Sotalol

Sotalol is a non selective beta blocker with potassium channel blocking (class III antiarrhythmic) properties. It is used to maintain sinus rhythm after cardioversion in atrial fibrillation and to prevent ventricular tachycardia. It prolongs the QT interval and can cause torsades de pointes, so initiation is supervised.

Classification. Class III antiarrhythmic and class II beta blocker; racemic mixture.

Mechanism. The l isomer blocks beta receptors; both isomers block the delayed rectifier potassium current (IKr), prolonging repolarisation and the QT interval.

Pharmacodynamics. Heart rate slows; QT prolongation is dose dependent and greatest at high doses and with slow heart rates, low potassium or magnesium.

Pharmacokinetics. Oral bioavailability 90 to 100%; not metabolised; half life 12 hours; excreted unchanged in urine, so renal function sets the dose. Food, especially dairy, reduces absorption by about 20%.

Maintenance of sinus rhythm in atrial fibrillation or atrial flutter, adult.

• Start in hospital with continuous ECG monitoring for at least 3 days (or 5 to 6 doses).

• Start 80 mg orally twice daily (40 mg twice daily if risk is high).

• Increase after 2 to 3 days to 120 mg twice daily, then 160 mg twice daily if needed and QTc allows.

• Maximum 320 mg daily for atrial fibrillation.

Ventricular tachycardia and life threatening ventricular arrhythmias, adult (specialist). Start 80 mg twice daily; titrate to 240 to 320 mg daily; up to 480 to 640 mg daily in refractory cases under inpatient monitoring.

Renal dosing. Creatinine clearance over 60 mL/min: every 12 hours; 40 to 60 mL/min: every 24 hours; under 40 mL/min: avoid (atrial fibrillation indication). Where licensed doses differ, halve the daily dose with creatinine clearance 30 to 60 mL/min.

Stopping rule. Reduce the dose or stop if QTc exceeds 500 ms or rises by more than 60 ms from baseline, or if heart rate falls under 50/min.

Children. Dosing is by body surface area and specialist only.

Contraindications. QTc over 450 ms at baseline; congenital or acquired long QT syndrome; torsades de pointes history; sinus bradycardia under 50/min; sick sinus syndrome; second or third degree atrioventricular block; uncontrolled heart failure; cardiogenic shock; asthma; severe peripheral arterial disease; potassium under 4 mmol/L or magnesium low; creatinine clearance under 40 mL/min (atrial fibrillation indication).

Warnings. Torsades de pointes, worse in women, with bradycardia, hypokalaemia, hypomagnesaemia and high doses. Heart failure worsening. Masks hypoglycaemia. Do not stop abruptly.

Adverse effects. Bradycardia, fatigue, dizziness, dyspnoea, palpitations, hypotension, QT prolongation, torsades de pointes, bronchospasm.

Interactions.

• QT prolonging drugs: class Ia and other class III antiarrhythmics, macrolides, fluoroquinolones, antipsychotics, tricyclic antidepressants, ondansetron, methadone.

• Antimalarials with QT effects (artemether with lumefantrine, quinine, chloroquine, halofantrine): avoid or monitor ECG closely in East Africa.

• Diuretics, amphotericin and laxatives lowering potassium or magnesium.

• Verapamil and diltiazem: bradycardia. Digoxin: bradycardia and arrhythmia. Insulin: masked hypoglycaemia. Antacids containing aluminium or magnesium reduce absorption; separate by 2 hours.

Special groups.

• Pregnancy: crosses the placenta; foetal bradycardia; use only when essential.

• Breastfeeding: concentrated in milk; avoid.

• Older adults: lower starting dose and renal dosing.

• Kidney impairment: dose reduction by creatinine clearance band given in the dosing section; contraindicated at lower clearance.

• Liver impairment: no adjustment.

Overdose and torsades. Magnesium sulphate 2 g IV over 10 to 15 minutes; correct potassium to 4.5 to 5 mmol/L; isoprenaline or pacing to raise the heart rate; defibrillation for pulseless torsades.

Formulations. Tablets 40, 80, 160 mg; oral solution; injection (specialist).

Administration. Oral twice daily, on an empty stomach where possible, 1 hour before food; avoid dairy products close to the dose.

Baseline. 12 lead ECG with QTc, potassium, magnesium, creatinine clearance, heart rate, ejection fraction, thyroid function.

Monitoring. ECG and QTc after each dose increase and at 2 to 4 hours post dose; potassium and magnesium; creatinine clearance at least every 6 months; heart rate and blood pressure.

Stopping. Taper over 1 to 2 weeks unless QT or torsades requires immediate withdrawal.

Common prescribing errors. Starting as an outpatient; ignoring renal function; combining with QT prolonging antimalarials or macrolides; using it in a patient with low potassium.