Brands, Medical Use, Clinical Data
Drug Category
- Adrenergic beta-Antagonists
- Anti-Arrhythmia Agents
- Sympatholytics
Dosage Forms
- Tablets (white, capsule-shaped, for oral administration)
Brands / Synonyms
Betapace; Betapace AF; Sorine; Sotalol; Sotalol HCL
Indications
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.
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.
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.
Biotrnasformation / Drug Metabolism
Sotalol is not metabolized.
Contraindications
BETAPACE AF™ (sotalol hydrochloride) is contraindicated in patients with sinus bradycardia
(<50 bpm during waking hours), sick sinus syndrome or second and third degree AV block (unless a functioning
pacemaker is present), congenital or acquired long QT syndromes, baseline QT interval >450 msec, cardiogenic
shock, uncontrolled heart failure, hypokalemia (<4 meq/L), creati-nine clearance <40 mL/min, bronchial asthma
and previous evidence of hypersensitivity to sotalol.
Drug Interactions
Drugs undergoing CYP450 metabolism
Sotalol is primarily eliminated by renal excretion; therefore, drugs that are metabolized by CYP450
are not expected to alter the pharmacokinetics of sotalol.
Digoxin
Proarrhythmic events were more common in sotalol treated patients also receiving digoxin; it is not
clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for
proarrhythmia, in the patients receiving digoxin.
Calcium blocking drugs
BETAPACE AF™ should be administered with caution in conjunction with calcium blocking drugs
because of possible additive effects on atrioventricular conduction or ventricular function. Additionally,
concomitant use of these drugs may have additive effects on blood pressure, possibly leading to hypotension.
Catecholamine-depleting agents
Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with a
beta-blocker may produce an excessive reduction of resting sympathetic nervous tone. Patients treated with BETAPACE
AF™ plus a catecholamine depletor should therefore be closely monitored for evidence of hypotension and/or
marked bradycardia which may produce syncope.
Insulin and oral antidiabetics
Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment.
Symptoms of hypoglycemia may be masked.
Beta-2-receptor stimulants
Beta-agonists such as salbutamol, terbutaline and isoprenaline may have to be administered in
increased dosages when used concomitantly with BETAPACE AF™.
Clonidine
Beta-blocking drugs may potentiate the rebound hypertension sometimes observed after discontinuation
of clonidine; therefore, caution is advised when discontinuing clonidine in patients receiving BETAPACE
AF™.
Other
No pharmacokinetic interactions were observed with hydrochlorothiazide or warfarin.
Antacids
Administration of BETAPACE AF™ within 2 hours of antacids containing aluminum oxide and
magnesium hydroxide should be avoided because it may result in a reduction in Cmax and AUC of 26% and 20%,
respectively and consequently in a 25% reduction in the bradycardic effect at rest. Administration of the antacid two
hours after BETAPACEAF™ has no effect on the pharmacoki-netics or pharmacodynamics of sotalol.
Drug/Laboratory Test Interactions
The presence of sotalol in the urine may result in falsely elevated levels of urinary metanephrine
when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma
and being treated with sotalol, a specific method, such as a high performance liquid chromato-graphic assay with
solid phase extraction (e.g., J. Chromatogr. 385:241, 1987) should be employed in determining levels of
catecholamines.
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