Data from FDA (Food and Drug Administration, USA) - Curated by Marshall Pearce - Last updated 02 September 2017

Indication(s)

1 INDICATIONS AND USAGE SORINE (sotalol hydrochloride) is 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 SORINE (sotalol hydrochloride) tablets are indicated for the treatment of life-threatening, documented ventricular arrhythmias, such as sustained ventricular tachycardia (VT). Limitation of Use: SORINE (sotalol hydrochloride) tablets may not enhance survival in patients with ventricular arrhythmias. Because of the proarrhythmic effects of SORINE (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) SORINE (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 SORINE (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 SORINE (sotalol hydrochloride) tablets.

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Oral Anticoagulation Reversal

Oral Anticoagulation Reversal

Experts discuss the use of non-vitamin K oral anticoagulants in the treatment and prevention of stroke, deep vein thrombosis and pulmonary embolism in atrial fibrillation patients.

Acute and Advanced Heart Failure

Acute and Advanced Heart Failure

What are the most effective treatments for acute heart failure? Can you define advanced heart failure? Discover here...

+ 3 more

Type 2 Diabetes

Type 2 Diabetes

View the latest epidemiology data, patient perspectives, ADA and EASD recommendations, treatment options and more.

Load more

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS SORINE (sotalol hydrochloride) tablets are contraindicated in patients with: Sinus bradycardia, sick sinus syndrome, second and third degree AV block, unless a functioning pacemaker is present Congenital or acquired long QT syndromes Cardiogenic shock or decompensated heart failure Serum potassium <4 mEq/L Bronchial asthma or related bronchospastic conditions Hypersensitivity to sotalol For the treatment of AFIB/AFL, SORINE (sotalol hydrochloride) tablets are also contraindicated in patients with: Baseline QT interval >450 ms Creatinine clearance <40 mL/min For the treatment of AFIB/AFL or ventricular arrhythmias Sinus bradycardia, 2nd or 3rd degree AV block, sick sinus syndrome (4) Congenital or acquired long QT syndrome (4) Serum potassium <4 mEq/L(4) Cardiogenic shock, decompensated heart failure (4) Bronchial asthma or related bronchospastic conditions (4) Hypersensitivity to sotalol (4) For the treatment of AFIB/AFL also contraindicated for: QT interval >450 ms (4) Creatinine clearance <40 mL/min (4)
Adverse reactions
6 ADVERSE REACTIONS The most common adverse reactions (≥2%) for SORINE 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 Upsher-Smith Laboratories, LLC at 1-855-899-9180 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) ( ) 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 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 ( ) Number of patients assessed <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) 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/m2 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/m2 daily, was discontinued because of increased frequency of sinus pauses/bradycardia. Additional cardiovascular AEs were seen at the 90 and 210 mg/m2 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/m2 daily dose level. Serious adverse events including death, Torsade de Pointes, other proarrhythmias, high-degree AV 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, 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 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 groups) in Four Placebo-controlled Studies of Patients with AFIB/AFL Body System/ Adverse Reaction (Preferred Term) Placebo Sotalol Hydrochloride 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 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.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION SORINE (sotalol hydrochloride) tablets: Initial dosage in adults is 80 mg twice daily. Increase the dose as needed in increments of 80 mg/day, every 3 days to a maximum 320 mg total daily dose (2.2) Pediatrics: Dosage depends on age (2.4) 2.1 General Safety Measures for Initiation of Oral Sotalol Therapy Withdraw other antiarrhythmic therapy before starting SORINE (sotalol hydrochloride) tablets and monitor carefully for a minimum of 2 to 3 plasma half-lives if the patient's clinical condition permits [see Drug Interactions (7)]. Hospitalize patients initiated or re-initiated on sotalol for at least 3 days or until steady-state drug levels are achieved, in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Initiate oral sotalol therapy in the presence of personnel trained in the management of serious arrhythmias. Perform a baseline ECG to determine the QT interval and measure and normalize serum potassium and magnesium levels before initiating therapy. Measure serum creatinine and calculate an estimated creatinine clearance in order to establish the appropriate dosing interval (insert cross ref to renal dosing). Continually monitor patients with each uptitration in dose, until they reach steady state. Determine QTc 2 to 4 hours after every dose. Discharge patients on sotalol therapy from an in-patient setting with an adequate supply of sotalol to allow uninterrupted therapy until the patient can fill a sotalol prescription. Advise patients who miss a dose to take the next dose at the usual time. Do not double the dose or shorten the dosing interval. 2.2 Adult Dose for Ventricular Arrhythmias The recommended initial dose is 80 mg twice daily. This dose may be increased in increments of 80 mg per day every 3 days provided the QTc <500 msec [see Warnings and Precautions (5.1)] . Continually monitor patients until steady state blood levels are achieved. In most patients, a therapeutic response is obtained at a total daily dose of 160 to 320 mg/day, given in two or three divided doses (because of the long terminal elimination half-life of sotalol, dosing more than a two times a day is usually not necessary). Oral doses as high as 480 to 640 mg/day have been utilized in patients with refractory life-threatening arrhythmias. 2.3 Adult Dose for Prevention of Recurrence of AFIB/AFL The recommended initial dose is 80 mg twice daily. This dose may be increased in increments of 80 mg per day every 3 days provided the QTc <500 msec [see Warnings and Precautions (5.1)] . Continually monitor patients until steady state blood levels are achieved. Most patients will have satisfactory response with 120 mg twice daily. Initiation of sotalol in patients with creatinine clearance <40 mL/min or QTc >450 is contraindicated [see Contraindication (4)] . 2.4 Pediatric Dose for Ventricular Arrhythmias or AFIB/AFL Use the same precautionary measures for children as you would use for adults when initiating and re-initiating sotalol treatment. For children aged about 2 years and older For children aged about 2 years and older, 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 is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide [see Clinical Pharmacology (12.1, 12.3)]. 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 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 preferably 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 aged about 2 years or younger For children aged 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, 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 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 three times daily. For a child aged about 1 week, the initial starting dose should be multiplied by 0.3; the starting dose would be (30 × 0.3) = 9 mg/m2. Use similar calculations for dose titration. 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. Figure 2.5 Dosage for Patients with Renal Impairment Adults Use of sotalol in any age group with decreased renal function should be at lower doses or increased intervals between doses. It will take much longer to reach steady-state with any dose and/or frequency of administration. Closely monitor heart rate and QTc. Dose escalations in renal impairment should be done after administration of at least 5 doses at appropriate intervals (Table 1). Sotalol is partly removed by dialysis; specific advice is unavailable on dosing patients on dialysis. The initial dose of 80 mg and subsequent doses should be administered at the intervals listed in Table 1 or Table 2. Table 1: Dosing Intervals for treatment of Ventricular Arrhythmias in renal impairment Creatinine Clearance mL/min Dosing Interval (hours) >60 12 30 to 59 24 10 to 29 36 to 48 <10 Dose should be individualized Table 2: Dosing Intervals for treatment of AFIB/AFL in renal impairment Creatinine Clearance mL/min Dosing Interval (hours) >60 12 40 to 59 24 <40 Contraindicated 2.6 Preparation of Extemporaneous Oral Solution Sotalol hydrochloride Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1% sodium benzoate (Syrup, NF) as follows: Measure 120 mL of Simple Syrup. Transfer the syrup to a 6-ounce amber plastic (polyethylene terephthalate [PET]) prescription bottle. An oversized bottle is used to allow for a headspace, so that there will be more effective mixing during shaking of the bottle. Add five (5) SORINE (sotalol hydrochloride) 120 mg tablets to the bottle. These tablets are added intact; it is not necessary to crush the tablets. The addition of the tablets can also be done first. The tablets can also be crushed if preferred. If the tablets are crushed, care should be taken to transfer the entire quantity of tablet powder into the bottle containing the syrup. Shake the bottle to wet the entire surface of the tablets. If the tablets have been crushed, shake the bottle until the endpoint is achieved. Allow the tablets to hydrate for at least two hours. After at least two hours have elapsed, shake the bottle intermittently over the course of at least another two hours until the tablets are completely disintegrated. The tablets can be allowed to hydrate overnight to simplify the disintegration process. The endpoint is achieved when a dispersion of fine particles in the syrup is obtained. This compounding procedure results in a solution containing 5 mg/mL of sotalol hydrochloride. The fine solid particles are the water-insoluble inactive ingredients of the tablets. Stability studies indicate that the suspension is stable for three months when stored at 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature] and ambient humidity.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category B There are no adequate and well-controlled studies in pregnant women. Sotalol has been shown to cross the placenta, and is found in amniotic fluid. In animal studies there was no increase in congenital anomalies, but an increase in early resorptions occurred at sotalol doses 18 times the maximum recommended human dose (MRHD, based on surface area). Animal reproductive studies are not always predictive of human response. Reproduction studies in rats and rabbits during organogenesis at 9 and 7 times the MRHD (based on surface area), respectively, did not reveal any teratogenic potential associated with sotalol. In rabbits, a dose of sotalol 6 times the MRHD produced a slight increase in fetal death as well as maternal toxicity. This effect did not occur at sotalol dose 3 times the MRHD. In rats, a sotalol dose 18 times the MRHD increased the number of early resorptions, while a dose 2.5 times the MRHD, produced no increase in early resorptions. 8.3 Nursing Mothers Sotalol is excreted in the milk of laboratory animals and has been reported to be present in human milk. Discontinue nursing on SORINE. 8.4 Pediatric Use The safety and effectiveness of sotalol in children have not been established. However, the Class III electrophysiologic and beta-blocking effects, the pharmacokinetics, and the relationship between the effects (QTc interval and resting heart rate) and drug concentrations have been evaluated in children aged between 3 days and 12 years old [see Dosage and Administration (2.4) and Clinical Pharmacology (12.2)] . 8.6 Renal Impairment Sotalol is mainly eliminated via the kidneys. Dosing intervals should be adjusted based on creatinine clearance [see Dosage and Administration (2.5)].
Pregnancy and lactation
8.3 Nursing Mothers Sotalol is excreted in the milk of laboratory animals and has been reported to be present in human milk. Discontinue nursing on SORINE.

Interactions

7 DRUG INTERACTIONS Class I or III Antiarrhythmics or other drugs that prolong the QT interval: Avoid concomitant use (7.1) Digoxin, calcium channel blocker: increased risk of bradycardia, hypotension, heart failure (7.2) Dosage of insulin or antidiabetic drugs may need adjustment (7.5) Aluminum or magnesium-based antacids reduce sotalol exposure (7.7) 7.1 Antiarrhythmics and other QT Prolonging Drugs Sotalol has not been studied with other drugs that prolong the QT interval such as antiarrhythmics, some phenothiazines, tricyclic antidepressants, certain oral macrolides and certain quinolone antibiotics. Discontinue Class I or Class III antiarrhythmic agents for at least three half-lives prior to dosing with sotalol. Class Ia antiarrhythmic drugs, such as disopyramide, quinidine and procainamide and other Class III drugs (for example, amiodarone) are not recommended as concomitant therapy with sotalol hydrochloride, because of their potential to prolong refractoriness [see Warnings and Precautions (5.2)]. There is only limited experience with the concomitant use of Class Ib or Ic antiarrhythmics. Additive Class II effects would also be anticipated with the use of other beta-blocking agents concomitantly with sotalol hydrochloride. 7.2 Digoxin Proarrhythmic events were more common in sotalol treated patients also receiving digoxin; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia, in the patients receiving digoxin. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. 7.3 Calcium-Channel Blocking Drugs Sotalol and calcium-blocking drugs can be expected to have additive effects on atrioventricular conduction or ventricular function. Monitor such patients for evidence of bradycardia and hypotension. 7.4 Catecholamine-Depleting Agents Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with a beta-blocker may produce an excessive reduction of resting sympathetic nervous tone. Monitor such patients for evidence of hypotension and/or marked bradycardia which may produce syncope. 7.5 Insulin and Oral Antidiabetics Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment [see Warnings and Precautions 5.7)] . 7.6 Clonidine Concomitant use with sotalol increases the risk of bradycardia. Because beta-blockers may potentiate the rebound hypertension sometimes observed after clonidine discontinuation, withdraw sotalol several days before the gradual withdrawal of clonidine to reduce the risk of rebound hypertension. 7.7 Antacids Avoid administration of oral sotalol within 2 hours of antacids containing aluminum oxide and magnesium hydroxide.

More information

Category Value
Authorisation number ANDA075500
Agency product number HEC37C70XX
Orphan designation No
Product NDC 0245-0014,0245-0015,0245-0012,0245-0013
Date Last Revised 30-06-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 1923424
Storage and handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP.
Marketing authorisation holder Upsher-Smith Laboratories, Inc.
Warnings WARNING: LIFE-THREATENING PROARRHYTHMIA To minimize the risk of drug-induced arrhythmia, initiate or reinitiate oral sotalol in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Sotalol can cause life-threatening ventricular tachycardia associated with QT interval prolongation. If the QT interval prolongs to 500 msec or greater, reduce the dose, lengthen the dosing interval, or discontinue the drug. Calculate creatinine clearance to determine appropriate dosing [see Dosage and Administration (2.5)] . WARNING: LIFE-THREATENING PROARRHYTHMIA See full prescribing information for complete boxed warning. SORINE (sotalol hydrochloride) tablets can cause life-threatening ventricular tachycardia associated with QT interval prolongation. If the QT interval prolongs to 500 msec or greater, reduce the dose, lengthen the dosing interval, or discontinue the drug. Initiate or reinitiate in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Adjust the dosing interval based on creatinine clearance.