This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
BETAPACE®/BETAPACE AF safely and effectively. See fullprescribing information for BETAPACE/BETAPACE AF.
BETAPACE (sotalol hydrochloride) tablets, for oral use
Initial U.S. Approval: 1992
BETAPACE AF (sotalol hydrochloride) tablets, for oral use
Initial U.S. Approval: 1992

•
•
•
•

WARNING: LIFE-THREATENING PROARRHYTHMIA
See full prescribing information for complete boxed warning.
Betapace/Betapace AF can cause life-threatening ventriculartachycardia 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.

----------------------------INDICATIONS AND USAGE--------------------------Betapace/Betapace AF 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•
Betapace has not been shown to enhance survival in patients with life
threatening ventricular arrhythmias (1.1)•
Avoid use in patients with minimally symptomatic or easily reversible
AFIB/AFL (1.2)----------------------DOSAGE AND ADMINISTRATION-----------------------•
Betapace/Betapace AF: Initial dosage in adults is 80 mg twice daily.
Increase the dose as needed in increments of 80 mg/day, every 3 days toa maximum 320 mg total daily dose (2.2)•
Pediatrics: Dosage depends on age (2.4)----------------------DOSAGE FORMS AND STRENGTHS--------------------80 mg, 120 mg, and 160 mg tablets (3)------------------------------CONTRAINDICATIONS-------------------------------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 msec (4)-----------------------WARNINGS AND PRECAUTIONS-----------------------•QT prolongation, bradycardia, AV block, hypotension, worsening
heart failure: Reduce dose or discontinue (5.1)•
Acute exacerbation of coronary artery disease upon cessation oftherapy: Do not abruptly discontinue (5.5)•
Correct any electrolyte disturbances (5.1)•
Diabetes: May mask symptoms of hypoglycemia and alter
glucose levels; monitor (5.7)-----------------------------ADVERSE REACTIONS------------------------------The most common adverse reactions (≥2%) for Betapace 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 Covis
Pharma at 1-866-488-4423 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
------------------------------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 ofbradycardia, hypotension, heart failure (7.2)•
Dosage of insulin or antidiabetic drugs may need adjustment (7.4)•
Aluminum- or magnesium-based antacids reduce sotalol exposure (7.7)---------------------------USE IN SPECIFIC POPULATIONS--------------------•
Lactation: Do not breastfeed (8.2)
See 17 for PATIENT COUNSELING INFORMATION

Revised: 06/2023

FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: LIFE-THREATENING PROARRHYTHMIA 1
INDICATIONS AND USAGE
1.1 Life-Threatening Ventricular Arrhythmias
1.2 Delay in Recurrence of Atrial Fibrillation/Atrial Flutter(AFIB/AFL)
2
DOSAGE AND ADMINISTRATION
2.1 General Safety Measures for Initiation of Oral Sotalol Therapy
2.2 Adult Dose for Ventricular Arrhythmias
2.3 Adult Dose for Prevention of Recurrence of AFIB/AFL
2.4 Pediatric Dose for Ventricular Arrhythmias or AFIB/AFL
2.5 Dosage for Patients with Renal Impairment
2.6 Preparation of Extemporaneous Oral Solution
3
DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS5WARNINGS AND PRECAUTIONS
5.1 QT Prolongation and Proarrhythmia
5.2 Bradycardia/Heart Block/Sick Sinus Syndrome
5.3 Hypotension
5.4 Heart Failure
5.5 Cardiac Ischemia after Abrupt Discontinuation
5.6 Bronchospasm
5.7 Masked Signs of Hypoglycemia in Diabetics
5.8 Thyroid Abnormalities
5.9 Anaphylaxis
5.10 Major Surgery
6
ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7
DRUG INTERACTIONS
7.1 Antiarrhythmics and Other QT Prolonging Drugs
7.2 Negative Chronotropes

Reference ID: 5194805

8

10
11
12

13
14
16
17

7.3 Catecholamine-Depleting Agents
7.4 Insulin and Oral Antidiabetics
7.5 Beta-2-Receptor Stimulants
7.6 Clonidine
7.7 Antacids
7.8 Drug/Laboratory Test Interactions
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.3 Females and Males of Reproductive Potential
8.4 Pediatric Use
8.6 Renal Impairment
OVERDOSAGEDESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
CLINICAL STUDIES
14.1 Ventricular Arrhythmias
14.2 Supraventricular Arrhythmias
HOW SUPPLIED/STORAGE AND HANDLINGPATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are notlisted.

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

FULL PRESCRIBING INFORMATIONWARNING: 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 dosinginterval, or discontinue the drug.
Calculate creatinine clearance to determine appropriate dosing [see Dosage andAdministration (2.5)].

1

INDICATIONS AND USAGE

1.1

Life-Threatening Ventricular Arrhythmias

Betapace/Betapace AF is indicated for the treatment of documented, life-threatening ventriculararrhythmias, such as sustained ventricular tachycardia (VT).
Limitation of Use:
Betapace/Betapace AF has not been shown to enhance survival in patients with life-threatening
ventricular arrhythmias.
1.2

Delay in Recurrence of Atrial Fibrillation/Atrial Flutter (AFIB/AFL)

Betapace/Betapace AF is indicated for the maintenance of normal sinus rhythm (delay in time torecurrence of AFIB/AFL) in patients with highly symptomatic AFIB/AFL who are currently insinus rhythm.
Limitation of Use:
Because Betapace/Betapace AF can cause life-threatening ventricular arrhythmias, reserve its
use for patients in whom AFIB/AFL is highly symptomatic. Patients with paroxysmal AFIB thatis easily reversed (by Valsalva maneuver, for example) should usually not be given
Betapace/Betapace AF.

Reference ID: 5194805

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2

DOSAGE AND ADMINISTRATION

2.1

General Safety Measures for Initiation of Oral Sotalol Therapy

Withdraw other antiarrhythmic therapy before starting Betapace/Betapace AF and monitor for aminimum of 2 to 3 plasma half-lives prior to initiating Betapace/Betapace AF therapy if thepatient's clinical condition permits [see Drug Interactions (7)].
Hospitalize patients being initiated or re-initiated on sotalol for at least 3 days or until steadystate 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 trainedin 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 theappropriate dosing interval. Monitor QTc 2 to 4 hours after each uptitration in 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 doseor 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, atherapeutic response is obtained at a total daily dose of 160 to 320 mg/day, given in two or three
divided doses. Oral doses as high as 480 to 640 mg/day have been utilized in patients withrefractory 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 havesatisfactory response with 120 mg twice daily. Initiation of sotalol in patients with QTc >450
msec is contraindicated [see Contraindications (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 bodysurface area are appropriate for both initial and incremental dosing. Since the Class III potency in

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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)].
For initiation of treatment, 1.2 mg/kg three times a day (3.6 mg/kg total daily dose) is
approximately equivalent to the initial 160 mg total daily dose for adults. Subsequent titration toa maximum of 2.4 mg/kg three times a day (approximately equivalent to the 360 mg total daily
dose for adults) can then occur. Titration should be guided by clinical response, heart rate, andQTc, with increased dosing being preferably conducted in-hospital. Allow at least 36 hours
between dose increments to attain steady-state plasma concentrations of sotalol in patients withage-adjusted normal renal function.
For Children Aged About 2 Years or Younger
For children aged about 2 years or younger, the pediatric dosage should be reduced by a factor
that depends upon age, as shown in the following graph (age plotted on a logarithmic scale inmonths):For a child aged 1 month, multiply the starting dose by 0.7; the initial starting dose would be(1.2 mg/kg X 0.7)=0.8 mg/kg, administered three times daily. For a child aged about 1 week,
multiply the initial starting dose by 0.3; the starting dose would be (1.2 mg/kg X 0.3)=0.4 mg/kg.
Use similar calculations for dose titration.

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2.5

Dosage for Patients with Renal Impairment

AdultsIn any age group with decreased renal function, sotalol doses should be lowered or the intervals
between doses increased. 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 atappropriate intervals (Table 1). Sotalol is partly removed by dialysis; specific advice isunavailable on dosing patients on dialysis.
Administer the initial dose of 80 mg and subsequent doses at the intervals listed in Table 1.
Table 1: Dosing Intervals in Renal Impairment
Creatinine Clearance mL/min
>60
30–59
10–29
<10
2.6

Dosing Interval (hours)
12
24
36–48
Dose should be individualized

Preparation of Extemporaneous Oral Solution

Betapace/Betapace AF Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1%
sodium benzoate (Syrup, NF) as follows:
1. Measure 120 mL of Simple Syrup.
2. 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.
3. Add five (5) Betapace/Betapace AF 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, take care totransfer the entire quantity of tablet powder into the bottle containing the syrup.
4. 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.
5. Allow the tablets to hydrate for at least two hours.
6. After at least two hours have elapsed, shake the bottle intermittently over the course of atleast another two hours until the tablets are completely disintegrated. The tablets can beallowed to hydrate overnight to simplify the disintegration process.
The endpoint is achieved when a dispersion of fine particles in the syrup is obtained.

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This compounding procedure results in a solution containing 5 mg/mL of sotalol HCl. The finesolid 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.
3

DOSAGE FORMS AND STRENGTHS

Betapace is supplied as capsule-shaped, light-blue, scored tablets:• 80 mg imprinted with “BETAPACE” on one side and 80 mg on the other• 120 mg imprinted with “BETAPACE” on one side and 120 mg on the other• 160 mg imprinted with “BETAPACE” on one side and 160 g on the other
Betapace AF is supplied as capsule-shaped, white scored tablet:• 80 mg imprinted with “BHCP” on one side and 80 mg on the other• 120 mg imprinted with “BHCP” on one side and 120 mg on the other• 160 mg imprinted with “BHCP” on one side and 160 mg on the other4

CONTRAINDICATIONS

Betapace/Betapace AF is contraindicated in patients with:• Sinus bradycardia, sick sinus syndrome, second and third degree AV block, unless afunctioning 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, Betapace/Betapace AF is also contraindicated in patients with:• Baseline QT interval >450 msec

Reference ID: 5194805

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5

WARNINGS AND PRECAUTIONS

5.1

QT Prolongation and Proarrhythmia

Betapace/Betapace AF can cause serious and potentially fatal ventricular arrhythmias such assustained VT/VF, primarily Torsade de Pointes (TdP) type ventricular tachycardia, apolymorphic ventricular tachycardia associated with QT interval prolongation. Factors such as
reduced creatinine clearance, female sex, higher doses, reduced heart rate, and history ofsustained VT/VF or heart failure increase the risk of TdP. The risk of TdP can be reduced byadjustment of the sotalol dose according to creatinine clearance and by monitoring the ECG forexcessive 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)].
Avoid use with other drugs known to cause QT prolongation [see Drug Interactions (7.1)].
5.2

Bradycardia/Heart Block/Sick Sinus Syndrome

Sinus bradycardia (heart rate less than 50 bpm) occurred in 13% of patients receiving sotalol inclinical trials, and led to discontinuation in about 3% of patients. Bradycardia itself increases therisk of Torsade de Pointes. Sinus pause, sinus arrest and sinus node dysfunction occur in lessthan 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.
5.3

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.
5.4

Heart Failure

New onset or worsening heart failure may occur during initiation or uptitration of sotalol becauseof its beta-blocking effects. Monitor for signs and symptoms of heart failure and discontinue
treatment if symptoms occur.
5.5

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 administeredBetapace/Betapace AF, particularly in patients with ischemic heart disease, gradually reduce theReference ID: 5194805

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dosage over a period of 1 to 2 weeks, if possible, and monitor the patient. If angina markedly
worsens or acute coronary ischemia develops, treat appropriately and consider use of analternative beta-blocker. Warn patients not to interrupt therapy without their physician’s advice.
Because coronary artery disease is common, but may be unrecognized, the abrupt
discontinuation of sotalol may unmask latent coronary insufficiency.
5.6

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.
5.7

Effects on Blood Sugar

Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, andincrease the risk for severe or prolonged hypoglycemia at any time during treatment, especiallyin patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, noteating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed toseek emergency treatment. Elevated blood glucose levels and increased insulin requirements canoccur in diabetic patients.
5.8

Thyroid Abnormalities

Avoid abrupt withdrawal of beta-blockade in patients with thyroid disease because it may lead toan exacerbation of symptoms of hyperthyroidism, including thyroid storm. Beta-blockade maymask certain clinical signs (for example, tachycardia) of hyperthyroidism.
5.9

Anaphylaxis

While taking beta-blockers, patients with a history of anaphylactic reaction to a variety ofallergens may have a more severe reaction on repeated challenge, either accidental, diagnostic, ortherapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat theallergic reaction.
5.10 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.
6

ADVERSE REACTIONS

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 trialsof another drug and may not reflect the rates observed in practice.

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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
Betapace/Betapace AF can cause serious and potentially fatal ventricular arrhythmias such assustained VT/VF, primarily Torsade de Pointes (TdP) [see Warnings and Precautions (5.1)].
The effect on QT and the risk of Torsade de Pointes are both dose related.
Pediatric Patients
In an unblinded multicenter trial of 25 pediatric patients aged ≤ 1 month to 12 years with SVT
and/or VT receiving daily doses of 30, 90, and 210 mg/m2 with dosing every 8 hours for a totalof 9 doses, no Torsade de Pointes or other serious new arrhythmias were observed. The clinical
trial safety profile in pediatric patients was similar to that in adult patients. Both the Class III
and beta-blocking effects of sotalol were linearly related to the plasma concentration [seeClinical Pharmacology (12.2)].
Atrial Fibrillation/Atrial Flutter
Placebo-controlled Clinical Trials
In a pooled clinical trial population consisting of 4 placebo-controlled studies with 275 patientswith atrial fibrillation (AFIB)/atrial flutter (AFL) treated with 160 to 320 mg of Betapace AF, thefollowing adverse reactions presented in Table 2 occurred in at least 2% of placebo-treatedpatients and at a lesser rate than Betapace-treated patients. The data are presented by incidence ofreactions in the Betapace AF and placebo groups by body system and daily dose.
Table 2: Incidence (%) of Common Adverse Reactions (≥ 2% in the Placebo Group andLess Frequent Than in the Betapace AF Groups) in Four Placebo-controlled
Studies of Patients with AFIB/AFL
Adverse Reaction

Placebo
N = 282 (%)

Bradycardia
Diarrhea
Nausea/Vomiting
Fatigue
Hyperhidrosis
Weakness
Dizziness
HeadacheDyspnea

Reference ID: 5194805

3
2
5
9
3
3
12
5
7

Betapace AF Total Daily Dose
160-240 mg>240-320 mg
N = 153 (%)
N = 122 (%)
13
12
5
6
8
6
20
19
5
5
5
5
16
13
3
12
9
10

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

Overall, discontinuation because of unacceptable adverse events was necessary in 17% of thepatients and occurred in 10% of patients less than two weeks after starting treatment. The mostcommon adverse reactions leading to discontinuation of Betapace AF were: fatigue 4.6%,
bradycardia 2.4%, proarrhythmia 2.2%, dyspnea 2%, and QT interval prolongation 1.4%.
6.2

Postmarketing Experience

The following adverse drug reactions have been identified during post-approval use of sotalol.
Because these reactions are reported voluntarily from a population of uncertain size, it is notalways possible to reliably estimate their frequency or establish a causal relationship to drug
exposure: emotional lability, slightly clouded sensorium, incoordination, vertigo, paralysis,
thrombocytopenia, eosinophilia, leukopenia, photosensitivity reaction, fever, pulmonary edema,
hyperlipidemia, myalgia, pruritis, and alopecia.
7

DRUG INTERACTIONS

7.1

Antiarrhythmics and Other QT Prolonging Drugs

Discontinue Class I or Class III antiarrhythmic agents for at least three half-lives prior to dosingwith sotalol. Class Ia antiarrhythmic drugs, such as disopyramide, quinidine, and procainamide,and other Class III drugs (for example, amiodarone) are not recommended as concomitanttherapy with Betapace/Betapace AF, because of their potential to prolong refractoriness [seeWarnings and Precautions (5.2)].
7.2

Negative Chronotropes

Digitalis glycosides, diltiazem, verapamil, and beta-blockers slow atrioventricular conduction
and decrease heart rate. Concomitant use with negative chronotropes can increase the risk ofbradycardia or hypotension.
7.3

Catecholamine-Depleting Agents

Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with abeta-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.
7.4

Insulin and Oral Antidiabetics

Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require
adjustment [see Warnings and Precautions 5.7)].
7.5

Beta-2-Receptor Stimulants

Beta-agonists such as albuterol, terbutaline and isoproterenol may have to be administered inincreased dosages when used concomitantly with sotalol.

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7.6

Clonidine

Concomitant use with sotalol increases the risk of bradycardia and AV block. Because betablockers 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 andmagnesium hydroxide.
7.8

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.
8

USE IN SPECIFIC POPULATIONS

8.1

Pregnancy

Risk Summary
Both the untreated underlying condition in pregnancy and the use of sotalol in pregnancy cause
adverse outcomes to the mother and fetus/neonate (see Clinical Considerations). In animal
reproduction studies in rats, early resorptions were increased at 15 times the maximum
recommended human dose (MRHD). In rabbits an increase in fetal death was observed at 2 times
the MRHD administered as a single dose. Sotalol did not reveal any teratogenic potential in rats
or rabbits at 15 and 2 times the MRHD respectively (see Data).
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The
estimated background risk of major birth defects and miscarriage for the indicated population is
unknown. In the United States (U.S.) general population, the estimated background risk of majorbirth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%,
respectively.
Clinical Considerations
The incidence of VT is increased and may be more symptomatic during pregnancy. Most
tachycardia episodes are initiated by ectopic beats and the occurrence of arrhythmia episodes
may, therefore, increase during pregnancy. Breakthrough arrhythmias may also occur during
pregnancy, as therapeutic treatment levels may be difficult to maintain due to the increased
volume of distribution and increased drug metabolism inherent in the pregnant state.
Fetal/Neonatal Adverse Reactions
Sotalol has been shown to cross the placenta and is found in amniotic fluid. From publishedobservational studies, the potential fetal adverse effects of sotalol use during pregnancy are

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growth restriction, transient fetal bradycardia, hyperbilirubinemia, hypoglycemia, uterine
contractions, and possible intrauterine death. Sotalol may have a greater effect on QT
prolongation in the immature heart than in the adult heart, and therefore, conveys an increased
risk of serious fetal arrhythmia and/or possible intrauterine death. Monitor the newborn for
symptoms of beta blockade.
Labor or Delivery
Generally, risk of arrhythmias increases during the labor and delivery process; therefore,
considering the proarrhythmia potential of the drug, patients treated with sotalol should bemonitored continuously during labor and delivery.
Data

Animal Data
Reproduction studies in rats and rabbits administered sotalol during organogenesis at 15 times
and 2 times the MRHD as mg/m2, respectively, did not reveal any teratogenic potential
associated with sotalol.
In pregnant rats, sotalol doses administered during organogenesis at approximately 15 times the
MRHD as mg/m2, increased the number of early resorptions, while no increase in earlyresorptions was noted at 2 times the MRHD as mg/m2.
In reproductive studies in rabbits, a sotalol dose (160 mg/kg/day) at 5 times the MRHD as
mg/m2 produced a slight increase in fetal death, and maternal toxicity. However, one study frompublished data reported an increase in fetal deaths in rabbits receiving a single dose (50 mg/kg)
at 2 times the MRHD as mg/m2 on gestation day 14.
8.2

Lactation

Risk Summary
Limited available data from published literature report that sotalol is present in human milk. The
estimated daily infant dose of sotalol received from breastmilk is 0.8-3.4 mg/kg, estimated at
22 to 25.5% of the maternal weight-adjusted dosage of Betapace (see Data). The amount of the
drug in breast milk is similar to the neonatal therapeutic dosage. Therefore, there is potential forbradycardia and other symptoms of beta blockade such as dry mouth, skin or eyes, diarrhea orconstipation in the breastfed infant. There is no information regarding the effects of sotalol on
milk production. Because of the potential serious adverse reactions to the breastfed child and thehigh level of sotalol in breast milk, advise women not to breastfeed while on treatment with
Betapace.
Data
Sotalol is present in human milk in high levels. A prospective study evaluated 20 paired samplesof breast milk and maternal blood from 5 mothers who elected to breastfeed. Breast milk samples
had a mean sotalol concentration of 10.5 µg/mL (± 1.1 µg/mL; range: 4.8 to 20.2 µg/mL)

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compared to a simultaneous mean maternal plasma concentration of 2.3 µg/mL (± 0.3 µg/mL;
range: 0.8 to 5.0 µg/mL). The mean milk plasma ratio was 5.4:1 (range: 2.2 to 8.8). The
estimated daily infant dose was 0.8-3.4 mg/kg, estimated at 22 to 25.5% of the maternal weightadjusted dosage of sotalol. This is similar to recommended therapeutic dose in neonates. None of
the mothers reported any adverse reactions in the breastfed infant.
8.3

Females and Males of Reproductive Potential

Infertility
Based on the published literature, beta blockers (including sotalol) may cause erectile
dysfunction.
8.4

Pediatric Use

The safety and effectiveness of sotalol in children have not been established. However, theClass III electrophysiologic and beta-blocking effects, the pharmacokinetics, and the relationshipbetween 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)].
Associated side effects of sotalol use in pediatric patients are those typical of a beta-blocking
agent, and lead to discontinuation of the drug in 3 to 6% of patients. As in adults, the Class III
antiarrhythmic action of sotalol in pediatric patients is associated with a significant
proarrhythmic potential for adverse effects. In pediatric patients, the incidence of proarrhythmicside effects of sotalol varies from 0 to 22%; however, sotalol-induced Torsade de Pointes
tachycardias are observed less frequently in the pediatric population.
Proarrhythmic effects of sotalol in pediatric patients included increased ventricular ectopy andexacerbation of bradycardia, the latter predominantly in patients with sinus node dysfunction
following surgery for congenital cardiac defects. Bradycardia may require emergency pacemaker
implantation. Close in-patient monitoring is recommended for several days.
8.6

Renal Impairment

Sotalol is mainly eliminated via the kidneys. Adjust dosing intervals based on creatinine
clearance [see Dosage and Administration (2.5)].
10 OVERDOSAGE
Intentional or accidental overdosage with sotalol has resulted in death.
Symptoms and Treatment of Overdosage
The most common signs to be expected are bradycardia, congestive heart failure, hypotension,bronchospasm, and hypoglycemia. In cases of massive intentional overdosage (2 to 16 grams) of
sotalol the following clinical findings were seen: hypotension, bradycardia, cardiac asystole,

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prolongation of QT interval, Torsade de Pointes, ventricular tachycardia, and premature
ventricular complexes. If overdosage occurs, therapy with sotalol should be discontinued and thepatient observed closely. Because of the lack of protein binding, hemodialysis is useful for
reducing sotalol plasma concentrations. Patients should be carefully observed until QT intervals
are normalized and the heart rate returns to levels >50 bpm.
The occurrence of hypotension following an overdose may be associated with an initial slow
drug elimination phase (half-life of 30 hours) thought to be due to a temporary reduction of renal
function caused by the hypotension. In addition, if required, the following therapeutic measures
are suggested:
Bradycardia or Cardiac Asystole: Atropine, another anticholinergic drug, a beta-adrenergic
agonist, or transvenous cardiac pacing.
Heart Block: (second and third degree) transvenous cardiac pacemaker.
Hypotension: (depending on associated factors) epinephrine rather than isoproterenol ornorepinephrine may be useful.
Bronchospasm: Aminophylline or aerosol beta-2-receptor stimulant. Higher than normal doses ofbeta-2-receptor stimulants may be required.
Torsade de Pointes: DC cardioversion, transvenous cardiac pacing, epinephrine, magnesium
sulfate.
11 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. Sotalolhydrochloride 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.

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12 CLINICAL PHARMACOLOGY
12.1 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 noncardioselective, 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. Althoughsignificant beta-blockade occurs at oral doses as low as 25 mg, significant Class III effects areseen 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 bodysurface area (BSA). A reduction of the resting heart rate due to the beta-blocking effect ofsotalol is observed at daily doses ≥90 mg/m2 in children.
12.2 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 therefractory periods of atrial and ventricular muscle and conduction tissue.
In man, the Class II (beta-blockade) electrophysiological effects of sotalol are manifested byincreased sinus cycle length (slowed heart rate), decreased AV nodal conduction and increased
AV nodal refractoriness. The Class III electrophysiological effects in man include prolongationof the atrial and ventricular monophasic action potentials, and effective refractory period
prolongation of atrial muscle, ventricular muscle, and atrio-ventricular 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 to 100 msec in QT and
10 to 40 msec in QTc [see Warnings and Precautions (5.1)]. 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 to 15 joules) compared to amean of 16 joules for a nonrandomized comparative group primarily receiving amiodarone.
Twenty-five children in an unblinded, multicenter trial with SVT and/or ventriculartachyarrhythmias, 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

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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 tothe 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 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 diastolicblood pressures. Although sotalol is usually well-tolerated hemodynamically, deterioration in
cardiac performance may occur in patients with marginal cardiac compensation [see Warnings
and Precautions (5.3)].
12.3 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 to 100%. After oral administration,
peak plasma concentrations are reached in 2.5 to 4 hours, and steady-state plasma concentrations
are attained within 2 to 3 days (that is, after 5 to 6 doses when administered twice daily). Overthe dosage range 160 to 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.

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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 (2.5)].
The mean elimination half-life of sotalol is 12 hours. Dosing every 12 hours results in troughplasma 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 anddaily doses of 30, 90, and 210 mg/m2 were administered every 8 hours in the multidose study.
After rapid absorption with peak levels occurring on average between 2 to 3 hours following
administration, sotalol was eliminated with a mean half-life of 9.5 hours. Steady-state wasreached after 1 to 2 days. The average peak to trough concentration ratio was 2. Body surface
area was the most important covariate and more relevant than age for the pharmacokinetics ofsotalol. The smallest children (BSA <0.33 m2) exhibited a greater drug exposure (+59%) than thelarger children who showed a uniform drug concentration profile. The intersubject variation fororal 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 andto 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. Adjust doses or dosingintervals based on creatinine clearance [see Dosage and Administration (2.5)].
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 inCmax and AUC of 26% and 20%, respectively, and consequently in a 25% reduction in thebradycardic effect at rest. Administration of the antacid two hours after oral sotalol has noeffect on the pharmacokinetics or pharmacodynamics of sotalol.
No pharmacokinetic interactions were observed with hydrochlorothiazide or warfarin.

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13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Calculations of safety margins are for the maximum recommended human dose (MRHD) of
640 mg/day of sotalol, administered for life-threatening ventricular arrhythmias in a 60-kg
human.
No evidence of carcinogenic potential was observed in rats during a 24-month study at 137 to
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 to
7122 mg/kg/day (approximately 450 to 750 times the MRHD as mg/kg or 36 to 63 times the
MRHD as mg/m2).
Sotalol has not been evaluated in any specific assay of mutagenicity or clastogenicity.
13.2

Animal Toxicology and/or Pharmacology

No significant reduction in fertility occurred in rats at oral doses of 1000 mg/kg/day(approximately 94 times the MRHD as mg/kg or 15 times the MRHD as mg/m2) prior to mating,
except for a small reduction in the number of offspring per litter.
14 CLINICAL STUDIES
14.1 Ventricular Arrhythmias
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 acuteresponders, chronically.
In a double-blind, randomized comparison of Betapace and procainamide in 104 patients 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) in 486 patients comparing the choice of antiarrhythmic therapy by PES
suppression vs. Holter monitor selection (in each case followed by treadmill exercise testing) inpatients with a history of sustained VT/VF who were also inducible by PES, the effectivenessacutely and chronically of Betapace was compared with that of 6 other drugs (procainamide,quinidine, mexiletine, propafenone, imipramine, and pirmenol). The Overall response, limited to
first randomized drug, was 39% for Betapace and 30% for the pooled other drugs. Acuteresponse rate for first drug randomized using suppression of PES induction was 36% for
Betapace vs. a mean of 13% for the pooled other drugs. Using the Holter monitoring endpoint(complete suppression of sustained VT, 90% suppression of NSVT, 80% suppression of PVC
pairs, and at least 70% suppression of PVCs), Betapace yielded 41% response vs. 45% for theother drugs combined. Among responders placed on long-term therapy identified acutely aseffective (by either PES or Holter), Betapace, when compared to the pool of other drugs, had theReference ID: 5194805

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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 to 80%). The most commonly used
doses of orally administered Betapace in this trial were 320 to 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. nopharmacologic 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.
14.2 Supraventricular 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 to 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 ventricularrepolarization; 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 recurrences at both 6 and12 months. The 120 mg dose was more effective than 80 mg, but 160 mg did not appear to havean added benefit. Note that these doses were given twice or once daily, depending on renal
function. The results are shown in Figure 1, Table 3, and Table 4.
Figure 1: Study 1 – Time to First ECG-Documented Recurrence of Symptomatic
AFIB/AFL Since Randomization

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Table 3: Study 1 – Patient Status at 12 Months
Placebo

80 mg

120 mg

160 mg

69

59

63

62

23%

22%

29%

23%

67%

58%

49%

42%

6%

12%

18%

29%

Randomized
On treatment in NSR
at 12 months without
recurrencea
Recurrenceab
D/C for AEs
ab

Betapace AF Dose

Symptomatic AFIB/AFL
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 4: Study 1 – Median Time to Recurrence of Symptomatic AFIB/AFL and Relative
Risk (vs. Placebo) at 12 Months
Placebon=69

Betapace AF Dose
80 mg
n=59

120 mgn=63

160 mgn=62

P-value vs. placebo

0.325

0.018

0.029

Relative Risk (RR) to placebo

0.81

0.59

0.59

106

229

175

Median time to recurrence (days)

27

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 from80 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.

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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 5 and 6 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 5: Study 2 – Patient Status at 6 Months
Placebon=114

Betapace AF
n=118

On treatment in NSR at 6
months without
recurrencea

29%

45%

Recurrenceab
D/C for AEs
Death

67%
3%
1%

49%
6%

a
b

Symptomatic or asymptomatic AFIB/AFL
Efficacy endpoint of Study 2; study treatment stopped.

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

Median time to recurrence(days)

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Placebon=114
44

Betapace AF
n=118
>180

Relative Risk

P-value

0.55

0.002

This label may not be the latest approved by FDA.
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Figure 2: Study 2 – Time to First ECG-Documented Recurrence of Symptomatic
AFIB/AFL/Death Since Randomization

16 HOW SUPPLIED/STORAGE AND HANDLING
Betapace (sotalol hydrochloride); capsule-shaped light-blue scored tablets, imprinted with thestrength and “BETAPACE,” are available as follows:
NDC 70515-105-10

80 mg strength, bottle of 100

NDC 70515-109-10

120 mg strength, bottle of 100

NDC 70515-106-10

160 mg strength, bottle of 100

Betapace AF (sotalol hydrochloride); capsule-shaped white scored tablets, imprinted with thestrength and “BHCP” are available as follows:
NDC 70515-115-06

80 mg strength, bottle of 60

NDC 70515-119-06

120 mg strength, bottle of 60

NDC 70515-116-06

160 mg strength, bottle of 60

Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled
Room Temperature].
17 PATIENT COUNSELING INFORMATION•

Advise patients to contact their healthcare provider in the event of syncope, pre-syncopal
symptoms or cardiac palpitations.

•

Advise patients that their electrolytes and ECG will be monitored during treatment [seeWarnings and Precautions (5.1)].

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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, lessappetite than normal, or excessive thirst [see Warnings and Precautions (5.1)].

•

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 (2)].

•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 ontime, so they do not interrupt treatment [see Dosage and Administration (2)].

•Advise patients to not start taking other medications without first discussing new
medications with their healthcare provider.

•

Advise patients to avoid taking Betapace/Betapace AF within two hours of taking antacids
that contain aluminum oxide or magnesium hydroxide [see Drug Interactions (7.7)].

•

Inform patients or caregivers that there is a risk of hypoglycemia when Betapace/Betapace
AF is given to patients who are fasting or who are vomiting. Inform patients to notify theirhealthcare provider if they experience symptoms of hypoglycemia. [See Warnings andPrecautions (5.7)].

Lactation•

Advise women not to breastfeed while on treatment with Betapace [see Use in Specific
Populations (8.2)]©2023, Covis Pharma. All rights reserved.
Manufactured for:Covis Pharma
Zug, 6300 Switzerland

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