Sotalol Hydrochloride
Generic: SOTALOL HYDROCHLORIDE
Basic Information
Manufacturer
Proficient Rx LP
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
6acf10b5-bbd9-4993-99a9-2cdb8cec96c5
Indications & Usage
1 INDICATIONS AND USAGE Sotalol hydrochloride tablets are an antiarrhythmic indicated for: • the treatment of life threatening ventricular arrhythmias ( 1.1 ) • the maintenance of normal sinus rhythm in patients with atrial fibrillation or flutter (AFIB/AFL) ( 1.2 ) Limitations of Use • Avoid use in patients with asymptomatic ventricular premature contraction ( 1.1 ) • Avoid use in patients with minimally symptomatic or easily reversible AFIB/AFL ( 1.2 ) 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 )].
1.2 Delay in Recurrence of Atrial Fibrillation/Atrial Flutter (AFIB/AFL) Sotalol hydrochloride tablets are indicated for the maintenance of normal sinus rhythm (delay in time to recurrence of AFIB/AFL) in patients with symptomatic AFIB/AFL who are currently in sinus rhythm.
Limitation of Use: Because sotalol hydrochloride tablets can cause life-threatening ventricular arrhythmias, reserve its use for patients in whom AFIB/AFL is highly symptomatic.
Patients with paroxysmal AFIB that is easily reversed (by Valsalva maneuver, for example) should usually not be given sotalol hydrochloride tablets.
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 )].
1.2 Delay in Recurrence of Atrial Fibrillation/Atrial Flutter (AFIB/AFL) Sotalol hydrochloride tablets are indicated for the maintenance of normal sinus rhythm (delay in time to recurrence of AFIB/AFL) in patients with symptomatic AFIB/AFL who are currently in sinus rhythm.
Limitation of Use: Because sotalol hydrochloride tablets can cause life-threatening ventricular arrhythmias, reserve its use for patients in whom AFIB/AFL is highly symptomatic.
Patients with paroxysmal AFIB that is easily reversed (by Valsalva maneuver, for example) should usually not be given sotalol hydrochloride tablets.
Adverse Reactions
6 ADVERSE REACTIONS The most common adverse reactions (≥2%) for sotalol hydrochloride 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 TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537 or drug.safety@tevapharm.com; 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 QTc and change in QTc from baseline in patients with ventricular arrhythmias.
It should be noted, however, that the highest on-therapy QTc 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 QTc.
Table 4: Relationship Between QTc Interval Prolongation and Torsade de Pointes On-Therapy QTc Interval (msec) Incidence of Torsade de Pointes Change from Baseline in QTc (msec) Incidence of Torsade de Pointes <500 1.3% (1787) <65 1.6% (1516) 500 to 525 3.4% (236) 65 to 80 3.2% (158) 525 to 550 5.6% (125) 80 to 100 4.1% (146) >550 10.8% (157) 100 to 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 in the sotalol hydrochloride 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 5.1 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 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 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 hours 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 QTc ≥ 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.
Atrial Fibrillation/Atrial Flutter Placebo-controlled Clinical Trials In a pooled clinical trial population consisting of 4 placebo-controlled studies with 275 patients with atrial fibrillation (AFIB)/atrial flutter (AFL) treated with 160 to 320 mg doses of sotalol hydrochloride (AF), the following adverse reactions presented in Table 6 occurred in at least 2% of placebo-treated patients and at a lesser rate than sotalol hydrochloride-treated patients.
The data are presented by incidence of reactions in the sotalol hydrochloride (AF) and placebo groups by body system and daily dose.
Table 6: Incidence (%) of Common Adverse Reactions (≥ 2% in the Placebo group and less frequent than in the sotalol hydrochloride (AF) groups) in Four Placebo-controlled Studies of Patients with AFIB/AFL Body System/Adverse Reaction (Preferred Term) Placebo Sotalol hydrochloride (AF) Total Daily Dose N = 282 (%) 160 to 240 mg N = 153 (%) > 240 to 320 mg N = 122 (%) CARDIOVASCULAR Bradycardia 2.5 13.1 12.3 GASTROINTESTINAL Diarrhea 2.1 5.2 5.7 Nausea/Vomiting 5.3 7.8 5.7 Pain abdomen 2.5 3.9 2.5 GENERAL Fatigue 8.5 19.6 18.9 Hyperhidrosis 3.2 5.2 4.9 Weakness 3.2 5.2 4.9 MUSCULOSKELETAL/CONNECTIVE TISSUE Pain musculoskeletal 2.8 2.6 4.1 NERVOUS SYSTEM Dizziness 12.4 16.3 13.1 Headache 5.3 3.3 11.5 RESPIRATORY Cough 2.5 3.3 2.5 Dyspnea 7.4 9.2 9.8 Overall, discontinuation because of unacceptable adverse events was necessary in 17% of the patients, and occurred in 10% of patients less than two weeks after starting treatment.
The most common adverse reactions leading to discontinuation of sotalol hydrochloride (AF) were: fatigue 4.6%, bradycardia 2.4%, proarrhythmia 2.2%, dyspnea 2%, and QT interval prolongation 1.4%.
6.2 Postmarketing Experience The following adverse drug reactions have been identified during post-approval use of sotalol.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Voluntary reports since introduction include reports (less than one report per 10,000 patients) of: emotional lability, slightly clouded sensorium, incoordination, vertigo, paralysis, thrombocytopenia, eosinophilia, leukopenia, photosensitivity reaction, fever, pulmonary edema, hyperlipidemia, myalgia, pruritis, alopecia.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537 or drug.safety@tevapharm.com; 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 QTc and change in QTc from baseline in patients with ventricular arrhythmias.
It should be noted, however, that the highest on-therapy QTc 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 QTc.
Table 4: Relationship Between QTc Interval Prolongation and Torsade de Pointes On-Therapy QTc Interval (msec) Incidence of Torsade de Pointes Change from Baseline in QTc (msec) Incidence of Torsade de Pointes <500 1.3% (1787) <65 1.6% (1516) 500 to 525 3.4% (236) 65 to 80 3.2% (158) 525 to 550 5.6% (125) 80 to 100 4.1% (146) >550 10.8% (157) 100 to 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 in the sotalol hydrochloride 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 5.1 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 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 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 hours 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 QTc ≥ 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.
Atrial Fibrillation/Atrial Flutter Placebo-controlled Clinical Trials In a pooled clinical trial population consisting of 4 placebo-controlled studies with 275 patients with atrial fibrillation (AFIB)/atrial flutter (AFL) treated with 160 to 320 mg doses of sotalol hydrochloride (AF), the following adverse reactions presented in Table 6 occurred in at least 2% of placebo-treated patients and at a lesser rate than sotalol hydrochloride-treated patients.
The data are presented by incidence of reactions in the sotalol hydrochloride (AF) and placebo groups by body system and daily dose.
Table 6: Incidence (%) of Common Adverse Reactions (≥ 2% in the Placebo group and less frequent than in the sotalol hydrochloride (AF) groups) in Four Placebo-controlled Studies of Patients with AFIB/AFL Body System/Adverse Reaction (Preferred Term) Placebo Sotalol hydrochloride (AF) Total Daily Dose N = 282 (%) 160 to 240 mg N = 153 (%) > 240 to 320 mg N = 122 (%) CARDIOVASCULAR Bradycardia 2.5 13.1 12.3 GASTROINTESTINAL Diarrhea 2.1 5.2 5.7 Nausea/Vomiting 5.3 7.8 5.7 Pain abdomen 2.5 3.9 2.5 GENERAL Fatigue 8.5 19.6 18.9 Hyperhidrosis 3.2 5.2 4.9 Weakness 3.2 5.2 4.9 MUSCULOSKELETAL/CONNECTIVE TISSUE Pain musculoskeletal 2.8 2.6 4.1 NERVOUS SYSTEM Dizziness 12.4 16.3 13.1 Headache 5.3 3.3 11.5 RESPIRATORY Cough 2.5 3.3 2.5 Dyspnea 7.4 9.2 9.8 Overall, discontinuation because of unacceptable adverse events was necessary in 17% of the patients, and occurred in 10% of patients less than two weeks after starting treatment.
The most common adverse reactions leading to discontinuation of sotalol hydrochloride (AF) were: fatigue 4.6%, bradycardia 2.4%, proarrhythmia 2.2%, dyspnea 2%, and QT interval prolongation 1.4%.
6.2 Postmarketing Experience The following adverse drug reactions have been identified during post-approval use of sotalol.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Voluntary reports since introduction include reports (less than one report per 10,000 patients) of: emotional lability, slightly clouded sensorium, incoordination, vertigo, paralysis, thrombocytopenia, eosinophilia, leukopenia, photosensitivity reaction, fever, pulmonary edema, hyperlipidemia, myalgia, pruritis, alopecia.