Sotalol hydrochloride

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 up-titrate 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. WARNING: LIFE THREATENING PROARRHYTHMIA See full prescribing information for complete boxed warning. Sotalol can cause life threatening ventricular tachycardia associated with QT interval prolongation. ( 5.1 ) Initiate or reinitiate in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. ( 2.3 ) 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 )

5 WARNINGS AND PRECAUTIONS QT prolongation, risk of life-threatening ventricular arrhythmias, particularly torsade de pointes ( 5.1 ) Bradyarrhythmia, AV block, sick sinus syndrome ( 5.2 , 5.3 ) Negative inotropy: hypotension, heart failure ( 5.4 , 5.5 ) Bronchospasm ( 5.6 ) Masked hypoglycemia ( 5.7 ) Masked hyperthyroidism ( 5.8 ) Anaphylaxis ( 5.9 ) 5.1 Proarrhythmia Sotalol can cause serious and potentially fatal ventricular arrhythmias , primarily Torsade de Pointes (TdP), a polymorphic ventricular tachycardia associated with QTc prolongation. QTc prolongation is directly related to the concentration of sotalol. Factors such as reduced renal function, female sex, higher dose, bradycardia, history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), atrial fibrillation with sinus node dysfunction, and heart failure increase the risk of 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. Correct hypokalemia or hypomagnesemia prior to initiating sotalol hydrochloride, as these conditions can increase the degree of QTc prolongation and potential for TdP. Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or patients receiving concomitant diuretic drugs. Proarrhythmic events should be anticipated upon initiating therapy and with every up-titration of sotalol. Avoid sotalol with other drugs known to cause QTc prolongation [see Dosage and Administration ( 2.1 ) and Drug Interactions ( 7.1 )]. 5.2 Bradycardia/Atrioventricular (AV) Block Sotalol can cause bradycardia, sinus pauses or sinus arrest. Sotalol-induced bradycardia increases the risk of Torsade de Pointes, particularly following cardioversion. Monitor the ECG in patients receiving concomitant negative chronotropes [see Drug Interactions ( 7.2 , 7.3 , 7.4 )] . 5.3 Sick Sinus Syndrome Sotalol is contraindicated in patients with sick sinus syndrome, because it may cause sinus bradycardia, sinus pauses, or sinus arrest. Sotalol augments bradycardia and QTc prolongation following cardioversion. 5.4 Hypotension Sotalol produces significant reductions in both systolic and diastolic blood pressures. Monitor hemodynamics during administration. 5.5 Heart Failure 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. 5.6 Bronchospasm Avoid beta-blockers, like sotalol, in patients with bronchospastic diseases. If sotalol is required, use the smallest effective dose. 5.7 Hypoglycemia Beta-blockade may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or pediatric patients who are fasting (i.e., surgery, not eating regularly, or vomiting). Monitor blood glucose as appropriate. 5.8 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. 5.9 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. 5.10 Anesthesia The impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere: Proarrhythmia [see Warnings and Precautions ( 5.1 , 5.2 )] Negative inotropy [see Warnings and Precautions ( 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. Bradycardia, dyspnea, fatigue, QTc prolongation 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 .