Clinical uses of sotalol

INTRODUCTION — Sotalol, a methanesulfonanilide, is a class III antiarrhythmic drug (table 1) that is used for the treatment of both atrial and ventricular arrhythmias. Sotalol was originally approved by the FDA (tradename Betapace) for the treatment of life-threatening ventricular arrhythmias. The present commercial product (tradename Betapace AF) is intended for use in atrial fibrillation (AF), with the caveat that sotalol is not effective for conversion of AF to sinus rhythm, but it may be used to prevent AF. Although both commercial presentations contain sotalol, Betapace should not be substituted for Betapace AF because of significant differences in the labeling sections on indications, dosing, administration, and safety profile. Additionally, an injectable form of sotalol was approved by the FDA in July 2009. The package inserts for Betapace and Betapace AF contain black box warnings regarding potential for QT prolongation and ventricular arrhythmias [1]. (See 'Cardiac toxicity' below.)

This topic will review the electrophysiology and mechanisms of action of sotalol, and will discuss dosing, the different settings in which sotalol has been used as an antiarrhythmic drug, and major side effects. Recommendations for the role of sotalol in the treatment of atrial and ventricular arrhythmias are presented separately. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations" and "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Choice of pharmacologic therapy'.)

ELECTROPHYSIOLOGY AND MECHANISM OF ACTION — Sotalol consists of a racemic mixture of d and l isomers in an approximate ratio of 1:1; this mixture is often called dl-sotalol. D- and l-stereoisomers of sotalol have been studied individually, but only dl-sotalol is commercially available. The two isomers contribute to the unique antiarrhythmic properties of sotalol [2-5]:

●The d isomer prolongs repolarization by blocking IKr (figure 1), the rapid component of the delayed rectifier potassium current that is responsible for phase 3 repolarization of the action potential (figure 2) [6,7]. This represents a class III effect. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".)

●The l isomer has two actions: it prolongs repolarization and it has beta blocking activity. The beta blocker effect is dose-dependent, is not cardioselective, and is not associated with membrane stabilizing activity or intrinsic sympathomimetic activity.

Class III activity — The antiarrhythmic activity of sotalol is primarily mediated by its class III property (table 1), which results in prolongation of the monophasic action potential duration as well as lengthening of the effective refractory period (ERP) in the atria, atrioventricular (AV) node (as reflected by the AH interval), ventricles, and antegrade and retrograde bypass tracts (when present) [4,8-10]. The class III effect results from blockade of the rapid component of the delayed rectifier potassium current (IKr) that is responsible for phase 3 repolarization of the action potential (figure 2) [6,7].The prolongation of cardiac action potential duration does not appear to be related to concurrent beta blockade, since d-sotalol, which has little beta blocking activity, produces a similar delay in repolarization as l-sotalol [2].

The effect of sotalol on the action potential duration shows reverse use dependence, which is seen with other class III antiarrhythmic drugs except for amiodarone. Reverse use dependence is defined as an inverse correlation between the heart rate and the QT interval [11]. As a result, the QT interval is prolonged as the heart rate slows, which could explain the association between bradycardia and antiarrhythmic drug-induced torsades de pointes and the possible decrease in drug efficacy at higher heart rates. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes", section on 'Pathophysiology' and 'Proarrhythmia' below.)

The clinical manifestations of sotalol-induced beta blockade include an increased sinus cycle length (slowed heart rate), decreased AV nodal conduction and increased AV nodal refractoriness (prolonged PR interval) [4].

Effects on the ECG — The combined actions of sotalol produce a variety of changes in the electrocardiogram (ECG) [4,12,13]:

●Because of its beta blocking activity, sotalol slows the sinus rate by approximately 25 percent and slightly prolongs the PR interval.

●The QRS duration is not altered, since ventricular conduction at normal sinus rates is unchanged [12,13]. This is thought to reflect a lack of effect of sotalol on the His-Purkinje (HV) interval [4,9,14].

●The QT interval is prolonged in a dose-dependent fashion [15]. Since the QRS duration is not prolonged, the increase in QT interval results solely from delayed repolarization (ie, the JT interval) [12,13]. In a review of 114 patients given chronic oral sotalol therapy, the average increase in QT interval was 80 and 91 msec with 320 and 640 mg/day [12]. However, the increase in QTc, which is corrected for heart rate, was less prominent (21 and 30 msec, respectively). (See "Congenital long QT syndrome: Diagnosis", section on 'QT rate correction'.)

PHARMACOKINETICS — Sotalol is, essentially, completely absorbed and not metabolized. Consequently, bioavailability is close to 100 percent. Age and food have slight but unimportant effects on bioavailability. The maximum concentration of sotalol is achieved within 2 to 3 hours with a half-life between 7 and 15 hours. Excretion of sotalol is primarily through the kidneys, with no metabolism by liver and no first-pass effect. Therefore, sotalol plasma levels and half-life are directly related to creatinine clearance and glomerular filtration rate. Appropriate dose adjustments must be made for patients with impaired renal function or increased renal blood flow, as in pregnancy. The beta-adrenoceptor antagonistic effects of sotalol are directly related to plasma levels, which, in turn, are directly related to dose. However, the beta-adrenoceptor antagonism half-life is longer than the sotalol plasma half-life [16]. 

DOSING — The dose of sotalol should be individualized on the basis of therapeutic response and tolerance. Because of its beta blocking activity, sotalol should not be used in patients with uncontrolled asthma, sinus bradycardia, Mobitz II second degree AV block or third degree AV block (unless the patient is treated with a pacemaker), cardiogenic shock, or uncontrolled heart failure [5]. In addition, because sotalol prolongs the QT interval, it should not be used in patients with congenital or acquired long QT syndrome, and should be used with caution in patients taking other medications known to prolong the QT interval (table 2). (See 'Proarrhythmia' below.)

Initiation of therapy — Bradycardic and proarrhythmic events can occur after the initiation of sotalol therapy and with each upward dosing adjustment [17,18]. As a result, sotalol should be initiated in a hospital with facilities for cardiac rhythm monitoring and assessment. The package insert for sotalol contains a black box warning regarding initiation of the drug in a center with QT monitoring and cardiac resuscitation capabilities. However, some providers have initiated sotalol (or uptitrated doses) in an off-label manner in the outpatient setting in patients felt to be at low risk of QT prolongation or polymorphic VT. Before beginning sotalol, previous antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of two to three half-lives, if clinically possible. (See 'Proarrhythmia' below.)

The recommended initial dose of oral sotalol in adults is 80 mg twice daily whether used for the treatment of ventricular arrhythmias or atrial fibrillation. If necessary, the initial dose can be increased gradually to a maximum daily of 240 mg or 320 mg. Dose adjustments should be made at three day intervals so that steady-state plasma concentrations can be attained and the QT interval monitored. In a retrospective analysis, this standard approach was compared with initiating sotalol at 120 to 160 mg orally twice per day [19]. The accelerated dosing regimen neither shortened hospitalization nor had any effect on treatment efficacy. Due to the marginally increased risk of cardiac and non-cardiac side effects with an accelerated regimen, we favor the traditional starting dose of 80 mg twice daily.

As of March 2020, intravenous sotalol has an updated FDA-approved dosing regimen for in-hospital initiation and reinitiation of patients on sotalol therapy. The key change is that with the use of intravenous sotalol, patients can now be initiated (titrated to steady-state blood levels) on sotalol therapy in the hospital in one day (versus three days). In addition, with intravenous sotalol (unlike with oral sotalol), patients can be initiated at either 80 or 120 mg. In other words, with intravenous sotalol, patients may be initiated at 120 mg without titrating up from 80 mg.

Dose adjustment with chronic kidney disease — Oral sotalol is primarily excreted unchanged in the urine, since it is not appreciably metabolized in the liver [3]. As a result, the elimination half-life is prolonged in patients with renal insufficiency. When sotalol is given for the treatment of ventricular arrhythmias, the dosing interval should be modified based upon the reduction in creatinine clearance:

●>60 mL/min – 12 hours

●30 to 60 mL/min – 24 hours

●10 to 29 mL/min – 36 to 48 hours

●<10 mL/min – should be individualized

Patients with severe renal disease are at risk for potentially life-threatening ventricular arrhythmia even if low doses are used [20,21].

When used for the treatment of atrial fibrillation, sotalol is considered contraindicated when the creatinine clearance is less than 40 mL/min.

Intravenous sotalol — Intravenous sotalol has primarily been used to terminate supraventricular tachyarrhythmias [22-24]. It has also been used to terminate spontaneous sustained ventricular tachycardia (VT) and to suppress inducible ventricular tachyarrhythmia during electrophysiology study [25,26].

Several reports have described the value and limitations of intravenous sotalol to convert arial fibrillation to sinus rhythm.

●A review concerning the effectiveness of antiarrhythmic drugs administered intravenously indicates that sotalol has a modest success on cardioversion of AF to sinus rhythm approximating 30 percent; it is less effective than class I agents or ibutilide [27]. In particular, high-dose ibutilide showed a greater conversion rate than intravenous sotalol [23].

●A meta-analysis concluded that intravenous and oral sotalol for conversion of AF of varied duration are as effective as class IA or class IC agents, and as effective as amiodarone for pharmacological conversion of AF [28].

●Another report found sotalol less efficient than flecainide, propafenone, or ibutilide and likely as effective as intravenous amiodarone [29].

●A prospective study from Australia compared intravenous administration of digoxin, amiodarone, and sotalol [30]. The results at 24 hours revealed conversion to sinus rhythm was 50 percent for digoxin, 69 percent for amiodarone, and 80 percent for sotalol. In addition, the conversion at 48 hours was 58 percent for digoxin, 77 percent for amiodarone, and 88 percent for sotalol.

Monitoring — After the sotalol loading dose is complete, generally the patient is asked to return for an electrocardiogram (ECG) within one and two weeks, looking for QT interval prolongation and bradyarrhythmia. Patients should typically have an ECG performed every six months while taking sotalol, and whenever any additional QT prolonging medications are newly prescribed. Routine laboratory studies are not needed to monitor sotalol levels or for potential toxicities.

CLINICAL INDICATIONS — Oral sotalol is used for the treatment of documented ventricular arrhythmias (ie, sustained ventricular tachycardia [VT]) that, in the judgment of the clinician are life-threatening, and for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation (AF) and atrial flutter who are currently in sinus rhythm.

What follows is a brief review of the major settings in which sotalol is given with links to the topic reviews in which the role of sotalol therapy is discussed in detail.

Ventricular arrhythmias

●Sotalol is used to prevent recurrence of sustained VT or ventricular fibrillation (VF) [12,31-33]. The main setting in which sotalol is used for VT/VF is as adjunctive therapy to an ICD to reduce the frequency of appropriate shocks or of inappropriate shocks due to supraventricular arrhythmias. However, sotalol may be used as primary therapy in patients who do not want or are not candidates for an ICD (eg, due to marked comorbidities or end-stage heart failure that make death likely). Although sotalol reduces both recurrent arrhythmia and the frequency of ICD shocks [34], sotalol is typically second-line therapy to empiric amiodarone. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Antiarrhythmic drugs' and "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Choice of pharmacologic therapy'.)

●Sotalol is effective in patients with arrhythmogenic right ventricular cardiomyopathy who have either inducible or noninducible non-life-threatening VT; in contrast, other antiarrhythmic drugs have little efficacy [35]. Thus, initial therapy with sotalol is a reasonable option for many such patients. For those that do not respond to sotalol, response to other drugs is unlikely, and consideration should be given to nonpharmacologic therapy such as radiofrequency catheter ablation. (See "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis", section on 'Antiarrhythmic drugs'.)

●A preparation containing only the d isomer has been developed as a "pure" class III drug [36,37]. However, in the Survival with Oral D-sotalol (SWORD) trial of patients with a reduced left ventricular ejection fraction and either a recent myocardial infarction (MI) or symptomatic heart failure and a remote MI, d-sotalol therapy, compared with placebo, was associated with a significant increase in mortality that was largely due to an increase in presumed arrhythmic deaths [37]. This observation suggests an important contribution from the beta blocking activity that is seen with dl-sotalol.

Atrial arrhythmias — Both the class III and beta blocking activity of dl-sotalol contribute to its use in the treatment of atrial arrhythmias, mostly atrial fibrillation (AF).

●Sotalol promotes maintenance of sinus rhythm after cardioversion in patients with AF. The main indication for sotalol, if a rhythm control strategy is chosen, is in patients with underlying coronary heart disease (algorithm 1). (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".)

●In comparison, oral sotalol has limited efficacy for pharmacologic cardioversion of AF to sinus rhythm [38] and, where available, intravenous sotalol is less effective than other drugs [23,24]. (See "Atrial fibrillation: Cardioversion", section on 'Pharmacologic cardioversion'.)

●Sotalol appears to be effective for the prevention of AF after cardiac surgery (eg, coronary artery bypass graft or valve surgery) [39]. In a meta-analysis of 15 studies involving sotalol for the prevention of AF after cardiac surgery, sotalol was significantly more effective in preventing AF than no treatment, placebo, or beta blockers, and it was equally as effective as amiodarone [40]. Recommendations about the choice of a particular agent for the prevention of AF after cardiac surgery are presented separately. (See "Atrial fibrillation and flutter after cardiac surgery".)

●The safety of sotalol was compared with dronedarone after AF ablation. Propensity-score matching resulted in 1815 patients receiving dronedarone matched 1:1 to patients receiving sotalol. Patients on dronedarone had lower risk of cardiovascular hospitalization compared with patients treated with sotalol, predominantly attributable to lower rates of ATA-related hospitalization. In addition, dronedarone-treated patients had a better safety profile after ablation compared with sotalol patients because of lower rates of combined proarrhythmia, predominantly driven by lower rates of bradycardic proarrhythmia and need for pacemaker implantation [41].

●The DASH-AF study compared the safety and feasibility of intravenous sotalol compared with the traditional five-dose inpatient titration of oral sotalol for the treatment of atrial arrhythmias. The nonrandomized study compared QT interval changes, safety outcomes, and cost in 120 patients receiving inpatient oral loading with 120 patients receiving intravenous sotalol at a loading dose of 125 mg for all patients with a CrCL >60 m/min for an intended maintenance regimen of 120 mg twice daily and 82.5 mg for CrCL >60 mL/min for an intended maintenance dose of 80 mg twice daily; oral sotalol was started four hours after the intravenous sotalol infusion. The majority (60 percent) of oral loading was at the 120 mg twice-daily dose. Patients were matched on AF type and CrCL. There was no significant change in QTc in both groups, and the risk of adverse events was also similar. The estimated cost savings with intravenous sotalol was $3,500.68 per admission.

Fetal arrhythmias — Fetal tachycardia is a serious condition for which treatment should be initiated, especially in the presence of hydrops fetalis. The management of fetal arrhythmias is discussed in detail separately. (See "Fetal arrhythmias".)

MAJOR SIDE EFFECTS — Sotalol is generally well tolerated. It has been estimated that sotalol is discontinued because of side effects in approximately 15 percent of patients [4,42]. The major causes for cessation of therapy are fatigue (4 percent), bradycardia, dyspnea, proarrhythmia (each 3 percent), and dizziness and asthenia (each 2 percent) [4]. However, some of these side effects, such as dizziness, fatigue, and anxiety, may not be more common than with placebo [34].

The potential for cardiac toxicity is clearly of greatest concern. Bradycardic and proarrhythmic events can occur after the initiation of sotalol therapy and with each upward dosing adjustment. As a result, sotalol should be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment. (See 'Initiation of therapy' above.)

Cardiac toxicity — The two major cardiac side effects of sotalol are proarrhythmia, most often torsades de pointes, and bradycardia. In addition, the beta blocking activity of sotalol can cause new or worsened heart failure.

The arrhythmic and bradycardic complications often occur within the first three days after the initiation of sotalol therapy and with each upward dosing adjustment [17,18]. As a result, sotalol should generally be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment. (See 'Initiation of therapy' above.)

Proarrhythmia — Sotalol, like other class III drugs, has the potential to be arrhythmogenic due to marked prolongation of the duration of the action potential that is manifested on the surface electrocardiogram (ECG) by prolongation of the QT interval [3,43]. This effect is mediated by blockade of IKr (figure 1), the rapid component of the delayed rectifier potassium current that is responsible for phase 3 repolarization of the action potential (figure 2) [6,7]. (See 'Class III activity' above.)

At standard doses between 160 and 320 mg/day, sotalol increases by QT interval by 40 to 100 msec [3]. However, the amount of change in the QT interval is highly variable and difficult to predict in an individual patient. In a cohort of 541 patients starting sotalol, the average change in corrected QT interval (QTc using the Bazett formula) was 3±42 milliseconds at two hours and 11±37 milliseconds at 48 hours following the initial dose [44]. The maximum recommended QTc interval on sotalol is 500 to 520 msec [3,4,45].

The effect of sotalol on the action potential duration shows reverse use dependence, which is seen with other class III antiarrhythmic drugs except for amiodarone. Reverse use dependence is defined as an inverse correlation between the heart rate and the QT interval [11]. As a result, the QT interval is prolonged as the heart rate slows, which could explain the association between bradycardia and antiarrhythmic drug-induced torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes", section on 'Pathophysiology'.)

The most important clinical manifestation of sotalol-induced proarrhythmia is torsades de pointes, characterized by a "twisting" of the peaks of the QRS complexes around the isoelectric line of the ECG (waveform 1). Triggered activity caused by early afterdepolarizations is thought to be responsible for the induction of this arrhythmia, which is most likely to occur in patients with prolongation of the QT interval.

The reported risk of torsades de pointes has varied from 1 to 4 percent [34,42,46]. The incidence of and risk factors for torsades de pointes were described in a 1996 review of 3135 patients who were treated with sotalol for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) (41 percent) or non-life-threatening arrhythmias such as ventricular premature beats, atrial fibrillation (AF), nonsustained VT, or paroxysmal supraventricular tachycardia (59 percent) [46]. The overall rate of torsades de pointes was 2.5 percent at a median follow-up of 164 days. However, a number of groups at significantly increased risk were identified:

●Sotalol dose above 320 mg/day (3.7 versus 1.8 and 0.1 percent at doses of 161 to 320 mg/day and ≤160 mg/day, respectively).

●Serum creatinine above 1.4 mg/dL [124 micromol/L] in women and 1.6 mg/dL [141 micromol/L] in men (5.1 versus 2.2 percent).

●Sustained VT/VT as the presenting arrhythmia (4.5 versus 1.1 percent with other arrhythmias such as atrial fibrillation).

●History of heart failure (5.0 versus 1.7 percent without heart failure) or coronary heart disease (3.1 versus 1.9 percent).

●Female gender (4.1 versus 1.9 percent in men). The gender difference was independent of dose-related bradycardic responses and was similar in women greater than 50 and ≤50 years of age, which suggests that estrogen may not be responsible for the increased risk in women.

An increase in risk in females has also been noted with torsades de pointes due to other antiarrhythmic drugs, noncardiac drugs, and the congenital long QT syndrome [47-49]. In each of these settings, females constitute approximately 70 percent of affected patients. Compared with males, females have a longer corrected QT interval and a greater response to drugs that block IKr, potentiating the development of torsades de pointes [50]. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes", section on 'Risk factors for drug-induced long QT syndrome'.)

There are also general predisposing factors such as bradycardia, which is thought to result from reverse use dependence in which the QT interval is prolonged as the heart rate slows, and other factors that prolong the baseline QT interval such as hypokalemia, hypomagnesemia, and the concomitant use of other drugs that prolong the QT interval, including antiarrhythmic drugs such as procainamide, quinidine, and the other class III agents (amiodarone, dofetilide, ibutilide) (table 2). All of these drugs predispose to torsades de pointes except for amiodarone. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring", section on 'Adverse cardiac effects' and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".)

Bradycardia — Sotalol has the potential to cause all of the rhythm effects induced by beta blockade, including sinus bradycardia and atrioventricular (AV) block. Bradyarrhythmias, mostly sinus bradycardia, occur in approximately 10 to 15 percent of patients [3,4,17,18,34,42]. By comparison, sinus node arrest and second or third degree heart block occur in ≤1 percent [4,42].

Heart failure — Many patients treated with sotalol, particularly for ventricular arrhythmias, have underlying cardiac disease. Fortunately, impairment of myocardial contractility in patients treated with sotalol is less than might be expected with a beta blocker. Most patients have no significant decrease in left ventricular ejection fraction [3], and it has been estimated that clinically significant heart failure aggravation occurs in only 1.5 to 3 percent of patients [42,45,51]. The risk is greater in patients with a prior history of heart failure, particularly those with a baseline ejection fraction of <30 percent [4,5,42,46]. In the review of 3135 patients cited above, the incidence to torsades de pointes was much higher in patients with heart failure (5.0 versus 1.7 percent without heart failure) [46].

Because of the concern related to the safety of sotalol in patients with heart failure, amiodarone is generally preferred for the treatment of ventricular arrhythmias and for maintenance of sinus rhythm in atrial fibrillation when pharmacologic therapy is given. However, sotalol safely reduces the frequency of recurrent arrhythmia and appropriate shocks in patients with an implantable cardioverter-defibrillator (ICD) [34]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "The management of atrial fibrillation in patients with heart failure".)

Contraindications — Sotalol should not be used in patients with uncontrolled asthma, sinus bradycardia, Mobitz II second degree AV block and third degree AV block, congenital long QT syndrome, acquired long QT syndrome (table 2), cardiogenic shock, or uncontrolled heart failure. In addition, it should be used with caution in patients with reduced renal function, since decreased clearance can result in drug accumulation and possible proarrhythmia [46].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Supraventricular arrhythmias".)

SUMMARY AND RECOMMENDATIONS

●Introduction – Sotalol consists of a racemic mixture of d and l isomers in an approximate ratio of 1:1. The two isomers contribute to the unique antiarrhythmic properties of sotalol, with d isomer prolonging repolarization by blocking the rapid component of the delayed rectifier potassium current that is responsible for phase 3 repolarization of the action potential, while the l isomer both prolongs repolarization and has beta blocking activity. (See 'Electrophysiology and mechanism of action' above.)

●Mechanism – The effect of sotalol on the action potential duration shows reverse use dependence, which is seen with other class III antiarrhythmic drugs, except for amiodarone. Reverse use dependence is defined as an inverse correlation between the heart rate and the QT interval. As a result, the QT interval is prolonged as the heart rate slows, with an associated risk of drug-induced torsades de pointes and a possible decrease in drug efficacy at higher heart rates. (See 'Class III activity' above.)

●Dosing – Bradycardic and proarrhythmic events occur in up to 20 percent of patients after the initiation of sotalol therapy and with each upward dosing adjustment. As a result, sotalol should be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment. (See 'Dosing' above.)

The recommended initial dose of oral sotalol in adults is 80 mg twice daily whether used for the treatment of ventricular arrhythmias or atrial fibrillation (AF). If necessary, the initial dose can be increased gradually to a total daily dose of 240 mg or 320 mg. Dose adjustments should be made at three day intervals so that steady-state plasma concentrations can be attained and the QT interval monitored. The dosing interval requires modification in patients with impaired renal function and reduced creatinine clearance. (See 'Dosing' above.)

●Proarrhythmia – Sotalol should not be given to patients with congenital or acquired long QT syndrome unless the cause can be reversed because of the risk of further QT interval prolongation and proarrhythmia, particularly torsades de pointes (table 2). (See 'Proarrhythmia' above.)

●Clinical indications – Oral sotalol is used for the treatment of ventricular arrhythmias (ie, sustained VT) that are potentially life-threatening and for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation and atrial flutter who are currently in sinus rhythm. (See 'Clinical indications' above.)

●Side effects – Sotalol is generally well tolerated, being discontinued because of side effects in approximately 15 percent of patients. The major causes for intolerance are fatigue, bradycardia, dyspnea, proarrhythmia, dizziness and asthenia. (See 'Major side effects' above.)