndrome
Severe congestive heart failure (unless caused by a tachyarrhythmia that can be controlled)
Known hypersensitivity to verapamil
Concurrent use of IV beta-blockers (e.g., propranolol) due to risk of severe bradycardia and asystole
Concurrent use of dantrolene (risk of hyperkalemia and cardiac depression)

Warnings & Clinical Precautions:

Use with caution in animals with hepatic or renal impairment; dose adjustment may be necessary.
Use with caution in animals with hypertrophic cardiomyopathy and concurrent heart failure; may worsen heart failure due to negative inotropic effects.
Use with caution in animals with myasthenia gravis; may exacerbate muscle weakness.
Use with caution in animals with gastrointestinal obstruction or decreased GI motility; may cause constipation.
In cats, use with caution due to sensitivity to negative inotropic effects; monitor for signs of heart failure.
In horses, use with caution as it may cause hypotension and GI disturbances.
Monitor heart rate, blood pressure, and ECG during therapy, especially when initiating or adjusting dose.
Do not crush or split extended-release tablets; administer whole.
Intravenous administration should be slow (over 2-3 minutes) with continuous ECG monitoring.
Have emergency drugs (atropine, calcium gluconate, dopamine) available during IV administration.

Adverse Effects & Reactions

Common:

Hypotension
Bradycardia
Constipation
Gastrointestinal upset (nausea, vomiting)
Dizziness or weakness

Serious / Severe:

Severe bradycardia or AV block
Worsening of heart failure
Cardiogenic shock
Asystole (with rapid IV administration or concurrent beta-blockers)
Hepatic toxicity (rare)

Rare:

Gingival hyperplasia
Peripheral edema
Skin rash
Elevated liver enzymes
Hyperprolactinemia (in humans; not documented in animals)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Beta-blockers (e.g., propranolol, atenolol)	Additive negative inotropic and chronotropic effects; risk of severe bradycardia, AV block, and asystole.	High
Digoxin	Verapamil increases serum digoxin levels by decreasing renal clearance and distribution; risk of digoxin toxicity.	High
Dantrolene	Hyperkalemia and cardiac depression may occur.	High
Cimetidine	May increase verapamil levels by inhibiting hepatic metabolism.	Moderate
Macrolide antibiotics (e.g., erythromycin, clarithromycin)	May increase verapamil levels by inhibiting CYP3A4.	Moderate
Azole antifungals (e.g., ketoconazole, itraconazole)	May increase verapamil levels by inhibiting CYP3A4.	Moderate
Inhalational anesthetics (e.g., halothane, isoflurane)	Additive negative inotropic and hypotensive effects.	Moderate
Fentanyl	Severe hypotension may occur.	Moderate
Rifampin	May decrease verapamil levels by inducing CYP3A4.	Mild
Phenobarbital	May decrease verapamil levels by inducing hepatic enzymes.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Severe hypotension
Bradycardia
AV block
Asystole
Metabolic acidosis
Hyperglycemia
Hyperkalemia
Seizures
Lethargy or coma

Emergency Treatment Protocol: Treatment is primarily supportive. Administer IV fluids for hypotension. For bradycardia or AV block, administer atropine (0.04 mg/kg IV) and consider temporary pacing. Calcium gluconate (10% solution, 0.5-1 mL/kg IV slowly) may be given to counteract cardiac effects. In severe cases, use inotropic agents such as dopamine or dobutamine. Glucagon (50-150 mcg/kg IV) may be used to increase cardiac contractility. For recent oral ingestion, consider gastric lavage and activated charcoal. Monitor ECG, blood pressure, and electrolytes closely.

Food Animal Withdrawal Times

Verapamil is not approved for use in food animals in the US. If used off-label, a withdrawal period should be established based on veterinary judgment and regulatory guidelines. No official withdrawal times are established.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C, 68-77°F). Protect from light and moisture.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Keep tablets in a tightly closed container. Injectable solution should be stored at controlled room temperature and protected from freezing.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, verapamil is not FDA-approved for veterinary use. Use in animals is extra-label and must comply with AMDUCA regulations. For food animals, a valid Veterinary-Client-Patient Relationship (VCPR) is required, and withdrawal times must be established by the veterinarian.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Verapamil is a valuable antiarrhythmic agent for controlling supraventricular tachyarrhythmias in dogs, cats, and horses. In cats, it is occasionally used for hypertrophic cardiomyopathy, but its use is controversial due to potential negative inotropic effects; other drugs like diltiazem are often preferred. When using verapamil, careful patient selection and monitoring are essential. Intravenous administration should be reserved for emergency situations and performed slowly with continuous ECG and blood pressure monitoring. Oral therapy is preferred for chronic management. Because of its negative inotropic effects, verapamil should be avoided in animals with significant systolic dysfunction or congestive heart failure. Drug interactions, particularly with beta-blockers and digoxin, must be considered. For food animals, extra-label use requires careful consideration of withdrawal times and regulatory compliance.

References & Literature

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