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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(SOE ta lole)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of documented ventricular arrhythmias (ie, sustained ventricular tachycardia), that in the judgment of the physician are life-threatening; maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation and atrial flutter who are currently in sinus rhythm. Manufacturer states substitutions should not be made for Betapace AF® since Betapace AF® is distributed with a patient package insert specific for atrial fibrillation/flutter.
Injection: Substitution for oral sotalol in those who are unable to take sotalol orally
Use: Unlabeled
Fetal tachycardia; alternative antiarrhythmic for the treatment of atrial fibrillation in patients with hypertrophic cardiomyopathy (HCM)
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events were not observed in the initial animal reproduction studies; therefore, the manufacturer classifies sotalol as pregnancy category B. Sotalol crosses the placenta and is found in amniotic fluid. In a cohort study, an increased risk of cardiovascular defects was observed following maternal use of beta-blockers during pregnancy. Intrauterine growth restriction (IUGR), small placentas, as well as fetal/neonatal bradycardia, hypoglycemia, and/or respiratory depression have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth should be available. Untreated chronic maternal hypertension and pre-eclampsia are also associated with adverse events in the fetus, infant, and mother; however, sotalol is currently not recommended for the initial treatment of hypertension in pregnancy. Because sotalol crosses the placenta in concentrations similar to the maternal serum, it has been used for the treatment of fetal atrial flutter or fetal supraventricular tachycardia without hydrops. The clearance of sotalol is increased during the third trimester of pregnancy, but other pharmacokinetic parameters do not significantly differ from nonpregnant values.
Lactation
Enters breast milk/consider risk:benefit (AAP rates "compatible"; AAP 2001 update pending)
Breast-Feeding Considerations
Sotalol is excreted into breast milk in concentrations higher than those found in the maternal serum. Although adverse events in nursing infants have not been observed in case reports, close monitoring for bradycardia, hypotension, respiratory distress, and hypoglycemia is advised. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.
Contraindications
Hypersensitivity to sotalol or any component of the formulation; bronchial asthma; sinus bradycardia; second- or third-degree AV block (unless a functioning pacemaker is present); congenital or acquired long QT syndromes; cardiogenic shock; uncontrolled heart failure
Additional contraindications: Betapace AF® and the injectable formulation: Baseline QTc interval >450 msec; bronchospastic conditions; Clcr <40 mL/minute; serum potassium <4 mEq/L; sick sinus syndrome
Warnings/Precautions
Boxed warnings:
• Dose initiation/increases: See “Other warnings/precautions” below.
• Proarrhythmia: See “Concerns related to adverse effects” below.
• Product interchange: See “Dosage form specific issues” below.
• Renal impairment: See “Disease-related concerns” below.
Concerns related to adverse effects:
• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Bradycardia/hypotension: May cause bradycardia and hypotension.
• Proarrhythmic effects: [U.S. Boxed Warning]: Sotalol injection: Sotalol can cause life-threatening ventricular tachycardia associated with QT interval prolongation (ie, torsade de pointes). Do not initiate if baseline QTc interval is >450 msec. If QTc exceeds 500 msec during therapy, reduce the dose, prolong the infusion duration, or discontinue use. If while on oral sotalol therapy baseline QTc interval is >500 msec, use I.V. sotalol with particular caution; serious consideration should be given to reducing the dose or discontinuing I.V. sotalol when QTc exceeds 520 msec. QTc prolongation is directly related to the concentration of sotalol; reduced creatinine clearance, female gender, and large doses increase the risk of QTc prolongation and subsequent torsade de pointes. Monitor and adjust dose to prevent QTc prolongation.
Disease-related concerns:
• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
• Electrolyte imbalances: Correct electrolyte imbalances before initiating (especially hypokalemia and hypomagnesemia).
• Heart failure (HF): Use with caution in patients with compensated heart failure and monitor for a worsening of the condition.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may worsen disease.
• Myocardial infarction: Use with caution within the first 2 weeks post-MI especially in patients with markedly impaired ventricular function (experience limited).
• Peripheral vascular disease (PVD) and Raynaud's disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease. Use with caution and monitor for progression of arterial obstruction.
• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.
• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
• Renal impairment: [U.S. Boxed Warning]: Adjust dosing interval based on creatinine clearance to decrease risk of proarrhythmia; QT interval prolongation is directly related to sotalol concentration. Creatinine clearance must be calculated with dose initiation and dose increases. Betapace AF® and the injectable formulation are contraindicated in patients with Clcr <40 mL/minute.
• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If thyrotoxicosis is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.
Concurrent drug therapy issues:
• Calcium channel blockers: Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur.
• Cardiac glycosides: Use with caution in patients receiving digoxin; bradycardia or heart block can occur.
• Inhaled anesthetic agents: Use with caution in patients receiving inhaled anesthetic agents known to depress myocardial contractility.
• QTc-prolonging drugs: Concurrent use with other QTc-prolonging drugs (including Class I and Class III antiarrhythmics) and use within 3 months of discontinuing amiodarone is generally not recommended. To reduce the chance of excessive QTc-prolongation, withhold QTc-prolonging drugs for at least 3 half-lives (or 3 months for amiodarone) before initiating sotalol.
Special populations:
• Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.
Dosage form specific issues:
• Product interchange: [U.S. Boxed Warning]: Betapace® should not be substituted for Betapace® AF; Betapace® AF is distributed with an educational insert specifically for patients with atrial fibrillation/flutter.
Other warnings/precautions:
• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.
• Dose initiation/increases: [U.S. Boxed Warning]: Manufacturer recommends initiation (or reinitiation) and dose increases be done in a hospital setting with continuous monitoring and staff familiar with the recognition and treatment of life-threatening arrhythmias. Some experts will initiate therapy on an outpatient basis in a patient without heart disease or bradycardia, who has a baseline uncorrected QT interval <450 msec, and normal serum potassium and magnesium levels; close ECG monitoring during this time is necessary. ACC/AHA guidelines for management of atrial fibrillation also recommend that for outpatient initiation the patient not have risk factors predisposing to drug-induced ventricular proarrhythmia (Fuster, 2006). Dosage should be adjusted gradually with 3 days between dosing increments to achieve steady-state concentrations, and to allow time to monitor QT intervals.
• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.
Adverse Reactions
Note: No clinical experience with I.V. sotalol; however, since exposure is similar between I.V. and oral sotalol, adverse reactions are expected to be similar.
>10%:
Cardiovascular: Bradycardia (13% to 16%), chest pain (3% to 16%), palpitation (14%)
Central nervous system: Fatigue (20%), dizziness (20%), lightheadedness (12%)
Neuromuscular & skeletal: Weakness (13%)
Respiratory: Dyspnea (21%)
1% to 10%:
Cardiovascular: Edema (8%), abnormal ECG (7%), hypotension (6%), proarrhythmia (5%), syncope (5%), CHF (5%), torsade de pointes (dose related; 1% to 4%), peripheral vascular disorders (3%), ventricular tachycardia worsened (1%), QTc interval prolongation (dose related)
Central nervous system: Headache (8%), sleep problems (8%), mental confusion (6%), anxiety (4%), depression (4%)
Dermatologic: Itching/rash (5%)
Endocrine & metabolic: Sexual ability decreased (3%)
Gastrointestinal: Nausea/vomiting (10%), diarrhea (7%), stomach discomfort (3% to 6%), flatulence (2%)
Genitourinary: Impotence (2%)
Hematologic: Bleeding (2%)
Neuromuscular & skeletal: Extremity pain (7%), paresthesia (4%), back pain (3%)
Ocular: Visual problems (5%)
Respiratory: Upper respiratory problems (5% to 8%), asthma (2%)
<1% (Limited to important or life-threatening): Alopecia, clouded sensorium, cold extremities, diaphoresis, emotional lability, eosinophilia, fever, hyperlipidemia, incoordination, leukopenia, myalgia, paralysis, phlebitis, photosensitivity reaction, pruritus, pulmonary edema, Raynaud's phenomenon, red crusted skin, serum transaminases increased, skin necrosis after extravasation, thrombocytopenia, vertigo, xerostomia
Postmarketing and/or case reports: Bronchiolitis obliterans with organized pneumonia, leukocytoclastic vasculitis, retroperitoneal fibrosis
Metabolism/Transport Effects
None known.
Drug Interactions
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Risk D: Consider therapy modification
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk D: Consider therapy modification
Alpha2-Agonists: Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy
Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Risk D: Consider therapy modification
Eribulin: May enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class III). Risk C: Monitor therapy
Fingolimod: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III). Management: Obtain baseline ECG (if not recently available) if initiating fingolimod during treatment with class III antiarrhythmic agents. Monitor for bradycardia and AV block. The Canadian labeling recommends avoiding concomitant use of these agents. Risk C: Monitor therapy
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Risk X: Avoid combination
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Indacaterol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Lidocaine: Beta-Blockers may increase the serum concentration of Lidocaine. Risk C: Monitor therapy
Lidocaine (Systemic): Beta-Blockers may decrease the metabolism of Lidocaine (Systemic). Risk C: Monitor therapy
Lidocaine (Topical): Beta-Blockers may decrease the metabolism of Lidocaine (Topical). Risk C: Monitor therapy
Lidocaine (Topical): May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III). Antiarrhythmic Agents (Class III) may increase the serum concentration of Lidocaine (Topical). This mechanism specifically applies to amiodarone and dronedarone. Risk C: Monitor therapy
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk X: Avoid combination
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
QuiNIDine: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk D: Consider therapy modification
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Food: Sotalol peak serum concentrations may be decreased if taken with food.
Herb/Nutraceutical: Avoid ephedra (may worsen arrhythmia).
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). To prepare sotalol infusion, see manufacturer's prescribing information.
Compatibility
Stable in D5W, NS, or lactated Ringer's.
Mechanism of Action
Beta-blocker which contains both beta-adrenoreceptor-blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) properties
Class II effects: Increased sinus cycle length, slowed heart rate, decreased AV nodal conduction, and increased AV nodal refractoriness Sotalol has both beta1- and beta2-receptor blocking activity. The beta-blocking effect of sotalol is a noncardioselective (half maximal at about 80 mg/day and maximal at doses of 320-640 mg/day). Significant beta-blockade occurs at oral doses as low as 25 mg/day.
Class III effects: Prolongation of the atrial and ventricular monophasic action potentials, and effective refractory prolongation of atrial muscle, ventricular muscle, and atrioventricular accessory pathways in both the antegrade and retrograde directions. Sotalol is a racemic mixture of d- and l-sotalol; both isomers have similar Class III antiarrhythmic effects while the l-isomer is responsible for virtually all of the beta-blocking activity. The Class III effects are seen only at oral doses ≥160 mg/day
Pharmacodynamics/Kinetics
Onset of action: Oral: Rapid, 1-2 hours; when administered I.V. for ongoing VT over 5 minutes, onset of action is ~5-10 minutes (Ho, 1994)
Duration: 8-16 hours
Absorption: Oral: Decreased 20% to 30% by meals compared to fasting
Distribution: Vd: 1.2-2.4 L/kg
Protein binding: None
Metabolism: None
Bioavailability: Oral: 90% to 100%
Half-life elimination: 12 hours; Children: 9.5 hours; terminal half-life decreases with age <2 years (time to steady state may be ≥1 week in neonates); increases with renal dysfunction
Time to peak, serum: Oral: 2.5-4 hours
Excretion: Urine (as unchanged drug)
Dosage
Baseline QTc interval and creatinine clearance must be determined prior to initiation. Sotalol should be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment. Proarrhythmic events can occur after initiation of therapy and with each upward dosage adjustment.
Children: Oral: The safety and efficacy of sotalol in children have not been established
Note: Dosing per manufacturer, based on pediatric pharmacokinetic data; wait at least 36 hours between dosage adjustments to allow monitoring of QT intervals
≤2 years: Dosage should be adjusted (decreased) by plotting of the child's age on a logarithmic scale; see graph or refer to manufacturer's package labeling.
>2 years: Initial: 90 mg/m2/day in 3 divided doses; may be incrementally increased to a maximum of 180 mg/m2/day
Adults:
I.V.: Note: The effects of the initial I.V. dose must be monitored and the dose titrated either upward or downward, if needed, based on clinical effect, QTc interval, or adverse reactions.
Symptomatic atrial fibrillation/flutter, ventricular arrhythmias: Substitution for oral sotalol: Initial dose: 75 mg infused over 5 hours twice daily
Dose adjustment: If the frequency of relapse does not reduce and excessive QTc prolongation does not occur, may increase to 112.5 mg twice daily. For ventricular arrhythmias, may increase dose every 3 days in increments of 75 mg/day.
Dose range for symptomatic atrial fibrillation/flutter: Usual therapeutic dose: 112.5 mg twice daily; maximum dose: 150 mg twice daily
Dose range for ventricular arrhythmias: Usual therapeutic dose: 75-150 mg twice daily; maximum dose: 300 mg twice daily.
Hemodynamically stable monomorphic VT, ongoing (unlabeled use): 1.5 mg/kg over 5 minutes (ACLS, 2010); Note: Clinical trial employed standard dose of 100 mg (Ho, 1994).
Conversion from oral sotalol to I.V. sotalol:
80 mg oral equivalent to 75 mg I.V.
120 mg oral equivalent to 112.5 mg I.V.
160 mg oral equivalent to 150 mg I.V.
Oral:
Ventricular arrhythmias (Betapace®, Sorine®):
Initial: 80 mg twice daily
Dose may be increased gradually to 240-320 mg/day; allow 3 days between dosing increments in order to attain steady-state plasma concentrations and to allow monitoring of QT intervals
Most patients respond to a total daily dose of 160-320 mg/day in 2-3 divided doses.
Some patients, with life-threatening refractory ventricular arrhythmias, may require doses as high as 480-640 mg/day; however, these doses should only be prescribed when the potential benefit outweighs the increased of adverse events.
Atrial fibrillation or atrial flutter (Betapace AF®): Initial: 80 mg twice daily. If the frequency of relapse does not reduce and excessive QTc prolongation does not occur after 3 days, the dose may be increased to 120 mg twice daily; may further increase to 160 mg twice daily if response is inadequate and QTc prolongation is not excessive.
Elderly: Age does not significantly alter the pharmacokinetics of sotalol, but impaired renal function in elderly patients can increase the terminal half-life, resulting in increased drug accumulation
Dosage adjustment for toxicity:
QTc ≥500 msec during initiation period:
Betapace AF®: Reduce dose or discontinue sotalol
Injectable formulation: Reduce dose, decrease infusion rate, or discontinue sotalol
QTc ≥520 msec (or JT interval ≥430 msec if the QRS >100 msec) during maintenance therapy (Betapace AF®, injectable formulation): Reduce dose and carefully monitor QTc until <520 msec. If QTc interval ≥520 msec on the lowest maintenance dose, discontinue sotalol.
QTc ≥550 msec (Betapace®, Sorine®): Reduce dose or discontinue sotalol.
Dosage adjustment in renal impairment: Adults: Impaired renal function can increase the terminal half-life, resulting in increased drug accumulation. Sotalol (Betapace AF®, injectable formulation) is contraindicated per the manufacturers for treatment of atrial fibrillation/flutter in patients with a Clcr <40 mL/minute.
Ventricular arrhythmias (Betapace®, Sorine®):
Clcr >60 mL/minute: Administer every 12 hours
Clcr 30-60 mL/minute: Administer every 24 hours
Clcr 10-29 mL/minute: Administer every 36-48 hours
Clcr <10 mL/minute: Individualize dose
Atrial fibrillation/flutter (Betapace AF®):
Clcr >60 mL/minute: Administer every 12 hours
Clcr 40-60 mL/minute: Administer every 24 hours
Clcr <40 mL/minute: Use is contraindicated
Note: The manufacturer of the injectable formulation recommends adjustment similar to that used for Betapace AF®. However, the injectable formulation may be used for either indication.
Dialysis: Hemodialysis would be expected to reduce sotalol plasma concentrations because sotalol is not bound to plasma proteins and does not undergo extensive metabolism; administer dose postdialysis or administer supplemental 80 mg dose; peritoneal dialysis does not remove sotalol; supplemental dose is not necessary
Administration: Oral
Administer without regard to meals.
Administration: I.V.
Substitution for oral: Administer over 5 hours.
Hemodynamically stable monomorphic VT: Administer I.V. push over 5 minutes; use with caution due to increased risk of adverse events (eg, bradycardia, hypotension, torsade de pointes) (ACLS, 2010)
Monitoring Parameters
Serum creatinine, magnesium, potassium; heart rate, blood pressure; ECG (eg, QTc interval, PR interval). If baseline QTc >450 msec (or JT interval >330 msec if QRS over 100 msec), sotalol is contraindicated.
For oral use (Betapace AF®) during initiation period, monitor QTc interval 2-4 hours after each dose. If QTc interval ≥500 msec, discontinue use; if QTc interval <500 msec after 3 days (after fifth or sixth dose if patient receiving once-daily dosing), patient may be discharged on current regimen. Monitor QTc interval periodically thereafter.
For I.V. use, measure QTc interval after completion of each infusion.
Test Interactions
May falsely increase urinary metanephrine values when fluorimetric or photometric methods are used; does not interact with HPLC assay with solid phase extraction for determination of urinary catecholamines
Dietary Considerations
May be taken without regard to meals.
Patient Education
Take pulse daily (prior to medication) and follow prescriber's instruction about holding of medication. If you have diabetes, monitor serum sugar closely; drug may alter glucose tolerance or mask signs of hypoglycemia. May cause fatigue, dizziness, lightheadedness, postural hypotension, alteration in sexual performance (reversible), nausea, vomiting, or diarrhea. Report immediately any chest pain, palpitations, irregular heartbeat; swelling of extremities, weight gain, respiratory difficulty, new cough, or unusual fatigue; persistent nausea, vomiting, or diarrhea; or unusual muscle weakness.
Geriatric Considerations
Since elderly frequently have Clcr <60 mL/minute, attention to dose, creatinine clearance, and monitoring is important. Make dosage adjustments at 3-day intervals or after 5-6 doses at any dosage.
Additional Information
Pharmacokinetics in children are more relevant for BSA than age.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Monitor QTc interval closely and adjust dose as appropriate, especially in patients with renal impairment. Risk of torsade de pointes with sotalol is highest in women, patients with baseline QT interval >450 msecs, renal impairment, significant bradycardia, or concomitant heart failure (see Contraindications). Avoid concomitant use of QT-prolonging agents.
Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.
Evidence-Based Information:
Surgery: The ACCF/AHA 2009 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery recommend beta-blockers be continued in patients undergoing surgery who are receiving beta-blockers to treat ACCF/AHA Class I guideline indications such as angina, symptomatic arrhythmias, or hypertension (Class I recommendation).
The majority of published trials suggest a benefit of perioperative beta-blocker use during noncardiac surgery especially in high-risk patients; however, more recent clinical trials have not shown a benefit to perioperative beta-blockade for noncardiac surgery especially when higher fixed-dose regimens are employed (Juul, 2006; POISE study group, 2008; Yang, 2006). Therefore, the guidelines suggest that perioperative beta-blocker therapy titrated to goal heart rate and blood pressure may be beneficial to patients undergoing intermediate risk (eg, carotid endarterectomy, prostate surgery) or vascular surgeries who have coronary artery disease identified or are at high cardiac risk (Class IIa recommendation). High cardiac risk is defined as having >1 of the following clinical risk factors: History of ischemic heart disease, compensated or prior heart failure, cerebrovascular disease, diabetes mellitus, or renal insufficiency (serum creatinine: >2 mg/dL). The use of beta-blockers is uncertain in patients undergoing intermediate risk or vascular surgery with ≤1 clinical risk factor (Class IIb recommendation). Based on available evidence, beta-blockers should be started days to weeks before elective surgery in selected patients when possible and titrated to adequate heart rate control (eg, between 60-80 beats per minute) while avoiding clinically significant bradycardia and hypotension. Routine administration of high fixed-dose beta-blockade without dose titration is not useful and may be harmful to beta-blocker naïve patients undergoing noncardiac surgery.
Cardiovascular Considerations
As with other antiarrhythmics, sotalol is proarrhythmic (eg, torsade de pointes) and therapy with the d-isomer (d-sotalol) increased mortality, presumably due to arrhythmias, in patients with heart failure and myocardial infarction. It is therefore prudent to carefully select and monitor patients on sotalol and avoid its use in patients with a history of heart failure or myocardial infarction.
Ventricular Tachycardia (VT): I.V.: The ACLS 2010 guidelines now recommend the use of sotalol for hemodynamically stable monomorphic VT (Class IIb recommendation). The use of I.V. sotalol in this setting is based on 2 studies. The first compared lidocaine with sotalol for sustained VT not causing cardiac arrest in 33 patients. Patients were randomized to either lidocaine 100 mg (n=17) or sotalol 100 mg (n=16) I.V. over 5 minutes. If the patient was in persistent VT 15 minutes after administration of study drug, they were crossed over to the other drug. Sotalol, after ECG rhythm analysis, was found to be significantly more effective than lidocaine in terminating VT (69% vs 20%, p=0.006). No patients experienced torsade de pointes. Two patients experienced sinus bradycardia post conversion from VT (Ho, 1994). The other study (Ho, 1995) evaluated the use of sotalol in patients (n=109) with a history of spontaneous and inducible sustained VT to determine effect on right ventricular effective refractory period (RVERP). Sotalol 1.5 mg/kg over 5 minutes was administered to the first 57 patients and over 1 minute to the next 52 patients. In this study, 2 patients developed symptomatic hypotension (1 in each group). The degree of increase in RVERP was the same in both groups; however, the onset of change occurred immediately with the bolus group (over 1 minute) versus 10 minutes with the slow I.V. push group. The current dosing recommendation within the 2010 ACLS guidelines is 1.5 mg/kg administered over 5 minutes. Avoid in patients with QT prolongation and heart failure.
Dental Health: Effects on Dental Treatment
Sotalol is a nonselective beta-blocker and may enhance the pressor response to epinephrine, resulting in hypertension and bradycardia. Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Use with caution; epinephrine has interacted with nonselective beta-blockers to result in initial hypertensive episode followed by bradycardia. Sotalol is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Sotalol is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Sotalol is considered as having a risk of causing torsade de pointes. Since it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval, a medical consult is suggested.
Mental Health: Effects on Mental Status
Dizziness and drowsiness are common; may cause confusion, anxiety, or depression
Mental Health: Effects on Psychiatric Treatment
Contraindicated with ziprasidone. May rarely cause leukopenia; use caution with clozapine and carbamazepine. Barbiturates may decrease the effects of beta-blockers; beta-blockers may alter the effects antipsychotics; monitor for altered response.
Nursing: Physical Assessment/Monitoring
Assess blood pressure and heart rate prior to and following first dose and with any change in dosage. Consider cardiac monitoring to observe for QT changes and arrhythmias, especially if giving I.V. Assess cardiac and pulmonary status. Advise patients with diabetes to monitor glucose levels closely (beta-blockers may alter glucose tolerance). Do not discontinue abruptly; dose should be tapered gradually. Teach patient hypotension precautions.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride [preservative free]: 15 mg/mL (10 mL)
Tablet, oral, as hydrochloride: 80 mg [atrial fibrillation], 80 mg, 120 mg [atrial fibrillation], 120 mg, 160 mg [atrial fibrillation], 160 mg, 240 mg
Betapace AF®: 80 mg, 120 mg, 160 mg [scored; atrial fibrillation]
Betapace®: 80 mg, 120 mg, 160 mg, 240 mg [scored]
Sorine®: 80 mg, 120 mg, 160 mg, 240 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Betapace)
80 mg (60): $255.15
160 mg (30): $214.18
240 mg (30): $266.00
Tablets (Betapace AF)
120 mg (60): $304.46
160 mg (60): $420.00
Tablets (Sotalol HCl)
80 mg (90): $23.99
Tablets (Sotalol HCl (AF))
80 mg (100): $85.97
120 mg (30): $96.99
160 mg (30): $123.99
Extemporaneously Prepared
A 5 mg/mL sotalol hydrochloride syrup may be made with Betapace® or Betapace AF® tablets and Simple Syrup containing sodium benzoate 0.1% (Syrup, NF). Place 120 mL Syrup, NF in a 6-ounce amber plastic (polyethylene terephthalate) prescription bottle; add five Betapace® or Betapace AF® 120 mg tablets and shake the bottle to wet the tablets. Allow tablets to hydrate for at least 2 hours, then shake intermittently over ≥2 hours until the tablets are completely disintegrated; a dispersion of fine particles (water-insoluble inactive ingredients) in syrup should be obtained. Note: To simplify the disintegration process, tablets can hydrate overnight; tablets may also be crushed, carefully transferred into the bottle and shaken well until a dispersion of fine particles in syrup is obtained. Label "shake well". Stable for 3 months at controlled room temperature (15°C to 30°C [59°F to 86°F]) and ambient humidity.
Betapace® prescribing information, Bayer HealthCare Pharmaceuticals Inc, Wayne, NJ, 2007.
Betapace AF® prescribing information, Bayer HealthCare Pharmaceuticals Inc, Wayne, NJ, 2009.
References
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Ho DS, Zecchin RP, Richards DA, et al, “Double-Blind Trial of Lignocaine versus Sotalol for Acute Termination of Spontaneous Sustained Ventricular Tachycardia,” Lancet, 1994, 344(8914):18-23.
Juul AB, Wetterslev J, Gluud C, et al, "Effect of Perioperative Beta-Blockade in Patients With Diabetes Undergoing Major Noncardiac Surgery: Randomized Placebo Controlled, Blinded Multicentre Trial," BMJ, 2006, 332(7556):1482.
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Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
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Waldo AL, Camm AJ, deRuyter H, et al, “Effect of d-sotalol on Mortality in Patients With Left Ventricular Dysfunction After Recent and Remote Myocardial Infarction. The SWORD Investigators. Survival With Oral d-Sotalol,” Lancet, 1996, 348(9019):7-12.
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International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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