Therapeutic use and major side effects of sotalol
- Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
- Professor of Medicine
- Director, Center for Women’s Health
- Columbia University Medical Center
- Section Editors
- Mark S Link, MD
Mark S Link, MD
- Section Editor — Cardiac Arrhythmias
- Professor of Medicine
- Tufts Medical School
- Hugh Calkins, MD
Hugh Calkins, MD
- Section Editor — Cardiac Arrhythmias
- Professor of Medicine
- Johns Hopkins Medical Institutions
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.
- Kato R, Ikeda N, Yabek SM, et al. Electrophysiologic effects of the levo- and dextrorotatory isomers of sotalol in isolated cardiac muscle and their in vivo pharmacokinetics. J Am Coll Cardiol 1986; 7:116.
- Hohnloser SH, Woosley RL. Sotalol. N Engl J Med 1994; 331:31.
- Anderson JL, Prystowsky EN. Sotalol: An important new antiarrhythmic. Am Heart J 1999; 137:388.
- Singh BN. Sotalol: Current Status and Expanding Indications. J Cardiovasc Pharmacol Ther 1999; 4:49.
- Numaguchi H, Mullins FM, Johnson JP Jr, et al. Probing the interaction between inactivation gating and Dd-sotalol block of HERG. Circ Res 2000; 87:1012.
- Sanguinetti MC, Jurkiewicz NK. Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol 1990; 96:195.
- Brodsky M, Saini R, Bellinger R, et al. Comparative effects of the combination of digoxin and dl-sotalol therapy versus digoxin monotherapy for control of ventricular response in chronic atrial fibrillation. dl-Sotalol Atrial Fibrillation Study Group. Am Heart J 1994; 127:572.
- Nademanee K, Feld G, Hendrickson J, et al. Electrophysiologic and antiarrhythmic effects of sotalol in patients with life-threatening ventricular tachyarrhythmias. Circulation 1985; 72:555.
- Mitchell LB, Wyse DG, Duff HJ. Electropharmacology of sotalol in patients with Wolff-Parkinson-White syndrome. Circulation 1987; 76:810.
- Hondeghem LM, Snyders DJ. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation 1990; 81:686.
- Hohnloser SH, Meinertz T, Stubbs P, et al. Efficacy and safety of d-sotalol, a pure class III antiarrhythmic compound, in patients with symptomatic complex ventricular ectopy. Results of a multicenter, randomized, double-blind, placebo-controlled dose-finding study. The d-Sotalol PVC Study Group. Circulation 1995; 92:1517.
- Waldo AL, Camm AJ, deRuyter H, et al. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet 1996; 348:7.
- Anastasiou-Nana MI, Gilbert EM, Miller RH, et al. Usefulness of d, I sotalol for suppression of chronic ventricular arrhythmias. Am J Cardiol 1991; 67:511.
- Creamer JE, Nathan AW, Shennan A, Camm AJ. Acute and chronic effects of sotalol and propranolol on ventricular repolarization using constant-rate pacing. Am J Cardiol 1986; 57:1092.
- Touboul P, Atallah G, Kirkorian G, et al. Clinical electrophysiology of intravenous sotalol, a beta-blocking drug with class III antiarrhythmic properties. Am Heart J 1984; 107:888.
- Wang T, Bergstrand RH, Thompson KA, et al. Concentration-dependent pharmacologic properties of sotalol. Am J Cardiol 1986; 57:1160.
- Maisel WH, Kuntz KM, Reimold SC, et al. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med 1997; 127:281.
- Chung MK, Schweikert RA, Wilkoff BL, et al. Is hospital admission for initiation of antiarrhythmic therapy with sotalol for atrial arrhythmias required? Yield of in-hospital monitoring and prediction of risk for significant arrhythmia complications. J Am Coll Cardiol 1998; 32:169.
- Kim RJ, Juriansz GJ, Jones DR, et al. Comparison of a standard versus accelerated dosing regimen for D,L-sotalol for the treatment of atrial and ventricular dysrhythmias. Pacing Clin Electrophysiol 2006; 29:1219.
- Rizza C, Valderrabano M, Singh BN. Recurrent Torsades de Pointes After Sotalol Therapy for Symptomatic Paroxysmal Atrial Fibrillation in a Patient with End-Stage Renal Disease. J Cardiovasc Pharmacol Ther 1999; 4:129.
- Reiffel JA, Appel G. Importance of QT interval determination and renal function assessment during antiarrhythmic drug therapy. J Cardiovasc Pharmacol Ther 2001; 6:111.
- https://www.apotex.com/us/en/products/downloads/pil/sota_imtb_ins.pdf (Accessed on August 26, 2015).
- Sung RJ, Tan HL, Karagounis L, et al. Intravenous sotalol for the termination of supraventricular tachycardia and atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled study. Sotalol Multicenter Study Group. Am Heart J 1995; 129:739.
- Vos MA, Golitsyn SR, Stangl K, et al. Superiority of ibutilide (a new class III agent) over DL-sotalol in converting atrial flutter and atrial fibrillation. The Ibutilide/Sotalol Comparator Study Group. Heart 1998; 79:568.
- Reisinger J, Gatterer E, Heinze G, et al. Prospective comparison of flecainide versus sotalol for immediate cardioversion of atrial fibrillation. Am J Cardiol 1998; 81:1450.
- Ho DS, Zecchin RP, Richards DA, et al. Double-blind trial of lignocaine versus sotalol for acute termination of spontaneous sustained ventricular tachycardia. Lancet 1994; 344:18.
- Singh BN, Kehoe R, Woosley RL, et al. Multicenter trial of sotalol compared with procainamide in the suppression of inducible ventricular tachycardia: a double-blind, randomized parallel evaluation. Sotalol Multicenter Study Group. Am Heart J 1995; 129:87.
- Kpaeyeh JA Jr, Wharton JM. Sotalol. Card Electrophysiol Clin 2016; 8:437.
- Roden DM. Usefulness of sotalol for life-threatening ventricular arrhythmias. Am J Cardiol 1993; 72:51A.
- Mason JW. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. N Engl J Med 1993; 329:452.
- Haverkamp W, Martinez-Rubio A, Hief C, et al. Efficacy and safety of d,l-sotalol in patients with ventricular tachycardia and in survivors of cardiac arrest. J Am Coll Cardiol 1997; 30:487.
- Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337:1576.
- Domanski MJ, Sakseena S, Epstein AE, et al. Relative effectiveness of the implantable cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular dysfunction who have survived malignant ventricular arrhythmias. AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators. J Am Coll Cardiol 1999; 34:1090.
- Pacifico A, Hohnloser SH, Williams JH, et al. Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group. N Engl J Med 1999; 340:1855.
- Wichter T, Borggrefe M, Haverkamp W, et al. Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. Circulation 1992; 86:29.
- AFFIRM First Antiarrhythmic Drug Substudy Investigators. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. J Am Coll Cardiol 2003; 42:20.
- Ferreira E, Sunderji R, Gin K. Is oral sotalol effective in converting atrial fibrillation to sinus rhythm? Pharmacotherapy 1997; 17:1233.
- Crystal E, Connolly SJ, Sleik K, et al. Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation 2002; 106:75.
- Kerin NZ, Jacob S. The efficacy of sotalol in preventing postoperative atrial fibrillation: a meta-analysis. Am J Med 2011; 124:875.e1.
- Capucci A, Botto G, Molon G, et al. The Drug And Pace Health cliNical Evaluation (DAPHNE) study: a randomized trial comparing sotalol versus beta-blockers to treat symptomatic atrial fibrillation in patients with brady-tachycardia syndrome implanted with an antitachycardia pacemaker. Am Heart J 2008; 156:373.e1.
- Oudijk MA, Michon MM, Kleinman CS, et al. Sotalol in the treatment of fetal dysrhythmias. Circulation 2000; 101:2721.
- Soyka LF, Wirtz C, Spangenberg RB. Clinical safety profile of sotalol in patients with arrhythmias. Am J Cardiol 1990; 65:74A.
- Multicentre randomized trial of sotalol vs amiodarone for chronic malignant ventricular tachyarrhythmias. Amiodarone vs Sotalol Study Group. Eur Heart J 1989; 10:685.
- Weeke P, Delaney J, Mosley JD, et al. QT variability during initial exposure to sotalol: experience based on a large electronic medical record. Europace 2013; 15:1791.
- Lehmann MH, Hardy S, Archibald D, et al. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation 1996; 94:2535.
- Somberg JC, Preston RA, Ranade V, et al. Gender differences in cardiac repolarization following intravenous sotalol administration. J Cardiovasc Pharmacol Ther 2012; 17:86.
- Makkar RR, Fromm BS, Steinman RT, et al. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA 1993; 270:2590.
- Zeltser D, Justo D, Halkin A, et al. Torsade de pointes due to noncardiac drugs: most patients have easily identifiable risk factors. Medicine (Baltimore) 2003; 82:282.
- Locati EH, Zareba W, Moss AJ, et al. Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. Circulation 1998; 97:2237.
- Drici MD, Clément N. Is gender a risk factor for adverse drug reactions? The example of drug-induced long QT syndrome. Drug Saf 2001; 24:575.
- Kehoe RF, Zheutlin TA, Dunnington CS, et al. Safety and efficacy of sotalol in patients with drug-refractory sustained ventricular tachyarrhythmias. Am J Cardiol 1990; 65:58A.
- Gottlieb SS, Singh S, Munger M, et al. Hemodynamic effects of the class III antiarrhythmic drug, d-sotalol, in patients with congestive heart failure. Am J Cardiol 1996; 78:1411.
- Dorian P, Newman D, Berman N, et al. Sotalol and type IA drugs in combination prevent recurrence of sustained ventricular tachycardia. J Am Coll Cardiol 1993; 22:106.
- Lee SD, Newman D, Ham M, Dorian P. Electrophysiologic mechanisms of antiarrhythmic efficacy of a sotalol and class Ia drug combination: elimination of reverse use dependence. J Am Coll Cardiol 1997; 29:100.
- ELECTROPHYSIOLOGY AND MECHANISM OF ACTION
- Class III activity
- - d-Sotalol
- Beta blockade
- Effects on the ECG
- Oral sotalol
- - Changing from other antiarrhythmic drugs
- - Renal insufficiency
- - Elderly
- - Children
- - Pregnancy
- - Post-operative atrial fibrillation
- Intravenous sotalol
- QT interval prolongation
- CLINICAL INDICATIONS
- Ventricular arrhythmias
- Atrial arrhythmias
- Fetal arrhythmias
- MAJOR SIDE EFFECTS
- Cardiac toxicity
- - Proarrhythmia
- - Bradycardia
- - Heart failure
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS