Sotalol - Drug Monograph

Introduction

Sotalol is a non-selective beta-adrenergic receptor blocker with additional class III antiarrhythmic properties. It is a racemic mixture where the d-isomer is responsible for its class III effects and the l-isomer provides beta-blocking activity. Sotalol is primarily used for the management of various cardiac arrhythmias and represents a unique therapeutic agent that combines beta-blockade with potassium channel blockade.

Mechanism of Action

Sotalol exerts its antiarrhythmic effects through two distinct mechanisms: 1. Beta-adrenergic blockade: Competitively blocks β1- and β2-adrenergic receptors, reducing sympathetic nervous system effects on the heart 2. Class III antiarrhythmic activity: Prolongs cardiac action potential duration and refractory period by blocking the rapid component of the delayed rectifier potassium current (IKr)

These combined actions result in:

• Decreased sinus rate
• Prolonged atrial and ventricular refractory periods
• Increased action potential duration
• Prolongation of QT interval on ECG

Indications

• Maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation/flutter
• Treatment of documented life-threatening ventricular arrhythmias (sustained ventricular tachycardia)

• Supraventricular tachycardia prophylaxis
• Electrical storm in patients with implantable cardioverter-defibrillators

Dosage and Administration

• Atrial fibrillation/flutter: 80 mg twice daily, may increase to 120-160 mg twice daily after 3 days if QT interval remains <500 ms
• Ventricular arrhythmias: 80 mg twice daily, may increase gradually to 160-320 mg daily in divided doses

• Oral administration with or without food
• Dose adjustments should be made at intervals of 3 days or longer to allow adequate assessment of therapeutic response and QT interval
• Renal function must be assessed before initiation

• Renal impairment: Dose adjustment required based on creatinine clearance

- CrCl >60 mL/min: Normal dosing - CrCl 30-60 mL/min: Reduce frequency to every 24 hours - CrCl 10-29 mL/min: Reduce frequency to every 36-48 hours - CrCl <10 mL/min: Individualize dosing

• Elderly: Consider reduced dosing due to decreased renal function
• Hepatic impairment: No specific dosage adjustment recommended, but use with caution

Pharmacokinetics

• Absorption: Well absorbed orally (90-100%) with bioavailability of 90-100%
• Distribution: Volume of distribution 1.2-1.8 L/kg; minimal protein binding
• Metabolism: Not significantly metabolized; excreted primarily unchanged in urine
• Elimination: Half-life 12 hours (prolonged in renal impairment); primarily renal excretion
• Time to peak effect: 2.5-4 hours post-dose
• Steady-state: Achieved in 2-3 days with normal renal function

Contraindications

• Hypersensitivity to sotalol or any component of the formulation
• Sinus bradycardia (heart rate <50 bpm)
• Second- or third-degree AV block (unless a functioning pacemaker is present)
• Congenital or acquired long QT syndromes
• Cardiogenic shock or uncontrolled heart failure
• Bronchial asthma or severe COPD
• Serum potassium <4.0 mEq/L
• CrCl <40 mL/min

Warnings and Precautions

• Sotalol can cause life-threatening ventricular tachycardia associated with QT interval prolongation
• Initiation and dose titration should be performed in a hospital setting with continuous ECG monitoring

• Proarrhythmia: Risk of torsades de pointes (2-4% incidence)
• Bradycardia: May cause significant slowing of heart rate
• Heart failure: May exacerbate pre-existing heart failure
• Electrolyte imbalances: Hypokalemia or hypomagnesemia increase proarrhythmic risk
• Abrupt withdrawal: May cause rebound tachycardia or hypertension
• Diabetes: May mask hypoglycemia symptoms
• Thyrotoxicosis: May mask clinical signs
• Major surgery: Use with caution due to beta-blockade effects

Drug Interactions

• Other QT-prolonging agents: Class IA/III antiarrhythmics, antipsychotics, antibiotics (macrolides, fluoroquinolones) - additive QT prolongation
• Diuretics: Increased risk of hypokalemia and proarrhythmia
• Calcium channel blockers: Additive bradycardia and AV conduction effects
• Digoxin: Increased risk of bradycardia
• Insulin and oral hypoglycemics: Masked hypoglycemia symptoms
• Catecholamine-depleting agents: Additive hypotensive effects

Adverse Effects

• Fatigue (20%)
• Dizziness (15%)
• Dyspnea (10%)
• Bradycardia (8%)
• Chest pain (7%)
• Palpitations (6%)

• Torsades de pointes (2-4%)
• New or worsened ventricular arrhythmias (4%)
• Heart failure exacerbation (3%)
• AV block (2%)
• Bronchospasm (in susceptible patients)

Monitoring Parameters

• Comprehensive cardiac evaluation
• ECG with QT measurement
• Renal function (serum creatinine, CrCl)
• Electrolytes (potassium, magnesium)
• Liver function tests

• Continuous ECG monitoring during initiation and dose titration
• Regular ECG monitoring (QTc interval should be <500 ms)
• Heart rate and blood pressure
• Renal function every 3-6 months
• Electrolyte levels regularly
• Signs/symptoms of heart failure
• Clinical response and arrhythmia control

Patient Education

• Take medication exactly as prescribed; do not miss doses or double doses
• Do not stop abruptly without medical supervision
• Understand the signs of abnormal heart rhythms (palpitations, dizziness, fainting)
• Report any difficulty breathing, swelling, or weight gain
• Monitor pulse regularly as instructed by healthcare provider
• Maintain regular follow-up appointments for ECG and blood tests
• Inform all healthcare providers about sotalol use before any procedures
• Avoid activities requiring alertness until effects are known
• Maintain adequate hydration and report diarrhea or vomiting
• Be aware that sotalol may mask symptoms of low blood sugar

References

1. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation. 2006;114(10):e385-e484. 2. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol. 2014;64(21):e1-e76. 3. Sotalol prescribing information. U.S. Food and Drug Administration. 4. Drew BJ, Ackerman MJ, Funk M, et al. Prevention of torsade de pointes in hospital settings. Circulation. 2010;121(8):1047-1060. 5. Naccarelli GV, Wolbrette DL, Khan M, et al. Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation. J Cardiovasc Electrophysiol. 2003;14(12 Suppl):S12-S17.