Verapamil - Drug Monograph

Introduction

Verapamil is a calcium channel blocker belonging to the phenylalkylamine class that has been widely used in clinical practice since the 1980s. It is primarily indicated for the management of cardiovascular conditions including hypertension, angina pectoris, and certain cardiac arrhythmias. As a prototypical calcium channel antagonist, verapamil represents an important therapeutic option in the cardiologist's arsenal.

Mechanism of Action

Verapamil exerts its pharmacological effects by selectively blocking L-type calcium channels in vascular smooth muscle and cardiac tissue. This inhibition prevents calcium influx during depolarization, resulting in:

• Coronary and peripheral vasodilation
• Reduced myocardial contractility (negative inotropy)
• Slowed atrioventricular (AV) nodal conduction (negative dromotropy)
• Decreased heart rate (negative chronotropy)

The drug preferentially affects cardiac tissue over vascular smooth muscle compared to other calcium channel blockers, making it particularly effective for arrhythmia management.

Indications

• Hypertension (monotherapy or combination therapy)
• Chronic stable angina
• Vasospastic angina
• Supraventricular tachyarrhythmias (including atrial fibrillation and flutter)
• Paroxysmal supraventricular tachycardia

• Migraine prophylaxis
• Cluster headache prevention
• Hypertrophic cardiomyopathy
• Raynaud's phenomenon

Dosage and Administration

• Immediate-release tablets: 80-120 mg three times daily (max 480 mg/day)
• Sustained-release tablets: 120-480 mg once daily (max 480 mg/day)

• Initial bolus: 5-10 mg over 2 minutes
• Repeat dose: 10 mg after 30 minutes if needed (max 20 mg total dose)

• Hepatic impairment: Reduce dose by 50-70%
• Renal impairment: Use caution; monitor carefully
• Elderly: Start with lower doses due to reduced clearance
• Pediatric: 4-8 mg/kg/day divided every 8 hours (max 480 mg/day)

Pharmacokinetics

Contraindications

• Severe left ventricular dysfunction
• Cardiogenic shock
• Sick sinus syndrome (except with functioning pacemaker)
• Second- or third-degree AV block (except with functioning pacemaker)
• Hypotension (SBP <90 mmHg)
• Atrial fibrillation with accessory pathway (WPW syndrome)
• Hypersensitivity to verapamil or components
• Concurrent IV beta-blocker administration

Warnings and Precautions

• Avoid use in patients with severe LV dysfunction (ejection fraction <30%) or significant HF symptoms
• May cause hypotension and worsening heart failure

• Hepatic impairment: Reduced metabolism may lead to accumulation
• Patients with neuromuscular transmission disorders (may exacerbate weakness)
• Constipation may be severe in elderly patients
• May mask hypoglycemia symptoms in diabetics
• Abrupt withdrawal may cause rebound angina
• Use cautiously in patients with renal impairment

Drug Interactions

• Beta-blockers: Increased risk of bradycardia and heart block
• Digoxin: Increases digoxin levels by 50-75%
• Statins (simvastatin, lovastatin): Increased risk of myopathy
• CYP3A4 inhibitors (ketoconazole, erythromycin): Increase verapamil levels
• CYP3A4 inducers (rifampin, phenytoin): Decrease verapamil levels
• Lithium: May increase neurotoxicity risk
• Theophylline: Reduced clearance
• Neuromuscular blocking agents: Prolonged neuromuscular blockade

Adverse Effects

• Constipation (up to 40%)
• Dizziness (5-15%)
• Headache (5-15%)
• Hypotension (5-10%)
• Edema (5-10%)
• Bradycardia (5-10%)

• Heart block (any degree)
• Congestive heart failure exacerbation
• Hepatotoxicity
• Severe hypotension
• Stevens-Johnson syndrome
• Gingival hyperplasia (with long-term use)
• Extrapyramidal symptoms

Monitoring Parameters

• Blood pressure and heart rate at initiation and regularly thereafter
• ECG for PR interval prolongation and signs of heart block
• Liver function tests periodically
• Renal function in patients with pre-existing impairment
• Signs and symptoms of heart failure
• Serum digoxin levels if co-administered
• Electrolytes, particularly in patients on diuretics

Patient Education

• Take with food to minimize gastrointestinal upset
• Do not crush or chew sustained-release formulations
• Rise slowly from sitting/lying position to prevent dizziness
• Report signs of constipation, which may require management
• Avoid grapefruit juice as it may increase drug levels
• Do not abruptly discontinue medication
• Inform all healthcare providers about verapamil use
• Use caution when driving or operating machinery until effects known
• Monitor for swelling in ankles or feet
• Report unusual bruising, bleeding, or signs of infection

References

1. FDA Prescribing Information: Verapamil Hydrochloride. Accessed 2023. 2. Whirl-Carrillo M, et al. Pharmacogenomics Knowledge for Personalized Medicine. Clin Pharmacol Ther. 2012;92(4):414-417. 3. Abrams J. Clinical practice. Chronic stable angina. N Engl J Med. 2005;352(24):2524-2533. 4. Epstein BJ, Vogel K, Palmer BF. Dihydropyridine calcium channel antagonists in the management of hypertension. Drugs. 2007;67(9):1309-1327. 5. McKeage K, Plosker GL. Verapamil: a review of its use in hypertension and angina. Drugs. 2002;62(17):2547-2570. 6. American College of Cardiology/American Heart Association Guidelines for the Management of Hypertension. J Am Coll Cardiol. 2018;71(19):e127-e248. 7. Lexicomp Online, Lexi-Drugs. Verapamil. Wolters Kluwer Clinical Drug Information, Inc. 2023.