Verapamil

Generic Name

Verapamil

Brand Names

Isoptin

Calan

Verelan

Cordilox

Covera-HS

Tarka (when combined with trandolapril)

Drug Class

Non-dihydropyridine calcium channel blocker

Phenylalkylamine derivative

Class IV antiarrhythmic agent

Mechanism of Action

Verapamil inhibits voltage-dependent L-type calcium channels in cardiac and vascular smooth muscle cells

Reduces transmembrane calcium influx during depolarization

Decreases intracellular calcium concentrations

In the myocardium this slows conduction through the sinoatrial SA and atrioventricular AV nodes

Reduces myocardial contractility negative inotropic effect

Slows heart rate negative chronotropic effect

Prolongs AV nodal conduction time

In the vascular system causes vasodilation by relaxing arterial smooth muscle

Results in reduced peripheral vascular resistance and blood pressure

Indications

Hypertension

Stable and variant angina pectoris

Supraventricular arrhythmias

Paroxysmal supraventricular tachycardia PSVT

Atrial fibrillation and atrial flutter with rapid ventricular response

Cluster headache prophylaxis off-label

Hypertrophic obstructive cardiomyopathy

Migraine prophylaxis off-label

Rate control in certain arrhythmias

Vasospastic angina

Dosage and Administration

Dosage depends on indication formulation and patient-specific factors

Immediate-release tablets

Commonly dosed 80 mg to 120 mg orally three to four times daily

Extended-release tablets or capsules

Commonly dosed 180 mg to 240 mg once daily

May titrate up to 360 mg to 480 mg daily based on response

IV administration

Used in arrhythmia management

Initial IV bolus 2.5 mg to 5 mg over 2 minutes

Second dose of 5 mg to 10 mg may be given after 15 to 30 minutes if needed

Total IV dose should not exceed 20 mg in most settings

Reduce IV dose and increase infusion time in elderly or small individuals

Doses should be individualized and titrated based on therapeutic response and tolerability

Pharmacokinetics

Bioavailability is approximately 20 to 35 percent due to extensive first-pass metabolism

Peak plasma levels within 1 to 2 hours for immediate-release and 5 to 7 hours for extended-release

Highly protein bound ~90 percent

Metabolized in the liver via CYP3A4 primarily

Main metabolite norverapamil retains activity

Half-life ranges from 3 to 7 hours for immediate-release

Extended-release forms may have half-lives of up to 10 to 20 hours

Eliminated primarily via hepatic metabolism and biliary excretion

Small fraction excreted unchanged in urine

Contraindications

Severe left ventricular dysfunction

Cardiogenic shock

Hypotension systolic blood pressure < 90 mmHg

Second or third-degree AV block without pacemaker

Sick sinus syndrome without functioning pacemaker

Wolff–Parkinson–White WPW syndrome with atrial fibrillation

Concurrent use with intravenous beta-blockers due to risk of AV block or severe hypotension

Severe bradycardia

Known hypersensitivity to verapamil or any component of the formulation

Warnings and Precautions

Caution in patients with heart failure due to negative inotropic effects

Can exacerbate AV block or bradycardia

Use with other rate-limiting drugs beta-blockers digoxin may increase bradyarrhythmia risk

May impair liver function

Use with caution in hepatic impairment adjust dose if needed

Hypotension may occur especially with IV use or high oral doses

Grapefruit juice may increase plasma levels through CYP3A4 inhibition

Do not crush or chew extended-release formulations

Abrupt discontinuation may precipitate angina or myocardial infarction in patients with coronary artery disease

Adverse Effects

Common

Constipation

Dizziness

Headache

Hypotension

Bradycardia

Peripheral edema

Nausea

Fatigue

Less common

AV block

Exacerbation of heart failure

Elevated liver enzymes

Gingival hyperplasia

Rare

Severe hypotension

Cardiogenic shock

Erythema multiforme

Allergic reactions

Overdose

Symptoms

Severe hypotension

Bradycardia

AV block

Cardiac arrest

Hyperglycemia

Lactic acidosis

Treatment

Supportive measures including fluid resuscitation and vasopressors

Atropine for bradycardia

Calcium gluconate or calcium chloride IV to reverse hypotension and AV block

Temporary cardiac pacing in severe AV block

Activated charcoal if ingestion is recent

Hemodialysis is not effective due to high protein binding

Drug Interactions

Verapamil is a substrate and inhibitor of CYP3A4 and P-glycoprotein

Increased plasma levels of coadministered CYP3A4 substrates

Statins especially simvastatin and lovastatin increased risk of myopathy

Increases levels of digoxin due to inhibition of P-glycoprotein

Caution with beta-blockers due to additive negative chronotropic effects

Enhanced hypotensive effects with other antihypertensives

Increases cyclosporine and tacrolimus levels

Reduces clearance of theophylline

May increase carbamazepine levels and associated toxicity

May enhance neuromuscular blockade effects of non-depolarizing muscle relaxants

Avoid grapefruit juice due to CYP3A4 inhibition and elevated verapamil levels

Use in Special Populations

Pregnancy

Category C

Use only if clearly needed

Limited human data but animal studies show potential fetal harm

Lactation

Excreted in breast milk

Use with caution

Monitor infant for signs of bradycardia and hypotension

Elderly

May be more sensitive to hypotensive and bradycardic effects

Start at lower doses and titrate slowly

Hepatic Impairment

Reduced clearance

Lower doses required

Renal Impairment

No dose adjustment generally needed

Monitor for adverse effects due to possible accumulation

Monitoring Parameters

Heart rate and blood pressure

Signs of heart failure including edema dyspnea fatigue

ECG for conduction abnormalities

Liver function tests with prolonged therapy

Monitor serum digoxin levels if used concomitantly

Assess for constipation particularly in elderly

Assess adherence due to multiple daily dosing in some formulations

Comparative Pharmacology

Compared to dihydropyridine calcium channel blockers such as amlodipine

Verapamil has stronger cardiac effects including AV nodal suppression

Amlodipine and others have more potent vasodilatory effects with less bradycardia

Compared to diltiazem

Verapamil is more potent in slowing AV nodal conduction

Diltiazem has more balanced cardiac and vascular effects

Compared to beta-blockers

Verapamil does not affect beta receptors and may be preferable in asthma or COPD patients

Formulations Available

Immediate-release tablets 40 mg 80 mg 120 mg

Extended-release tablets and capsules 120 mg 180 mg 240 mg 360 mg

Injectable solution for IV use 25 mg in 5 mL

Fixed-dose combinations with trandolapril and hydrochlorothiazide available in some regions

Regulatory and Legal Status

Prescription-only medicine worldwide

Approved by FDA and other global regulatory bodies for multiple cardiovascular indications

Not classified as a controlled substance