Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms.[1] Evidence does not support a decreased risk of death with long term use.[1] It is taken by mouth or given by injection into a vein.[1]
Sotalol was first described in 1964 and came into medical use in 1974.[5] It is available as a generic medication.[4] In 2020, it was the 296th most commonly prescribed medication in the United States, with more than 1million prescriptions.[6][7]
According to the FDA, sotalol should not be used in people with a waking heart rate lower than 50 beats per minute.[8] It should not be used in people with sick sinus syndrome, long QT syndrome, cardiogenic shock, uncontrolled heart failure, asthma or a related bronchospastic condition, or people with serum potassium below 4 meq/L.[8] It should only be used in people with a second and third degree AV block if a functioning pacemaker is present.[8]
Since sotalol is removed from the body through the kidneys, it should not be used in people with a creatinine clearance rate below 40 mL/min.[8] It is also excreted in breast milk, so mothers should not breastfeed while taking sotalol.[8]
Since sotalol prolongs the QT interval, the FDA recommends against using it in conjunction with other medications that prolong the QT interval.[8] Studies have found serious side effects to be more common in individuals also taking digoxin, possibly because of pre-existing heart failure in those people.[8] As with other beta blockers, it may interact with calcium channel blockers, catecholamine-depleting drugs, insulin or antidiabetic drugs, β2-adrenergic receptor agonists, and clonidine.[8]
Some evidence suggests that sotalol should be avoided in the setting of heart failure with a reduced ejection fraction (resulting in the heart squeezing little blood out into the circulation with each pump) due to an increased risk of death.[10]
In rare cases, the QT prolongation caused by sotalol can lead to the development of life-threatening torsade de pointes (TdP) polymorphic ventricular tachycardia. Across several clinical trials, 0.6% of oral sotalol patients with supraventricular abnormal heart rhythms (such as atrial fibrillation) developed TdP.[3] For patients who had a history of sustained ventricular tachycardia (abnormal rhythm lasting more than 30 seconds), 4% developed TdP. Risk increases with dosage, female sex, or having a history of an enlarged heart or congestive heart failure.[3] The incidence of TdP for sustained ventricular tachycardia patients was 0% with an 80 mg daily dose, 0.5% at 160 mg, 1.6% at 320 mg, 4.4% at 480 mg, 3.7% at 640 mg, and 5.8% at doses greater than 640 mg.[3] Due to this risk, the U.S. Food and Drug Administration requires affected individuals to be hospitalized for at least three days in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring upon starting or restarting sotalol.[3]
Without the binding of catecholamines to the β-adrenergic receptor, the G protein complex associated with the receptor cannot activate production of cyclic AMP, which is responsible for turning on calcium inflow channels.[13] A decrease in activation of calcium channels will therefore result in a decrease in intracellular calcium. In heart cells, calcium is important in generating electrical signals for heart muscle contraction, as well as generating force for this contraction.[14] In consideration of these important properties of calcium, two conclusions can be drawn. First, with less calcium in the cell, there is a decrease in electrical signals for contraction, thus allowing time for the heart's natural pacemaker to rectify arrhythmic contractions.[15] Secondly, lower calcium means a decrease in strength and rate of the contractions, which can be helpful in treatment of abnormally fast heart rates.[15]
Type III antiarrhythmic action
Sotalol also acts on potassium channels and causes a delay in relaxation of the ventricles.[16] By blocking these potassium channels, sotalol inhibits efflux of K+ ions, which results in an increase in the time before another electrical signal can be generated in ventricular myocytes.[14] This increase in the period before a new signal for contraction is generated, helps to correct arrhythmias by reducing the potential for premature or abnormal contraction of the ventricles but also prolongs the frequency of ventricular contraction to help treat tachycardia.[medical citation needed]
^Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, et al. (July 1996). "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. 348 (9019): 7–12. doi:10.1016/S0140-6736(96)02149-6. PMID8691967. S2CID21284044.
^Bertrix L, Timour-Chah Q, Lang J, Lakhal M, Faucon G (May 1986). "Protection against ventricular and atrial fibrillation by sotalol". Cardiovascular Research. 20 (5): 358–63. doi:10.1093/cvr/20.5.358. PMID3756977.
^Charnet P, Lory P, Bourinet E, Collin T, Nargeot J (1995). "cAMP-dependent phosphorylation of the cardiac L-type Ca channel: a missing link?". Biochimie. 77 (12): 957–62. doi:10.1016/0300-9084(95)80008-5. PMID8834778.
^ abKassotis J, Sauberman RB, Cabo C, Wit AL, Coromilas J (November 2003). "Beta receptor blockade potentiates the antiarrhythmic actions of d-sotalol on reentrant ventricular tachycardia in a canine model of myocardial infarction". Journal of Cardiovascular Electrophysiology. 14 (11): 1233–44. doi:10.1046/j.1540-8167.2003.02413.x. PMID14678141. S2CID24561848.
^ abcAntonaccio MJ, Gomoll A (August 1993). "Pharmacologic basis of the antiarrhythmic and hemodynamic effects of sotalol". The American Journal of Cardiology. 72 (4): 27A–37A. doi:10.1016/0002-9149(93)90022-5. PMID8346723.
^Edvardsson N, Hirsch I, Emanuelsson H, Pontén J, Olsson SB (October 1980). "Sotalol-induced delayed ventricular repolarization in man". European Heart Journal. 1 (5): 335–43. doi:10.1093/eurheartj/1.5.335. PMID7274246.
^ abcAnderson JL, Askins JC, Gilbert EM, Miller RH, Keefe DL, Somberg JC, et al. (October 1986). "Multicenter trial of sotalol for suppression of frequent, complex ventricular arrhythmias: a double-blind, randomized, placebo-controlled evaluation of two doses". Journal of the American College of Cardiology. 8 (4): 752–62. doi:10.1016/S0735-1097(86)80414-4. PMID2428852.