SOTALOL AF (Generic for BETAPACE)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-May administer without regard to meals.
Oral Liquid Formulations
-Measure dosage with calibrated measuring device.
-Extemporaneous Oral Suspension: Shake well prior to use.

Extemporaneous Compounding-Oral
Extemporaneous 5 mg/mL Oral Suspension Preparation
NOTE: A 5 mg/mL oral solution is commercially available.
-Measure 120 mL of Simple Syrup containing 0.1% sodium benzoate (Syrup, NF).
-Transfer the syrup to a 6-ounce amber plastic bottle.
-Add five 120 mg sotalol tablets to the bottle. The tablets may be added intact or they may be crushed.
-If the tablets are crushed, carefully transfer the entire amount of powder to the bottle and shake the bottle until dispersion of the fine particles in the syrup is obtained.
-If the tablets are intact, shake the bottle to wet the entire surface of the tablet and allow it to hydrate for approximately 2 hours. The tablets may also be hydrated overnight to allow for easier disintegration.
-Shake the bottle intermittently over the next 2 hours until the tablets are completely disintegrated and dispersion of fine particles in the syrup is achieved.
-Storage: The resulting suspension is stable for 3 months at 15 to 30 degrees C (59 to 86 degrees F).



Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Initiate or titrate intravenous sotalol in a facility that can provide continuous ECG monitoring and cardiac resuscitation.
Intravenous Administration
NOTE: Specific recommendations for administration in pediatric patients are not available; the following dilution and infusion instructions are based on recommended adult doses.

Dilution
-Dilute in 0.9% Sodium Chloride Injection, Dextrose 5% Injection, or Lactated Ringer's Injection.
-Choose a volume convenient for administration and consistent with fluid restriction.

IV Infusion
-Use a volumetric infusion pump.
-The infusion rate varies by indication:-For substitution of oral sotalol: Infuse over 5 hours.
-For loading dose: Infuse over 1 hour. Measure and normalize serum potassium and magnesium concentrations before initiation. Monitor QTc interval every 15 minutes during infusion.

New onset or worsening heart failure may occur during sotalol initiation and titration because of its beta-blocking effects. Monitor patients for signs and symptoms of heart failure and discontinue sotalol if symptoms occur.

Sotalol can induce or worsen QT prolongation, contributing to potentially fatal ventricular arrhythmias such as ventricular fibrillation (VF), sustained ventricular tachycardia (VT), and/or torsade de pointes (TdP). In addition, sotalol can cause symptomatic bradycardia, which is a risk factor for the development of TdP. These effects are dose-related. If the QT interval prolongs to more than 500 milliseconds, reduce the dose, lengthen the dosing interval, or discontinue the drug. In pediatric patients, the incidence of proarrhythmic adverse effects (e.g., bradycardia, AV block, ectopic ventricular activity, TdP) varies from 0% to 22%; however, drug-induced TdP is observed less frequently in pediatric patients compared to adults. Bradycardia is more common in patients with sinus node dysfunction after surgery for congenital heart defects; monitor patients closely for several days. Emergency pacemaker implantation may be required. The QTc interval appears to be longer in neonates and smaller children compared to older or larger children. In clinical studies of sotalol in pediatric patients for the management of various arrhythmias, QTc prolongation (more than 470 milliseconds) was reported in 4% to 12% of patients and sinus pause or bradycardia was reported in 1% to 4% of patients. In adult trials (n = 659), TdP was reported in 4 patients (0.6%). The incidence of TdP was 4% and the incidence of worsened VT was 1% in trials of adults with a history of sustained VT; in patients with less serious ventricular arrhythmias, the incidence of TdP was 1% and the incidence of new or worsened VT was 0.7%. Death was considered possibly drug-related in approximately 1% of patients, most likely associated with proarrhythmic events. Patients with sustained VT and a history of congestive heart failure had the highest incidence of serious proarrhythmia (7%). Although sotalol was discontinued in most patients with TdP, 17% continued sotalol therapy on a lower dose. Sinus pause, sinus arrest, and sinus node dysfunction occurred in less than 1% of patients. The incidence of second- or third-degree AV block is approximately 1%. Bradycardia (12% to 13%) was also reported.

Sotalol produces significant reductions in both systolic and diastolic blood pressures and may cause hypotension. Monitor hemodynamics during sotalol administration. Other cardiovascular reactions including chest pain (unspecified) (7.9% to 15.4%), palpitations (5.1% to 7.9%), and vasodilation (0% to 5.1%) have been reported during adult clinical trials for sotalol. Pulmonary edema has been rarely reported with postmarketing use. In pediatric trials (n = 25), chest pain was reported in 1 patient (4%).

Non-selective beta-blockers may inhibit catecholamine-induced glycogenolysis, gluconeogenesis, and lipolysis, predisposing to hypoglycemia. Additionally, beta-blockers can mask signs of hypoglycemia (e.g., tachycardia) and increase the risk for severe or prolonged hypoglycemia at any time during treatment. Persons should be instructed to seek emergency treatment if severe hypoglycemia occurs. Elevated blood glucose concentrations and increased insulin requirements can occur in persons with diabetes mellitus. Beta-blocker-induced hyperglycemia is thought to be due to blockade of beta-2-receptors on pancreatic islet cells, which inhibit insulin secretion. Monitor blood glucose concentrations closely if a beta-blocker is used in a person with diabetes mellitus. In addition to acute blood glucose effects, beta-blockers have been shown to increase the risk of developing diabetes mellitus in adult hypertensive patients. The risk in pediatric patients is undefined.

A single case of peripheral neuropathy, which resolved upon discontinuation of sotalol and recurred with rechallenge, was reported in an early dose tolerance study.

Diarrhea (5.2% to 5.7%), nausea/vomiting (5.7% to 7.8%), and abdominal pain (2.5% to 3.9%) have been reported during adult clinical trials for sotalol. Abdominal pain has been reported in 7% of pediatric and young adult patients (1 week to 26 years of age) receiving sotalol.

Fatigue (2% to 6%), dizziness (3%), depression (2%), and headache (2%) have been reported in pediatric patients. Asthenia (10.5% to 20.5%), dizziness (13.2% to 17.9%), fatigue (18.9% to 26.3%), headache (3.3% to 11.5%), lightheaded (5.1% to 15.8%), sleep problem (2.6% to 7.7%), and visual impairment (0% to 5.3%) have been reported during adult clinical trials for sotalol. Emotional lability, slightly clouded sensorium (confusion), incoordination, vertigo, and muscle paralysis have been rarely reported with postmarketing use.

Musculoskeletal pain (2.6% to 4.1%), hyperhidrosis (4.9% to 5.2%), and weakness (4.9% to 5.2%) have been reported during adult clinical trials for sotalol. Myalgia and fever have been rarely reported postmarketing use.

Upper respiratory tract problem (2.6% to 12.8%) and cough (2.5% to 3.3%) have been reported during adult clinical trials for sotalol. Dyspnea was reported in 9.2% to 9.8% of patients with atrial fibrillation/atrial flutter and in 18.4% to 20.5% of those with ventricular arrhythmias. As with other beta-blockers, bronchospasm may be associated with sotalol use.

Photosensitivity reaction, pruritus, and alopecia have been rarely reported with postmarketing use.

Withdrawal symptoms, including headache, diaphoresis, palpitations, sinus tachycardia, tremor, and hypertension have been associated with abrupt discontinuation of beta-blockers in hypertensive patients. If possible, gradually reduce the dosage of sotalol over 1 to 2 weeks; prolonged administration of small doses prior to complete cessation may prevent adverse events. In adult patients with ischemic heart disease, occasional cases of exacerbation of angina, arrhythmias, and myocardial infarction have been reported after abrupt discontinuation of beta-blocker therapy.

Thrombocytopenia, eosinophilia, leukopenia, and hyperlipidemia have been rarely reported with postmarketing use.

Sotalol is contraindicated in patients with a known hypersensitivity to sotalol. Use sotalol with caution in patients with a history of anaphylactic reactions. These patients may have a more severe reaction if rechallenge to the allergen occurs while receiving a beta-blocker, such as sotalol. The patient may also be unresponsive to the usual doses of epinephrine used to treat the reaction.

Abrupt discontinuation of beta-blockers can exacerbate angina and precipitate a heart attack. Further, abrupt discontinuation of sotalol may unmask latent coronary insufficiency. When discontinuing chronically administered sotalol, gradually reduce the dose over 1 to 2 weeks, if possible, and monitor the patient. Consider use of an alternative beta-blocker if angina worsens or acute coronary ischemia develops. Advise patients not to interrupt therapy without their health care provider's advice.

Beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Avoid abrupt withdrawal of beta-blockade in patients with thyroid disease because it may lead to an exacerbation of symptoms of hyperthyroidism, including thyroid storm.

Sotalol is contraindicated in patients with sinus bradycardia (less than 50 beats per minute), sick sinus syndrome, second or third-degree AV block without a pacemaker, congenital or acquired long QT syndrome, cardiogenic shock, decompensated heart failure, and/or serum potassium less than 4 mEq/L (hypokalemia). Sotalol is also contraindicated in patients with a baseline QT interval of more than 450 milliseconds; for Betapace/Betapace AF and Sorine, this contraindication only applies for the treatment of atrial fibrillation or atrial flutter. Sotalol has proarrhythmic effects and may induce or worsen cardiac arrhythmias, primarily ventricular arrhythmias. Use has been associated with QT prolongation, which can lead to sustained ventricular fibrillation (VF), sustained ventricular tachycardia (VT), and/or torsade de pointes (TdP). To minimize the risk of drug-induced arrhythmia, the initiation or uptitration of intravenous sotalol and initiation or reinitiation of oral sotalol requires a specialized care setting, specifically a facility that can provide continuous ECG monitoring and cardiac resuscitation, and requires an experienced clinician who is trained in the management of serious ventricular arrhythmias. Hospitalize patients initiated or reinitiated on sotalol for at least 3 days or until steady-state concentrations are achieved. Correct hypokalemia and hypomagnesemia before initiating sotalol. Assess electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or those receiving concomitant diuretics. Use sotalol with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Reduced renal function, higher doses, bradycardia, history of sustained VT/VF, and atrial fibrillation with sinus node dysfunction can also increase the risk of TdP. Adjust the sotalol dosage according to renal function and monitor the ECG for excessive increases in the QT interval.

Sorine for atrial fibrillation/atrial flutter is contraindicated in patients with a creatinine clearance less than 40 mL/minute (i.e., renal failure or renal impairment). Adjustments to sotalol dosage are necessary based on creatinine clearance.

The presence of sotalol in the urine may cause laboratory test interference and result in falsely elevated concentrations of urinary metanephrine when measured by fluorimetric or photometric method.

The impaired ability of the heart to respond to reflex adrenergic stimuli due to beta-blocking therapy may augment the risks of general anesthesia and surgical procedures. In general, do not routinely withdraw chronically administered beta-blocking therapy before major surgery.

Sotalol is contraindicated in patients with bronchial asthma or related bronchospastic conditions (e.g., acute bronchospasm). Avoid sotalol in patients with bronchospastic diseases (e.g., chronic lung disease (CLD), like chronic bronchitis). If sotalol is to be administered, use the smallest effective dose to minimize inhibition of bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta-2 receptors.

Non-selective beta-blockers may inhibit catecholamine-induced glycogenolysis, gluconeogenesis, and lipolysis, predisposing to hypoglycemia. Additionally, beta-blockers can mask signs of hypoglycemia (e.g., tachycardia) and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in persons with diabetes mellitus or children and persons who are fasting (i.e., surgery, not eating regularly, or are vomiting). Persons should be instructed to seek emergency treatment if severe hypoglycemia occurs. Elevated blood glucose concentrations and increased insulin requirements can occur in persons with diabetes mellitus. Beta-blocker-induced hyperglycemia is thought to be due to blockade of beta-2-receptors on pancreatic islet cells, which inhibit insulin secretion. Monitor blood glucose concentrations closely if a beta-blocker is used in a person with diabetes mellitus.

Avoid sotalol in patients with Raynaud's phenomenon or peripheral vascular disease because reduced cardiac output and the relative increase in alpha stimulation can exacerbate symptoms.

Use sotalol with caution and careful dosage titration in the first 2 weeks after acute myocardial infarction, especially in patients with markedly impaired ventricular function. Sotalol (320 mg/day PO; non-titrated) did not significantly affect mortality in a large double-blind, placebo-controlled secondary prevention (post-infarction) trial including 1,456 adults; however, there was a suggestion of early (within the first 10 days of treatment) excess mortality in sotalol-treated patients. In a second smaller trial (n = 17 randomized to sotalol), 4 fatalities and 3 serious hemodynamic/electrical events occurred within 2 weeks of sotalol initiation in high-risk post-infarction patients (ejection fraction less than 40% and either more than 10 VPC/hour or VT on Holter) receiving high dose sotalol (320 mg PO twice daily). During investigation of the d-isomer of sotalol (virtually devoid of beta-blocking activity and considered a pure Class III antiarrhythmic) as an antiarrhythmic in high-risk patients post-MI, a higher mortality rate was observed with d-sotalol vs. placebo, presumably due to increased arrhythmic deaths.

Description: Sotalol is a hydrophilic, nonselective beta-adrenergic blocking agent, with low lipid-solubility. It is used to treat ventricular and supraventricular arrhythmias. Sotalol is a unique beta-blocker that has both Vaughn Williams Classification class II and III antiarrhythmic properties. As a Class II nonselective beta-blocker, it has no intrinsic sympathomimetic activity (ISA) or membrane-stabilizing activity (MSA). The Class III antiarrhythmic effects, like amiodarone, prolong the action potential duration and increase cardiac tissue refractoriness. Sotalol is associated with serious proarrhythmic effects, including QT prolongation and torsade de pointes. As a result, sotalol is used in the treatment of symptomatic atrial arrhythmias or life-threatening ventricular arrhythmias, including sustained ventricular tachycardia and is not recommended for mild arrhythmias. Due to the risk of proarrhythmic effects, hospitalization in a facility that can provide continuous ECG monitoring and the presence of personnel trained in cardiac resuscitation and the management of serious ventricular arrhythmias for a minimum of 3 days is recommended when initiating or titrating sotalol. In October 2014, the first oral liquid preparation was approved by the FDA, making administration to children more convenient. Although not FDA-approved, sotalol has been used in pediatric patients as young as neonates.

General Dosing Information
-Withdraw other antiarrhythmic therapy before starting sotalol for a minimum of 2 to 3 plasma half-lives if the patient's clinical condition permits.
-Initiate or uptitrate intravenous sotalol and initiate or reinitiate oral sotalol in a facility that can provide continuous ECG monitoring and cardiac resuscitation and by personnel who are trained in the management of serious ventricular arrhythmias. Hospitalize patients initiated or reinitiated on sotalol for at least 3 days or until steady-state concentrations are achieved.
-Perform a baseline ECG, and measure and normalize serum potassium and magnesium concentrations before initiation.
-Measure serum creatinine and calculate an estimated CrCl to establish the appropriate dosing interval.
-Continuously monitor patients with each dosage increase until they reach steady-state.
-In patients receiving oral sotalol, monitor the QTc interval every 2 to 4 hours after each dose. In patients receiving an intravenous sotalol loading dose, monitor the QTc interval every 15 minutes during the infusion, then every 2 to 4 hours after the first oral dose in all patients and after the second oral dose in patients with CrCl 60 mL/minute or less.
-Allow at least 36 hours between dosage adjustments to attain steady-state plasma concentrations of sotalol in pediatric patients with age-adjusted normal renal function.

For the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation or atrial flutter who are currently in sinus rhythm:
Oral dosage:
Neonates: Reducing the usual starting dose recommended for a child 2 years or older (1.2 mg/kg/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information), is recommended by FDA-approved product labeling. Use similar calculations for dose titration. A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.
Infants and Children younger than 2 years: Reducing the usual starting dose recommended for a child 2 years or older (1.2 mg/kg/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information), is recommended by FDA-approved product labeling. Use similar calculations for dose titration. A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.
Children 2 to 5 years: 1.2 mg/kg/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 2.4 mg/kg/dose PO 3 times daily) is recommended by FDA-approved labeling. A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients.
Children and Adolescents 6 to 17 years: 1.2 mg/kg/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 2.4 mg/kg/dose PO 3 times daily) is recommended by FDA-approved labeling. A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients.
Intravenous dosage*:
Neonates 3 to 5 days: 0.32 mg/kg IV as a starting dose.
Neonates 6 to 8 days: 0.51 mg/kg IV as a starting dose.
Neonates 9 to 11 days: 0.69 mg/kg IV as a starting dose.
Neonates 12 to 13 days: 0.81 mg/kg IV as a starting dose.
Neonates 2 weeks: 0.9 mg/kg IV as a starting dose.
Neonates 3 weeks: 1 mg/kg IV as a starting dose.
Infants and Children 1 month to 5 years: 1.2 mg/kg IV as a starting dose.
Children 6 to 12 years: 1.1 mg/kg IV as a starting dose.
Adolescents: 0.95 mg/kg IV as a starting dose.

For the treatment of life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia:
Oral dosage:
Neonates: Reducing the usual starting dose recommended for a child 2 years or older (1.2 mg/kg/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information), is recommended by FDA-approved product labeling. Use similar calculations for dose titration. A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.
Infants and Children younger than 2 years: Reducing the usual starting dose recommended for a child 2 years or older (1.2 mg/kg/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information), is recommended by FDA-approved product labeling. Use similar calculations for dose titration. A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.
Children 2 to 5 years: 1.2 mg/kg/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 2.4 mg/kg/dose PO 3 times daily) is recommended by FDA-approved labeling. A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients.
Children and Adolescents 6 to 17 years: 1.2 mg/kg/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 2.4 mg/kg/dose PO 3 times daily) is recommended by FDA-approved labeling. A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients.
Intravenous dosage*:
Neonates 3 to 5 days: 0.32 mg/kg IV as a starting dose.
Neonates 6 to 8 days: 0.51 mg/kg IV as a starting dose.
Neonates 9 to 11 days: 0.69 mg/kg IV as a starting dose.
Neonates 12 to 13 days: 0.81 mg/kg IV as a starting dose.
Neonates 2 weeks: 0.9 mg/kg IV as a starting dose.
Neonates 3 weeks: 1 mg/kg IV as a starting dose.
Infants and Children 1 month to 5 years: 1.2 mg/kg IV as a starting dose.
Children 6 to 12 years: 1.1 mg/kg IV as a starting dose.
Adolescents: 0.95 mg/kg IV as a starting dose.

For the maintenance of sinus rhythm in patients with supraventricular arrhythmias*, including paroxysmal supraventricular tachycardia (PSVT)*, Wolff-Parkinson-White (WPW) syndrome*, junctional ectopic tachycardia*, and atrioventricular node reentrant tachycardia*:
Oral dosage:
Neonates: Reducing the usual starting dose recommended for a child 2 years or older (1.2 mg/kg/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information), is recommended by FDA-approved product labeling. Use similar calculations for dose titration. A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.
Infants and Children younger than 2 years: Reducing the usual starting dose recommended for a child 2 years or older (1.2 mg/kg/dose PO 3 times daily) by an age-specific reduction factor, which is determined by plotting the child's age on the manufacturer-provided logarithmic scale (see complete prescribing information), is recommended by FDA-approved product labeling. Use similar calculations for dose titration. A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study.
Children 2 to 5 years: 1.2 mg/kg/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 2.4 mg/kg/dose PO 3 times daily) is recommended by FDA-approved labeling. A target dose of 6 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients treated for atrial fibrillation/atrial flutter and 640 mg/day PO for adult patients treated for ventricular arrhythmias.
Children and Adolescents 6 to 17 years: 1.2 mg/kg/dose PO 3 times daily titrated up as needed at intervals of 36 hours or more (Max: 2.4 mg/kg/dose PO 3 times daily) is recommended by FDA-approved labeling. A target dose of 4 mg/kg/day PO given in 3 divided doses has been recommended based on the results of a population pharmacokinetic/pharmacodynamic study. An absolute maximum dose for pediatric patients has not been specified; FDA-approved labeling recommends a maximum dose of 320 mg/day PO for adult patients treated for atrial fibrillation/atrial flutter and 640 mg/day PO for adult patients treated for ventricular arrhythmias.

Therapeutic Drug Monitoring:
Dosage Adjustments for QTc Interval Prolongation

-Perform a baseline ECG to determine the QT interval.

Oral therapy

-Continuously monitor patients with each dosage increase until they reach steady-state.
-Monitor the QTc interval every 2 to 4 hours after each dose. If the QTc interval prolongs to 500 milliseconds or more, decrease the dose, lengthen the dosing interval, or discontinue the drug.
-Allow at least 36 hours between dosage adjustments to attain steady-state plasma concentrations in pediatric patients with age-adjusted normal renal function.

Intravenous loading
-In patients receiving an intravenous loading dose, monitor the QTc interval every 15 minutes during the infusion, then every 2 to 4 hours after the first oral dose in all patients and after the second oral dose in patients with CrCl 60 mL/minute or less.
-If the QTc interval prolongs to more than 500 milliseconds or increases 20% from baseline when initiating for an oral dose of 80 mg, discontinue sotalol; if initiating for an oral dose of 120 mg, discontinue sotalol and consider a lower dose. If reinitiation at a lower oral dose of 80 mg is desired, wait at least 1 day in patients with CrCl 60 mL/minute or less, or at least 3 days in patients with CrCl 31 to 59 mL/minute, or 7 days in patients with CrCl 16 to 30 mL/minute.

Maximum Dosage Limits:
-Neonates
See full prescribing information for age-specific dosing chart; target dose of 4 mg/kg/day PO has been recommended.
-Infants
See full prescribing information for age-specific dosing chart; target dose of 6 mg/kg/day PO has been recommended.
-Children
1 year: See full prescribing information for age-specific dosing chart; target dose of 6 mg/kg/day PO has been recommended.
2 to 5 years: 7.2 mg/kg/day PO recommended by FDA-approved labeling; target dose of 6 mg/kg/day PO has been recommended.
6 to 12 years: 7.2 mg/kg/day PO recommended by FDA-approved labeling; target dose of 4 mg/kg/day PO has been recommended.
-Adolescents
7.2 mg/kg/day PO recommended by FDA-approved labeling; target dose of 4 mg/kg/day PO has been recommended.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Sotalol has not been studied in pediatric patients with renal impairment; although lower doses, increased dosing intervals, and/or slower titration are recommended, specific dosage adjustments are not available. It will take longer to reach steady-state in pediatric patients with renal impairment; closely monitor heart rate and QTc interval. Recommended dose adjustments for adult patients are dependent on the formulation and/or indication:

Betapace/Betapace AF (all indications), Sorine (ventricular arrhythmias), and Sotylize (all indications):
CrCl 60 mL/minute or more: No dosage adjustment needed.
CrCl 30 to 59 mL/minute: Extend dosage interval to every 24 hours. Dose may be titrated after at least 5 doses.
CrCl 10 to 29 mL/minute: Extend dosage interval to every 36 to 48 hours according to clinical response. Dose may be titrated after at least 5 doses.
CrCl less than 10 mL/minute: Individualize dosage.

Sorine (atrial fibrillation/atrial flutter):
CrCl 60 mL/minute or more: No dosage adjustment needed.
CrCl 40 to 59 mL/minute: Extend dosage interval to every 24 hours. Dose may be titrated after at least 5 doses.
CrCl less than 40 mL/minute: Use is contraindicated.

Intermittent hemodialysis
Sorine for atrial fibrillation/atrial flutter is contraindicated in patients with CrCl less than 40 mL/minute. The half-life of sotalol is prolonged up to 69 hours in anuric patients. While sotalol is partially removed by hemodialysis, subsequent partial rebound in sotalol concentrations will occur once the dialysis session is completed. Both heart rate and QT interval, as well as efficacy (arrhythmia control), must be carefully monitored.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Sotalol is a racemic mixture of isomers. The levorotatory isomer has all of the beta-blocking activity and both the levorotatory and dextrorotatory isomers possess Class III antiarrhythmic activity. A reduction in resting heart rate due the beta-blocking effect occurs at doses of 90 mg/m2/day or more in pediatric patients, while Class III antiarrhythmic effects occur at doses of 210 mg/m2/day.

The beta-blocker activity of the drug increases sinus cycle length, decreases AV nodal conduction, and increases AV nodal refractoriness. Hemodynamic effects of sotalol include reduced heart rate and cardiac index as well as increased systemic vascular resistance, stroke volume, and pulmonary capillary wedge pressure. Significant reductions in systolic and diastolic blood pressure are also seen in hypertensive patients. In general, beta-blockers without intrinsic sympathomimetic activity (ISA), like sotalol, exert detrimental effects on LVH and the lipid profile.

The antiarrhythmic activity is exerted by a combination of Class II activity and Class III activity, which lengthens repolarization or the plateau phase of the action potential and lengthens the refractory period in all cardiac tissues. In addition, sotalol prolongs the QT interval (a Class III effect), which must be carefully monitored to avoid predisposing patients to proarrhythmic events.

Pharmacokinetics: Sotalol is administered orally or intravenously. Distribution occurs to a central (plasma) and peripheral compartment. Sotalol does not bind to plasma proteins and has poor penetration of the blood-brain barrier. Sotalol is not metabolized and is excreted primarily unchanged by the kidneys via glomerular filtration and tubular secretion. The plasma half-life in adult patients with normal renal function is 12 hours; in pediatric patients (3 days to 12 years), the mean half-life is 9.5 hours.

Affected cytochrome P450 isoenzymes and drug transporters: none


-Route-Specific Pharmacokinetics
Oral Route
After oral administration, bioavailability is 90% to 100%. Food reduces the rate of absorption by approximately 20%, but sotalol may be taken with or without food. Peak plasma concentrations after oral administration are reached within 2 to 3 hours in pediatric patients (3 days to 12 years) and 2.5 to 4 hours in adult patients. Steady-state plasma concentrations are reached within 1 to 2 days in pediatric patients and 2 to 3 days in adult patients.


-Special Populations
Pediatrics
Sotalol exposure was greater (+59%) in smaller pediatric patients (BSA less than 0.33 m2) compared to larger pediatric patients (BSA more than 0.33 m2) with BSA being the most important covariate for the pharmacokinetics. In a single-dose pharmacokinetic study, the clearance and Vd were 9 to 16 mL/minute and 6.6 to 14.39 L, respectively, for patients with a BSA less than 0.33 m2 vs. 96 to 186 mL/minute and 66.16 to 183.34 L, respectively, for patients with a BSA more than 1.22 to 1.48 m2. The AUC and Cmax of sotalol were 72% and 21.3% higher, respectively, in patients with a BSA less than 0.33m2 compared to those with a BSA of more than 0.33 m2 after a single oral dose of 30 mg/m2.

Neonates
The mean half-life, clearance, and Vd of sotalol in neonatal patients (n = 2) after a single oral dose of 30 mg/m2 were 8.4 hours, 11 mL/minute, and 7.79 L, respectively.

Infants and Children
The half-life, clearance, and Vd of sotalol increased with increasing age in infants and children (n = 31, age: 1 month to 12 years) after a single oral dose of 30 mg/m2. The mean half-life was 7.4 hours in patients 1 to 24 months, 9.1 hours in patients 2 to 6 years, and 9.2 hours in patients 7 to 12 years. The mean clearance and Vd were 32 mL/minute and 19.59 L in patients 1 to 24 months, 63 mL/minute and 49.91 L in patients 2 to 6 years, and 95 mL/minute and 76.45 L in patients 7 to 12 years, respectively.

Hepatic Impairment
Patients with hepatic impairment show no alteration in the clearance of sotalol.

Renal Impairment
There is a direct relationship between renal function and the elimination rate of sotalol. The half-life of sotalol is prolonged up to 69 hours in anuric patients.