Highlights of Prescribing Information

Boxed Warning, Indications, and Important Safety Information

Sotalol is an antiarrhythmic indicated for:

the treatment of documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia in adult and pediatric patients.
Limitations of Use:
Sotalol has not been shown to enhance survival in patients with life-threatening ventricular arrhythmias.

the maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)) in adults and pediatric patients with highly symptomatic AFIB/AFL who are currently in sinus rhythm.
Limitations of Use:
Because sotalol can cause life-threatening ventricular arrhythmias, reserve its use for patients in whom AFIB/AFL is highly symptomatic.

Important Safety Information

WARNING: LIFE THREATENING PROARRHYTHMIA

Sotalol can cause life threatening ventricular tachycardia associated with QT interval prolongation. To minimize the risk of drug induced arrhythmia, initiate or uptitrate intravenous sotalol in a facility that can provide continuous electrocardiographic monitoring and cardiac resuscitation [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].
Do not initiate intravenous sotalol therapy if the baseline QTc is longer than 450 ms. If the QTc prolongs to 500 ms or greater, reduce the dose or discontinue. (2.3)

CONTRAINDICATIONS

Sotalol hydrochloride is contraindicated in patients with:

Bradyarrhythmia, sick sinus syndrome or 2^nd or 3^rd degree atrioventricular (AV) block without a pacemaker (4)
Congenital or acquired long QT syndrome (4)
Cardiogenic shock or decompensated heart failure (4)
Serum potassium < 4mEq (4)
Bronchial asthma or related bronchospastic conditions (4)
Hypersensitivity to sotalol (4)

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 renal function and by monitoring the ECG for excessive increases in QTc. (5.1)
Bradyarrhythmia, AV 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)
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)
Thyroid Abnormalities. 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

Antiarrhythmic and other QT-prolonging Drugs – Concomitant use with antiarrhythmic and other QT prolonging drugs is not recommended due to the risk of additive QTc prolongation. (7.1)
Negative chronotropes – Concomitant use with digitalis glycosides and beta-blockers increases the risk of bradycardia. (7.2)
Calcium blocking drugs – Sotalol and calcium blocking drugs can be expected to have additive effects slowing atrioventricular conduction, ventricular function, and blood pressure. (7.3)

Catecholamine-Depleting Agents – Concomitant use with catecholamine-depleting drugs may produce an excessive reduction of resting sympathetic nervous tone. Monitor for hypotension and marked bradycardia which may produce syncope (7.4)
Insulin and Oral Antidiabetics – Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment. Symptoms of hypoglycemia may be masked. (7.5)
Beta-2-Receptor Stimulants – Beta-agonists may have to be administered in increased dosages when used concomitantly with sotalol. (7.6)
Clonidine – Concomitant use with sotalol increases the risk of bradycardia. (7.7)
Drug/Laboratory Test Interactions – The presence of sotalol in the urine may result in falsely elevated levels of urinary metanephrine when measured by fluorimetric or photometric methods. (7.8)

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)
- Sotalol is indicated for:
  - The treatment of documented, life-threatening VT in pediatric patients
  - The maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)] in pediatric patients with highly symptomatic AFIB/AFL who are currently in sinus rhythm.
- Side effects from use of other sotalol-containing drug products in pediatric patients are those typical of a beta blocking agent.
- Bradycardia may require emergency pacemaker implantation. Close inpatient monitoring is recommended until steady state drug levels are achieved
Renal Impairment (8.5)
- Sotalol is eliminated predominantly via the kidney. Sotalol exposure increases with decrease in renal function. Sotalol dose should be reduced and interval between doses should be increased based on the patient’s renal function.

These highlights do not include all the information needed to use sotalol hydrochloride injection safely and effectively. See full Prescribing Information for sotalol hydrochloride injection.