Sotalol (Betapace) is a non-selective beta-blocker that is used as an anti-arrhythmic drug. It has class II (Beta-receptor blocking) and Class III (Prolongs the cardiac action potential) properties.

Sotalol Uses:

• Symptomatic atrial fibrillation or flutter:

  • Maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter) in patients with symptomatic atrial fibrillation/atrial flutter who are currently in sinus rhythm.
  • According to the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS), sotalol is not effective for the conversion of atrial fibrillation to sinus rhythm but may be used to prevent atrial fibrillation.

• Ventricular arrhythmias:

  • Treatment of documented, life-threatening ventricular arrhythmias (ie, sustained ventricular tachycardia)

• Off Label Use of Sotalol in Adults:

  • Atrial fibrillation in patients with hypertrophic cardiomyopathy (HCM) (alternative antiarrhythmic);
  • Hemodynamically stable monomorphic ventricular tachycardia;
  • Supraventricular tachycardia;
  • Ventricular premature beats

Sotalol Dose in Adults

• Baseline QTc interval and creatinine clearance must be determined before initiation.
• If CrCl ≤60 mL/minute, dosing interval adjustment will be necessary.
• Sotalol should be initiated and doses titrated in a hospital for at least 3 days with facilities for cardiac rhythm monitoring and assessment.
• Proarrhythmic events can occur after starting of therapy and with each upward dosage adjustment.

Sotalol Dose in the treatment of patients with symptomatic atrial fibrillation or atrial flutter:

• IV: Substitution for oral sotalol:
• Note:
  • The effects of the initial IV dose must be monitored and the dose should be titrated, if needed, based on clinical effect, QTc interval, or adverse reactions.
• Initial dose: 75 mg is infused over 5 hours twice a day

• Dose adjustment:

  • If the initial dose does not reduce the frequency of relapse and excessive QTc prolongation does not occur (eg, QTc < 500 msec),
  • The dose may be increased after at least 3 days to 112.5 mg twice daily.
  • If at steady-state this dose still does not control arrhythmia and QTc prolongation does not occur may further increase the dose to 150 mg twice daily.

• Dose range:

  • Usual therapeutic dose: 112.5 mg twice a day;
  • The maximum dose: 150 mg twice a day
  • Initial: 80 mg orally twice daily.
  • If the initial dose does not reduce the frequency of relapse and excessive QTc prolongation does not occur (eg, QTc <500 msec) after 3 days, the dose may be increased to 120 mg twice daily;
  • The dose may be further increased to a maximum dose of 160 mg twice daily if the response is inadequate and QTc prolongation is not excessive.

Sotalol Dose in the treatment of Ventricular arrhythmias:

• IV: Substitution for oral sotalol:

• Note:

  • The effects of the initial IV dose must be monitored and the dose titrated either upward or downward, if needed, based on clinical effect, QTc interval, or adverse reactions.
• Initial dose: 75 mg infused over 5 hours twice daily

• Dose adjustment:

  • If the initial dose does not reduce the frequency of relapse and excessive QTc prolongation does not occur (eg, QTc <500 msec);
  • The dose may be increased after at least 3 days to 112.5 mg twice daily.
  • May further increase the dose in 3 days by 75 mg/day;
  • The maximum dose: 300 mg twice daily

• Dose range:

  • Usual therapeutic dose: 75 to 150 mg twice daily

  • Oral:

    • Initial dose: 80 mg twice daily;
    • The dose may be increased gradually (in increments of 80 mg/day) if excessive QTc prolongation does not occur (eg, QTc <500 msec) to 160 to 320 mg/day in 2 divided doses;
    • Allow 3 days between dosing increments in order to attain steady-state plasma concentrations and to allow for monitoring of QT intervals.

  • Maximum dose:

    • Some patients, with life-threatening refractory ventricular arrhythmias, may require total daily doses as high as 480 to 640 mg; however, these doses should only be prescribed when the potential benefit outweighs the increased risk of adverse events.

Sotalol Dose in the treatment of Monomorphic VT in a hemodynamically stable patient:

• 1.5 mg/kg intravenous over 5 minutes.
• Note: Clinical trial employed a standard dose of 100 mg.

Sotalol Dose in the treatment of Ventricular premature beats (off-label):

• Initial dose: 80 mg orally twice daily;
• The dose may be increased gradually (in increments of 80 mg/day) to 160 to 320 mg/day in 2 divided doses;
• The maximum dose: 320 mg/day;
• Allow 3 days between dosing increments in order to attain steady-state plasma concentrations and to allow for monitoring of QT intervals.

Sotalol dose in the treatment of Supraventricular tachycardia.

• 40 to 80 mg orally every 12 hours;
• The maximum maintenance dose: 160 mg every 12 hours.

• Conversion from oral sotalol to IV sotalol:

  • 80 mg oral equivalent to 75 mg IV
  • 120 mg oral equivalent to 112.5 mg IV
  • 160 mg oral equivalent to 150 mg IV

Sotalol Dose in Childrens

• Note:

  • Baseline QT interval and CrCl must be determined prior to initiation.
  • Dosage must be adjusted to individual response and tolerance;
  • Doses should be initiated or increased in a hospital facility that can provide continuous ECG monitoring, recognition and treatment of life-threatening arrhythmias, and CPR.
  • In pediatric patients, dosing may be based on either BSA (mg/m²) or weight (mg/kg);
  • Use extra precaution to verify dosing parameters during calculations.
  • Sotalol is indicated for both the treatment of documented life-threatening ventricular arrhythmias (marketed as Betapace/Sorine/Sotylize) and for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation/flutter who are currently in sinus rhythm (marketed as Betapace AF/Sotylize).

Oral Sotalol Dose in the treatment of Arrhythmias:

• Manufacturer's dosing recommendations are based on doses per m² (that are equivalent to the doses recommended in adults) and on pediatric pharmacokinetic and pharmacodynamic studies.
• BSA, rather than body weight, better predicted apparent clearance of sotalol; however, for a given dose per m², a larger drug exposure (larger AUC) and greater pharmacologic effects were observed in smaller subjects (ie, those with BSA <0.33 m² versus those with BSA ≥0.33 m²).
• For infants and children ≤2 years of age, the manufacturer recommends a dosage reduction based on an age factor determined from a graph.

Manufacturer's labeling: Note:

• Use with extreme caution if QT is >500 msec while receiving sotalol; reduce the dose or discontinue drug if QT >550 msec.

• Infants and children less than 2 years of age:

  • The manufacturer recommended pediatric dosage of 30 mg/m²/dose every 8 hours must be REDUCED using an age-related factor

• Children >2 years and Adolescents:

  • Initial: 30 mg/m²/dose given every 8 hours;
  • Increase the dosage gradually if needed;
  • Allow at least 36 hours between dosage increments to achieve new steady-state and to monitor clinical response, heart rate, and QT intervals;
  • The dose may be increased gradually to a maximum of 60 mg/m²/dose given every 8 hours; not to exceed adult doses (usual maximum adult daily dose: 320 mg/day)

Sotalol alternate dosing:

• 2 mg/kg/day divided every 8 hours;
• if needed, increase dosage gradually by 1 to 2 mg/kg/day increments;
• allow 3 days between dosage increments to achieve new steady-state and to monitor clinical response, heart rate, and QT intervals;
• The maximum dose is: 10 mg/kg/day (if no limiting side effects occur)
• Do not exceed from adult doses (usual maximum adult daily dose: 320 mg/day)

• Proposed Sotalol target doses:

Note: It is not required to increase to target dosage if the desired clinical effect has been achieved at a lower dosage.

• Infants and Children 1 month to 6 years:

  • 6 mg/kg/day divided every 8 hours

• Children >6 years and Adolescents:

  • at 4 mg/kg/day divided every 8 hours not to exceed than adult doses (usual maximum adult daily dose: 320 mg/day)

Sotalol Dosing adjustment for toxicity:

• QT ≥500 msec during the initiation period (Betapace AF, Sotylize):

  • Reduce dose, prolong the dosing interval (Sotylize), or discontinue sotalol.

• QT ≥520 msec (or JT interval ≥430 msec if the QRS >100 msec) during maintenance therapy (Betapace AF):

  • Reduce dose and carefully monitor QT until <520 msec. If QTc interval ≥520 msec on the lowest maintenance dose, discontinue sotalol.

• QT ≥550 msec (Betapace, Sorine):

  • Reduce dose or discontinue sotalol.

Pregnancy Risk Factor B

• In the initial animal reproduction studies, adverse events were not detected. 
• Sotalol crosses into the placenta and can be found in amniotic liquid. In utero beta-blockers have been linked to adverse events such as hypoglycemia and fetal/neonatal bradycardia. 
• It is generally recommended that infants be monitored at birth in a way that is safe and effective.
• Sotalol crosses over the placenta at a concentration similar to that of the maternal serum. It is preferred for treating fetal atrial fibrillation.
• While sotalol clearance is higher in the third trimester, other parameters of pharmacokinetics are not significantly different from those of nonpregnant women.
• Sotalol might be used to treat some arrhythmias in the heart, if a beta-blocker is required during pregnancy.

Sotalol use during breastfeeding:

• Breast milk contains higher levels of sotalol than the maternal serum.
• Even though adverse events in nursing infants were not reported in cases, it is recommended to monitor for hypoglycemia, bradycardia and respiratory distress.
• The manufacturer suggests that the mother decide whether to stop breastfeeding or discontinue using the drug. This is in consideration of the risk of serious adverse reactions in breastfed babies.

Sotalol Dose in Kidney Disease:

• Dose escalations in renal impairment should be done after administration of at least 5 doses at appropriate intervals.

Atrial fibrillation/flutter: Oral and IV:

• CrCl >60 mL/minute:

  • Administer every 12 hours.

• CrCl 40 to 60 mL/minute:

  • • Administer every 24 hours.

• CrCl <40 mL/minute:

  • Use is contraindicated.

Ventricular arrhythmia:

• Oral Tablets:

  • CrCl >60 mL/minute:

    • Administer every 12 hours.

  • CrCl 30 to 60 mL/minute:

    • Administer every 24 hours.

  • CrCl 10 to 29 mL/minute:

    • Administer every 36 to 48 hours.

  • CrCl <10 mL/minute:

    • There are no specific dosage adjustments provided in the manufacturer's labeling; individualize dose

  • Hemodialysis:

    • The manufacturer's labeling for some products recommends extreme caution should be employed if sotalol is used in patients with renal failure undergoing hemodialysis.
    • Multiple cases of torsades de pointes have been reported when sotalol was used even at low dosages (eg, 80 mg daily) in patients with the end-stage renal disease treated with hemodialysis.
    • If sotalol is used in hemodialysis, some experts recommend a starting dose of 40 mg once daily with careful monitoring.
    • Hemodialysis would be expected to reduce sotalol plasma concentrations because sotalol is not bound to plasma proteins and does not undergo extensive metabolism.

  • Peritoneal dialysis:

    • Cases of torsades de pointes have been reported when sotalol was used even at low dosages (eg, 80 mg daily) in patients with the end-stage renal disease treated with peritoneal dialysis.

• Intravenous:

  • CrCl >60 mL/minute:

    • Administer every 12 hours.

  • CrCl 40 to 60 mL/minute:

    • Administer every 24 hours.

  • CrCl <40 mL/minute:

    • Use is contraindicated.

Sotalol Dose in Liver disease:

• There are no dosage adjustments provided in the drug manufacturer's labeling.
• However, dosage adjustment unlikely because sotalol is not metabolized by the liver.

• There is minimal clinical experience with IV sotalol; however, since exposure is similar between IV and oral sotalol, adverse reactions are expected to be similar.

Common Side Effects of Sotalol:

• Cardiovascular:

  • Bradycardia
  • Chest Pain
  • Palpitations

• Central Nervous System:

  • Fatigue
  • Dizziness
  • Headache

• Neuromuscular & Skeletal:

  • Weakness

• Respiratory:

  • Dyspnea

Less Common Side Effects Of Sotalol:

• Cardiovascular:

  • Edema
  • ECG Abnormality
  • Hypotension
  • Cardiac Failure
  • Syncope
  • Proarrhythmia
  • Torsades De Pointes
  • Peripheral Vascular Disorder
  • Angina Pectoris
  • Presyncope
  • Cardiovascular Signs And Symptoms
  • Worsened Ventricular Tachycardia
  • Cerebrovascular Accident
  • Hypertension
  • Vasodilation
  • Prolonged Q-T Interval On ECG

• Central Nervous System:

  • Sleep Disorder
  • Insomnia
  • Anxiety
  • Depression
  • Paresthesia
  • Sensation Of Cold
  • Impaired Consciousness
  • Mood Changes

• Dermatologic:

  • Hyperhidrosis
  • Skin Rash
  • Diaphoresis

• Endocrine & Metabolic:

  • Weight Changes

• Gastrointestinal:

  • Nausea And Vomiting
  • Diarrhea
  • Abdominal Pain
  • Dyspepsia
  • Abdominal Distention
  • Decreased Appetite
  • Change In Appetite
  • Colonic Disease
  • Flatulence

• Genitourinary:

  • Sexual Disorder
  • Genitourinary Complaint

• Hematologic & Oncologic:

  • Hemorrhage

• Infection:

  • Infection
  • Influenza

• Local:

  • Local Pain

• Neuromuscular & Skeletal:

  • Limb Pain
  • Musculoskeletal Pain
  • Musculoskeletal Chest Pain
  • Back Pain

• Ophthalmic:

  • Visual Disturbance

• Respiratory:

  • Upper Respiratory Complaint
  • Pulmonary Disease
  • Tracheobronchitis
  • Asthma

• Miscellaneous:

  • Fever
  • Laboratory Test Abnormality
  • AICD Discharge

Contraindications to Sotalol:

• Hypersensitivity/allergy to sotalol or any component of the formulation;
• Bronchitis or other bronchospastic conditions.
• Sinus bradycardia (50 beats per hour during the day);
• If a pacemaker is not present, second- or third-degree AV block.
• Congenital and acquired long QT syndromes
• Cardiogenic shock
• Uncontrolled heart failure
• sick sinus syndrome;
• serum potassium <4 mEq/L;
• Use of atrial fibrillation/flutter sotalol should be avoided if the baseline QTc interval is >450 msec, or CrCl 40 mg/minute
• There is not much documentation of allergenic cross-reactivity with beta-adrenergic blocking drugs.
• Cross-sensitivity can be possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Anaphylactic reactions

  • Patients who have had severe allergic reactions to allergens in the past should be cautious. Beta-blockers can make it more difficult for patients to react to the same challenges.
  • Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

• Bradycardia and Hypotension

  • Bradycardia, including heart block, and hypotension may occur. Sotalol may require dosage adjustments for agents that slow AV Nodal Conduction.

• Proarrhythmic effects: [US Boxed Warning]

  • You can reduce the risk of drug-induced arrhythmia by initiating or reinitiating sotalol at a facility that provides continuous electrocardiographic (ECG), monitoring and cardiac resuscitation.
  • Sotalol may cause dangerous ventricular tachycardia due to QT interval prolongation.
  • If the baseline QTc is greater than 450msec, do not start sotalol therapy
  • Reduce the dose or increase the duration of the QT interval if it exceeds 500 msec.
  • Calculate creatinine clearance to determine appropriate dosing.
  • If the patient is sinus rhythm, some experts will start oral therapy as an outpatient. However, if the QT interval is normal and the serum potassium is normal, the patient does not need any QT-interval prolonging medication. Atrial fibrillation patients may require hospitalization.
  • Before administering the first dose, it is necessary to calculate CrCl.
  • To maintain steady-state concentrations, dosing intervals should be gradually increased with three days between each increment. This will allow for time to monitor QT intervals.
  • To prevent QTc prolongation, monitor and adjust the dose.

• Bronchospastic Disease:

  • Patients with bronchospastic diseases should not be given beta-blockers. If they are, they should be closely monitored and used with caution.
  • Patients with bronchial asthma and related bronchospastic conditions should not take Sotalol.

• Conductive abnormality

  • Before you start, consider preexisting conditions like sick sinus syndrome.

• Diabetes:

  • Patients with diabetes mellitus should be cautious.
  • It can increase hypoglycemia or mask symptoms.

• Electrolyte imbalances:

  • You must correct electrolyte imbalances prior to initiating any exercise (hypokalemia and/or hypomagnesemia). These conditions can increase the likelihood of developing torsades.

• Heart failure (HF):

  • During initiation or titration, it is possible to have new onset or worsening of heart failure.
  • Patients with compensated cardiac failure should be cautious. Monitor for signs of worsening and stop using the medication if they develop.
  • Patients with uncontrolled or decompensated heart failure are not advised to use this medication.

• Myasthenia gravis:

  • Patients with myasthenia Gravis should be cautious. It may worsen their condition.

• Myocardial Infarction

  • Avoid excessive use within the first two weeks after MI, particularly in patients with severely impaired ventricular function (experience limit).

• Raynaud and peripheral vascular disease (PVD).

  • It can cause or exacerbate arterial insufficiency symptoms in patients with Raynaud and PVD. Be cautious and watch for signs of arterial obstruction.

• Untreated Pheochromocytoma

  • Adequate alpha-blockade is required prior to the use of any beta-blocker.

• Renal impairment: [US-Boxed Warning]

  • To reduce the risk of pro-arrhythmia, adjust the dosing interval using CrCl
  • QT interval lengthening is directly linked to sotalol concentration.
  • Calculating CrCl with dose initiation or dose increases is necessary.
  • When used for atrial fibrillation/flutter, sotalol is contraindicated in patients with CrCl <40 mL/minute.

• Thyroid disease:

  • Hyperthyroidism may be disguised (eg, Tachycardia).
  • Thyrotoxicosis should be suspected. Carefully manage and monitor the situation. Sudden withdrawal could exacerbate hyperthyroidism symptoms or cause a thyroid storm.

Sotalol: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Serum creatinine (creatinine clearance),
• magnesium,
• potassium;
• heart rate,
• blood pressure;
• ECG (eg, QTc interval, PR interval).

Oral:

• During the initiation and titration period, monitor QTc interval 2 to 4 hours after each dose.
• If the QTc interval is ≥500 msec, reduce dose, prolong the dosing interval, or discontinue sotalol.
• If the QTc interval is <500 msec after 3 days (after the fifth or sixth dose if a patient receiving once-daily dosing), the patient may be discharged on the current regimen.
• Monitor the QTc interval periodically thereafter.

Intravenous:

• Measure the QTc interval after completion of each infusion.
• Consult individual institutional policies and procedures.

How to administer Sotalol?

• Oral: Administer without regard to meals.

Intravenous:

• Substitution for oral: Administer over 5 hours; may prolong duration of infusion if QT interval prolongs to ≥500 msec.
• Hemodynamically stable monomorphic VT: Administer IV push over 5 minutes; use with caution because of increased risk of adverse events (eg, bradycardia, hypotension, torsade de pointes).

Mechanism of action of Sotalol:

• Beta-blocker which contains both beta-adrenoreceptor-blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation properties

• Effects of Class II:

  • An increase in sinus cycle length, slowed heart beat, decreased AV Nodal conduction and increased AV Nodal refractoriness are all signs that Sotalol has both beta-1 as well as beta-2 receptor blocking activity.
  • Beta-blocking effects of sotalol are non-cardioselective. Half-maximal at 80 mg/day, maximal at doses between 320 and 640 mg/day.
  • Oral doses as low 25 mg/day can cause significant beta-blockade

• Effects of Class III:

  • Extension of the atrial and ventral monophasic action pots and effective refractory lengthening of atrial, ventricular, and atrioventricular accessory paths in both the retrograde and antegrade directions.
  • Sotalol, a racemic combination of d-and l-sotalol, has similar Class III antiarrhythmic properties. The l-isomer however is responsible for almost all beta-blocking activity.
  • Only oral doses greater than 160 mg per day are believed to cause Class III symptoms.

The onset of action:

• Oral:
  • Rapid; at 1 to 2 hours post-dosing (steady-state) reductions in heart rate and the cardiac index have been seen.
• IV:
  • When administered IV over 5 minutes for ongoing VT, the onset of action is ~5 to 10 minutes.

Absorption:

• Oral: Well absorbed (Hanyok 1993); decreased by about ~20% by meals compared with fasting

Protein binding:

• None

Metabolism:

• None

Bioavailability:

• Oral: 90% to 100%

Half-life elimination: Oral:

• Neonates ≤1 month: 8.4 hours.
• Infants and Children >1 month to 24 months: about 7.4 hours.
• Children >2 years to <7 years: 9.1 hours.
• Children 7 to 12 years: 9.2 hours.
• Adults: 12 hours
• Adults with renal failure (anuric): Up to 69 hours
• IV: Pharmacokinetics of the IV formulation (administered over 5 hours) is similar to the oral formulations.

Time to peak serum concentration:

• Oral: Infants and Children 3 days to 12 years:
• Mean range: 2 to 3 hours;
• Adults: 2.5 to 4 hours

Excretion:

• Urine (as unchanged drug)

Clearance (apparent) (Saul 2001b):

• Neonates ≤1 month: 11 mL/minute
• Infants and Children >1 month to 24 months: 32 mL/minute
• Children >2 years to <7 years: 63 mL/minute
• Children 7 to 12 years: 95 mL/minute

International Brand Names of Sotalol:

• Betapace
• Betapace AF
• Sorine
• Sotylize
• APO-Sotalol
• CO Sotalol
• DOM-Sotalol
• JAMP-Sotalol
• MED Sotalol
• MYLAN-Sotalol
• NOVO-Sotalol
• PHL-Sotalol
• PMS-Sotalol
• PRO-Sotalol
• RATIO-Sotalol
• RIVA-Sotalol
• SANDOZ Sotalol
• Alosot
• Beta-Cardone
• Betacor
• Betades
• Betalol
• Cardol
• Darob
• Gilucor
• Hipecor
• Jutalex
• Rentibloc
• Solavert
• Solet
• Soritmik
• Sotacor
• Sotagamma
• Sotagard
• Sotahexal
• Sotalex
• Sotalex Mite
• Sotaloc
• Sotalol Knoll
• Sotalon
• Sotapor
• Sotax
• Sotoger

Sotalol Brand Names in Pakistan:

No Brands Available in Pakistan.