[CK] [ ] Q Sotalol loading.

75 year old male with PMH of CAD (Stent to OM in 2014), and sustained VT. He underwent St Jude DDD ICD implant 7/8/2016. In 2017 he received multiple shocks for sustained VT. He then underwent EPS and ablation at UVA on 4/24/17, at that time LV and RV endocardial voltages were normal and ablation was done in the LVOT and RVOT based on pace mapping (per reports). He has since had recurrent sustained VT treated by ATP and NSVT.

He underwent repeat VT ablation (thought to be triggered VT from aorto-mitral contuinity ) with non inducible VT at the end of the procedure. however, last night he had recurrent episodes of ventricular tachycardia in the VT monitor zone of the device (asymptomatic , no therapies recieved). He has been on sotalol 80 mg TID at home. Will plan to go upto 120 mg BID today and then 160 mg BID tomorrow if the 120 mg dose is tolerated.

1- Increase sotalol to 120 mg BID today
2- ECG 2 hours after each dose
3- If QTc remains < 500 ms/ increase in QTc <15%,will increase to 160 mg BID tomorrow.
4- Avoid other QT prolonging meds

https://www.uptodate.com/contents/therapeutic-use-and-major-side-effects-of-sotalol

Therapeutic use and major side effects of sotalol

Author:

Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA

Section Editors:

Mark S Link, MD

Hugh Calkins, MD

Deputy Editor:

Brian C Downey, MD, FACC

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2018. | This topic last updated: Feb 09, 2018.

INTRODUCTION — Sotalol, a methanesulfonanilide, is a class III antiarrhythmic drug (table 1) that is used for the treatment of both atrial and ventricular arrhythmias.

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. Racemic, dl-sotalol was approved by the US Food and Drug Administration (FDA) for use in the treatment of ventricular tachycardia (VT) in October of 1992 and subsequently for atrial fibrillation (AF) in February of 2000. Since the patent for dl-sotalol has expired, generic dl-sotalol preparations are now available. 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 [1-4]:

●The d isomer prolongs repolarization by blocking IKr, the rapid component of the delayed rectifier potassium current that is responsible for phase 3 repolarization of the action potential (figure 1) [5,6]. This represents a class III effect. (See "Myocardial action potential and action of antiarrhythmic drugs".)

●The l isomer has two actions: it prolongs repolarization and it has beta blocking activity. The latter 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 [3,7-9]. 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 [1].

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 1) [5,6]. Sotalol does not affect either the resting potential or rapid phase 0 depolarization that is mediated by sodium entry into the cells. (See "Myocardial action potential and action of antiarrhythmic drugs".)

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 [10]. 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 (TdP) and the possible decrease in drug efficacy at higher heart rates. (See "Acquired long QT syndrome: Definitions, causes, and pathophysiology", section on 'Pathophysiology' and 'Proarrhythmia' below.)

d-Sotalol — A preparation containing only the d isomer has been developed as a "pure" class III drug [11,12]. 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 [12]. This observation suggests an important contribution from the beta blocking activity that is seen with dl-sotalol.

Beta blockade — 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) [3].

Effects on the ECG — The combined actions of sotalol produce a variety of changes in the electrocardiogram (ECG) [3,13,14]:

●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 [13,14]. This is thought to reflect a lack of effect of sotalol on the His-Purkinje (HV) interval [3,8,15].

●The QT interval is prolonged in a dose-dependent fashion [16]. Since the QRS duration is not prolonged, the increase in QT interval results solely from delayed repolarization (ie, the JT interval) [13,14]. 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 [13]. 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'.)

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 [4]. In addition, because sotalol prolongs the QT interval, it should not be used in patients with congenital or acquired long QT syndrome.

Hospitalization — 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 'Proarrhythmia' below.)

The frequency with which adverse cardiac events occur was illustrated in a retrospective study of 417 patients who underwent 597 drug trials for conversion of atrial fibrillation (AF) or for initiation of maintenance therapy after electrical cardioversion [17]. Among the 72 trials with sotalol (80 mg orally twice daily), adverse cardiac events occurred in 18 percent: bradyarrhythmias occurred in eight (11 percent), ventricular arrhythmias in two (2.8 percent), and QT prolongation in one (1.4 percent). The risk was greatest within the first 24 hours of therapy and in patients with a previous myocardial infarction (MI).

Similar findings were noted in a report of 120 patients who were admitted to the hospital for sotalol therapy for atrial arrhythmias [18]. A complication occurred in 25 patients (21 percent), which triggered a change in therapy (eg, dose reduction or sotalol cessation) in 21. The most common complications were bradycardia in 20 (including a heart rate below 40/min in 13), excessive prolongation of the QT interval in eight, and new or increased ventricular arrhythmias in seven (including two cases of TdP [torsades de pointes]). Complications occurred within the first three days in 22 of the patients (88 percent).

After discharge, we generally have the patient return for an electrocardiogram (ECG) at 48 to 72 hours and again at one and two weeks, looking for QT interval prolongation and bradyarrhythmias.

Oral sotalol — 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 240 or 320 mg/day. 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.

A therapeutic response is usually obtained at a total daily dose of 160 to 320 mg/day given in two or three divided doses. Some patients with ventricular arrhythmias require doses as high as 480 to 640 mg/day; however, these doses are more likely to be associated with proarrhythmia and should only be considered when the potential benefit outweighs the increased risk [3].

Changing from other antiarrhythmic drugs — Before beginning sotalol, previous antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of two to three half-lives, if clinically possible. After discontinuation of amiodarone, for example, sotalol should not be initiated until the QT interval has returned to normal.

Renal insufficiency — Oral sotalol is primarily excreted unchanged in the urine, since it is not appreciably metabolized in the liver [2]. 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.

Elderly — Age alone does not alter the pharmacokinetics of sotalol. However, impaired renal function in older patients can increase the elimination half-life, resulting in drug accumulation.

Children — The safety and efficacy of sotalol in children have not been established. The manufacturer's dosing recommendations for children more than two years of age is 30 mg/m2 per dose, which is given three times daily. For infants and children ≤2 years of age, the manufacturer recommends a dosing reduction based upon an age factor determined from a graph that is available with the package insert [22].

The dose can be increased gradually, if necessary, to a maximum of 60 mg/m2 per dose, which is given three times daily. There should be at least 36 hours between dose increments to permit attainment of a new steady-state and to monitor the clinical response, heart rate, and QT interval.

Pregnancy — The clinical experience with sotalol is extremely limited in pregnancy. (See "Ventricular arrhythmias during pregnancy".)

Post-operative atrial fibrillation — Sotalol and amiodarone are commonly prescribed for the treatment of postoperative atrial fibrillation (POAF) following cardiac surgery and are effective in maintaining sinus rhythm in this population. The efficacy and safety of these agents is discussed separately. (See "Atrial fibrillation and flutter after cardiac surgery", section on 'Prevention of AF'.)

Intravenous sotalol — Intravenous sotalol has primarily been used to terminate supraventricular tachyarrhythmias [23-25]. It has also been used to terminate spontaneous sustained ventricular tachycardia (VT) and to suppress inducible ventricular tachyarrhythmia during electrophysiology study [26,27].

The usual dose is 1.5 mg/kg, which is given slowly over 10 minutes. However, intravenous sotalol appears to be less effective in converting atrial fibrillation or atrial flutter than intravenous ibutilide or flecainide (figure 2) [24,25]. (See "Atrial fibrillation: Cardioversion to sinus rhythm", section on 'Less effective or ineffective drugs'.)

QT interval prolongation — 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 TdP. A number of drugs can prolong the QT interval, including antiarrhythmic drugs such as procainamide, quinidine, and the other class III agents (amiodarone, dofetilide, ibutilide) (table 2). All predispose to TdP except for amiodarone. Hypokalemia and hypomagnesemia are additional risk factors. Because of reverse use dependence, QT prolongation is more likely in patients with a bradyarrhythmia [10]. (See 'Class III activity' above and 'Proarrhythmia' below and "Acquired long QT syndrome: Definitions, causes, and pathophysiology".)

There is a near linear relationship between sotalol dose and QT interval prolongation, with a sharp increase in the risk of proarrhythmia above a cumulative daily dose of 320 mg [28].

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 can prevent recurrence of sustained VT or ventricular fibrillation (VF) [13,29-31]. However, sotalol is generally less effective than an implantable cardioverter-defibrillator (ICD); this difference is primarily seen in patients with a left ventricular ejection fraction ≤35 percent [32,33]. Thus, the main settings in which antiarrhythmic drugs are used as primary therapy are 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). More often, antiarrhythmic drugs are given as adjunctive therapy to an ICD to reduce the frequency of appropriate shocks or of inappropriate shocks due to supraventricular arrhythmias. 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 highly 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. (See "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis", section on 'Antiarrhythmic drugs'.)

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 can promote maintenance of sinus rhythm after cardioversion in patients with AF. It appears to be as effective as and less toxic than quinidine, as effective as propafenone, but less effective than amiodarone [36]. 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 [37] and, where available, intravenous sotalol is less effective than other drugs [24,25]. (See "Atrial fibrillation: Cardioversion to sinus rhythm", 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) [38]. 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 [39]. 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".)

●In the Drug and Pace Health Clinical Evaluation (DAPHNE) trial 137 patients with the brady-tachycardia form of sinus node disease were treated with a dual chamber rate adaptive pacemaker and then randomly assigned to either beta blockers (atenolol or metoprolol) or sotalol [40]. After 12 months, 29 percent of patients were free from atrial arrhythmias recurrences in both groups. Similarly, there was no difference in the rates of cardioversion or hospitalization, both of which were lower in both groups in the 12 months after therapy compared with the 12 months before therapy.

Fetal arrhythmias — Fetal tachycardia is a serious condition for which treatment should be initiated, especially in the presence of hydrops fetalis. The use of sotalol for fetal tachycardia was evaluated in 21 fetuses with atrial flutter, supraventricular tachycardia, or ventricular tachycardia [41]. Sotalol restored sinus rhythm in 8 of 10 fetuses with atrial flutter and in 6 of 10 with supraventricular tachycardia. However, the fetal mortality rate was 19 percent and occurred primarily in those with supraventricular tachycardia.

Sotalol should be considered a drug of choice to treat fetal atrial flutter; however, the high mortality in those with supraventricular tachycardia suggests that the utility of sotalol therapy is limited for the treatment of this arrhythmia.

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 [3,42]. The major causes for cessation of therapy are fatigue (4 percent), bradycardia, dyspnea, proarrhythmia (each 3 percent), and dizziness and asthenia (each 2 percent) [3]. 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 'Hospitalization' above.)

Cardiac toxicity — The two major cardiac side effects of sotalol are proarrhythmia, most often torsades de pointes (TdP), 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 be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment. (See 'Hospitalization'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 [2,43]. As mentioned above, this effect is mediated by blockade of IKr, the rapid component of the delayed rectifier potassium current that is responsible for phase 3 repolarization of the action potential (figure 1) [5,6]. (See 'Class III activity' above.)

At standard doses between 160 and 640 mg/day, sotalol increases by QT interval by 40 to 100 msec [2]. 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 (200 women, 37 percent) 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 [2,3,36].

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 [10]. As a result, the QT interval is prolonged as the heart rate slows, which could explain the association between bradycardia and antiarrhythmic drug-induced TdP. (See "Acquired long QT syndrome: Definitions, causes, and pathophysiology", section on 'Pathophysiology'.)

The most important clinical manifestation of sotalol-induced proarrhythmia is TdP, 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 TdP has varied from 1 to 4 percent [34,42,45]. The incidence of and risk factors for TdP were best addressed 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) [45].

The overall rate of TdP 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.

In a study of 15 healthy volunteers (9 female) designed to determine the relationship between dose and QTc, a significantly longer QTc was found in females compared with males following the infusion of 75 mg of sotalol over 2.5 hours [46]. The single predictor for the greater QTc prolongation was female gender, suggesting that an enhanced response to drug action may explain the higher incidence of drug-induced TdP seen in females.

An increase in risk in females has also been noted with TdP 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 TdP [50]. (See "Acquired long QT syndrome: Definitions, causes, and pathophysiology", section on 'Risk factors'.)

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 TdP except for amiodarone. (See "Amiodarone: Monitoring and management of side effects", section on 'Cardiac toxicity' and "Acquired long QT syndrome: Definitions, causes, and pathophysiology", section on 'Torsades de pointes'.)

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 [2,3,17,18,34,42]. By comparison, sinus node arrest and second or third degree heart block occur in ≤1 percent [3,42].

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 [2], and it has been estimated that clinically significant heart failure aggravation occurs in only 1.5 to 3 percent of patients [36,42,51]. The risk is greater in patients with a prior history of heart failure, particularly those with a baseline ejection fraction of <30 percent [3,4,42,45]. In the review of 3135 patients cited above, the incidence to TdP was much higher in patients with heart failure (5.0 versus 1.7 percent without heart failure) [45].

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".)

In comparison to dl-sotalol, d-sotalol has only class III antiarrhythmic action and is devoid of beta blocking activity. When given intravenously to patients with heart failure, d-sotalol exerts no clinically important acute hemodynamic effects even at doses that prolong the QT interval [52]. However, in patients with left ventricular dysfunction due to a recent or remote myocardial infarction (MI), d-sotalol increases mortality, presumably due to arrhythmic death [12].

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 [45].

It has been stated that sotalol should not be given with class IA antiarrhythmic drugs (such as quinidine, procainamide, or disopyramide) because these drugs may also prolong refractoriness and the combination would further increase the propensity for proarrhythmia. Data exists, however, suggesting that the combination of low dose sotalol and a class IA agent is very effective in preventing the induction of ventricular tachycardia and the spontaneous recurrence of arrhythmia [53]. In a study of 32 patients, for example, this combination markedly prolonged ventricular refractoriness (especially at higher heart rates), thereby eliminating the "reverse use dependency" (a reduction in refractoriness as heart rate increases) observed when sotalol is administered as a sole agent [54].

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

●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(=PROLONGED QTc = III effect) 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.)

●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 (TdP) and a possible decrease in drug efficacy at higher heart rates. (See 'Class III activity' above.); not too slow(too dangerous) but not too fast(not effective) 

●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. 

=>when do we need to uptitrate(unless >500 or >15% of increasing QTc!) 

A therapeutic response is usually obtained at a total daily dose of 160 to 320 mg/day(80 BID or 160 BID!)  given in two or three divided doses. Some patients with ventricular arrhythmias require doses as high as 480 to 640 mg/day; however, these doses are more likely to be associated with proarrhythmia and should only be considered when the potential benefit outweighs the increased risk

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 'Oral sotalol' above and 'Renal insufficiency' above.)

●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 TdP. (See 'QT interval prolongation' above.)

●Oral sotalol is used for the treatment of ventricular arrhythmias (ie, sustained VT) that are potentially life-threatening; like AMIODARONE loading. (Peak = 1.5 HOURS, HAlF = 12HRs)

 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.)

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