indication

For the maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus rhythm. Also for the treatment of documented life-threatening ventricular arrhythmias.

pharmacology

Sotalol is an antiarrhythmic drug. It falls into the class of beta blockers (and class II antiarrhythmic agents) because of its primary action on the β-adrenergic receptors in the heart. In addition to its actions on the beta receptors in the heart, sotalol inhibits the inward potassium ion channels of the heart. In so doing, sotalol prolongs repolarization, therefore lengthening the QT interval and decreasing automaticity. It also slows atrioventricular (AV) nodal conduction. Because of these actions on the cardiac action potential, it is also considered a class III antiarrhythmic agent. The beta-blocking effect of sotalol is non-cardioselective, half maximal at about 80mg/day and maximal at doses between 320 and 640 mg/day. Sotalol does not have partial agonist or membrane stabilizing activity. Although significant beta-blockade occurs at oral doses as low as 25 mg, significant Class Ieffects are seen only at daily doses of 160 mg and above.

mechanism of action

Sotalol has both beta-adrenoreceptor blocking (Vaughan Williams Class I) and cardiac action potential duration prolongation (Vaughan Williams Class I) antiarrhythmic properties. Sotalol is a racemic mixture of d- and l-sotalol. Both isomers have similar Class I antiarrhythmic effects, while the l-isomer is responsible for virtually all of the beta-blocking activity. Sotalol inhibits response to adrenergic stimuli by competitively blocking β₁-adrenergic receptors within the myocardium and β₂-adrenergic receptors within bronchial and vascular smooth muscle. The electrophysiologic effects of sotalol may be due to its selective inhibition of the rapidly activating component of the potassium channel involved in the repolarization of cardiac cells. The class II electrophysiologic effects are caused by an increase in sinus cycle length (slowed heart rate), decreased AV nodal conduction, and increased AV nodal refractoriness, while the class III electrophysiological effects include prolongation of the atrial and ventricular monophasic action potentials, and effective refractory period prolongation of atrial muscle, ventricular muscle, and atrio-ventricular accessory pathways (where present) in both the anterograde and retrograde directions.

toxicity

The most common signs to be expected are bradycardia, congestive heart failure, hypotension, bronchospasm and hypoglycemia. In cases of massive intentional overdosage (2-16 grams) of sotalol the following clinical findings were seen: hypotension, bradycardia, cardiac asystole, prolongation of QT interval, Torsade de Pointes, ventricular tachy-cardia, and premature ventricular complexes.

biotransformation

Sotalol is not metabolized.

absorption

In healthy subjects, the oral bioavailability of sotalol is 90-100%. Absorption is reduced by approximately 20% compared to fasting when administered with a standard meal.

half life

Mean elimination half-life is 12 hours. Impaired renal function in geriatric patients can increase the terminal elimination half-life.

route of elimination

Excretion is predominantly via the kidney in the unchanged form. Sotalol is excreted in the milk of laboratory animals and has been reported to be present in human milk.

drug interactions

Acetohexamide: The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.

Aminophylline: Antagonism of action and increased effect of theophylline

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Chlorpropamide: The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Clarithromycin: Increased risk of cardiotoxicity and arrhythmias

Clonidine: Increased hypertension when clonidine stopped

Dihydroergotamine: Ischemia with risk of gangrene

Disopyramide: The beta-blocker, sotalol, may increase the toxicity of disopyramide.

Epinephrine: Hypertension, then bradycardia

Ergotamine: Ischemia with risk of gangrene

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Fenoterol: Antagonism

Formoterol: Antagonism

Gatifloxacin: Increased risk of cardiotoxicity and arrhythmias

Gliclazide: The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.

Glyburide: The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Ibuprofen: Risk of inhibition of renal prostaglandins

Indomethacin: Risk of inhibition of renal prostaglandins

Insulin Glargine: The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Methyldopa: Possible hypertensive crisis

Methysergide: Ischemia with risk of gangrene

Moxifloxacin: Increased risk of cardiotoxicity and arrhythmias

Orciprenaline: Antagonism

Oxtriphylline: Antagonism of action and increased effect of theophylline

Pipobroman: Antagonism

Piroxicam: Risk of inhibition of renal prostaglandins

Prazosin: Risk of hypotension at the beginning of therapy

Ranolazine: Possible additive effect on QT prolongation

Repaglinide: The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Telithromycin: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Terazosin: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Terbutaline: Antagonism

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Theophylline: Antagonism of action and increased effect of theophylline

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Voriconazole: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).