Verapamil

Overview

Verapamil (Securon®, Verapamil®) is a calcium-channel blocker used primarily in dogs and cats for the management of supraventricular tachyarrhythmias. Its antiarrhythmic effects result from slowing conduction through the atrioventricular (AV) node, making it useful for controlling heart rate in certain supraventricular rhythm disturbances.

Although effective, verapamil is generally considered a second-line calcium-channel blocker behind diltiazem in veterinary cardiology because it produces a more pronounced negative inotropic effect. Careful patient selection is therefore important, particularly in animals with impaired cardiac function or reduced myocardial contractility.

Verapamil undergoes extensive hepatic metabolism, and dose reduction may be required in patients with significant liver disease. Its cardiovascular effects include slowing AV conduction, reducing myocardial contractility, and promoting vasodilation, all of which contribute to its therapeutic and adverse effects.

Mechanism of Action (MOA): Verapamil inhibits the influx of calcium ions through L-type calcium channels in myocardial cells, cardiac conduction tissue, and vascular smooth muscle. This results in slowed AV nodal conduction, reduced myocardial contractility, and vasodilation of coronary and peripheral blood vessels.

Indications

Verapamil is used in dogs and cats primarily for the management of supraventricular tachyarrhythmias, particularly those involving abnormal AV nodal conduction.

• Supraventricular tachycardia (SVT): Used to control heart rate in patients with supraventricular tachyarrhythmias.
• Accessory pathway-mediated SVT: Helps slow conduction associated with re-entrant supraventricular arrhythmias.
• Atrial tachycardia: Used for rate control in atrial tachyarrhythmias.
• Atrial flutter: May be used to reduce ventricular response by slowing AV nodal conduction.

Dosage (Reference)

Dog

In dogs, verapamil may be administered orally for long-term control of supraventricular tachyarrhythmias or intravenously for more rapid rate control. Intravenous administration should be performed slowly with continuous ECG monitoring.

Cat

In cats, verapamil may be used orally for maintenance therapy or intravenously for acute control of supraventricular tachyarrhythmias. Careful ECG monitoring is recommended during IV administration.

Warnings & Precautions

Verapamil can significantly affect cardiac conduction, myocardial contractility, and blood pressure. Careful patient selection and cardiovascular monitoring are essential during therapy.

• AV block: Contraindicated in patients with second- or third-degree atrioventricular (AV) block due to the risk of worsening conduction abnormalities.
• Hypotension: Contraindicated in hypotensive patients because vasodilation may further decrease blood pressure and risk circulatory collapse.
• Sick sinus syndrome: Contraindicated in patients with sick sinus syndrome because marked slowing of cardiac conduction may occur.
• Heart failure: Avoid use in patients with left ventricular dysfunction or congestive heart failure due to its negative inotropic effects.
• Hepatic impairment: Severe liver disease may reduce drug metabolism and increase drug exposure. reduce dose by 70% in severe hepatic disease.
• IV administration: IV doses should be administered slowly with continuous ECG monitoring. Critical safety signal: verapamil has caused sudden cardiac arrest with IV administration. Have CPR support, IV calcium salts, atropine, and pressors immediately available.
• Cardiogenic shock / severe CHF: contraindication of verapamil in cardiogenic shock and severe CHF (unless the CHF is secondary to a verapamil-amenable SVT).
• WPW + atrial fibrillation: high-risk combination — verapamil may cause rapid hemodynamic deterioration and ventricular fibrillation by enhancing antegrade conduction through the accessory pathway. Avoid in dogs with known WPW + AF.
• IV verapamil + IV beta-blocker timing: IV verapamil is contraindicated within a few hours of IV beta-blocker administration. Combined AV-nodal and contractility depression can cause profound bradycardia, complete AV block, and ventricular fibrillation.
• P-gp inhibitor / MDR1 dogs: Verapamil is a P-glycoprotein (P-gp) INHIBITOR. In MDR1 (ABCB1-1delta)-mutant dogs (Collies, Australian Shepherds, Shelties, etc.), combining verapamil with P-gp substrates (vincristine, butorphanol, loperamide, doxorubicin) can significantly increase systemic and CNS exposure of the substrate and elevate toxicity risk.
• Pregnancy & lactation: Verapamil crosses the placenta and is excreted in milk. Embryocidal and fetal growth retardation reported in rats at 1.5–6× human therapeutic doses. Consider discontinuing nursing if the dam requires verapamil; use in pregnancy only when potential benefit outweighs risk.
• Diabetic animals — blood glucose: verapamil may elevate blood glucose in dogs and may confuse blood glucose determinations. Use with care + closer glucose monitoring in diabetic patients.

Drug Interactions

The most clinically important interactions with verapamil involve additive cardiovascular depression or changes in the blood concentrations of concurrently administered drugs.

• Beta-blockers: Concurrent use should be avoided. IV verapamil is contraindicated within a few hours of IV beta-blocker administration — combined effect can cause profound bradycardia, complete AV conduction failure, hypotension, and ventricular fibrillation.
• Sodium-channel blockers: May increase the risk of cardiovascular depression and hypotension when administered with verapamil.
• Digoxin and digitoxin: Verapamil may increase serum concentrations, potentially leading to toxicity; monitoring is recommended.
• Theophylline: Blood concentrations may increase, increasing the risk of adverse effects and toxicity.
• Cimetidine: May increase the effects of verapamil by reducing its metabolism.
• Calcium salts and vitamin D: May reduce the therapeutic effects of verapamil by opposing calcium-channel blockade.
• Vincristine: Calcium-channel blockers may increase intracellular vincristine concentrations, potentially enhancing toxicity.
• Non-depolarizing neuromuscular blocking agents: Neuromuscular blockade may be enhanced or prolonged when used concurrently.
• Dantrolene: Cardiovascular collapse has been reported in animals when dantrolene is used concurrently with verapamil — critical interaction; avoid the combination.
• Cyclosporine: Verapamil may increase cyclosporine concentrations and risk of toxicity.
• Doxorubicin: Verapamil may increase doxorubicin concentrations.
• Azole antifungals: ketoconazole may inhibit verapamil metabolism and increase exposure plus toxicity risk.
• Macrolide antibiotics: (erythromycin, clarithromycin) may increase verapamil concentrations and toxicity risk.
• Opioids + midazolam: Opioids (fentanyl, hydrocodone, morphine) and midazolam: verapamil may prolong sedation and increase opioid concentrations. Adjust sedation/analgesia plans accordingly; monitor for excessive sedation, respiratory depression.
• P-gp substrates (MDR1 dogs): P-gp substrates (butorphanol, loperamide, vincristine, others): verapamil is a P-gp inhibitor, so concurrent use with P-gp substrates in MDR1 (ABCB1-1delta)-mutant dogs (Collies, Australian Shepherds, Shelties) can significantly increase substrate exposure and toxicity.
• Quinidine: Additive alpha-adrenergic blockade and increased hypotensive effect. Verapamil may also block quinidine’s AV conductive effects and increase quinidine levels.
• Hepatic enzyme inducers: Phenobarbital and rifampin may reduce verapamil concentrations through hepatic enzyme induction and compromise efficacy.
• Additive hypotensives: ACE inhibitors, alpha-blockers, and diuretics: additive hypotensive effects. Monitor blood pressure when starting verapamil in patients on these drugs.
• Clopidogrel: Verapamil may decrease the antiplatelet effect of clopidogrel and increase the risk of thrombotic events.
• Lab interference (glucose): verapamil may elevate blood glucose in dogs and confuse blood glucose determinations. Account for this in diabetic patients and when interpreting glucose results.

Side Effects & Overdose

Side Effects

Adverse effects of verapamil are primarily related to its effects on cardiac conduction, myocardial contractility, and vascular smooth muscle. Most reactions are dose-dependent and occur more commonly in patients with underlying cardiovascular disease.

• Hypotension: May occur due to peripheral vasodilation and reduced cardiac output.
• Bradycardia: Excessive slowing of heart rate may develop, particularly in susceptible patients.
• Worsening heart failure: May precipitate or exacerbate congestive heart failure because of its negative inotropic effects.
• Dizziness or weakness: Reported in humans and may occur secondary to reduced blood pressure or decreased cardiac output.
• Gastrointestinal effects: Nausea and constipation have been reported, particularly with oral therapy.
• Fatigue: May occur during treatment due to cardiovascular and systemic effects.
• Peripheral edema: Dependent limb swelling has been reported in patients on verapamil. Monitor for limb/peripheral edema, especially in cardiac-compromised patients.
• AV block: Complete or progressive AV block has been reported as an adverse effect. Discontinue or reduce dose if heart block develops during therapy.
• Pulmonary edema: noncardiogenic pulmonary edema may be noted particularly in cardiac-compromised patients receiving verapamil.
• Sudden cardiac arrest (IV): verapamil has caused sudden cardiac arrest in some patients with IV administration. Reserve IV verapamil for monitored cardiac settings with immediate CPR support and reversal agents available.
• Anorexia: anorexia may happen particularly with oral dosing.
• Reflex sinus tachycardia: Paradoxical sinus tachycardia from carotid-sinus reflex activation has been described and may complicate the picture if monitoring is not in place.

Overdose

Verapamil overdose can result in severe cardiovascular toxicity due to excessive calcium-channel blockade. Clinical signs are typically related to profound depression of cardiac conduction, contractility, and vascular tone.

• Severe hypotension: May occur as a result of marked vasodilation and reduced myocardial performance.
• Marked bradycardia: Excessive slowing of the heart rate can lead to poor tissue perfusion.
• Advanced AV block: Significant impairment of cardiac conduction may develop in severe intoxication.
• Cardiovascular collapse: Severe overdose may result in life-threatening circulatory compromise.
• Management: Treatment is supportive. For acute oral exposure (<2 hours) in an asymptomatic patient, consider GI decontamination (emesis + activated charcoal ± sorbitol). Cardiovascular support: IV calcium salts (calcium chloride or gluconate) for negative inotropy — may not adequately treat heart block. IV fluids + pressors (dopamine, norepinephrine) for hypotension. Atropine + isoproterenol + cardiac pacing for bradyarrhythmias / AV block.
• Additional OD signs: QT prolongation, hyperglycemia, junctional rhythms, sinus tachycardia (carotid reflex), GI upset, hypothermia, CNS depression, noncardiogenic pulmonary edema, hypokalemia, metabolic acidosis, and elevated lactate.
• Rare CNS stimulation: Rarely, CNS stimulation with seizures, agitation, ataxia, and tremors has been reported with overdose.
• Acute oral — GI decon: Acute oral ingestion (<2 hours, asymptomatic patient): consider GI decontamination — emesis followed by activated charcoal ± sorbitol cathartic.
• WPW — DC cardioversion: WPW patients with rapid ventricular response after verapamil: DC cardioversion plus lidocaine or procainamide is the recommended treatment to suppress accessory-pathway conduction.
• Refractory — glucagon / insulin / lipid: Refractory cardiovascular collapse may respond to specific therapies: glucagon, high-dose insulin / glucose euglycemic infusion, and IV lipid emulsion .
• 24-hour poison consult: Strongly consult a 24-hour veterinary poison center for any severe verapamil toxicity due to the complex management of CCB overdoses.

Key Notes

Practical clinical points that help optimize the safe and effective use of verapamil in dogs and cats:

• Second-line calcium-channel blocker: Verapamil is generally used less frequently than diltiazem because its negative inotropic effects are more pronounced. verapamil has practically become an outdated drug in veterinary medicine. The preferred drug from this class to use in animals is usually diltiazem.
• Best suited for supraventricular arrhythmias: Its primary antiarrhythmic benefit comes from slowing conduction through the AV node, making it most useful for supraventricular tachyarrhythmias.
• Rapid IV effect: Intravenous administration can provide relatively rapid control of supraventricular tachyarrhythmias when immediate rate reduction is required.
• Oral therapy for long-term control: Oral administration is commonly used when ongoing management of recurrent supraventricular arrhythmias is needed.
• Multiple cardiovascular actions: In addition to its antiarrhythmic effects, verapamil influences myocardial contractility and vascular tone, which contribute to its overall clinical response.
• Individual response varies: The degree of heart rate control and antiarrhythmic response may differ among patients, requiring individualized dose titration and follow-up assessment.
• Monitoring: Monitor heart rate, rhythm (ECG), and blood pressure during initiation and IV administration. Periodic recheck during long-term oral therapy. Consider periodic liver enzymes in patients on chronic therapy or with hepatic disease.
• Tablet / capsule handling: Tablet handling: SR tablets may be split in half without altering the sustained-release characteristic. ER capsules may be opened and the contents sprinkled on soft food — but the contents must NOT be crushed or chewed.
• Post-bolus CRI option: Post-bolus CRI: 2–10 µg/kg/min IV CRI provides sustained rate control beyond the ~30-minute bolus duration; the cumulative IV bolus cap is 0.15 mg/kg.
• Pregnancy / lactation: Pregnancy & lactation: verapamil crosses the placenta and is excreted in milk. In rats, 1.5–6× human dose was embryocidal. Consider discontinuing nursing or using an alternative agent if dam requires verapamil.