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Sotalol Hydrochloride

Pronunciation

Pronunciation: SOE-ta-lol HYE-droe-KLOR-ide
Class: Beta-adrenergic blocking agent

Trade Names

Betapace
- Tablets 80 mg
- Tablets 120 mg
- Tablets 160 mg
- Tablets 240 mg

Betapace AF
- Tablets 80 mg
- Tablets 120 mg
- Tablets 160 mg

Sotalol Hydrochloride
- Injection, solution, concentrate 15 mg/mL

Apo-Sotalol (Canada)
CO Sotalol (Canada)
Gen-Sotalol (Canada)
PMS-Sotalol (Canada)
ratio-Sotalol (Canada)
Sandoz Sotalol (Canada)

Pharmacology

Blocks beta receptors, which primarily affect heart (slows rate), lungs (reduces function), and vascular musculature (decreases BP), and prolongs the duration of cardiac action potential.

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Pharmacokinetics

Absorption

Oral bioavailability is 90% to 100% and T max is 2.5 to 4 h. Absorption was reduced approximately 20% compared to fasting when administered with a standard meal. Steady state is reached after 2 to 3 days (oral) and 1 to 2 days (IV).

Distribution

Does not bind to plasma proteins and crosses the blood-brain barrier poorly.

Metabolism

Sotalol is not metabolized.

Elimination

Half-life is 12 h (oral) and 9.5 h (IV). It is excreted unchanged predominantly via the kidney.

Special Populations

Renal Function Impairment

Lower doses are necessary in renal function impairment.

Hepatic Function Impairment

Patients with hepatic function impairment show no alteration in sotalol Cl.

Indications and Usage

Betapace

Management or prevention of life-threatening ventricular arrhythmias.

Betapace AF

Maintenance of normal sinus rhythm in patients with highly symptomatic atrial fibrillation/atrial flutter (AFIB/AFL).

Sotalol IV

Maintenance of normal sinus rhythm in patients with symptomatic AFIB/AFL; treatment of documented life-threatening ventricular arrhythmias.

Contraindications

Betapace

Hypersensitivity to beta-blockers; greater than first-degree heart block; CHF unless secondary to tachyarrhythmia treatable with beta-blockers; overt cardiac failure; sinus bradycardia; cardiogenic shock; bronchial asthma or bronchospasm, including severe COPD; congenital or acquired long QT syndromes.

Betapace AF , sotalol IV

Sinus bradycardia (less than 50 bpm during waking hours); sick sinus syndrome or second- and third-degree AV block (unless a functioning pacemaker is present); congenital or acquired QT syndromes; baseline QT interval greater than 450 msec; cardiogenic shock; uncontrolled heart failure; hypokalemia (less than 4 mEq/L); CrCl less than 40 mL/min; bronchial asthma; previous evidence of hypersensitivity to sotalol.

Dosage and Administration

Do not substitute Betapace for Betapace AF because of significant differences in labeling (eg, patient package insert, dosing administration, safety information).

Betapace
Adults

PO 80 mg twice daily; may increase up to 320 mg/day in 2 or 3 divided doses. Patients with a history of symptomatic AFIB/AFL currently receiving Betapace should be transferred to Betapace AF because of the significant differences in labeling.

Betapace AF
Adults

PO Initiate therapy at 80 mg twice daily if CrCl is greater than 60 mL/min, and 80 mg once daily if the CrCl is 40 to 60 mL/min. Begin continuous ECG monitoring with QT interval measurements 2 to 4 h after each dose. If the 80 mg dose level is tolerated and QT interval remains less than 500 msec after at least 3 days, the patient may be discharged. Alternatively, during hospitalization, if 80 mg level does not reduce the frequency of relapse of AFIB/AFL and is tolerated without excessive QT interval prolongation (ie, greater than 520 msec), after following the patient for 3 days, the dose level may be increased to 120 mg (once or twice daily depending on CrCl). The max recommended dosage in patients with CrCl greater than 60 mL/min is 160 mg twice daily.

Children 2 years of age and older

PO 30 mg/m 2 3 times a day initially (approximately equivalent to the initial 160 mg total oral daily dose in adults). Titrate to a maximum of 60 mg/m 2 (approximately equivalent to the 360 mg total daily dose for adults) based on clinical response, heart rate, and QTc. Allow at least 36 h between dose increases.

Children 2 years of age and younger

PO Reduce the dosage provided above by a factor that depends heavily upon age. Please refer to the graph in the Betapace package insert. For example, for a child 20 mo of age, the initial starting dose would be 30 mg/m 2 × 0.97 = 29.1 mg/m 2 , administered orally 3 times daily.

Sotalol Injection
AFIB/AFL Adults

IV 75 mg infused over 5 h twice daily if CrCl is greater than 60 mL/min or once daily if CrCl is 40 to 60 mL/min, initially. If after at least 3 days the 75 mg dose does not reduce the frequency of relapses of symptomatic AFIB/AFL and is tolerated without excessive (to greater than 500 msec) QTc prolongation, increase the dosage to 112.5 mg once or twice daily depending on the CrCl. An additional increase to 150 mg once or twice daily depending on the CrCl may be made after at least 3 days if necessary and if previous dose is tolerated without excessive QTc prolongation (greater than 520 msec).

Ventricular Arrhythmias Adults

IV 75 mg infused over 5 h twice daily if CrCl is greater than 60 mL/min or once daily if CrCl is 40 to 60 mL/min, initially. If after at least 3 days, the 75 mg dose does not reduce the frequency of relapses of symptomatic AFIB/AFL and is tolerated without excessive (to greater than 500 msec) QTc prolongation, increase the dosage to 112.5 mg once or twice daily depending on the CrCl. Additional increases in increments of 75 mg/day may be made every 3 days if necessary. Dosages as high as 225 to 300 mg once or twice daily depending on CrCl have been used in patients with refractory life-threatening arrhythmias.

Conversion From Oral to IV Sotalol

The 80 mg oral dose is equivalent to 75 mg of sotalol IV. 120 mg orally is equivalent to 112.5 mg of sotalol IV. 160 mg orally is equivalent to 150 mg of sotalol IV.

General Advice

  • Therapy with Betapace AF or sotalol injection must be initiated and, if necessary, titrated in a setting that provides continuous ECG monitoring and personnel trained in the management of serious ventricular arrhythmias. Monitor patients in this way for a minimum of 3 days on the maintenance dose and do not discharge within 12 h of electrical or pharmacological conversion to normal sinus rhythm.
  • Sotalol injection is for IV infusion only; not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
  • Infuse sotalol IV over 5 h.
  • Dilute solution for injection prior to administration following manufacturer's guidelines using sodium chloride 0.9% injection, dextrose 5% injection, or Ringer's lactate injection.

Storage/Stability

Store at 59° to 86°F. Protect from light.

Drug Interactions

Alpha-1 adrenergic blocking agents (eg, prazosin)

The severity and duration of hypotension following the first dose of an alpha-1 adrenergic blocker may be enhanced in patients receiving sotalol. Patients already receiving an alpha-1 adrenergic blocker may not be affected by addition of sotalol. Use with caution, closely monitoring the clinical response of the patient.

Aluminum salts

Bioavailability of sotalol may be decreased, reducing the pharmacologic effects. Administration of aluminum salts at least 2 h after sotalol may minimize this interaction.

Anticholinesterases (eg, neostigmine)

Severe or prolonged bradycardia may occur in patients receiving sotalol. Use with caution.

Beta-2 receptor stimulants (eg, albuterol, isoproterenol, terbutaline)

Beta-2 receptor stimulant efficacy may be reduced. Increased dosage may be needed when sotalol is coadministered.

Calcium channel blockers (eg, diltiazem, verapamil)

Increased risk of hypotension; possible increased effect on AV conduction or ventricular function. Use with caution. Monitor the clinical response of the patient.

Clonidine

May enhance or reverse antihypertensive effects; may increase clonidine rebound hypertension. Use with caution.

Cocaine

Pharmacologic and cardiotoxic effects of cocaine may be increased by sotalol. Avoid coadministration in patients with cocaine-induced myocardial ischemia or infarction.

Digoxin

Proarrhythmic events are more common when digoxin and sotalol are coadministered. Use with caution.

Drugs that prolong the QT interval (eg, antiarrhythmic agents [eg, amiodarone, disopyramide, dofetilide, procainamide, quinidine], arsenic trioxide, chloroquine, chlorpromazine, cisapride, dolasetron, droperidol, fluconazole, halofantrine, haloperidol, macrolide and related antibiotics [eg, clarithromycin, telithromycin], maprotiline, mefloquine, mesoridazine, methadone, nilotinib, paliperidone, pentamidine, perflutren, phosphodiesterase type 5 inhibitors [eg, sildenafil], pimozide, propafenone, quinolone antibiotics [ie, gatifloxacin, moxifloxacin], tacrolimus, tetrabenazine, thioridazine, tricyclic antidepressants [eg, doxepin, nortriptyline], tyrosine kinase receptor antagonists [eg, lapatinib], ziprasidone

The risk of CV toxicity, including prolongation of the QT interval and fatal cardiac arrhythmias (torsades de pointes), may be increased. Coadministration is not recommended.

Epinephrine

Increased BP and bradycardia may occur as a result of unopposed alpha-adrenergic effects of epinephrine. Avoid coadministration.

Guanethidine, reserpine

Increased risk of hypotension or bradycardia. Monitor the clinical response of the patient.

Insulin, meglitinide antidiabetic agents (eg, repaglinide), oral sulfonylurea hypoglycemic agents (eg, glyburide, tolbutamide)

Hyperglycemia; symptoms of hypoglycemia may be masked. Antidiabetic dosage may require adjustments.

NSAIDs (ie, ibuprofen, indomethacin, naproxen, piroxicam)

Some agents may impair antihypertensive effect. Monitor BP and adjust the sotalol dose as needed.

Theophyllines (eg, aminophylline, theophylline)

The bronchodilating effect of theophyllines may be impaired. Avoid coadministration.

Laboratory Test Interactions

May interfere with glucose or insulin tolerance tests; may result in falsely elevated urinary levels of metanephrine.

Adverse Reactions

Cardiovascular

Bradycardia, chest pain (16%); palpitation (14%); subjective rhythm disturbance (10%); ECG abnormal (7%); hypotension (6%); heart failure, nonanginal cardiac chest pain, proarrhythmia, syncope (5%); presyncope, torsade de pointes (4%); automatic implantable cardiac defibrillator discharge, CV disorder, vasodilation (3%); angina pectoris, atrial rhythm disturbance, hypertension (2%); worsened ventricular tachycardia (1%).

CNS

Dizziness, fatigue (20%); asthenia (13%); headache, light-headedness (12%); sleep problem (8%); perspiration (6%); weakness (5%); altered consciousness, anxiety, depression, insomnia, paresthesia (4%); mood change (3%); stroke (1%); paralysis (postmarketing).

Dermatologic

Rash (5%).

EENT

Vision problem (5%).

GI

Nausea/vomiting (10%); diarrhea (7%); dyspepsia (6%); abdominal pain (4%); abdominal distension, appetite disorder, colon problem, dyspepsia/heartburn (3%); flatulence (2%).

Genitourinary

GU disorder, sexual dysfunction (3%).

Hematologic

Eosinophilia, leukopenia, thrombocytopenia (postmarketing).

Hepatic

Elevated serum liver enzymes.

Metabolic-Nutritional

Edema (8%); abnormal lab (4%); weight change (2%); elevated blood glucose levels; hyperlipidemia (postmarketing).

Musculoskeletal

Extremity pain (7%); pain, musculoskeletal (4%); back pain, chest pain, (3%).

Respiratory

Dyspnea (21%); pulmonary problem (8%); upper respiratory tract problem (5%); cough, tracheobronchitis, upper respiratory tract infection (3%); asthma (2%); pulmonary edema (postmarketing).

Miscellaneous

Hyperhidrosis (5%); fever, infection (4%); cold sensation, localized pain (3%); bleeding, influenza (2%).

Precautions

Warnings

Life-threatening proarrhythmia

To minimize risk of induced arrhythmia, initiate or reinitiate therapy for at least 3 days in facility that can provide cardiac resuscitation and ECG monitoring.

Sotalol can cause life-threatening ventricular tachycardia associated with QT-interval prolongation. Do not initiate sotalol therapy if the baseline QTc is longer than 450 msec. If the QTc interval prolongs to 500 msec or greater, reduce the dose, prolong the duration of IV infusion, or discontinue the medicine.

Do not substitute Betapace for Betapace AF . Betapace does not have an atrial fibrillation indication or package insert information for patient.


Monitor

Perform a baseline ECG to determine QT interval and measure and normalize serum potassium and magnesium levels before initiating therapy. Measure serum creatinine and calculate an estimated CrCl to establish the appropriate dosing interval for sotalol. During initiation and titration, monitor QT interval after the completion of each infusion. Monitor heart rate frequently and monitor hemodynamics in patients with marginal cardiac compensation as deterioration in cardiac performance may occur.


Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Hypersensitivity

May occur in patients withdrawn from beta-blockers. Patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge and may be unresponsive to usual doses of epinephrine.

Renal Function

Alteration of dosage interval and reduced daily dose are advised.

Abrupt withdrawal

Has been associated with adverse effects, including exacerbation of angina pectoris, arrhythmias, and MI; gradually decrease dose over 1 to 2 wk. Carefully monitor patients, especially those with ischemic heart disease, and consider temporary use of an alternative beta-blocker if appropriate.

Anesthesia

Severe hypotension and difficulty in restoring and maintaining cardiac rhythm after anesthesia have been reported.

Bradycardia

May occur and increase the risk of torsades de pointes.

CHF

New or worsening heart failure has occurred. Administer cautiously in patients with CHF controlled by digitalis and diuretics.

Diabetic patients

Drug may mask signs and symptoms of hypoglycemia (eg, tachycardia, BP changes). Drug may potentiate insulin-induced hypoglycemia.

Electrolyte disturbances

Do not use in patients with uncorrected hypokalemia or hypomagnesemia. Give special attention to electrolyte and acid base balance in patients experiencing severe or prolonged diarrhea.

Hypotension

Significant reductions in both systolic and diastolic BP may occur.

Nonallergic bronchospasm

Give drug with caution in patients with bronchospastic disease.

Thyrotoxicosis

May mask clinical signs (eg, tachycardia) of developing or continuing hyperthyroidism. Abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm.

Overdosage

Symptoms

Bradycardia, bronchospasm, cardiac asystole, CHF, hypoglycemia, hypotension, premature ventricular complexes, prolongation of QT interval, torsades de pointes, ventricular tachycardia.

Patient Information

  • Explain importance of not discontinuing drug suddenly, and advise that dosage will be decreased over 1 to 2 wk.
  • Explain that drug may mask signs and symptoms of hypoglycemia.
  • Teach patient to take pulse daily and to notify health care provider if pulse is less than 60.
  • Tell patient to call health care provider if adverse reaction occurs.
  • Instruct patients to report syncopal events or new presyncopal symptoms.

Copyright © 2009 Wolters Kluwer Health.

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