Sotalol
Generic: SOTALOL HYDROCHLORIDE
Basic Information
Manufacturer
Bryant Ranch Prepack
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
c824f6b2-80c5-45a6-a491-4c14c9f5e33d
Indications & Usage
1.
INDICATIONS AND USAGE Sotalol Hydrochloride Tablets are an antiarrhythmic indicated for: the treatment of life threatening ventricular arrhythmias ( 1.1 ) Limitations of Use Avoid use in patients with asymptomatic ventricular premature contraction ( 1.1 ) 1.1 Life-Threatening Ventricular Arrhythmias Sotalol Hydrochloride Tablets are indicated for the treatment of life-threatening, documented ventricular arrhythmias, such as sustained ventricular tachycardia (VT).
Limitation of Use: Sotalol Hydrochloride Tablets may not enhance survival in patients with ventricular arrhythmias.
Because of the proarrhythmic effects of Sotalol Hydrochloride Tablets, including a 1.5 to 2% rate of Torsade de Pointes (TdP) or new ventricular tachycardia/fibrillation (VT/VF) in patients with either non-sustained ventricular tachycardia (NSVT) or supraventricular arrhythmias (SVT), its use in patients with less severe arrhythmias, even if the patients are symptomatic, is generally not recommended.
Avoid treatment of patients with asymptomatic ventricular premature contractions [ see Warnings and Precautions (5.2) .]
INDICATIONS AND USAGE Sotalol Hydrochloride Tablets are an antiarrhythmic indicated for: the treatment of life threatening ventricular arrhythmias ( 1.1 ) Limitations of Use Avoid use in patients with asymptomatic ventricular premature contraction ( 1.1 ) 1.1 Life-Threatening Ventricular Arrhythmias Sotalol Hydrochloride Tablets are indicated for the treatment of life-threatening, documented ventricular arrhythmias, such as sustained ventricular tachycardia (VT).
Limitation of Use: Sotalol Hydrochloride Tablets may not enhance survival in patients with ventricular arrhythmias.
Because of the proarrhythmic effects of Sotalol Hydrochloride Tablets, including a 1.5 to 2% rate of Torsade de Pointes (TdP) or new ventricular tachycardia/fibrillation (VT/VF) in patients with either non-sustained ventricular tachycardia (NSVT) or supraventricular arrhythmias (SVT), its use in patients with less severe arrhythmias, even if the patients are symptomatic, is generally not recommended.
Avoid treatment of patients with asymptomatic ventricular premature contractions [ see Warnings and Precautions (5.2) .]
Adverse Reactions
6 ADVERSE REACTIONS The most common adverse reactions (≥2%) for Sotalol Hydrochloride Tablets are: fatigue 4%, bradycardia (less than 50 bpm) 3%, dyspnea 3%, proarrhythmia 3%, asthenia 2%, and dizziness 2%.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Beximco Pharmaceuticals USA Inc.
at 877-372-6093 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse reactions that are clearly related to sotalol are those which are typical of its Class II (beta-blocking) and Class III (cardiac action potential duration prolongation) effects and are dose related.
Ventricular Arrhythmias Serious Adverse Reactions In patients with a history of sustained ventricular tachycardia, the incidence of Torsade de Pointes during oral sotalol treatment was 4% and worsened VT was about 1%; in patients with other less serious ventricular arrhythmias the incidence of Torsade de Pointes was 1% and new or worsened VT was about 0.7%.
Incidence of Torsade de Pointes arrhythmias in patients with VT/VF are shown in Table 3 below.
Table 3: Percent Incidence of Torsade de Pointes and Mean QTc Interval by Dose For Patients With Sustained VT/VF Daily Dose (mg) Torsade de Pointes Incidence Mean QTc highest on-therapy value (msec) 80 0 (69) 463 (17) 160 0.5 (832) 467 (181) 320 1.6 (835) 473 (344) 480 4.4 (459) 483 (234) 640 3.7 (324) 490 (185) >640 5.8 (103) 512 (62) ( ) Number of patients assessed Table 4 below relates the incidence of Torsade de Pointes to on-therapy QT c and change in QT c from baseline in patients with ventricular arrhythmias.
It should be noted, however, that the highest on-therapy QT c was in many cases the one obtained at the time of the Torsade de Pointes event, so that the table overstates the predictive value of a high QT c .
Table 4: Relationship Between QTc Interval Prolongations and Torsade de Pointes On-Therapy QT c Interval (msec) Incidence of Torsade de Pointes Change from Baseline in QT c (msec) Incidence of Torsade de Pointes <500 1.3% (1787) <65 1.6% (1516) 500-525 3.4% (236) 65-80 3.2% (158) 525-550 5.6% (125) 80-100 4.1% (146) >550 10.8% (157) 100-130 5.2% (115) >130 7.1% (99) ( ) Number of patients assessed Table 5: Incidence (%) of Common Adverse Reactions (2% in the Placebo group and less frequent than Sotalol Hydrochloride Tablets groups) in a Placebo-controlled Parallel-group Comparison Study of Patients with Ventricular Ectopy Body System/Adverse Reaction (Preferred Term) Placebo Sotalol Hydrochloride Total Daily Dose N=37 (%) 320 mg N=38 (%) 640 mg N=39 (%) CARDIOVASCULAR Chest Pain 5.4 7.9 15.4 Dyspnea 2.7 18.4 20.5 Palpitation 2.7 7.9 5.4 Vasodilation 2.7 0.0 5.1 NERVOUS SYSTEM Asthenia 8.1 10.5 20.5 Dizziness 5.4 13.2 17.9 Fatigue 10.8 26.3 25.6 Headache 5.4 5.3 7.7 Lightheaded 8.1 15.8 5.1 Sleep Problem 2.7 2.6 7.7 RESPIRATORY Upper Respiratory Tract Problem 2.7 2.6 12.8 SPECIAL SENSES Visual Problem 2.7 5.3 0.0 The most common adverse reactions leading to discontinuation of Sotalol Hydrochloride Tablets in trials of patients with ventricular arrhythmias are: fatigue 4%, bradycardia (less than 50 bpm) 3%, dyspnea 3%, proarrhythmia 3%, asthenia 2%, and dizziness 2%.
Incidence of discontinuation for these adverse reactions was dose related.
One case of peripheral neuropathy that resolved on discontinuation of Sotalol Hydrochloride Tablets and recurred when the patient was rechallenged with the drug was reported in an early dose tolerance study.
Pediatric Patients In an unblinded multicenter trial of 25 pediatric patients with SVT and/or VT receiving daily doses of 30, 90 and 210 mg/m 2 with dosing every 8 ours for a total of 9 doses, no Torsade de Pointes or other serious new arrhythmias were observed.
One (1) patient, receiving 30 mg/m 2 daily, was discontinued because of increased frequency of sinus pauses/bradycardia.
Additional cardiovascular AEs were seen at the 90 and 210 mg/m 2 daily dose levels.
They included QT prolongation (2 patients), sinus pauses/bradycardia (1 patient), increased severity of atrial flutter and reported chest pain (1 patient).
Values for QT c 525 msec were seen in 2 patients at the 210 mg/m 2 daily dose level.
Serious adverse events including death, Torsade de Pointes, other proarrhythmias, high-degree A-V blocks, and bradycardia have been reported in infants and/or children.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Beximco Pharmaceuticals USA Inc.
at 877-372-6093 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse reactions that are clearly related to sotalol are those which are typical of its Class II (beta-blocking) and Class III (cardiac action potential duration prolongation) effects and are dose related.
Ventricular Arrhythmias Serious Adverse Reactions In patients with a history of sustained ventricular tachycardia, the incidence of Torsade de Pointes during oral sotalol treatment was 4% and worsened VT was about 1%; in patients with other less serious ventricular arrhythmias the incidence of Torsade de Pointes was 1% and new or worsened VT was about 0.7%.
Incidence of Torsade de Pointes arrhythmias in patients with VT/VF are shown in Table 3 below.
Table 3: Percent Incidence of Torsade de Pointes and Mean QTc Interval by Dose For Patients With Sustained VT/VF Daily Dose (mg) Torsade de Pointes Incidence Mean QTc highest on-therapy value (msec) 80 0 (69) 463 (17) 160 0.5 (832) 467 (181) 320 1.6 (835) 473 (344) 480 4.4 (459) 483 (234) 640 3.7 (324) 490 (185) >640 5.8 (103) 512 (62) ( ) Number of patients assessed Table 4 below relates the incidence of Torsade de Pointes to on-therapy QT c and change in QT c from baseline in patients with ventricular arrhythmias.
It should be noted, however, that the highest on-therapy QT c was in many cases the one obtained at the time of the Torsade de Pointes event, so that the table overstates the predictive value of a high QT c .
Table 4: Relationship Between QTc Interval Prolongations and Torsade de Pointes On-Therapy QT c Interval (msec) Incidence of Torsade de Pointes Change from Baseline in QT c (msec) Incidence of Torsade de Pointes <500 1.3% (1787) <65 1.6% (1516) 500-525 3.4% (236) 65-80 3.2% (158) 525-550 5.6% (125) 80-100 4.1% (146) >550 10.8% (157) 100-130 5.2% (115) >130 7.1% (99) ( ) Number of patients assessed Table 5: Incidence (%) of Common Adverse Reactions (2% in the Placebo group and less frequent than Sotalol Hydrochloride Tablets groups) in a Placebo-controlled Parallel-group Comparison Study of Patients with Ventricular Ectopy Body System/Adverse Reaction (Preferred Term) Placebo Sotalol Hydrochloride Total Daily Dose N=37 (%) 320 mg N=38 (%) 640 mg N=39 (%) CARDIOVASCULAR Chest Pain 5.4 7.9 15.4 Dyspnea 2.7 18.4 20.5 Palpitation 2.7 7.9 5.4 Vasodilation 2.7 0.0 5.1 NERVOUS SYSTEM Asthenia 8.1 10.5 20.5 Dizziness 5.4 13.2 17.9 Fatigue 10.8 26.3 25.6 Headache 5.4 5.3 7.7 Lightheaded 8.1 15.8 5.1 Sleep Problem 2.7 2.6 7.7 RESPIRATORY Upper Respiratory Tract Problem 2.7 2.6 12.8 SPECIAL SENSES Visual Problem 2.7 5.3 0.0 The most common adverse reactions leading to discontinuation of Sotalol Hydrochloride Tablets in trials of patients with ventricular arrhythmias are: fatigue 4%, bradycardia (less than 50 bpm) 3%, dyspnea 3%, proarrhythmia 3%, asthenia 2%, and dizziness 2%.
Incidence of discontinuation for these adverse reactions was dose related.
One case of peripheral neuropathy that resolved on discontinuation of Sotalol Hydrochloride Tablets and recurred when the patient was rechallenged with the drug was reported in an early dose tolerance study.
Pediatric Patients In an unblinded multicenter trial of 25 pediatric patients with SVT and/or VT receiving daily doses of 30, 90 and 210 mg/m 2 with dosing every 8 ours for a total of 9 doses, no Torsade de Pointes or other serious new arrhythmias were observed.
One (1) patient, receiving 30 mg/m 2 daily, was discontinued because of increased frequency of sinus pauses/bradycardia.
Additional cardiovascular AEs were seen at the 90 and 210 mg/m 2 daily dose levels.
They included QT prolongation (2 patients), sinus pauses/bradycardia (1 patient), increased severity of atrial flutter and reported chest pain (1 patient).
Values for QT c 525 msec were seen in 2 patients at the 210 mg/m 2 daily dose level.
Serious adverse events including death, Torsade de Pointes, other proarrhythmias, high-degree A-V blocks, and bradycardia have been reported in infants and/or children.