Highlights of Prescribing Information

Black Box Warning, Indication and Important Safety Information

Sotalol is an antiarrhythmic indicated for:

• the maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial flutter in patients with symptomatic AFIB/AFL] who are currently in sinus rhythm.
• the treatment of life-threatening ventricular tachycardia.

Important Safety Information

Sotalol IV (sotalol hydrochloride injection) should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits of sotalol therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment.

CONTRAINDICATIONS

Sotalol hydrochloride is contraindicated in patients with:

• Sinus bradycardia (<50 bpm), sick sinus syndrome or second or third degree AV block without a pacemaker
• Congenital or acquired long QT syndromes, QT interval >450 ms
• Cardiogenic shock, decompensated heart failure
• Serum potassium <4 mEq/L
• Bronchial asthma or related bronchospastic conditions
• Known hypersensitivity to sotalol

WARNINGS AND PRECAUTIONS

• Risk of life-threatening ventricular arrhythmias, particularly torsade de pointes (TdP). The risk of TdP can be reduced by adjustment of the sotalol dose according to creatinine clearance and by monitoring the ECG for excessive increases in QTc. (5.1)
• Bradyarrhythmia, heart block, sick sinus syndrome. Sotalol-induced bradycardia increases the risk of Torsade de Pointe, particularly following cardioversion. In general, sotalol is not recommended in patients with sick sinus syndrome associated with symptomatic arrhythmias, because it may cause sinus bradycardia, sinus pauses, or sinus arrest. (5.2, 5.3)
• Negative inotropy: hypotension, heart failure. Monitor hemodynamics during administration. New onset or worsening heart failure may occur during initiation or up-titration of sotalol because of its beta-blocking effects. Monitor for signs and symptoms of heart failure and discontinue treatment if symptoms occur. (5.4, 5.5)
• Bronchospasm. Avoid sotalol use in patients with bronchospastic diseases. If sotalol is required, use the smallest effective dose. (5.6)
• Masked hypoglycemia. Beta-blockade may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. Diabetic patients may experience elevated blood glucose levels and increased insulin requirements. (5.7)
• Masked hyperthyroidism. Avoid abrupt withdrawal of beta-blockade which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. Beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. (5.8)
• Anaphylaxis. While taking beta-blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction. (5.9)
• Anesthesia The impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. (5.10)

ADVERSE REACTIONS

• Proarrhythmia (5.1, 5.2)
• Negative inotropy (5.3, 5.4)
• Adverse reactions related to sotalol use are those which are typical of its Class II (beta-blocking) and Class III (cardiac action potential duration prolongation) effects. The common documented beta-blocking adverse reactions (bradycardia, dyspnea, and fatigue) and Class III effects (QT interval prolongation) are dose related.

To report SUSPECTED ADVERSE REACTIONS, contact AltaThera Pharmaceuticals LLC at 1-800-524-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Negative Chronotropes-Concomitant use can increase the risk of bradycardia. (7.1)
• Calcium Blocking Drugs-Can be expected to have additive effects on atrioventricular conduction, ventricular function, and blood pressure. (7.2)
• Catecholamine-Depleting Agents-Concomitant use may produce an excessive reduction of resting sympathetic nervous tone. Monitor such patients for hypotension and marked bradycardia which may produce syncope. (7.3)
• Insulin and Oral Antidiabetics-Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment. Symptoms of hypoglycemia may be masked. (7.4)
• Beta-2-Receptor Stimulants-May have to be administered in increased dosages when used concomitantly with sotalol. (7.5)
• Clonidine-Concomitant use increases the risk of bradycardia. Because beta-blockers may potentiate the rebound hypertension sometime observed after clonidine discontinuation, withdraw sotalol several days before the gradual withdrawal of clonidine to reduce the risk of rebound hypertension. (7.6)
• Drug/Laboratory Test Interactions-Presence in the urine may result in falsely elevated levels of urinary metanephrine when measured by fluorimetric or photometric methods. (7.7)

USE IN SPECIFIC POPULATIONS

• Pregnancy (8.1)
  • Fetal/Neonatal Adverse Reactions-Sotalol has been shown to cross the placenta and is found in amniotic fluid.
  • Labor or Delivery-Risk of arrhythmias increases during the labor and delivery process. Patients treated with sotalol should be monitored continuously during labor and delivery.
• Lactation (8.2)
  • Sotalol is present in human milk in high levels.
  • Advise women not to breastfeed while on treatment with sotalol.
  • Females and Males of Reproductive Potential (8.3)
  • Infertility-Based on the published literature, beta blockers (including sotalol) may cause erectile dysfunction.
• Pediatric Use (8.4)
  • The safety and effectiveness of sotalol in children has not been established. However, the Class III electrophysiologic and beta-blocking effects, the pharmacokinetics, and the relationship between the effects (QTc interval and resting heart rate) and drug concentrations have been evaluated in children aged between 3 days and 12 years old.