Sotalol Hydrochloride

Class: beta-Adrenergic Blocking Agents
VA Class: CV100
Chemical Name: Methanesulfonamide,N-[4-[1-Hydroxy-2-[(1-methylethyl)amino]ethyl]phenyl]monohydrochloride
Molecular Formula: C₁₂H₂₀N₂O₃S•ClH
CAS Number: 959-24-0
Brands: Betapace, Sorine

• 
  

  To minimize the risk of induced arrhythmias, patients initiated or re-initiated on sotalol should be placed in a facility that can provide cardiac resuscitation and continuous ECG monitoring for at least 3 days (on maintenance dosage).^{b c} (See Proarrhythmic Effects under Cautions.)

  
  


• 
  

  Calculate Cl_cr prior to dosing.^{b c} (See General under Dosage and Administration.)

  
  


• 
  

  Sotalol is marketed in the US under separate trade names for ventricular (Betapace) or atrial (Betapace AF) arrhythmias.^{a b c}

  
  


• 
  

  Betapace is not approved for atrial arrhythmias, and should not be substituted for Betapace AF because professional labeling differs (e.g., for cautions, precautions, and contraindications; patient instructions and advice; and dosage and administration) for the products, and only Betapace AF is distributed with patient labeling appropriate for patients with atrial arrhythmias.^{a b c}

  
  

Introduction

Nonselective β-adrenergic blocking agent; a methanesulfonanilide derivative.^{1 2 7 8 63 77}

Uses for Sotalol Hydrochloride

Ventricular Arrhythmias

Treatment to suppress and prevent recurrence of documented life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia);^{1 4 5 6 7 8 11 12 26} designated an orphan drug by FDA for such use.⁹

Alternative antiarrhythmic agent (to amiodarone) in the treatment of sustained, stable monomorphic ventricular tachycardia.⁷⁷

Because of sotalol’s arrhythmogenic potential, lack of evidence for improved survival, and risk of serious adverse effects (see Proarrhythmic Effects under Cautions), use for less severe arrhythmias, even if symptomatic, is notrecommended¹ and treatment of asymptomatic ventricular premature complexes (VPCs) should be avoided.^{1 3 4 7 8 12 14}

As effective as some other first-line antiarrhythmic agents (e.g., procainamide, quinidine) for the management of severe refractory arrhythmias.^{1 48 63 64}

Can reduce ventricular premature contractions (VPCs), paired VPCs, and nonsustained ventricular tachycardia in patients with frequent VPCs^{1 7 11 12} and can suppress the recurrence of ventricular tachyarrhythmias in patients with ventricular tachycardia and/or fibrillation.^{1 4 5 6 7 11 12}

Supraventricular Tachyarrhythmias

Betapace AF is used to maintain normal sinus rhythm in patients with highly symptomatic atrial fibrillation or flutter who are currently in sinus rhythm.^{41 63}

Only Betapace AF is approved for atrial fibrillation and flutter; Betapace or generic sotalol should not be substituted for Betapace AF.^{b d} (See Supraventricular Tachyarrhythmias under General in Dosage and Administration.)

Reserve for highly symptomatic atrial fibrillation because of the potential to cause life-threatening ventricular arrhythmias.^{41 42 51 56 57} (See Proarrhythmic Effects under Cautions.) Do not use for easily reversible paroxysmal atrial fibrillation (e.g., by the Valsalva maneuver).⁴¹

Alternative to direct-current (DC) cardioversion to control rhythm in atrial fibrillation or flutter in patients with preexcitation (Wolff-Parkinson-White [WPW]) syndrome† and preserved ventricular function when the duration of the arrhythmia is ≤48 hours.⁷⁷

Efficacy in preventing atrial fibrillation or flutter recurrences is comparable to that of quinidine or propafenone and less than that of amiodarone.^{43 44 45 47} Maintenance of sinus rhythm with oral sotalol does not appear to be related to either duration of previous episodes of atrial fibrillation (e.g., paroxysmal or persistent atrial fibrillation) or the degree of atrial enlargement.⁴⁷

Sotalol Hydrochloride Dosage and Administration

General

• 
  

  Individualize dosage carefully according to individual requirements and response, patient tolerance, renal function, and general condition and cardiovascular status.^{1 4 8 41}

  
  


• 
  

  Initiate therapy and subsequent dosage increases in an institutional setting that can provide cardiac resuscitation, continuous ECG monitoring, and calculations of Cl_cr.^{1 7 8 41 42 48}

  
  


• 
  

  Calculate Cl_cr before initiating therapy.^{b c d}

  
  


• 
  

  Estimate Cl_cr by using the following formula. If S_cr concentration is given in mcmol/L, divide the value by 88.4 (1 mg/dL = 88.4 mcmol/L).⁴¹

  
  


• 
  

  Clinical and ECG monitoring, including appropriate ambulatory ECG monitoring (e.g., Holter monitoring) is recommended.^{1 12 41} Monitor patients for at least 3 days on maintenance dosage following initiation, reinitiation, and, if necessary, dosage titration.^{1 7 8 41}

  
  

Ccr male = [(140 - age) × weight (in kg)] / [72 × serum creatinine (in mg/dL)]Ccr female = 0.85 × Ccr male

Ventricular Arrhythmias

• 
  

  Gradual upward titration and appropriate monitoring for efficacy (e.g., PES, Holter) and safety (e.g., QT interval, heart rate, electrolytes) prior to dose escalation should reduce the risk of precipitating arrhythmias.¹ (See Proarrhythmic Effects under Cautions.)

  
  

Supraventricular Tachyarrhythmias

• 
  

  Only Betapace AF is approved for atrial fibrillation and flutter; Betapace or generic sotalol should not be substituted for Betapace AF; only Betapace AF is distributed with patient information appropriate for atrial arrhythmias.^{b d} Patients with a history of symptomatic atrial fibrillation or flutter receiving Betapace for maintenance of normal sinus rhythm should be transferred to Betapace AF because of appreciable differences in labeling (i.e., patient information, dosage and administration, safety information).^{b d}

  
  


• 
  

  Determine QT interval prior to initiating therapy and 2–4 hours after each dose during inpatient dosage-titration phase.⁴¹

  
  


• 
  

  If baseline QRS interval is >100 msec, adjust dosage using the JT interval; use is contraindicated if baseline JT interval is ≥330 msec.⁴¹ (See Contraindications under Cautions.)

  
  


• 
  

  Adequate anticoagulation is recommended prior to initiating therapy.^{c 51 54 63} (See Adjunctive Antithrombotic Therapy under Dosage and Administration.)

  
  


• 
  

  Do not discharge from institutional setting within 12 hours of pharmacologic or electrical cardioversion to normal sinus rhythm.⁴¹

  
  


• 
  

  For maintenance therapy, measure Cl_cr and QT interval periodically as medically warranted.⁴¹

  
  

Adjunctive Antithrombotic Therapy

• 
  

  Patients with persistent (i.e., >48 hours’ duration) atrial fibrillation (e.g., geriatric patients <75 years of age, those with hypertension, atrial and ventricular dysfunction, diabetes mellitus, recent heart failure, prior history of stroke or transient ischemic attacks) must be adequately anticoagulated (INR of 2–3), generally for at least 3 weeks before administration of antiarrhythmic agents and continued for 4 weeks after cardioversion.^{51 54 59}

  
  


• 
  

  In marginal patients, in addition to anticoagulation, consultation with a cardiologist and diagnostic procedures to exclude atrial thrombi recommended.⁴¹

  
  


• 
  

  In patients who require earlier cardioversion, use transesophageal echocardiography to identify atrial thrombi; patients without preexisting thrombi may receive anticoagulation with heparin, cardioversion within 1–2 days of initiation of anticoagulation, followed by administration of warfarin for 4 weeks.^{51 54}

  
  


• 
  

  Aspirin may be administered to prevent stroke in patients who cannot tolerate anticoagulation.⁵¹

  
  

Transfer from Antiarrhythmic Agents

• 
  

  A transition period is recommended for patients being transferred from another antiarrhythmic agent to sotalol.^{1 41}

  
  


• 
  

  In general, withdraw current antiarrhythmic agent and delay initiation of sotalol for at least 2–3 elimination half-lives of the other drug; monitor carefully during this period.^{1 41}

  
  


• 
  

  In patients being transferred from amiodarone, withhold sotalol until the QT interval has normalized.^{1 41}

  
  


• 
  

  Sotalol has been initiated in some patients prior to discontinuance of IV lidocaine without ill effect.^{1 41}

  
  


• 
  

  Transfer patients with a history of symptomatic atrial fibrillation or flutter who are receiving Betapace for maintenance of sinus rhythm to Betapace AF because of appreciable differences in labeling (i.e., patient information, dosage and administration, safety information) provided by the manufacturer.^{41 c}

  
  

Administration

Oral Administration

Administer orally with or without food, at approximately the same time(s) each day.^{1 41 46}

Do not administer aluminum oxide and magnesium hydroxide-containing antacids within 2 hours of administration of sotalol.^{1 41 46} (See Specific Drugs and Laboratory Tests under Interactions.)

May give in 2 or 3 divided doses daily; administration > twice daily usually is not necessary since the drug has a long terminal elimination half-life.¹ (See Elimination under Pharmacokinetics.)

Extemporaneous Oral Solution

Prepare sotalol 5 mg/mL solution using Simple Syrup with 0.1% sodium benzoate (Syrup N.F.).^{b c}

Add 5 tablets (120 mg each) to 120 mL of Simple Syrup in an oversized (180 mL) plastic (PET) prescription bottle to allow more effective shaking of the mixture.^{b c}

May add tablets intact to syrup, add syrup to tablets, or crush tablets (making sure to add entire quantity of tablet powder to syrup).^{b c}

If intact tablets are used, shake the mixture to wet tablets, allow to hydrate for at least 2 hours, then shake intermittently over another 2 hours until dispersion of fine particles is obtained; may hydrate overnight to simplify disintegration process.^{b c}

If tablets are crushed, shake until a dispersion of fine particles is obtained.^{b c}

Resulting preparation contains 5 mg/mL of sotalol hydrochloride in solution with suspended inactive solid particles (water-insoluble tablet ingredients); shake well before each use to assure dose of inactive tablet particles remains constant.^{b c}

Dosage

Prior to dose escalation, monitor for efficacy (e.g., PES, Holter) and safety (e.g., QT interval, heart rate, electrolytes) to reduce the risk of precipitating arrhythmias.¹ (See Proarrhythmic Effects under Cautions.)

Pediatric Patients

Dosage for children ≤2 years of age must be calculated by multiplying the recommended initial dosage for children ≥2 years of age (i.e., 30 mg/m² 3 times daily) by an age-dependent factor obtained from the age and factor graph in the manufacturer prescribing information.^{b c} (See Table 1.)

For children ≥2 years of age, normalize initial and incremental dosage based on body surface area.^{b c}

The manufacturer states that reaching plasma concentrations occurring within the therapeutic adult range is an appropriate guide.^{b c}

Oral

To obtain dosages for ages not mentioned in this table, see age/factor graph in manufacturer prescribing information

See age/factor graph in manufacturer prescribing information for age-dependent factor

Table 1. Initial Pediatric Dosages (age-adjusted)bc

Age	Initial dosage calculation (dosage for children ≥2 years of age [30 mg/m2] multiplied by an age-dependent factor)	Total Initial Daily Dosage
Neonates about 1 week of age	30 mg/m2 X 0.3 (9 mg/m2) three times daily	27 mg/m2 daily
Infants 1 month of age	30 mg/m2 X 0.68 (20 mg/m2) three times daily	60 mg/m2 daily
Infants 20 months of age	30 mg/m2 X 0.97 (29.1 mg/m2) three times daily	87.3 mg/m2 daily
Children ≥2 years of age	30 mg/m2 X 1 (30 mg/m2) three times daily	90 mg/m2 daily (equivalent to initial 160 mg daily adult dosage)

Children ≤2 years of age: dosage may be increased using similar calculations (e.g., multiply dose by age-dependent factor).^{b c} (See age and factor graph in manufacturer prescribing information).^{b c}

Children ≥2 years of age: dosage may be increased gradually up to 60 mg/m² three times daily (equivalent to 360 mg daily adult dosage).^{b c}

Allow at least 36 hours between dose increments to attain steady state plasma concentrations.^{b c}

Time to reach steady-state plasma concentration is longer in neonates and infants, and decreases with increasing age up to about 2 years of age; in neonates, time to steady-state may be a week or longer.^{b c}

Adults

Life-threatening Ventricular Arrhythmias

Oral

Initially, 80 mg twice daily.¹ If necessary, dosage may be increased gradually after appropriate evaluation to 240–320 mg daily given in divided doses; allow 3 days between dosing increments.¹

Usual maintenance dosage: 160–320 mg daily in divided doses.¹

May increase to 480–640 mg daily in divided doses, but risk of potentially serious toxicity increases with such doses; use only when potential benefits outweigh the possible risks.¹ (See Proarrhythmic Effects under Cautions.)

Supraventricular Arrhythmias

Individualize dosage carefully according to renal function and QT interval.⁴¹ Use not recommended if baseline QT interval is >450 msec.^{41 42} (See Contraindications under Cautions.)

If a dose is missed, take only the next scheduled dose; do not double a dose.^{41 46}

Initiation and Dosage Titration

Initially, 80 mg twice daily in adults with normal renal function (Cl_cr > 60 mL/minute) and a near normal QT interval (≤450 msec).^{41 42 61} If arrhythmia is well controlled (e.g., no recurrences of atrial fibrillation or flutter) during first 3 days of inpatient monitoring and QT interval is <500 msec, may discharge patient on current treatment with an adequate supply to allow uninterrupted therapy until the outpatient prescription is filled.⁴¹

Discontinue or reduce dosage if QT interval is ≥500 msec during inpatient dosage-titration phase.^{26 41 42}

If atrial fibrillation or flutter recur during initiation, may increase dosage gradually to 120 or 160 mg twice daily (the maximum recommended dosage), allowing 3 days of inpatient monitoring between dosing increments.^{26 41 47 50}

For recurrences after completion of inpatient monitoring despite therapy at lower than maximum recommended dosage, readmit to an institutional setting and increase dosage gradually after appropriate evaluation to maximum of 160 mg twice daily, allowing inpatient monitoring for an additional 3 days for each increase in dosage.^{26 41}

In a large dose-ranging study, 120 mg twice daily was most effective in delaying the time to a recurrence of atrial fibrillation or flutter.^{41 42 45}

Maintenance Dosage

If QT interval is ≥520 msec or if JT interval is ≥430 msec in patients with a QRS interval >100 msec, reduce dosage and monitor until the QT or JT interval returns to <520 or 430 msec, respectively.⁴¹

Discontinue therapy if QT interval is ≥520 msec at the lowest maintenance dosage of 80 mg twice daily.⁴¹

Prescribing Limits

Adults

Life-threatening Ventricular Arrhythmias

Oral

Maximum 480–640 mg daily in divided doses.¹

Supraventricular Arrhythmias

Oral

Maximum 320 mg daily (160 mg twice daily);^{26 41} increased incidence of torsades de pointes with higher dosages.^{41 47} (See Proarrhythmic Effects under Cautions.)

Special Populations

Renal Impairment

Adjust dosage if Cl_cr is <60 mL/minute.^{1 26 41}

Dosage in children with renal impairment has not been established.^{b c} However, decreased dosage or increased dosage intervals are recommended for all age groups with renal impairment.^{b c}

Ventricular Arrhythmias

Oral

Initially, in adults, 80 mg; modify frequency according to Table 2.^{1 26 b}

Table 2. Dosing Interval in Renal Impairment

Clcr (mL/minute)	Dosing Interval (hours)
>60	12
30–59	24
10–29	36–48
<10	individualize

Increase dosage only after a given dose has been repeated at least 5 or 6 times at the dosing interval appropriate for the degree of renal impairment.^{1 8}

Administer with extreme caution in patients with renal failure undergoing hemodialysis; possible increased elimination half-life in anuric patients.¹ (See Special Populations under Pharmacokinetics.)

Supraventricular Arrhythmias

Contraindicated if Cl_cr <40 mL/minute.^{41 42 46} (See Contraindications under Cautions.)

If a dose is missed, take only the next scheduled dose; do not double a dose (may increase risk of sotalol-induced arrhythmias).^{41 46}

Initiate therapy in a setting that can provide dosage adjustments based on Cl_cr and continuous ECG monitoring (e.g., QT interval) for at least 5–6 days (when steady-state plasma concentrations are reached) after initiation.^{41 42}

Initiation and Dosage Titration

Initially, 80 mg once daily for Cl_cr of 40–60 mL/minute.⁴¹ If arrhythmia is well controlled (e.g., no recurrences of atrial fibrillation or flutter) during inpatient monitoring of the first 5–6 doses and the QT interval is <500 msec, may discharge patient on current treatment.⁴¹

Reduce dosage or discontinue if QT_c interval is prolonged to ≥500 msec after first or subsequent daily dosage.⁴¹

If recurrences of atrial fibrillation or flutter occur during initiation of therapy at a daily dosage of 80 mg, may increase dosage gradually after appropriate evaluation to 120 or 160 mg once daily, allowing inpatient monitoring for 5–6 doses between dosing increments.^{26 41 47}

For recurrences after completion of inpatient monitoring despite therapy at lower than maximum recommended dosage, readmit to an institutional setting and increase dosage gradually after appropriate evaluation to a maximum of 160 mg once daily, allowing inpatient monitoring for 5–6 doses between dosing increments.⁴¹

>160 mg once daily is not recommended⁴¹ (increased incidence of torsades de pointes).⁴¹

Geriatric Patients

Modification of dosage based on age alone is not necessary.¹

Because geriatric patients may have decreased renal function and because patients with renal impairment may be at increased risk of sotalol-induced toxicity, monitor closely and adjust dosage accordingly.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Sotalol Hydrochloride

Contraindications

• 
  

  Bronchial asthma.^{1 41 42 43 44 46 47 48 49 b c d}

  
  


• 
  

  Sinus bradycardia (<50 bpm while awake).^{1 41 42 43 44 46 47 48 49 b c d}

  
  


• 
  

  Sick sinus syndrome or second or third degree AV block unless a functioning pacemaker is present.^{1 41 42 43 44 45 46 47 48 49 b c d}

  
  


• 
  

  Congenital or acquired long QT interval syndromes.^{1 41 42 43 44 46 47 48 49 b c d}

  
  


• 
  

  Baseline QT interval >450 msec (JT interval of ≥330 msec if QRS >100 msec).^{41 42 c}

  
  


• 
  

  Cardiogenic shock.^{1 41 42 43 44 46 47 48 49 b c d}

  
  


• 
  

  Uncontrolled heart failure.^{1 41 42 43 44 46 47 48 49 b c d}

  
  


• 
  

  Hypokalemia (<4 mEq/L) in patients with supraventricular arrhythmias (atrial fibrillation or flutter);^{41 42 46 c} do not use in hypokalemia or hypomagnesemia prior to correction of imbalance in patients with ventricular arrhythmias.^{1 41 42 45 48 b d}

  
  


• 
  

  Cl_cr <40 mL/minute in patients with supraventricular arrhythmias (atrial fibrillation or flutter).^c

  
  


• 
  

  Known hypersensitivity to sotalol or any ingredient in the formulation.^{1 41 42 43 44 46 47 48 49 b c d}

  
  

Warnings/Precautions

Warnings

Mortality

Substantially increased mortality (total, short- and long-term) and nonfatal cardiac arrest rates occurred with encainide or flecainide studied for treatment of recent MI, mild-to-moderate left ventricular dysfunction, and asymptomatic or mildly symptomatic ventricular arrhythmias.^{1 17 18 19 20 21 b d} Relevance to other patient populations (e.g., without recent MI or with life-threatening ventricular arrhythmias)^{1 17 18 19 22} and other class I antiarrhythmic agents currently is not known.¹

Sotalol is devoid of class I antiarrhythmic activity; no evidence of excess mortality associated with sotalol dosages up to 320 mg daily studied in patients with recent MI (but not necessarily concurrent ventricular arrhythmias).^{1 10 41}

Possible early (within 2 weeks) sudden death with initial (i.e., not titrated) dosage of 320 mg daily, and with high dosages (320 mg twice daily).^{1 41} Use with caution; titrate dosage carefully during the first 2 weeks following an acute MI, particularly with markedly impaired ventricular function.¹ Observe usual precautions regarding heart failure, avoidance of hypokalemia, bradycardia, or prolonged QT interval.⁴¹

Proarrhythmic Effects

Can cause serious ventricular arrhythmias, principally torsades de pointes, associated with prolonged QT interval; risk increases progressively with QT interval prolongation.^{1 6 8 28 b c}

Arrhythmogenic events occur most often during the initial 7 days of instituting sotalol therapy or an upward dosage adjustment.^{1 3 4 7 41 47}

QT interval prolongation is dose-related.^{41 1 41 b c}

Increased torsades de pointes risk with decreased Cl_cr, female gender, larger doses, reduction of heart rate, hypokalemia,^{1 3 41 b c} presence of sustained ventricular tachycardia, excessive QT_c interval prolongation, history of cardiomegaly or CHF.^c Decrease risk by adjusting dosage based on Cl_cr and monitoring ECG for excessive QT interval prolongation.^{b c d}

For ventricular arrhythmias, use particular caution if QT_c interval is >500 msec on therapy, and seriously consider discontinuing if QT_c interval is >550 msec, but use caution regardless of the QT_c interval because of multiple risk factors for torsades de pointes.^{b d}

Cardiac Failure

Possible precipitation of CHF.^{1 41} Use contraindicated in patients with overt CHF.^{1 41 46} Use cautiously in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics);^{1 41 46} sotalol and cardiac glycosides slow AV conduction.^{1 b d} Use with caution in patients with inadequate cardiac function and when initiating therapy if there is any evidence of left ventricular dysfunction.^{1 41}

Electrolyte Disturbances

Electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia) may exaggerate the degree of QT prolongation and increase the risk of torsades de pointes.^{1 3 41} Use not recommended until these imbalances are corrected.^{1 41 42 45 48}

Carefully monitor electrolyte and acid-base balance in patients with severe or prolonged diarrhea and in patients receiving diuretics concomitantly.^{1 45 47 50}

Bradycardia

Potential bradycardia in patients treated for supraventricular arrhythmias; associated with increased risk of torsades de pointes.^c

Abrupt Withdrawal of Therapy

Abrupt withdrawal may exacerbate angina symptoms and/or precipitate MI and ventricular arrhythmias in patients with CAD, or may precipitate thyroid storm in patients with thyrotoxicosis.^{1 41} Avoid abrupt discontinuance.^{1 41} Gradually decrease dosage over a period of 1–2 weeks, particularly in patients with CAD or suspected thyrotoxicosis and monitor patients carefully; consider temporary use of another β-blocker if appropriate.^{1 41 46} If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly (at least temporarily).^{1 23 24 25 41}

Bronchospastic Disease

Possible inhibition of bronchodilation produced by endogenous catecholamines; use generally not recommended in patients with bronchospastic disease.^{1 41 43 46 77}

Use caution with nonallergic bronchospasm (e.g., chronic bronchitis, emphysema);^{1 41} use smallest effective dosage to minimize inhibition of bronchodilation produced by endogenous or exogenous catecholamine stimulation of β₂-adrenergic receptors.^{1 41}

History of Anaphylactic Reactions

Possible increased reactivity to a variety of allergens; patients may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions.^{1 41}

Major Surgery

Possible increased risks associated with general anesthesia (e.g., severe, protracted hypotension; difficulty in restarting or maintaining a heart beat);^{1 34 35 36 41} however, withdrawal of β-adrenergic blocking agent prior to major surgery is controversial.^{1 34 35 36 37 41} Use with caution in patients undergoing major surgery involving general anesthesia.^{1 34 41}

Effects of sotalol can be reversed by administration of β-agonists (e.g., dobutamine, isoproterenol).^{34 77}

Use particular caution if patients continue to receive sotalol prior to surgery and if anesthetics that depress the myocardium are used (e.g., cyclopropane, ether, trichloroethylene); use the lowest possible dosage of sotalol.³⁴ (See Specific Drugs and Laboratory Tests under Interactions.)

Diabetes Mellitus

Possible decreased signs and symptoms of acute hypoglycemia (e.g., tachycardia); use caution in patients with diabetes mellitus (especially labile diabetes) or history of episodic spontaneous hypoglycemia.^{1 41 c}

Sick Sinus Syndrome

Potential for sinus bradycardia, pauses, or arrest; use only with extreme caution in patients with sick sinus syndrome associated with symptomatic arrhythmia.^{1 41}

Possible increased risk of torsades de pointes in patients with atrial fibrillation and sinus node dysfunction, especially after cardioversion.^{41 49 50} Use contraindicated in patients with atrial fibrillation or flutter and sick sinus syndrome, unless a functioning pacemaker is present.^{41 45 46 48}

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked.^{1 41} Possible thyroid storm if therapy is abruptly withdrawn; closely monitor patients having or suspected of developing thyrotoxicosis.^{1 41} (See Abrupt Withdrawal of Therapy under Cautions.)

General Precautions

Other Precautions

Shares the toxic potentials of other nonselective β-adrenergic blocking agents; observe usual precautions of these agents.^{1 3 4 5 6 7 8 41}

Specific Populations

Pregnancy

Category B.^{b c d}

Lactation

Distributed into milk.^{b c d} Discontinue nursing or the drug.^{b c d}

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 26 41 b c d}

Class III electrophysiologic and β-blocking effects, pharmacokinetics and the relationship between plasma concentrations and effects (e.g., QT_c intervals, resting heart rate) have been evaluated in children 3 days to 12 years of age.^{b c d}

Has been effective in a limited number of infants <3 months of age^{29 30} and children <18 years of age³⁰ for supraventricular arrhythmias; ^{29 30} less effective for ventricular arrhythmias.³⁰

Mild sinus bradycardia occurred in most infants;²⁹ fatigue occurred in several children and required discontinuance in a few.³⁰

Recommendations on sotalol use are not included in current guidelines for cardiopulmonary resuscitation and emergency cardiovascular care in pediatric advanced life support (PALS).^{63 77}

Geriatric Use

Insufficient experience in geriatric patients to determine whether safety and efficacy in geriatric patients differ from safety and efficacy in younger adults; however clinical trials of sotalol included many patients >50 years of age.^{3 4 5 6 8}

Overall risk of cardiac death was associated with increasing age in clinical trials.⁸

Monitor closely and adjust dosage accordingly due to greater frequency of decreased renal function and increased risk of toxicity observed in the elderly.¹

Renal Impairment

Clearance is decreased depending on degree of renal impairment.^{b c} (See Special Populations under Pharmacokinetics.)

Dosage adjustments necessary based on degree of renal impairment.^{a b c d} (See Renal Impairment under Dosage and Administration.)

Partially removed by dialysis; plasma concentrations usually rebound when dialysis is completed.¹ Monitor closely for efficacy of arrhythmia control and adverse effects (changes in heart rate and/or QT interval).¹

Common Adverse Effects

Sinus bradycardia (heart rate <50 bpm),^{1 3 4 5 28 41} arrhythmogenic effects,^{1 41} chest pain,^{1 3 28} palpitation,^{1 3 28} hypotension,¹ fatigue,^{1 3 28 41 42} dizziness,^{1 3 28 42} asthenia,^{1 3 28} lightheadedness,¹ dyspnea,^{1 3 28 41} nausea,^{1 3 41} vomiting.¹