Betapace

Name: Betapace

What special dietary instructions should I follow?

Talk to your doctor before using salt substitutes containing potassium. If your doctor prescribes a low-salt or low-sodium diet, follow these directions carefully.

Clinical pharmacology

Mechanism Of Action

Sotalol has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. The two isomers of sotalol have similar Class III antiarrhythmic effects, while the l-isomer is responsible for virtually all of the beta-blocking activity. The beta-blocking effect of sotalol is non-cardioselective, half maximal at about 80 mg/day and maximal at doses between 320 and 640 mg/day. Sotalol does not have partial agonist or membrane stabilizing activity. Although significant beta-blockade occurs at oral doses as low as 25 mg, significant Class III effects are seen only at daily doses of 160 mg and above.

In children, a Class III electrophysiologic effect can be seen at daily doses of 210 mg/m² body surface area (BSA). A reduction of the resting heart rate due to the beta-blocking effect of sotalol is observed at daily doses ≥ 90 mg/m² in children.

Pharmacodynamics

Cardiac Electrophysiological Effects

Sotalol hydrochloride prolongs the plateau phase of the cardiac action potential in the isolated myocyte, as well as in isolated tissue preparations of ventricular or atrial muscle (Class III activity). In intact animals it slows heart rate, decreases AV nodal conduction and increases the refractory periods of atrial and ventricular muscle and conduction tissue.

In man, the Class II (beta-blockade) electrophysiological effects of sotalol are manifested by increased sinus cycle length (slowed heart rate), decreased AV nodal conduction and increased AV nodal refractoriness. The Class III electrophysiological effects in man include prolongation of the atrial and ventricular monophasic action potentials, and effective refractory period prolongation of atrial muscle, ventricular muscle, and atrioventricular accessory pathways (where present) in both the anterograde and retrograde directions. With oral doses of 160 to 640 mg/day, the surface ECG shows dose-related mean increases of 40–100 msec in QT and 10–40 msec in QTc [See WARNINGS AND PRECAUTIONS]. No significant alteration in QRS interval is observed.

In a small study (n=25) of patients with implanted defibrillators treated concurrently with Betapace, the average defibrillatory threshold was 6 joules (range 2–15 joules) compared to a mean of 16 joules for a nonrandomized comparative group primarily receiving amiodarone.

Twenty-five children in an unblinded, multicenter trial with SVT and/or ventricular tachyarrhythmias, aged between 3 days and 12 years (mostly neonates and infants), received an ascending titration regimen with daily doses of 30, 90 and 210 mg/m² with dosing every 8 hours for a total 9 doses. During steady-state, the respective average increases above baseline of the QTc interval were 2, 14, and 29 msec at the 3 dose levels. The respective mean maximum increases above baseline of the QTc interval were 23, 36, and 55 msec at the 3 dose levels. The steady-state percent increases in the RR interval were 3, 9 and 12%. The smallest children (BSA < 0.33 m²) showed a tendency for larger Class III effects (ΔQTc) and an increased frequency of prolongations of the QTc interval as compared with larger children (BSA ≥ 0.33 m²). The beta-blocking effects also tended to be greater in the smaller children (BSA < 0.33 m²). Both the Class III and beta-blocking effects of sotalol were linearly related to the plasma concentrations.

Hemodynamics

In a study of systemic hemodynamic function measured invasively in 12 patients with a mean LV ejection fraction of 37% and ventricular tachycardia (9 sustained and 3 non-sustained), a median dose of 160 mg twice daily of Betapace produced a 28% reduction in heart rate and a 24% decrease in cardiac index at 2 hours post-dosing at steady-state. Concurrently, systemic vascular resistance and stroke volume showed nonsignificant increases of 25% and 8%, respectively. One patient was discontinued because of worsening congestive heart failure. Pulmonary capillary wedge pressure increased significantly from 6.4 mmHg to 11.8 mmHg in the 11 patients who completed the study. Mean arterial pressure, mean pulmonary artery pressure and stroke work index did not significantly change. Exercise and isoproterenol induced tachycardia are antagonized by Betapace, and total peripheral resistance increases by a small amount.

In hypertensive patients, sotalol produces significant reductions in both systolic and diastolic blood pressures. Although sotalol is usually well-tolerated hemodynamically, deterioration in cardiac performance may occur in patients with marginal cardiac compensation [see WARNINGS AND PRECAUTIONS].

Pharmacokinetics

The pharmacokinetics of the d and l enantiomers of sotalol are essentially identical.

Absorption

In healthy subjects, the oral bioavailability of sotalol is 90–100%. After oral administration, peak plasma concentrations are reached in 2.5 to 4 hours, and steady-state plasma concentrations are attained within 2–3 days (that is, after 5–6 doses when administered twice daily). Over the dosage range 160–640 mg/day sotalol displays dose proportionality with respect to plasma concentrations. When administered with a standard meal, the absorption of sotalol was reduced by approximately 20% compared to administration in fasting state.

Distribution

Sotalol does not bind to plasma proteins. Distribution occurs to a central (plasma) and to a peripheral compartment. Sotalol crosses the blood brain barrier poorly.

Metabolism

Sotalol is not metabolized and is not expected to inhibit or induce any CYP450 enzymes.

Excretion

Excretion of sotalol is predominantly via the kidney in the unchanged form, and therefore lower doses are necessary in conditions of renal impairment [see DOSAGE AND ADMINISTRATION]. The mean elimination half-life of sotalol is 12 hours. Dosing every 12 hours results in trough plasma concentrations which are approximately one-half of those at peak.

Specific Populations

Pediatric: The combined analysis of a single-dose study and a multiple-dose study with 59 children, aged between 3 days and 12 years, showed the pharmacokinetics of sotalol to be first order. A daily dose of 30 mg/m² of sotalol was administered in the single dose study and daily doses of 30, 90 and 210 mg/m² were administered every 8 hours in the multi-dose study. After rapid absorption with peak levels occurring on average between 2–3 hours following administration, sotalol was eliminated with a mean half-life of 9.5 hours. Steady-state was reached after 1–2 days. The average peak to trough concentration ratio was 2. BSA was the most important covariate and more relevant than age for the pharmacokinetics of sotalol. The smallest children (BSA < 0.33m²) exhibited a greater drug exposure (+59%) than the larger children who showed a uniform drug concentration profile. The intersubject variation for oral clearance was 22%.

Geriatric: Age does not significantly alter the pharmacokinetics of Betapace/Betapace AF, but impaired renal function in geriatric patients can increase the terminal elimination half-life, resulting in increased drug accumulation.

Renal Impairment: Sotalol is mainly eliminated 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. The half-life of sotalol is prolonged (up to 69 hours) in anuric patients. Doses or dosing intervals should be adjusted based on creatinine clearance [see DOSAGE AND ADMINISTRATION].

Hepatic Impairment: Patients with hepatic impairment show no alteration in clearance of sotalol.

Drug-Drug Interactions

Antacids: Administration of oral sotalol within 2 hours of antacids may result in a reduction in Cmax and AUC of 26% and 20%, respectively, and consequently in a 25% reduction in the bradycardic effect at rest. Administration of the antacid two hours after oral sotalol has no effect on the pharmacokinetics or pharmacodynamics of sotalol.

No pharmacokinetic interactions were observed with hydrochlorothiazide or warfarin.

Clinical Studies

Ventricular Arrhythmias

Betapace (sotalol hydrochloride) has been studied in life-threatening and less severe arrhythmias. In patients with frequent premature ventricular complexes (VPC), Betapace (sotalol hydrochloride) was significantly superior to placebo in reducing VPCs, paired VPCs and non-sustained ventricular tachycardia (NSVT); the response was dose-related through 640 mg/day with 80–85% of patients having at least a 75% reduction of VPCs. Betapace was also superior, at the doses evaluated, to propranolol (40–80 mg TID) and similar to quinidine (200–400 mg QID) in reducing VPCs. In patients with life-threatening arrhythmias [sustained ventricular tachycardia/fibrillation (VT/VF)], Betapace was studied acutely [by suppression of programmed electrical stimulation (PES) induced VT and by suppression of Holter monitor evidence of sustained VT] and, in acute responders, chronically.

In a double-blind, randomized comparison of Betapace and procainamide given intravenously (total of 2 mg/kg Betapace vs. 19 mg/kg of procainamide over 90 minutes), Betapace suppressed PES induction in 30% of patients vs. 20% for procainamide (p=0.2).

In a randomized clinical trial [Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) Trial] comparing choice of antiarrhythmic therapy by PES suppression vs. Holter monitor selection (in each case followed by treadmill exercise testing) in patients with a history of sustained VT/VF who were also inducible by PES, the effectiveness acutely and chronically of Betapace was compared with that of 6 other drugs (procainamide, quinidine, mexiletine, propafenone, imipramine and pirmenol). Overall response, limited to first randomized drug, was 39% for Betapace and 30% for the pooled other drugs. Acute response rate for first drug randomized using suppression of PES induction was 36% for Betapace vs. a mean of 13% for the other drugs. Using the Holter monitoring endpoint (complete suppression of sustained VT, 90% suppression of NSVT, 80% suppression of VPC pairs, and at least 70% suppression of VPCs), Betapace yielded 41% response vs. 45% for the other drugs combined. Among responders placed on long-term therapy identified acutely as effective (by either PES or Holter), Betapace, when compared to the pool of other drugs, had the lowest two-year mortality (13% vs. 22%), the lowest two-year VT recurrence rate (30% vs. 60%), and the lowest withdrawal rate (38% vs. about 75–80%). The most commonly used doses of Betapace in this trial were 320– 480 mg/day (66% of patients), with 16% receiving 240 mg/day or less and 18% receiving 640 mg or more.

It cannot be determined, however, in the absence of a controlled comparison of Betapace vs. no pharmacologic treatment (for example, in patients with implanted defibrillators) whether Betapace response causes improved survival or identifies a population with a good prognosis.

Betapace has not been shown to enhance survival in patients with ventricular arrhythmias.

Clinical Studies In Supra-ventricular Arrhythmias

Betapace AF has been studied in patients with symptomatic AFIB/AFL in two principal studies, one in patients with primarily paroxysmal AFIB/AFL, the other in patients with primarily chronic AFIB.

In one study, a U.S. multicenter, randomized, placebo-controlled, double-blind, dose-response trial of patients with symptomatic primarily paroxysmal AFIB/AFL, three fixed dose levels of Betapace AF (80 mg, 120 mg and 160 mg) twice daily and placebo were compared in 253 patients. In patients with reduced creatinine clearance (40-60 mL/min) the same doses were given once daily. Patients were excluded for the following reasons: QT > 450 msec; creatinine clearance < 40 mL/min; intolerance to beta-blockers; bradycardia-tachycardia syndrome in the absence of an implanted pacemaker; AFIB/AFL was asymptomatic or was associated with syncope, embolic CVA or TIA; acute myocardial infarction within the previous 2 months; congestive heart failure; bronchial asthma or other contraindications to beta-blocker therapy; receiving potassium losing diuretics without potassium replacement or without concurrent use of ACE-inhibitors; uncorrected hypokalemia (serum potassium < 3.5 meq/L) or hypomagnesemia (serum magnesium < 1.5 meq/L); received chronic oral amiodarone therapy for > 1 month within previous 12 weeks; congenital or acquired long QT syndromes; history of Torsade de Pointes with other antiarrhythmic agents which increase the duration of ventricular repolarization; sinus rate < 50 bpm during waking hours; unstable angina pectoris; receiving treatment with other drugs that prolong the QT interval; and AFIB/AFL associated with the Wolff-Parkinson-White (WPW) syndrome. If the QT interval increased to ≥ 520 msec (or JT ≥ 430 msec if QRS > 100 msec) the drug was discontinued. The patient population in this trial was 64% male, and the mean age was 62 years. No structural heart disease was present in 43% of the patients. Doses were administered once daily in 20% of the patients because of reduced creatinine clearance.

Betapace AF was shown to prolong the time to the first symptomatic, ECG-documented recurrence of AFIB/AFL, as well as to reduce the risk of such recurrence at both 6 and 12 months. The 120 mg dose was more effective than 80 mg, but 160 mg did not appear to have an added benefit. Note that these doses were given twice or once daily, depending on renal function. The results are shown in Figure 2, Table 7 and Table 8.

Figure 2: Study 1 – Time to First ECG-Documented Recurrence of Symptomatic AFIB/AFL Since Randomization

Table 7: Study 1 – Patient Status at 12 Months

  Placebo Betapace AF Dose
80 mg 120 mg 160 mg
Randomized 69 59 63 62
On treatment in NSR at 12 months without recurrencea 23% 22% 29% 23%
Recurrenceab 67% 58% 49% 42%
D/C for AEs 6% 12% 18% 29%
a Symptomatic AFIB/AFL
b Efficacy endpoint of Study 1; study treatment stopped.
Note that columns do not add up to 100% due to discontinuations (D/C) for “other” reasons.

Table 8: Study 1 – Median Time to Recurrence of Symptomatic AFIB/AFL and Relative Risk (vs. Placebo) at 12 Months

  Placebo
n=69
Betapace AF Dose
80 mg
n=59
120 mg
n=63
160 mg
n=62
P-value vs. placebo   0.325 0.018 0.029
Relative Risk (RR) to placebo   0.81 0.59 0.59
Median time to recurrence (days) 27 106 229 175

Discontinuation because of adverse events was dose related.

In a second multicenter, randomized, placebo-controlled, double-blind study of 6 months duration in 232 patients with chronic AFIB, Betapace AF was titrated over a dose range from 80 mg/day to 320 mg/day. The patient population of this trial was 70% male with a mean age of 65 years. Structural heart disease was present in 49% of the patients. All patients had chronic AFIB for > 2 weeks but < 1 year at entry with a mean duration of 4.1 months. Patients were excluded if they had significant electrolyte imbalance, QTc > 460 msec, QRS > 140 msec, any degree of AV block or functioning pacemaker, uncompensated cardiac failure, asthma, significant renal disease (estimated creatinine clearance < 50 mL/min), heart rate < 50 bpm, myocardial infarction or open heart surgery in past 2 months, unstable angina, infective endocarditis, active pericarditis or myocarditis, ≥ 3 DC cardioversions in the past, medications that prolonged QT interval, and previous amiodarone treatment. After successful cardioversion patients were randomized to receive placebo (n=114) or Betapace AF (n=118), at a starting dose of 80 mg twice daily. If the initial dose was not tolerated it was decreased to 80 mg once daily, but if it was tolerated it was increased to 160 mg twice daily. During the maintenance period 67% of treated patients received a dose of 160 mg twice daily, and the remainder received doses of 80 mg once daily (17%) and 80 mg twice daily (16%).

Tables 9 and 10 show the results of the trial. There was a longer time to ECG-documented recurrence of AFIB and a reduced risk of recurrence at 6 months compared to placebo.

Table 9: Study 2 – Patient Status at 6 Months

  Placebo
n=114
Betapace AF
n=118
On treatment in NSR at 6 months without recurrencea 29% 45%
Recurrenceab 67% 49%
D/C for AEs 3% 6%
Death 1%  
a Symptomatic or asymptomatic AFIB/AFL
b Efficacy endpoint of Study 2; study treatment stopped.

Table 10: Study 2 – Median Time to Recurrence of Symptomatic AFIB/AFL/Death and Relative Risk (vs. Placebo) at 6 Months

  Placebo
n=114
Betapace AF
n=118
P-value vs. placebo   0.002
Relative Risk (RR) to placebo   0.55
Median time to recurrence (days) 44 > 180

Figure 3: Study 2 – Time to First ECG-Documented Recurrence of Symptomatic AFIB/AFL/Death Since Randomization

Clinical Studies In Patients With Myocardial Infarction

In a large double-blind, placebo controlled secondary prevention (postinfarction) trial (n=1,456); Betapace (sotalol hydrochloride) was given as a non-titrated initial dose of 320 mg once daily. Betapace did not produce a significant increase in survival (7.3% mortality on Betapace vs. 8.9% on placebo, p=0.3), but overall did not suggest an adverse effect on survival. There was, however, a suggestion of an early (i.e., first 10 days) excess mortality (3% on Betapace vs. 2% on placebo).

In a second small trial (n=17 randomized to Betapace) where Betapace was administered at high doses (for example, 320 mg twice daily) to high-risk post-infarction patients (ejection fraction < 40% and either > 10 VPC/hr or VT on Holter), there were 4 fatalities and 3 serious hemodynamic/electrical adverse events within two weeks of initiating Betapace.

Patient information

  • Advise patients to contact their health care provider in the event of syncope, pre-syncopal symptoms or cardiac palpitations.
  • Advise patients that their electrolytes and ECG will be monitored during treatment [see WARNINGS AND PRECAUTIONS].
  • Advise patients to contact their healthcare provider in the event of conditions that could lead to electrolyte changes such as severe diarrhea, unusual sweating, vomiting, less appetite than normal or excessive thirst [see WARNINGS AND PRECAUTIONS].
  • Advise patients not to change the Betapace/Betapace AF dose prescribed by their healthcare provider.
  • Advise patients that they should not miss a dose, but if they do miss a dose they should not double the next dose to compensate for the missed dose: they should take the next dose at the regularly scheduled time [see DOSAGE AND ADMINISTRATION].
  • Advise patients to not interrupt or discontinue Betapace/Betapace AF without their physician's advice, that they should get their prescription for sotalol filled and refilled on time so they do not interrupt treatment [see DOSAGE AND ADMINISTRATION].
  • Advise patients to not start taking other medications without first discussing new medications with their healcare provider.
  • Advice patients that they should avoid taking Betapace/Betapace AF within two hours of taking antacids that contain aluminum oxide or magnesium hydroxide [see DRUG INTERACTIONS].

Betapace Drug Class

Betapace is part of the drug class:

  • Beta blocking agents, non selective

What is Betapace (sotalol)?

Sotalol is a beta-blocker that affects the heart and circulation (blood flow through arteries and veins).

Sotalol is used to help keep the heart beating normally in people with certain heart rhythm disorders of the ventricles (the lower chambers of the heart that allow blood to flow out of the heart). Sotalol is used in people with ventricular tachycardia or ventricular fibrillation.

Another form of this medicine, called sotalol AF, is used to treat heart rhythm disorders of the atrium (the upper chambers of the heart that allow blood to flow into the heart). Sotalol AF is used in people with atrial fibrillation or atrial flutter.

Sotalol (Betapace, Sorine, Sotylize) is not used for the same conditions that sotalol AF (Betapace AF) is used for.

Sotalol may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Betapace (sotalol)?

You will receive your first few doses of sotalol in a hospital setting where your heart can be monitored in case the medicine causes serious side effects.

You should not use sotalol if you have asthma, certain serious heart conditions, or a history of Long QT syndrome.

What should I avoid while taking Betapace (sotalol)?

Avoid taking an antacid within 2 hours before or 2 hours after you take sotalol. Some antacids can make it harder for your body to absorb sotalol.

Betapace (sotalol) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;

  • slow heartbeats;

  • a light-headed feeling, like you might pass out;

  • trouble breathing;

  • severe diarrhea or vomiting, loss of appetite;

  • dry mouth, unusual sweating, increased thirst; or

  • swelling, rapid weight gain.

Common side effects may include:

  • headache;

  • dizziness;

  • tired feeling; or

  • slow heartbeats.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Commonly used brand name(s)

In the U.S.

  • Betapace
  • Betapace AF
  • Sorine
  • Sotylize

Available Dosage Forms:

  • Tablet
  • Solution

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Beta-Adrenergic Blocker, Nonselective

How is this medicine (Betapace) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Take Betapace at the same time of day.
  • Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
  • Do not take antacids that have aluminum or magnesium in them within 2 hours of Betapace.
  • A liquid (suspension) can be made if you cannot swallow pills. Talk with your doctor or pharmacist.
  • If a liquid (suspension) is made, shake well before use.

Liquid (suspension):

  • Measure liquid doses carefully. Use the measuring device that comes with this medicine. If there is none, ask the pharmacist for a device to measure Betapace.

What do I do if I miss a dose?

  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

How do I store and/or throw out Betapace?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • If a liquid (suspension) is made from the tablets, store at room temperature. Throw away any part not used after 3 months.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Warnings and Precautions

QT Prolongation and Proarrhythmia

Betapace/Betapace AF can cause serious and potentially fatal ventricular arrhythmias such as sustained VT/VF, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QT interval prolongation. Factors such as reduced creatinine clearance, female sex, higher doses, reduced heart rate and history of sustained VT/VF or heart failure 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 the QT interval [see Dosage and Administration (2.1)].

Correct hypokalemia or hypomagnesemia prior to initiating Betapace/Betapace AF, as these conditions can exaggerate the degree of QT prolongation, and 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.

Proarrhythmic events must be anticipated not only on initiating therapy, but with every upward dose adjustment [see Dosage and Administration (2.1)].

In general, do not use sotalol with other drugs known to cause QT prolongation [see Drug Interactions (7.1)].

Bradycardia/Heart Block/Sick Sinus Syndrome

Sinus bradycardia (heart rate less than 50 bpm) occurred in 13% of patients receiving sotalol in clinical trials, and led to discontinuation in about 3% of patients. Bradycardia itself increases the risk of Torsade de Pointes. Sinus pause, sinus arrest and sinus node dysfunction occur in less than 1% of patients. The incidence of 2nd- or 3rd-degree AV block is approximately 1%.

Betapace/Betapace AF is contraindicated in patients with sick sinus syndrome because it may cause sinus bradycardia, sinus pauses or sinus arrest.

Hypotension

Sotalol produces significant reductions in both systolic and diastolic blood pressures and may result in hypotension. Monitor hemodynamics in patients with marginal cardiac compensation.

Heart Failure

New onset or worsening heart failure may occur during initiation or uptitration of sotalol because of its beta-blocking effects. Monitor for signs and symptoms of heart failure and discontinue treatment if symptoms occur.

Cardiac Ischemia after Abrupt Discontinuation

Following abrupt cessation of therapy with beta adrenergic blockers, exacerbations of angina pectoris and myocardial infarction may occur. When discontinuing chronically administered Betapace/Betapace AF, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of 1–2 weeks, if possible, and monitor the patient. If angina markedly worsens or acute coronary ischemia develops, treat appropriately (consider use of an alternative beta blocker). Warn patients not to interrupt therapy without their physician’s advice. Because coronary artery disease may be common, but unrecognized, in patients treated with sotalol, abrupt discontinuation may unmask latent coronary insufficiency.

Bronchospasm

Patients with bronchospastic diseases (for example chronic bronchitis and emphysema) should not receive beta-blockers. If Betapace/Betapace AF is to be administered, use the smallest effective dose, to minimize inhibition of bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta 2 receptors.

Masked Signs of Hypoglycemia in Diabetics

Beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. Elevated blood glucose levels and increased insulin requirements can occur in diabetic patients.

Thyroid Abnormalities

Avoid abrupt withdrawal of beta-blockade in patients with thyroid disease because it may lead to an exacerbation of symptoms of hyperthyroidism, including thyroid storm. Beta-blockade may mask certain clinical signs (for example, tachycardia) of hyperthyroidism.

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.

Major Surgery

Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Betapace Description

Betapace/Betapace AF contains sotalol hydrochloride, an antiarrhythmic drug with Class II (beta-adrenoreceptor blocking) and Class III (cardiac action potential duration prolongation) properties. Betapace is supplied as a light-blue, capsule-shaped tablet for oral administration. Betapace AF is supplied as a white, capsule-shaped tablet for oral administration. Sotalol hydrochloride is a white, crystalline solid with a molecular weight of 308.8. It is hydrophilic, soluble in water, propylene glycol and ethanol, but is only slightly soluble in chloroform. Chemically, sotalol hydrochloride is d,l-N-[4-[1-hydroxy-2-[(1-methylethyl) amino]ethyl]phenyl]methane-sulfonamide monohydrochloride. The molecular formula is C12H20N2O3 S·HCl and is represented by the following structural formula:

Betapace Tablets contain the following inactive ingredients: microcrystalline cellulose, lactose, starch, stearic acid, magnesium stearate, colloidal silicon dioxide, and FD&C blue color #2 (aluminum lake, conc.).

Betapace AF Tablets contain the following inactive ingredients: microcrystalline cellulose, lactose, starch, stearic acid, magnesium stearate, and colloidal silicon dioxide.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenic potential was observed in rats during a 24-month study at 137–275 mg/kg/day (approximately 30 times the maximum recommended human oral dose (MRHD) as mg/kg or 5 times the MRHD as mg/m2) or in mice, during a 24-month study at 4141–7122 mg/kg/day (approximately 450–750 times the MRHD as mg/kg or 36–63 times the MRHD as mg/m2).

Sotalol has not been evaluated in any specific assay of mutagenicity or clastogenicity.

No significant reduction in fertility occurred in rats at oral doses of 1000 mg/kg/day (approximately 100 times the MRHD as mg/kg or 18 times the MRHD as mg/m2) prior to mating, except for a small reduction in the number of offspring per litter.

Reproduction studies in rats and rabbits during organogenesis at 100 and 22 times the MRHD as mg/kg (9 and 7 times the MRHD as mg/m2), respectively, did not reveal any teratogenic potential associated with sotalol HCl. In rabbits, a high dose of sotalol HCl (160 mg/kg/day) at 16 times the MRHD as mg/kg (6 times the MRHD as mg/m2) produced a slight increase in fetal death, and maternal toxicity. Eight times the maximum dose (80 mg/kg/day or 3 times the MRHD as mg/m2) did not result in an increased incidence of fetal deaths. In rats, 1000 mg/kg/day sotalol HCl, 100 times the MRHD (18 times the MRHD as mg/m2), increased the number of early resorptions, while at 14 times the maximum dose (2.5 times the MRHD as mg/m2), no increase in early resorptions was noted. However, animal reproduction studies are not always predictive of human response.

PRINCIPAL DISPLAY PANEL - 160 mg Betapace AF

NDC 70515-116-06
60 tablets unit of use

Betapace AF®
(sotalol HCl)
Patient Pack

160 mg

Rx only

COVIS          84607460

Each tablet contains 160 mg
of sotalol hydrochloride.

Dosage: Take as prescribed by
your physician.

Please see patient information.

Store at 25°C (77°F); excursions
permitted to 15-30°C (59-86°F)
[See USP Controlled Room
Temperature].

Manufactured for:
Covis Pharma
Zug, 6300 Switzerland

Made in Switzerland     Rev. 5/16

Betapace 
sotalol hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:70515-105
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SOTALOL HYDROCHLORIDE (SOTALOL) SOTALOL HYDROCHLORIDE 80 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE  
STARCH, CORN  
STEARIC ACID  
MAGNESIUM STEARATE  
SILICON DIOXIDE  
FD&C BLUE NO. 2  
Product Characteristics
Color BLUE (light) Score 2 pieces
Shape OVAL Size 12mm
Flavor Imprint Code Betapace;80;MG
Contains     
Packaging
# Item Code Package Description
1 NDC:70515-105-10 100 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA019865 09/01/2016
Betapace 
sotalol hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:70515-109
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SOTALOL HYDROCHLORIDE (SOTALOL) SOTALOL HYDROCHLORIDE 120 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE  
STARCH, CORN  
STEARIC ACID  
MAGNESIUM STEARATE  
SILICON DIOXIDE  
FD&C BLUE NO. 2  
Product Characteristics
Color BLUE (light) Score 2 pieces
Shape OVAL Size 14mm
Flavor Imprint Code Betapace;120;MG
Contains     
Packaging
# Item Code Package Description
1 NDC:70515-109-10 100 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA019865 09/01/2016
Betapace 
sotalol hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:70515-106
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SOTALOL HYDROCHLORIDE (SOTALOL) SOTALOL HYDROCHLORIDE 160 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE  
STARCH, CORN  
STEARIC ACID  
MAGNESIUM STEARATE  
SILICON DIOXIDE  
FD&C BLUE NO. 2  
Product Characteristics
Color BLUE (light) Score 2 pieces
Shape OVAL Size 15mm
Flavor Imprint Code Betapace;160;MG
Contains     
Packaging
# Item Code Package Description
1 NDC:70515-106-10 100 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA019865 09/01/2016
Betapace AF 
sotalol hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:70515-115
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SOTALOL HYDROCHLORIDE (SOTALOL) SOTALOL HYDROCHLORIDE 80 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE  
STARCH, CORN  
STEARIC ACID  
MAGNESIUM STEARATE  
SILICON DIOXIDE  
Product Characteristics
Color WHITE Score 2 pieces
Shape OVAL Size 12mm
Flavor Imprint Code BHCP;80;MG
Contains     
Packaging
# Item Code Package Description
1 NDC:70515-115-06 60 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021151 09/01/2016
Betapace AF 
sotalol hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:70515-119
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SOTALOL HYDROCHLORIDE (SOTALOL) SOTALOL HYDROCHLORIDE 120 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE  
STARCH, CORN  
STEARIC ACID  
MAGNESIUM STEARATE  
SILICON DIOXIDE  
Product Characteristics
Color WHITE Score 2 pieces
Shape OVAL Size 14mm
Flavor Imprint Code BHCP;120;MG
Contains     
Packaging
# Item Code Package Description
1 NDC:70515-119-06 60 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021151 09/01/2016
Betapace AF 
sotalol hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:70515-116
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SOTALOL HYDROCHLORIDE (SOTALOL) SOTALOL HYDROCHLORIDE 160 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE  
STARCH, CORN  
STEARIC ACID  
MAGNESIUM STEARATE  
SILICON DIOXIDE  
Product Characteristics
Color WHITE Score 2 pieces
Shape OVAL Size 15mm
Flavor Imprint Code BHCP;160;MG
Contains     
Packaging
# Item Code Package Description
1 NDC:70515-116-06 60 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021151 09/01/2016
Labeler - Covis Pharma (486209070)
Revised: 05/2016   Covis Pharma

What should i avoid while taking sotalol (betapace, sorine)?

Avoid taking an antacid within 2 hours before or after you take sotalol. Some antacids can make it harder for your body to absorb sotalol.

For Healthcare Professionals

Applies to sotalol: intravenous solution, oral solution, oral tablet

Cardiovascular

Very common (10% or more): Bradycardia (up to 16%), chest pain (up to 16%), palpitation (up to 14%)
Common (1% to 10%): Edema, abnormal ECG, hypotension, proarrhythmia (including Torsade de Pointes), syncope, heart failure, presyncope, vasodilation, Automatic Implantable Cardioverter-Defibrillator (AICD) discharge, hypertension, stroke[Ref]

Nervous system

Very common (10% or more): Fatigue (up to 20%), dizziness (up to 20%), asthenia (up to 13%), light headedness (up to 12%)
Common (1% to 10%): Headache, perspiration, paresthesia[Ref]

Respiratory

Very common (10% or more): Dyspnea (up to 21%)
Common (1% to 10%): Pulmonary problem, upper respiratory tract problem, asthma[Ref]

Gastrointestinal

Very common (10% or more): Nausea/vomiting (up to 10%)
Common (1% to 10%): Appetite disorder, diarrhea, dyspepsia, abdominal pain, colon problem, flatulence, cramps[Ref]

Metabolic

Common (1% to 10%): Weight change[Ref]

Dermatologic

Common (1% to 10%): Rash[Ref]

Musculoskeletal

Common (1% to 10%): Extremity pain, back pain[Ref]

Genitourinary

Common (1% to 10%): Genitourinary disorder, sexual dysfunction[Ref]

Hematologic

Common (1% to 10%): Bleeding[Ref]

Immunologic

Common (1% to 10%): Infection[Ref]

Local

Common (1% to 10%): Localized pain[Ref]

Ocular

Common (1% to 10%): Vision problem[Ref]

Other

Common (1% to 10%): Fever, abnormal lab value
Frequency not reported: Taste abnormalities, hearing disturbances[Ref]

Psychiatric

Common (1% to 10%): Depression, sleep problem, altered consciousness, anxiety, mood change[Ref]

Some side effects of Betapace may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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