Generic Name: sotalol hydrochloride
Dosage Form: injection
FULL PRESCRIBING INFORMATION
To minimize the risk of induced arrhythmia, patients initiated or re-initiated on intravenous sotalol, and patients who are converted from intravenous to oral administration should be hospitalized in a facility that can provide cardiac resuscitation, continuous electrocardiographic monitoring and calculations of creatinine clearance.
- Sotalol can cause life threatening ventricular tachycardia associated with QT interval prolongation
- Do not initiate sotalol therapy if the baseline QTc is longer than 450 ms. If the QT interval prolongs to 500 ms or greater, the dose must be reduced, the duration of the infusion prolonged or the drug discontinued
- Adjust the dosing interval based on creatinine clearance
Indications and Usage for Sotalol Injection
Substitution for Oral Sotalol Therapy
Intravenous sotalol can substitute for oral sotalol in patients who are unable to take sotalol orally.
Delay in Recurrence of Atrial Fibrillation/Atrial Flutter
Sotalol is indicated for the maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus rhythm. Because sotalol can cause life-threatening ventricular arrhythmias, it should be reserved for patients in whom AFIB/AFL is highly symptomatic. Patients with paroxysmal AFIB whose AFIB/AFL is easily reversed (by Valsalva maneuver, for example) should usually not be given sotalol. In general, antiarrhythmic therapy for AFIB/AFL aims to prolong the time in normal sinus rhythm. Recurrence is expected in some patients [see Clinical Studies (14.2)].
Patients with atrial fibrillation should be anticoagulated according to usual medical practice.
Documented Life-Threatening Ventricular Arrhythmia
Sotalol is indicated for the treatment of documented life-threatening ventricular arrhythmias. Because of the proarrhythmic effects of sotalol [see Warnings and Precautions (5.1)] including a 1.5 to 2% rate of Torsade de Pointes or new VT/VF in patients with either NSVT or supraventricular arrhythmias, its use in patients with less severe arrhythmias, even if the patients are symptomatic, is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. In life-threatening ventricular arrhythmias, the response to treatment should then be evaluated by a suitable method (e.g., PES or Holter monitoring) at steady state blood levels of drug prior to continuing the patient on chronic therapy. Antiarrhythmic drugs may not enhance survival in patients with ventricular arrhythmias.
Sotalol Injection Dosage and Administration
General Rules and Safety Measures of Intravenous Sotalol Therapy
For the safety of the patient, the safety measures required of oral sotalol administration must also be applied for intravenous route. To minimize the risk of induced arrhythmia, patients initiated or re-initiated on sotalol should be hospitalized for at least three days or until steady state drug levels are achieved, in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Initiate intravenous sotalol therapy in the presence of personnel trained in the management of serious ventricular arrhythmias. Perform a baseline ECG to determine the QT interval and measure and normalize serum potassium and magnesium levels before initiating therapy with starting Sotalol Injection. Measure serum creatinine and calculate an estimated creatinine clearance in order to establish the appropriate dosing interval for sotalol.
If the baseline QT is greater than 450 ms (JT >330 ms if QRS over 100 ms), sotalol is not recommended.
The patient's creatinine clearance should be calculated using the one of several formulas. The Cockcroft-Gault formula to determine creatinine clearance is:
| Creatinine clearance (male) = | (140-age) × body weight in kg |
| 72 × serum creatinine (mg/dL) | |
| Creatinine clearance (female) = | (140-age) × body weight in kg ×0.85 |
| 72 × serum creatinine (mg/dL) |
When serum creatinine is given in µmol/L, divide the value by 88.4 (1 mg/dL = 88.4 µmol/L).
Start sotalol therapy only if the baseline QT interval is <450 ms. During initiation and titration, monitor the QT interval after the completion of each infusion If the QT interval prolongs to 500 ms or greater, reduce the dose, decrease the infusion rate, or discontinue the drug.
Administer sotalol twice daily in patients with a creatinine clearance >60 mL/min or once daily) in patients with a creatinine clearance between 40 and 60 mL/min. Sotalol is not recommended in patients with a creatinine clearance <40 mL/min. The recommended initial IV dose of sotalol is 75 mg (once or twice daily) and is initiated as shown in the dosing algorithm described below. The 75 mg dose can be titrated upward to 112.5 or 150 mg after at least 3 days [see Dosage and Administration (2.5)].
Dose of Intravenous Sotalol
The bioavailability of oral sotalol is between 90% and 100%. The corresponding dose of intravenous sotalol is, therefore, slightly less than that of the oral dose. The effects of the initial intravenous dose must be monitored and the dose titrated either upward or downward, if needed, based on clinical effect, QT interval, or adverse reactions.
| Oral dose Once or twice daily | Intravenous dose Once or twice daily Administered over 5 hours |
|---|---|
| 80 mg | 75 mg (5 mL Sotalol Injection) |
| 120 mg | 112.5 mg (7.5 mL Sotalol Injection) |
| 160 mg | 150 mg (10 mL Sotalol Injection) |
Preparation of Sotalol Infusion
Intravenous sotalol must be diluted for infusion. Appropriate diluents are saline, 5% dextrose in water (D5W), or Ringer's lactate. Usually, prepare in a volume of 100-250 mL. Use a volumetric infusion pump to infuse intravenous sotalol at a constant rate. The following table compensates for dead space in the infusion set.
| Target Dose | Sotalol Injection | Diluent | Volume Prepared | Volume to Infuse |
|---|---|---|---|---|
| 75 mg | 6 mL | 114 mL | 120 mL | 100 mL |
| 112.5 mg | 9 mL | 111 mL | 100 mL | |
| 150 mg | 12 mL | 108 mL | 100 mL | |
| 75 mg | 6 mL | 294 mL | 300 mL | 250 mL |
| 112.5 mg | 9 mL | 291 mL | 250 mL | |
| 150 mg | 12 mL | 288 mL | 250 mL | |
Initiation of Intravenous Sotalol Therapy
The starting dose of intravenous sotalol is 75 mg infused over 5 hours once or twice daily based on the creatinine clearance. Monitor ECG for excessive increase in QTc.
Upward Titration of Dose
If the 75 mg dose of intravenous sotalol does not reduce the frequency of relapses of life threatening ventricular arrhythmias or symptomatic AFIB/AFL and is tolerated without excessive (i.e., to >500 ms) QTc prolongation, increase the dose to 112.5 mg infused over 5 hours, once or twice daily depending upon the creatinine clearance. Continue to monitor QTc during dose escalations.
Dose for Ventricular Arrhythmias
The recommended initial dose of intravenous sotalol is 75 mg infused over 5 hours, once or twice daily based on creatinine clearance. The dose may be increased in increments of 75 mg/day every 3 days. The usual therapeutic effect is observed with oral doses of 80 to 160 mg once or twice a day (corresponding to 75 to 150 mg intravenous sotalol). Oral doses as high as 240-320 mg once or twice a day (corresponding to 225 to 300 mg intravenous sotalol) have been utilized in patients with refractory life-threatening arrhythmias.
Dose for Symptomatic AFIB/AFL
In the U.S. multicenter dose-response study, 120 mg orally once or twice a day (corresponding to 112.5 mg intravenous sotalol) was found to be the most effective dose in prolonging the time to ECG-documented symptomatic recurrence of AFIB/AFL. If that dose level, at steady state, does not reduce the frequency of early relapse of arrhythmia and is tolerated without excessive QTc prolongation (>520 ms), increase the dose to 160 mg orally once or twice a day (corresponding to 150 mg intravenous sotalol).
Dosing and Administration in Children
Intravenous sotalol has not been studied in children. As in adults the following precautionary measures should be considered when initiating sotalol treatment in children: initiation of treatment in the hospital after appropriate clinical assessment; individualized regimen as appropriate; gradual increase of doses if required; careful assessment of therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.
For children aged about 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children [see Clinical Pharmacology (12.2)] is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric pharmacokinetic data the following is recommended. For initiation of treatment, 30 mg/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total oral daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steady-state plasma concentrations of sotalol in patients with age-adjusted normal renal function.
For children about 2 years or younger the above pediatric dosage should be reduced by a factor that depends heavily upon age, as shown in the following graph which shows age plotted on a logarithmic scale in months.
For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years or greater should be multiplied by about 0.97; the initial starting dose would be (30 × 0.97) = 29.1 mg/m2, administered orally three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 × 0.68) = 20 mg/m2, administered orally three times daily. For a child aged 1 week, the initial starting oral dose should be multiplied by 0.3; the starting dose would be (30 × 0.3) = 9 mg/m2. Similar calculations should be made for increased doses as titration proceeds. Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.
In all children, individualization of dosage is required. As in adults sotalol should be used with particular caution in children if the QTc is greater than 500 ms on therapy and serious consideration should be given to reducing the dose or discontinuing therapy when QTc exceeds 550 ms.
The use of oral sotalol in children with renal impairment has not been investigated. Sotalol elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with decreased renal function should be at lower doses or at increased intervals between doses. Monitoring of heart rate and QTc is most important. It will take much longer to reach steady-state with any dose and/or frequency of administration in these children.
Dosage Forms and Strengths
150 mg sotalol hydrochloride in 10 mL vial (15 mg/mL).
Contraindications
- Sinus bradycardia (<50 bpm), sick sinus syndrome or second or third degree AV block unless a functioning pacemaker is present
- Congenital or acquired long QT syndromes, QT interval >450 ms
- Cardiogenic shock, uncontrolled heart failure
- Creatinine clearance <40 mL/min
- Serum potassium <4 meq/L
- Bronchial asthma or related bronchospastic conditions
- Known hypersensitivity to sotalol
Warnings and Precautions
QT Prolongation and Proarrhythmia
Sotalol can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QTc prolongation. QTc prolongation is directly related to the concentration of sotalol. Factors such as reduced creatinine clearance, gender (female) and larger doses increase the risk of 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.
Initiate sotalol only in a facility that can provide ECG monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Steady-state plasma levels of sotalol and maximum QTc prolongation occur by 3 days. Calculation of the creatinine clearance must precede administration of the first dose of sotalol. For detailed instructions regarding dose selection [see Dosage and Administration (2)].
Use with Drugs that Prolong QT Interval and Antiarrhythmic Agents
The use of sotalol in conjunction with other drugs that prolong the QT interval has not been studied and is not recommended. Such drugs include many antiarrhythmics, some phenothiazines, tricyclic antidepressants, and certain oral macrolides. Class I or Class III antiarrhythmic agents should be withheld for at least three half-lives prior to dosing with sotalol. In clinical trials, sotalol was not administered to patients previously treated with oral amiodarone for >1 month in the previous three months. Class Ia antiarrhythmic drugs, such as disopyramide, quinidine and procainamide and other Class III drugs (e.g., amiodarone) are not recommended as concomitant therapy with intravenous sotalol because of their potential to prolong refractoriness. There is only limited experience with the concomitant use of Class Ib or Ic antiarrhythmics.
Bradycardia/Heart Block
In studies of oral sotalol, the incidence of bradycardia (as determined by the investigators) in the supraventricular arrhythmia population treated with oral sotalol was 13% and led to discontinuation in 2.4%. Bradycardia itself increases the risk of Torsade de Pointes, so carefully monitor patients receiving concomitant digoxin.
Sick Sinus Syndrome
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. In patients with AFIB and sinus node dysfunction, sotalol increases the risk of Torsade de Pointes, especially after cardioversion. Sotalol augments bradycardia and QTc prolongation following cardioversion. Patients with AFIB/AFL associated with the sick sinus syndrome may be treated with sotalol if they have an implanted pacemaker for control of bradycardia symptoms.
Hypotension
Sotalol produces significant reductions in both systolic and diastolic blood pressures and may result in hypotension. Although sotalol is usually well-tolerated, monitor hemodynamics in patients with marginal cardiac compensation as deterioration in cardiac performance may occur.
Heart Failure
Sympathetic stimulation is necessary in supporting circulatory function in heart failure, and beta-blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In a pooled data base of four placebo-controlled AFIB/AFL and PSVT studies, new or worsening heart failure occurred during therapy with oral sotalol in 5 (1.2%) of 415 patients. In these studies patients with uncontrolled heart failure were excluded (i.e., NYHA Functional Classes III or IV).
In other premarketing oral sotalol studies, new or worsened heart failure occurred in 3% of patients and led to discontinuation in approximately 1% of patients receiving sotalol. The incidence was higher in patients presenting with sustained ventricular tachycardia/fibrillation (5%), or a prior history of heart failure (7%). Based on a life-table analysis, the one-year incidence of new or worsened heart failure was 3% in patients without a prior history and 10% in patients with a prior history of heart failure.
Recent Acute MI
Oral sotalol has been used in a controlled trial following an acute myocardial infarction without evidence of increased mortality [see Clinical Studies (14.3)]. Although specific studies of its use in treating atrial arrhythmias after infarction have not been conducted, the usual precautions regarding heart failure, avoidance of hypokalemia, bradycardia or prolonged QT interval apply. Experience in the use of sotalol to treat ventricular arrhythmias in the early phase of recovery from acute MI is limited. In the first 2 weeks post-MI careful dose titration is especially important, particularly in patients with markedly impaired ventricular function.
Abrupt Withdrawal
Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy. Occasional cases of exacerbation of angina pectoris, arrhythmias and, in some cases, myocardial infarction have been reported after abrupt discontinuation of beta-blocker therapy. Therefore, when discontinuing chronically administered sotalol, particularly in patients with ischemic heart disease, carefully monitor the patient and consider the temporary use of an alternative beta-blocker if appropriate. If possible, the dosage of sotalol should be gradually reduced over a period of one to two weeks. If angina or acute coronary insufficiency develops, appropriate therapy should be instituted promptly. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized in patients receiving sotalol, abrupt discontinuation in patients with arrhythmias may unmask latent coronary insufficiency.
Electrolyte Disturbances
Sotalol should not be used in patients with hypokalemia or hypomagnesemia prior to correction of imbalance, as these conditions increase the potential for Torsade de Pointes. Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or patients receiving concomitant diuretic drugs.
Renal Impairment
Sotalol is eliminated principally via the kidneys through glomerular filtration and to a small degree by tubular secretion. There is a direct relationship between renal function, as measured by serum creatinine or creatinine clearance, and the elimination rate of sotalol [see Dosage and Administration (2)].
Non-Allergic Bronchospasm
Patients with bronchospastic diseases should, in general, not receive beta-blockers. If sotalol is to be administered, use the smallest effective dose, to minimize inhibition of bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta2 receptors.
Diabetes
Beta-blockade may mask some important premonitory signs of acute hypoglycemia (e.g., tachycardia) n patients with diabetes (especially labile diabetes) or with a history of episodes of spontaneous hypoglycemia.
Thyrotoxicosis
Beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Avoid abrupt withdrawal of beta-blockade which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. The beta-blocking effects of sotalol may be useful in controlling heart rate in AFIB associated with thyrotoxicosis, but no study has been conducted to evaluate this.
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.
Anesthesia
The management of patients undergoing major surgery who are being treated with beta-blockers is controversial. Protracted severe hypotension and difficulty in restoring and maintaining normal cardiac rhythm after anesthesia have been reported in patients receiving beta-blockers.
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.
Adverse Reactions
Clinical Trials Experience
There is no clinical experience with intravenous sotalol. However, because of the similarity of exposure with intravenous sotalol and oral sotalol, the adverse reactions should be similar.
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. The common documented beta-blocking adverse reactions (bradycardia, dyspnea, and fatigue) and Class III effects (QT interval prolongation) are dose related.
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.
Serious Adverse Reactions
Sotalol can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QT interval prolongation. QT interval prolongation is directly related to the plasma level of sotalol. Factors such as reduced creatinine clearance, gender (female) and larger doses increase the risk of TdP [see Warning and Precautions (5.1].
Proarrhythmia in Atrial Fibrillation Patients: In eight controlled trials of patients with AFIB/AFL and other supraventricular arrhythmias (N=659) there were four cases of TdP reported (0.6%) during the controlled phase of treatment with oral sotalol.
Prolongation of the QT interval is dose related, increasing from baseline an average of 25, 40, and 50 ms in the 80, 120, and 160 mg groups, respectively, in the oral dose-response study.
Proarrhythmia in Ventricular Arrhythmia Patients: 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%. Additionally, in approximately 1% of patients, deaths were considered possibly drug related; such cases, although difficult to evaluate, may have been associated with proarrhythmic events. Torsade de Pointes arrhythmias in patients with VT/VF were dose related, as was the prolongation of QT (QTc) interval, as shown in Table 1 below.
| Daily Dose [mg] | Incidence of Torsade de Pointes | Mean QTc * [ms] |
|---|---|---|
| ( ) Number of patients assessed | ||
| ||
| 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) |
Table 2 below relates the incidence of Torsade de Pointes to on-therapy QTc and change in QTc from baseline. 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.
| On-Therapy QTc Interval [ms] | Incidence of Torsade de Pointes | Change in QTc Interval From Baseline [ms] | Incidence of Torsade de Pointes |
|---|---|---|---|
| ( ) Number of patients assessed | |||
| less than 500 | 1.3% (1787) | less than 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) | ||
In addition to dose and presence of sustained VT, other risk factors for Torsade de Pointes were gender (females had a higher incidence), excessive prolongation of the QTc interval and history of cardiomegaly or congestive heart failure. Patients with sustained ventricular tachycardia and a history of congestive heart failure appear to have the highest risk for serious proarrhythmia (7%). Of the ventricular arrhythmia patients experiencing Torsade de Pointes, approximately two-thirds spontaneously reverted to their baseline rhythm. The others were either converted electrically (D/C cardioversion or overdrive pacing) or treated with other drugs [see Overdosage (10)]. It is not possible to determine whether some sudden deaths represented episodes of Torsade de Pointes, but in some instances sudden death did follow a documented episode of Torsade de Pointes. Although sotalol therapy was discontinued in most patients experiencing Torsade de Pointes, 17% were continued on a lower dose.
Nonetheless, intravenous sotalol should be used with particular caution if the QTc is greater than 500 ms on-therapy and serious consideration should be given to reducing the dose or discontinuing therapy when the QTc exceeds 520 ms. Proarrhythmic events must be anticipated not only on initiating therapy, but with every upward dose adjustment.
Other Adverse Reactions
No data are available with intravenous sotalol. In a pooled clinical trial population consisting of four placebo-controlled studies with 275 patients with AFIB/AFL treated with 160-320 mg doses of oral sotalol the following adverse events were reported at a rate of 2% or more in the 160-240 mg treated patients and greater than the rate in placebo patients (See Table 3). The data are presented by incidence of events in the sotalol and placebo groups by body system and daily dose. No significant irreversible non-cardiac end-organ toxicity was observed.
| Placebo | Sotalol Total Daily Dose | ||
|---|---|---|---|
| Body System/ Adverse Reactions (Preferred Term) | N=282 | 160-240 N=153 | >240-320 N=122 |
| CARDIOVASCULAR | |||
| Bradycardia | 2.5 | 13.1 | 12.3 |
| Disturbance Rhythm Subjective | 9.9 | 9.8 | 7.4 |
| Abnormality ECG | 0.4 | 3.3 | 2.5 |
| Chest Pain Cardiac/Non-Anginal | 4.6 | 4.6 | 2.5 |
| Angina Pectoris | 1.1 | 2.0 | 1.6 |
| Disturbance Rhythm Atrial | 2.1 | 2.0 | 1.6 |
| GASTROINTESTINAL | |||
| Diarrhea | 2.1 | 5.2 | 5.7 |
| Nausea/Vomiting | 5.3 | 7.8 | 5.7 |
| Distention Abdomen | 0.4 | 0.7 | 2.5 |
| Dyspepsia/Heartburn | 1.8 | 2.0 | 2.5 |
| Pain Abdomen | 2.5 | 3.9 | 2.5 |
| Appetite Decreased | 0.4 | 2.0 | 1.6 |
| GENERAL | |||
| Fatigue | 8.5 | 19.6 | 18.9 |
| Hyperhidrosis | 3.2 | 5.2 | 4.9 |
| Weakness | 3.2 | 5.2 | 4.9 |
| Fever | 0.7 | 0.7 | 3.3 |
| Sensation Cold | 0.7 | 2.0 | 2.5 |
| Influenza | 0.4 | 2.0 | 0.8 |
| MUSCULOSKELETAL/CONNECTIVE TISSUE | |||
| Pain Musculoskeletal | 2.8 | 2.6 | 4.1 |
| Pain Chest Musculoskeletal | 1.4 | 2.0 | 2.5 |
| NERVOUS SYSTEM | |||
| Dizziness | 12.4 | 16.3 | 13.1 |
| Headache | 5.3 | 3.3 | 11.5 |
| Insomnia | 1.1 | 2.6 | 4.1 |
| RESPIRATORY | |||
| Dyspnea | 7.4 | 9.2 | 9.8 |
| Infection Upper Respiratory | 1.1 | 2.6 | 3.3 |
| Tracheobronchitis | 0.7 | 0.7 | 3.3 |
| Cough | 2.5 | 3.3 | 2.5 |
| SPECIAL SENSES | |||
| Disturbance Vision | 0.7 | 2.6 | 0.8 |
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 events leading to discontinuation of sotalol were: fatigue 4.6%, bradycardia 2.4%, proarrhythmia 2.2%, dyspnea 2%, and QT interval prolongation 1.4%.
In clinical trials involving 1292 patients with sustained VT/VF, the common adverse events (occurring in ≥2% of patients) were similar to those described for the AFIB/AFL population. Table 4 lists as a function of dosage the most common (incidence of 2% or greater) adverse events, regardless of relationship to therapy and the percent of patients discontinued due to the event, as collected from clinical trials involving 1292 patients with sustained VT/VF.
| Daily Dose | % Disc | ||||||
|---|---|---|---|---|---|---|---|
| 160mg | 240mg | 320mg | 480mg | 640mg | Any Dose* | ||
| Body System | n=832 | n=263 | n=835 | n=459 | n=324 | n=1292 | n=1292 |
| |||||||
| BODY AS A WHOLE | |||||||
| Infection | 1 | 2 | 2 | 2 | 3 | 4 | <1 |
| Fever | 1 | 2 | 3 | 2 | 2 | 4 | <1 |
| Localized pain | 1 | 1 | 2 | 2 | 2 | 3 | <1 |
| CARDIOVASCULAR (CV) | |||||||
| Dyspnea | 5 | 8 | 11 | 15 | 15 | 21 | 2 |
| Bradycardia | 8 | 8 | 9 | 7 | 5 | 16 | 2 |
| Chest pain | 4 | 3 | 10 | 10 | 14 | 16 | <1 |
| Palpitation | 3 | 3 | 8 | 9 | 12 | 14 | <1 |
| Edema | 2 | 2 | 5 | 3 | 5 | 8 | 1 |
| ECG abnormal | 4 | 2 | 4 | 2 | 2 | 7 | 1 |
| Hypotension | 3 | 4 | 3 | 2 | 3 | 6 | 2 |
| Proarrhythmia | <1 | <1 | 2 | 4 | 5 | 5 | 3 |
| Syncope | 1 | 1 | 3 | 2 | 5 | 5 | 1 |
| Heart failure | 2 | 3 | 2 | 2 | 2 | 5 | 1 |
| Presyncope | 1 | 2 | 2 | 4 | 3 | 4 | <1 |
| Periph vascular | 1 | 2 | 1 | 1 | 2 | 3 | <1 |
| CV disorder | 1 | <1 | 2 | 2 | 2 | 3 | <1 |
| Vasodilation | 1 | <1 | 1 | 2 | 1 | 3 | <1 |
| AICD discharge | <1 | 2 | 2 | ||||
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