Introduction
Calan (verapamil hydrochloride) is a calcium channel blocker medication primarily used in the management of cardiovascular conditions. First approved by the FDA in 1981, it remains an important therapeutic option for hypertension, angina pectoris, and certain cardiac arrhythmias. As a phenylalkylamine calcium channel blocker, Calan exerts its effects by selectively inhibiting calcium influx through slow channels in vascular smooth muscle and cardiac cells.
Mechanism of Action
Calan inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle cells by blocking L-type calcium channels. This inhibition results in:
- Coronary and peripheral vasodilation
- Decreased myocardial contractility (negative inotropy)
- Slowed conduction through the atrioventricular node (negative dromotropy)
- Reduced heart rate (negative chronotropy)
The drug's vasodilatory effects reduce peripheral vascular resistance and blood pressure, while its cardiac effects make it particularly useful for rate control in atrial arrhythmias.
Indications
FDA-approved indications:
- Hypertension (alone or in combination with other antihypertensive agents)
- Chronic stable angina (vasospastic angina, classic effort-associated angina)
- Angina at rest (vasospastic angina)
- Supraventricular tachyarrhythmias (paroxysmal supraventricular tachycardia)
- Atrial flutter or fibrillation (for ventricular rate control)
Off-label uses:
- Hypertrophic cardiomyopathy
- Migraine prophylaxis
- Cluster headache prophylaxis
Dosage and Administration
Hypertension/Angina:- Initial dose: 80-120 mg orally three times daily
- Maintenance dose: 240-480 mg daily in divided doses
- Extended-release formulation: 180-480 mg daily as a single dose
- Initial dose: 240-320 mg daily in 3-4 divided doses
- Maximum dose: 480 mg daily in divided doses
- Hepatic impairment: Reduce dose by 30-50%
- Renal impairment: Use with caution; monitor closely
- Geriatric patients: Start with lower initial doses
- Pediatric patients: Safety not established
Pharmacokinetics
Absorption: >90% oral bioavailability, but extensive first-pass metabolism reduces absolute bioavailability to 20-35% Distribution: Volume of distribution: 4-5 L/kg; 90% protein bound Metabolism: Extensive hepatic metabolism via CYP3A4 to active (norverapamil) and inactive metabolites Elimination: Biphasic elimination; half-life: 2-8 hours (immediate-release); 12 hours (extended-release); primarily excreted in urine (70%) and feces (16%)Contraindications
- Severe left ventricular dysfunction
- Hypotension (systolic pressure <90 mmHg) or cardiogenic shock
- Sick sinus syndrome or second- or third-degree AV block (except with functioning pacemaker)
- Atrial flutter/fibrillation with accessory pathway (WPW syndrome)
- Known hypersensitivity to verapamil
- Concurrent intravenous beta-blocker administration
Warnings and Precautions
Black Box Warning: None Important Precautions:- May cause hypotension and bradycardia
- Can exacerbate heart failure in patients with systolic dysfunction
- May cause constipation (up to 40% of patients)
- Liver enzyme elevations reported; monitor hepatic function
- May prolong PR interval; use caution in patients with conduction abnormalities
- Discontinuation should be gradual to avoid rebound effects
Drug Interactions
Major Interactions:- Beta-blockers: Increased risk of bradycardia, AV block, and heart failure
- Digoxin: Increases digoxin levels by 50-75%
- CYP3A4 inhibitors (ketoconazole, erythromycin): Significantly increase verapamil levels
- Statins (simvastatin, lovastatin): Increased risk of myopathy
- Lithium: May increase lithium neurotoxicity
- Neuromuscular blocking agents: Prolonged neuromuscular blockade
- Theophylline: Decreased theophylline clearance
Adverse Effects
Common (>10%):- Constipation (up to 40%)
- Dizziness (3-10%)
- Headache (2-9%)
- Hypotension (2-5%)
- Peripheral edema (2-8%)
- Heart failure exacerbation
- AV block (first-, second-, or third-degree)
- Bradycardia
- Hepatotoxicity
- Rash and hypersensitivity reactions
- Gingival hyperplasia (with long-term use)
Monitoring Parameters
Baseline:- Blood pressure and heart rate
- ECG (assess PR interval)
- Liver function tests
- Renal function
- Signs/symptoms of heart failure
- Blood pressure at each visit
- Heart rate and rhythm
- Signs of fluid overload or heart failure
- Liver function (periodically)
- Serum digoxin levels if co-administered
- Monitor for constipation and manage proactively
Patient Education
- Take with food to reduce gastrointestinal upset
- Do not crush or chew extended-release tablets
- Rise slowly from sitting/lying position to prevent dizziness
- Report signs of hypotension (dizziness, lightheadedness)
- Monitor for constipation and maintain adequate fluid/fiber intake
- Do not discontinue abruptly without medical supervision
- Avoid grapefruit juice (may increase drug levels)
- Inform all healthcare providers about Calan use before any procedures
- Use caution when driving or operating machinery until effects are known
References
1. FDA Prescribing Information: Calan (verapamil HCl) 2. Whirl-Carrillo M, et al. Pharmacogenomics Knowledge for Personalized Medicine. Clin Pharmacol Ther. 2012;92(4):414-7 3. Abrams J. Calcium channel blockers. In: Brunton LL, Hilal-Dandan R, Knollmann BC, eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. McGraw Hill; 2017 4. Elliott WJ, Ram CV. Calcium channel blockers. J Clin Hypertens (Greenwich). 2011;13(9):687-9 5. McKeever RG, Hamilton RJ. Calcium Channel Blockers. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 6. Mancia G, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104 7. January CT, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. Circulation. 2019;140(2):e125-e151
This monograph is for educational purposes only and does not replace professional medical advice. Always consult with a healthcare provider for personalized medical recommendations.