General Information

Betapace/Betapace AF is an antiarrhythmic.

Betapace/Betapace AF is specifically indicated for:

• the treatment of documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia (VT).
• the maintenance of normal sinus rhythm (delay in time to recurrence of AFIB/AFL) in patients with highly symptomatic AFIB/AFL who are currently in sinus rhythm.

Betapace/Betapace AF is supplied as tablets for oral administration. See drug label G\for general safety measures for initiation of oral sotalol therapy. 

Adult Dose for Ventricular Arrhythmias

The recommended initial dose is 80 mg twice daily. This dose may be increased in increments of 80 mg per day every 3 days provided the QTc <500 msec. Continually monitor patients until steady state blood levels are achieved. In most patients, a therapeutic response is obtained at a total daily dose of 160 to 320 mg/day, given in two or three divided doses. Oral doses as high as 480 to 640 mg/day have been utilized in patients with refractory life-threatening arrhythmias.

Adult Dose for Prevention of Recurrence of AFIB/AFL

The recommended initial dose is 80 mg twice daily. This dose may be increased in increments of 80 mg per day every 3 days provided the QTc <500 msec. Continually monitor patients until steady state blood levels are achieved. Most patients will have satisfactory response with 120 mg twice daily. Initiation of sotalol in patients with QTc >450 msec is contraindicated.

Pediatric Dose for Ventricular Arrhythmias or AFIB/AFL

Use the same precautionary measures for children as you would use for adults when initiating and re-initiating sotalol treatment.

• For Children Aged About 2 Years and Older
  • For children aged about 2 years and older, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide 
  • For initiation of treatment, 1.2 mg/kg three times a day (3.6 mg/kg total daily dose) is approximately equivalent to the initial 160 mg total daily dose for adults. Subsequent titration to a maximum of 2.4 mg/kg three times a day (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate, and QTc, with increased dosing being preferably conducted in-hospital. Allow at least 36 hours between dose increments to attain steady-state plasma concentrations of sotalol in patients with age‑adjusted normal renal function.
• For Children Aged About 2 Years or Younger
  •  For children aged about 2 years or younger, the pediatric dosage should be reduced by a factor that depends upon age. For a child aged 1 month, multiply the starting dose by 0.7; the initial starting dose would be (1.2 mg/kg X 0.7)=0.8 mg/kg, administered three times daily. For a child aged about 1 week, multiply the initial starting dose by 0.3; the starting dose would be (1.2 mg/kg X 0.3)=0.4 mg/kg. Use similar calculations for dose titration.

Mechanism of Action

Sotalol has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. The two isomers of sotalol have similar Class III antiarrhythmic effects, while the l-isomer is responsible for virtually all of the beta-blocking activity. The beta-blocking effect of sotalol is non-cardioselective, half maximal at about 80 mg/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 III effects are seen only at daily doses of 160 mg and above.

In children, a Class III electrophysiologic effect can be seen at daily doses of 210 mg/m2 body surface area (BSA). A reduction of the resting heart rate due to the beta-blocking effect of sotalol is observed at daily doses ≥90 mg/m2 in children.

Side Effects

Adverse effects associated with the use of Betapace/Betapace AF may include, but are not limited to, the following:

• Bradycardia
• Fatigue
• Fainting
• Dizziness
• Tachycardia
• Severe diarrhea
• Unusual sweating
• Vomiting
• Decreased appetite
• Increased thirst

The Betapace/Betapase AF drug label comes with the following Black Box Warning: Betapace/Betapace AF can cause life-threatening ventricular tachycardia associated with QT interval prolongation. If the QT interval prolongs to 500 msec or greater, reduce the dose, lengthen the dosing interval, or discontinue the drug. Initiate or reinitiate in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Adjust the dosing interval based on creatinine clearance.

Clinical Trial Results

Two primary studies of Betapace were conducted in patients with symptomatic AFIB/AFL. The first of these studies investigated patients with primarily paroxysmal AFIB/AFL. No structural heart disease was present in 43% of the patients. Patients were given either one or two doses daily, depending on renal function. Results indicated that the drug prolonged the time to the first symptomatic recurrence of AFIB/AFL and also reduced the risk of recurrence at six and twelve months. The 120 mg dose was shown to be more effective than the 80 mg dose. However, there were no significant differences between the 160 mg and 120 mg doses.

The second study investigated patients whose AFIB/AFL was chronic. Structural heart disease was present in 49% of the patients. All patients had chronic AFIB for more than two weeks and less than one year. Results showed that compared to a placebo, there was a longer time to recurrence of AFIB and there was a reduced risk of recurrence at six months.

Further trials also investigated the effect of Betapace's active ingredient, sotalol, on post- myocardial infarction (MI) patients. The drug did not significantly decrease the mortality rate in patients taking the drug, compared to a placebo. However, the investigation determined that there was no increased risk for post-MI patients receiving the drug.

In eight clinical trials with a total of 659 patients, there were four cases of torsade de pointes (TdP), a serious and dangerous ventricular arrhythmia.