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Sotalol Hydrochloride

Pronunciation

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

Warning(s)

  • 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 Clcr 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

Slideshow: Atrial Fibrillation - Stroke Prevention Guidelines & Treatment Options

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 VPCs1 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 Clcr.1 7 8 41 42 48

  • Calculate Clcr before initiating therapy.b c d

  • Estimate Clcr by using the following formula. If Scr 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 Clcr 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 (Clcr > 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 Clcr 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 Clcr <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 Clcr 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 Clcr 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 QTc 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

  • Clcr <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 Clcr, female gender, larger doses, reduction of heart rate, hypokalemia,1 3 41 b c presence of sustained ventricular tachycardia, excessive QTc interval prolongation, history of cardiomegaly or CHF.c Decrease risk by adjusting dosage based on Clcr and monitoring ECG for excessive QT interval prolongation.b c d

For ventricular arrhythmias, use particular caution if QTc interval is >500 msec on therapy, and seriously consider discontinuing if QTc interval is >550 msec, but use caution regardless of the QTc 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., QTc 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 age29 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 3 41

Interactions for Sotalol Hydrochloride

Drugs metabolized by CYP isoenzymes do not alter the pharmacokinetics of sotalol; sotalol does not induce or inhibit any CYP isoenzymes.b c d

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Amiodarone

May prolong refractorinessb c d

Concomitant use not recommended b c d

When transferring from amiodarone, withhold sotalol until QT interval has normalized1 41

Anesthetics, general (myocardial depressants)

Increased risk of hypotension, myocardial depression, and difficulty in restarting or maintaining a heart beat1 1 34 35 36 41

Antacids (aluminum- or magnesium-containing)

Decreased absorption of sotalol and reduced bradycardic effect1 41 46

Do not administer within 2 hours of sotalol; no effects on sotalol pharmacokinetics or pharmacodynamics observed when administered 2 hours after sotalol1 41 46

Antiarrhythmics, class I or class III

Prolongs QT intervalb c d

Use concomitantly with caution for ventricular arrhythmias1 38 39 41 42 b c d

Concomitant use not recommended for supraventricular arrhythmias;1 38 39 41 42 c withhold for at least 3 half-lives before initiating Betapace AF c

Antiarrhythmics, class Ia (e.g., disopyramide, quinidine, procainamide)

May prolong refractorinessb c d

Concomitant use not recommendedb c d

Antiarrhythmics, class Ib or Ic

Limited experience with concomitant useb c d

Antiarrhythmics, class II (β-blockers)

Possible additive class II (β-adrenergic receptor blocking) effectsb d

Use concomitantly with particular caution; use the lowest possible dosage of sotalol34 (see Major Surgery under Cautions)

Antidepressants, tricyclics

Prolongs QT interval38 39 41 42 b c d

Use concomitantly with caution for ventricular arrhythmias1 38 39 41 42 b d

Concomitant use not recommended for supraventricular arrhythmias38 39 41 42 c

Astemizole (no longer commercially available in the US)

Prolongs QT interval1 38 39 b c d

Use concomitantly with caution for ventricular arrhythmiasb c d 1 38 39 41 42

Concomitant use not recommended for supraventricular arrhythmias1 38 39 41 42 c

Bepridil

Prolongs QT intervalb c d

Use concomitantly with caution for ventricular arrhythmias1 38 39 41 42 b c d

Concomitant use not recommended for supraventricular arrhythmias1 38 39 41 42 c

Calcium-channel blocking agents

Possible additive effects on AV conduction or ventricular function; also potential for additive hypotensive effectsb c d

Use concomitantly with cautionb c d

Cisapride

Prolongs QT interval38 39 41 42

Use concomitantly with caution for ventricular arrhythmias1 38 39 c

Concomitant use not recommended for supraventricular arrhythmias1 38 39 41 42

Clonidine

β-blockers may potentiate rebound hypertension that occasionally occurs after discontinuance of clonidineb c d

When used concomitantly, use caution when discontinuing clonidineb c d

Digoxin

Possible increased proarrhythmic eventsb c d

Digoxin levels not substantially affected; unclear if proarrhythmias are the result of interaction or presence of CHF (known proarrhythmia risk factor)b c d

Guanethidine

Concomitant use may cause excessive decrease in resting sympathetic toneb c d

Monitor closely for evidence of hypotension or marked bradycardia that may produce syncopeb c d

Hydrochlorothiazide

No pharmacokinetic interaction observedb c d

Macrolides

Possible prolonged QT intervalb c d

Use concomitantly with caution for ventricular arrhythmias1 b c d

Concomitant use not recommended for supraventricular arrhythmias1 c

Phenothiazines

May prolong QT intervalb c d

Use concomitantly with caution for ventricular arrhythmias 1 38 39 41 42 b c d

Concomitant use not recommended for supraventricular arrhythmias1 38 39 41 42 c

Quinolone antibiotics (grepafloxacin, sparfloxacin)

May prolong QT interval38 39 41 42 b c d

Use concomitantly with caution for ventricular arrhythmias1 38 39 41 42 b c d

Concomitant use not recommended for supraventricular arrhythmias1 38 39 41 42 c

β2-Receptor agonists (e.g., salbutamol, terbutaline, isoprenaline)

Increased dosages of β2-receptor agonists may be requiredb c d

Reserpine

Concomitant use may cause excessive decrease in resting sympathetic toneb c d

Monitor closely for evidence of hypotension or marked bradycardia that may produce syncopeb c d

Terfenadine (no longer commercially available in the US)

Prolongs QT interval38 39 41 42

Use concomitantly with caution for ventricular arrhythmias1 38 39 41 42

Concomitant use not recommended for supraventricular arrhythmias38 39 41 42

Test, fluorimetric or photometric urinary metanephrine (screen for pheochromocytoma)

Presence of sotalol may falsely elevate urine metanephrine levelsb c d

To screen for pheochromocytoma, determine catecholamine levels with specific method (e.g., HPLC with solid phase extraction)b c d

Warfarin

No pharmacokinetic interaction observedb c d

Sotalol Hydrochloride Pharmacokinetics

Absorption

Bioavailability

90–100%.b c d

Food

Food reduces oral bioavailability by about 20%.1 41

Distribution

Plasma Protein Binding

Does not bind to plasma proteins.b c d

Elimination

Metabolism

Not metabolized.b c d

Elimination Route

Eliminated principally by glomerular filtration and tubular secretion; excreted principally unchanged in urine.b c d

Half-life

12 hours.b c d

Special Populations

Renal impairment may reduce clearance.b c d Elimination half-life in anuric patients may be prolonged (up to 69 hours).1 (See Renal Impairment under Dosage and Administration.)

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).b c d

Extemporaneous Solution

15–30°C at ambient humidity; stable for 3 months.b c d

Actions

  • Inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium and β2-adrenergic receptors within bronchial and vascular smooth muscle.1 2 7 8

  • Exhibits antiarrhythmic activity characteristic of class II antiarrhythmic agents.1 2 7 8 b c d

  • Does not exhibit membrane-stabilizing activity,1 8 but exhibits electrophysiologic effects characteristic of class III antiarrhythmic agents (e.g., prolongs repolarization and refractoriness without affecting conduction).1 2 7 8 12 13 14 15 b c d

  • Does not exhibit intrinsic sympathomimetic activity.1 8

  • Selectively inhibits the rapidly activating component of the potassium channel involved in repolarization of cardiac cells (i.e., the rapidly activated inward component of the delayed rectifier potassium current IKr) in vitro.12 13 14 15

  • Does not appear to block sodium channels at usual doses (although it may at relatively high doses).12 16 26 27

  • Racemic mixture of 2 optical isomers that both exhibit class III antiarrhythmic activity,1 7 11 14 15 but only the l-isomer exhibits β-blocking activity.1 7 11 14

Advice to Patients

  • Importance of taking at the same time(s) each day.c

  • Importance of not making up for a missed dose; resume the prescribed regimen at the next scheduled dose.41

  • Importance of taking the drug exactly as prescribed, and of contacting their clinician if a higher than prescribed dosage is taken.46

  • Importance (especially with ischemic heart disease) of not interrupting or discontinuing therapy without consulting clinician;1 41 46 patients should temporarily limit their physical activity when discontinuing therapy.24 25

  • Importance of immediately reporting to their clinician any conditions, concomitant therapy (e.g., diuretics), and/or manifestations associated with altered electrolyte balance (e.g., severe or prolonged diarrhea, unusual sweating, vomiting, loss of appetite, or thirst).41 46

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.a

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Sotalol Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

80 mg*

Betapace (scored)

Berlex

Betapace AF (scored)

Berlex

Sorine

Upsher-Smith

Sotalol Hydrochloride AF Tablets

120 mg*

Betapace (scored)

Berlex

Betapace AF (scored)

Berlex

Sorine

Upsher-Smith

Sotalol Hydrochloride AF Tablets

160 mg*

Betapace (scored)

Berlex

Betapace AF (scored)

Berlex

Sorine

Upsher-Smith

Sotalol Hydrochloride AF Tablets

240 mg*

Betapace (scored)

Berlex

Sorine

Upsher-Smith

Sotalol Hydrochloride AF Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Betapace 160MG Tablets (BAYER HEALTHCARE PHARMA): 30/$214.18 or 90/$621.52

Betapace 240MG Tablets (BAYER HEALTHCARE PHARMA): 30/$266.00 or 90/$797.99

Betapace 80MG Tablets (BAYER HEALTHCARE PHARMA): 60/$255.15 or 180/$725.57

Betapace AF 120MG Tablets (BAYER HEALTHCARE PHARMA): 60/$304.46 or 180/$877.77

Betapace AF 160MG Tablets (BAYER HEALTHCARE PHARMA): 60/$420.00 or 180/$1,228.54

Sotalol HCl 120MG Tablets (QUALITEST): 30/$15.99 or 60/$20.96

Sotalol HCl 80MG Tablets (SANDOZ): 90/$23.99 or 180/$36.97

Sotalol HCl (AF) 120MG Tablets (MYLAN): 30/$96.99 or 90/$263.98

Sotalol HCl (AF) 160MG Tablets (MYLAN): 30/$123.99 or 90/$325.96

Sotalol HCl (AF) 80MG Tablets (MYLAN): 100/$85.97 or 300/$199.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Betapace (sotalol hydrochloride) tablets prescribing information. Wayne, NJ; 2000 May.

2. Bigger JT, Hoffman BF. Antiarrhythmic drugs. In: Gilman AG, Rall TW, Nies AS, Taylor P, eds. The pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:867.

3. Soyka LF, Wirtz C, Spangenberg RB. Clinical safety profile of sotalol in patients with arrhythmias. Am J Cardiol. 1990; 65:74-81A.

4. Kehoe RF, Zheutlin TA, Dunnington CS et al. Safety and efficacy of sotalol in patients with drug-refractory sustained ventricular tachyarrhythmias. Am J Cardiol. 1990; 65:58-64A.

5. Amiodarone vs Sotalol Study Group. Multicentre randomized trial of sotalol vs amiodarone for chronic malignant ventricular tachyarrhythmias. Eur Heart J. 1989; 10:685-94. [PubMed 2676535]

6. Obel IWP, Jardine R, Haitus B et al. Efficacy of oral sotalol in reentrant ventricular tachycardia. Cardiovasc Drugs Ther. 1990; 4:613-8. [PubMed 2275891]

7. Singh BN. Antiarrhythmic actions of DL-sotalol in ventricular and supraventricular arrhythmias. J Cardiovasc Pharmacol. 1992; 20(Suppl 2):S75-90. [PubMed 1279313]

8. Berlex Laboratories. Betapace (sotalol hydrochloride) product monograph. Wayne, NJ; 1992 Dec.

9. Food and Drug Administration Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD: 1996 Jul.

10. Julian DG, Prescott RJ, Jackson FS et al. Controlled trial of sotalol for one year after myocardial infarction. Lancet. 1982; 1:1142-7. [IDIS 150431] [PubMed 6122937]

11. Anon. Sotalol for cardiac arrhythmias. Med Lett Drugs Ther. 1993; 35:27-8. [PubMed 8450806]

12. Mason JW, for the Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. N Engl J Med. 1993; 329:452-8. [IDIS 318403] [PubMed 8332150]

13. Jurkiewicz NK, Sanguinetti MC. Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent: specific block of rapidly activating delayed rectifier K+ current by dofetilide. Circ Res. 1993; 72:75-83. [PubMed 8417848]

14. Sanguinetti MC. Modulation of potassium channels by antiarrhythmic and antihypertensive drugs. Hypertension. 1992; 19:228-36. [PubMed 1548049]

15. Sanguinetti MC, Jurkiewicz NK. Two components of cardiac delayed rectifier K+ current: differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol. 1990; 96:195-215. [PubMed 2170562]

16. Singh BN, Vaughan Williams EM. A third class of anti-arrhythmic action: effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474. Br J Pharmacol. 1970; 39:675-87. [PubMed 5485144]

17. The Cardiac Arrhythmia Suppression Trial (CAST) investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989; 321:406-12. [IDIS 257848] [PubMed 2473403]

18. Ruskin JN. The Cardiac Arrhythmia Suppression Trial (CAST). N Engl J Med. 1989; 321:386-8. [IDIS 257833] [PubMed 2501683]

19. Echt DS, Liebson PR, Mitchell LB et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991; 324:781-8. [IDIS 279004] [PubMed 1900101]

20. Food and Drug Administration. Enkaid and Tambocor use in non-life-threatening arrhythmias halted. FDA Talk Paper. 1989 Apr 25.

21. Department of Health and Human Services. Background statement regarding encainide, flecainide, and moricizine. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1989 Apr.

22. The Cardiac Arrhythmia Suppression Trial II investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992; 327:227-33. [IDIS 299111] [PubMed 1377359]

23. Wyeth-Ayerst. Inderal (propranolol hydrochloride) tablets prescribing information. In: Physicians’ desk reference. 47th ed. Montvale, NJ: Medical Economics Company Inc; 1993:2571.

24. ICI Pharma. Tenormin (atenolol) tablets and I.V. injection prescribing information. In: Physicians’ desk reference. 47th ed. Montvale, NJ: Medical Economics Company Inc; 1993:1132.

25. Wyeth-Ayerst. Sectral (acebutolol hydrochloride) capsules prescribing information. In: Physicians’ desk reference. 47th ed. Montvale, NJ: Medical Economics Company Inc; 1993:2634.

26. Berlex Laboratories, Wayne, NJ: Personal communication.

27. Carmeliet E. Electrophysiologic and voltage clamp analysis of the effects of sotalol on isolated cardiac muscle and purkinje fibers. J Pharmacol Exp Ther. 1985; 323: 817-25.

28. MacNeil DJ, Davies RO, Deitchman D. Clinical safety profile of sotalol in the treatment of arrhythmias. Am J Cardiol. 1993; 72:44-50A.

29. Tipple M, Sandor G. Efficacy and safety of oral sotalol in early infancy. PACE Pacing Clin Electrophysiol. 1991; 14(11 Pt 2):2062-5. [PubMed 1721225]

30. Maragnès P, Tipple M, Fournier A. Effectiveness of oral sotalol for treatment of pediatric arrhythmias. Am J Cardiol. 1992; 69:751-4. [IDIS 292849] [PubMed 1546649]

31. O’Hare MF, Murnaghan GA, Russell CJ et al. Sotalol as a hypotensive agent in pregnancy. Br J Obstet Gynaecol. 1980; 87:814-20. [PubMed 7426541]

32. Wagner X, Jouglard J, Moulin M et al. Coadministration of flecainide acetate and sotalol during pregnancy: lack of teratogenic effects, passage across the placenta, and excretion in human breast milk. Am Heart J. 1990; 119:700-2. [IDIS 297335] [PubMed 1689933]

33. Hackett LP, Wojnar-Horton RE, Dusci LJ et al. Excretion of sotalol in breast milk. Br J Clin Pharmacol. 1990; 29:277-8. [IDIS 263882] [PubMed 2306424]

34. Sectral (acebutolol hydrochloride) prescribing information. In: Barnhart ER, publisher. Physicians’ desk reference. 45th ed. Oradell, NJ: Medical Economics Company Inc; 1991:2444-6.

35. Merck Sharp & Dohme. Blocadren prescribing information. West Point, PA; 1985 Apr.

36. Geigy Pharmaceuticals. Lopressor prescribing information. In: Huff BB, ed. Physicians’ desk reference. 41st ed. Oradell, NJ: Medical Economics Company Inc; 1987:956-60.

37. Martin DE, Kammerer WS. The hypertensive surgical patient: controversies in management. Surg Clin North Am. 1983; 63:1017-33. [PubMed 6138862]

38. Glaxo Wellcome. Raxar (grepafloxacin hydrochloride) tablets prescribing information. Research Triangle Park, NC; 1997 Nov.

39. Rhone-Poulenc Rorer Pharmaceuticals, Inc. Zagam (sparfloxacin) tablets prescribing information. Collegeville, PA; 1996 Nov.

40. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: apporaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9A-38A.

41. Berlex. Betapace AF (sotalol hydrochloride) tablets prescribing information. Wayne, NJ; 2000 Feb.

42. Benditt DG, Williams JH, Jin J et al. Maintenance of sinus rhythm with oral d,L-sotalol therapy in patients with symptomatic atrial fibrillation and/or flutter. Am J Cardiol. 1999; 84:270-7. [IDIS 433366] [PubMed 10496434]

43. Roy D, Talajic M, Dorian P et al. Amiodarone to prevent recurrence of atrial fibrillation. N Engl J Med. 2000; 342:913-20. [IDIS 442917] [PubMed 10738049]

44. Southworth MR, Zarembski D, Viana M et al. Comparison of sotalol versus quinidine for maintenance of sinus rhythm in patients with chronic atrial fibrillation. Am J Cardiol. 1999; 83:1629-32. [IDIS 430201] [PubMed 10392866]

45. De Paola AAV, Veloso HH. Efficacy and safety of sotalol versus quindine for the maintenance of sinus rhythm after conversion of atrial fibrillation. Am J Cardiol. 1999; 84:1033-7. [IDIS 439535] [PubMed 10569659]

46. Berlex. Betapace AF patient information: what you should know about Betapace AF (sotalol hydrochloride). Wayne, NJ; 2000 Feb.

47. Reimold SC, Cantillon CO, Friedman PL et al. Propafenone versus sotalol for suppression of recurrent atrial fibrillation. Am J Cardiol. 1993; 71:558-63. [IDIS 310595] [PubMed 8438741]

48. Anderson JL, Prystowsky EN. Sotalol: an important new antiarrhythmic. Am Heart J. 1999; 137:388-409. [IDIS 424916] [PubMed 10047618]

49. Chung MK, Schweikert RA, Wilkoff BL et al. Is hospital admission for initiation of antiarrhytmic therapy with sotalol for atrial arrhtymias required? Yield of in-hospital monitoring and prediction of risk for significant arrhtymia complications. J Am Coll Cardiol. 1998; 32:169-76. [IDIS 410416] [PubMed 9669266]

50. Marcus FI. Risks of initiating therapy with sotalol for treatment of atrial fibrillation. J Am Coll Cardiol. 1998; 32:177-80. [IDIS 410417] [PubMed 9669267]

51. Prystowsky EN, Benson W Jr, Fuster V et al. Management of patients with atrial fibrillation: a statement for healthcare professionals from the subcommittee on electrocardiography and electrophysiology, American Heart Association. Circulation. 1996; 93:1262-77. [IDIS 364782] [PubMed 8653857]

52. McClellan KJ, Markham A. Dofetilide: a review of its use in atrial fibrillation and atrial flutter. Drugs. 1999; 58:1043-59. [PubMed 10651390]

53. Singh S, Berk M, Yellen L et al. Restoration and maintenance of sinus rhythm reduces the frequency and severity of symptoms associated with atrial fibrillation and flutter. Pacing Clin Electrophysiol. 1998; 21:813.

54. Prystowsky EN. Prespectives and controversies in atrial fibrillation. Am J Cardiol. 1998; 82(suppl. 4A):3I-6I. [IDIS 410347] [PubMed 9737648]

55. Reiffel JA. Selecting an antiarrhythmic agent for atrial fibrillation should be a patient-specific, data-driven decision. Am J Cardiol. 1998; 82(Suppl. 8A):72N-81N. [IDIS 423286] [PubMed 9809904]

56. Kalus JS, Mauro VF. Doefetilide: a class III-specific antiarrhythmic agent. Ann Pharmacother. 2000; 34:44-56. [IDIS 439892] [PubMed 10669186]

57. Pfizer. Tikosyn (dofetilide) capsules prescribing information. New York, NY; 1999 Nov.

58. Singh BN. Antiarrhythmic drugs: a reorientation in light of recent developments in the control of disorders of rhythm. Am J Cardiol. 1998; 81(Suppl. 6A):3D-13D. [IDIS 404079] [PubMed 9537217]

59. Waldo AL. Management of atrial fibrillation: the need for AFFIRMative action. Am J Cardiol. 1999; 84:698-700. [PubMed 10498142]

60. Roden DM. Mechanisms and management of proarrhythmia. Am J Cardiol. 1998; 82(Suppl. 4A):49I-57I. [IDIS 410353] [PubMed 9737654]

61. Goldschlager N. Electrocardiography. In: Goldman L, Bennett JC, eds. Cecil textbook of medicine. 21st ed. Philadelphia: WB Saunders Company; 2000:185-91.

62. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). From website.

63. American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: advanced cardiovascular life support. Circulation. 2000;102(Suppl I):I86-171.

64. Fitton A, Sorkin EM. Sotalol: an udated review of its pharmacological properties and therapeutic use in cardiac arrhythmias. Drugs. 1993; 46:678-719. [PubMed 7506652]

65. Thadani U. Beta blockers in hypertension. Am J Cardiol. 1983; 52:10-5D.

66. Conolly ME, Kersting F, Dollery CT. The clinical pharmacology of beta-adrenoceptor-blocking drugs. Prog Cardiovasc Dis. 1976; 19:203-34. [PubMed 10600]

67. Shand DG. State-of-the-art: comparative pharmacology of the β-adrenoceptor blocking drugs. Drugs. 1983; 25(Suppl 2):92-9.

68. Breckenridge A. Which beta blocker? Br Med J. 1983; 286:1085-8. (IDIS 169422)

69. Anon. Choice of a beta-blocker. Med Lett Drugs Ther. 1986; 28:20-2. [PubMed 2869400]

70. Wallin JD, Shah SV. β-Adrenergic blocking agents in the treatment of hypertension: choices based on pharmacological properties and patient characteristics. Arch Intern Med. 1987; 147:654-9. [IDIS 227948] [PubMed 2881524]

71. McDevitt DG. β-Adrenoceptor blocking drugs and partial agonist activity: is it clinically relevant? Drugs. 1983; 25:331-8.

72. McDevitt DG. Clinical significance of cardioselectivity: state-of-the-art. Drugs. 1983; 25(Suppl 2):219-26.

73. Frishman WH. β-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med. 1981; 305:500-6. [IDIS 136600] [PubMed 6114433]

74. Thadani U, Davidson C, Chir B et al. Comparison of the immediate effects of five β-adrenoceptor-blocking drugs with different ancillary properties in angina pectoris. N Engl J Med. 1979; 300:750-5. [PubMed 581782]

75. Lewis RV, McDevitt DG. Adverse reactions and interactions with β-adrenoceptor blocking drugs. Med Toxicol. 1986; 1:343-61. [IDIS 239050] [PubMed 2878346]

76. Frishman WH. Clinical differences between beta-adrenergic blocking agents: implications for therapeutic substitution. Am Heart J. 1987; 113:1190-8. [IDIS 229873] [PubMed 2883867]

77. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211.

a. AHFS Drug Information 2004. McEvoy GK, ed. Sotalol. Bethesda, MD: American Society of Health-System Pharmacists; 2004:1784-90.

b. Berlex Laboratories. Betapace (sotalol hydrochloride) tablets prescribing information. Wayne, NJ; 2001 Nov.

c. Berlex Laboratories. Betapace AF (sotalol hydrochloride) tablets prescribing information. Montvale, NJ; 2004 Jan.

d. Par Pharmaceutical. Sotalol hydrochloride tablets prescribing information. Spring Valley, NY; 2002 Nov.

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