SOTALOL HYDROCHLORIDE- sotalol hydrochloride tablet

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Active ingredient:
SOTALOL HYDROCHLORIDE (UNII: HEC37C70XX) (SOTALOL - UNII:A6D97U294I)
Available from:
Cardinal Health
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Sotalol hydrochloride tablets, USP are indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that in the judgment of the physician are life-threatening. Because of the proarrhythmic effects of sotalol hydrochloride tablets, USP (see WARNINGS ), including a 1.5 to 2% rate of Torsade de Pointes or new VT/VF in patients with either NSVT or supraventricular arrhythmias, its use in patients with less severe arrhythmias, even if the patients are symptomatic, is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Initiation of sotalol hydrochloride treatment or increasing doses, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. The response to treatment should then be evaluated by a suitable method (e.g., PES or Holter monitoring) prior to continuing the patient on chronic therapy. Various approaches have been used to determi
Product summary:
Sotalol Hydrochloride Tablets, USP 80 mg are available for oral administration as white to off-white capsule shaped, scored tablets, imprinted “APO” on one side and “SO” bisect “80” on the other side; Available: Overbagged with 10 tablets per bag, NDC 55154-8179-0 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. FOR YOUR PROTECTION: Do not use if blister is torn or broken. Betapace AF ® is a trademark of Berlex. Distributed by: American Health Packaging Columbus, OH 43217 Distributed by: Cardinal Health Dublin, OH 43017 8265401/0116 L55203900319
Authorization status:
Abbreviated New Drug Application
Authorization number:
55154-8179-0

SOTALOL HYDROCHLORIDE- sotalol hydrochloride tablet

Cardinal Health

----------

Sotalol Hydrochloride Tablets, USP

8265401/0116

Rx only

To minimize the risk of induced arrhythmia, patients initiated or reinitiated on sotalol

hydrochloride tablets should be placed for a minimum of three days (on their maintenance

dose) in a facility that can provide cardiac resuscitation and continuous

electrocardiographic monitoring. Creatinine clearance should be calculated prior to dosing.

For detailed instructions regarding dose selection and special cautions for people with renal

impairment, see DOSAGE AND ADMINISTRATION. Sotalol is also indicated for the

maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial

flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus

rhythm and is marketed under the brand name Betapace AF

. Sotalol hydrochloride

tablets, USP are not approved for the AFIB/AFL indication and should not be substituted

for Betapace AF because only Betapace AF is distributed with a patient package insert that

is appropriate for patients with AFIB/AFL.

DESCRIPTION

Sotalol hydrochloride tablets, USP are an antiarrhythmic drug with Class II (beta-adrenoreceptor

blocking) and Class III (cardiac action potential duration prolongation) properties. It is supplied as a

white to off-white, capsule-shaped, scored 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 C

SHCl and is represented by the following structural formula:

Each tablet, for oral administration, contains 80 mg, 120 mg, 160 mg or 240 mg of sotalol

hydrochloride. In addition, each tablet also contains the following inactive ingredients: magnesium

stearate and microcrystalline cellulose.

CLINICAL PHARMACOLOGY

Mechanism of Action

Sotalol hydrochloride has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac

action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. Sotalol

hydrochloride is a racemic mixture of d-and l-sotalol. Both isomers 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/m

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/m

in children.

Electrophys iology

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 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 QT

. (See WARNINGS for description

of relationship between QT

and Torsade de Pointes type arrhythmias). No significant alteration in

QRS interval is observed.

In a small study (n=25) of patients with implanted defibrillators treated concurrently with sotalol, the

average defibrillatory threshold was 6 joules (range 2 to 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 supraventricular (SVT) and/or ventricular

(VT) 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/m

with dosing every 8 hours for a

total 9 doses. During steady-state, the respective average increases above baseline of the QT

interval,

in msec (%), were 2(+1%), 14(+4%) and 29(+7%) msec at the 3 dose levels. The respective mean

maximum increases above baseline of the QT

interval, in msec (%), were 23(+6%), 36(+9%) and

55(+14%) msec at the 3 dose levels. The steadystate percent increases in the RR interval were 3, 9 and

12%. The smallest children (BSA<0.33m

) showed a tendency for larger Class III effects (ΔQT

) and

an increased frequency of prolongations of the QT

interval as compared with larger children

(BSA≥0.33m

). The beta-blocking effects also tended to be greater in the smaller children

(BSA<0.33m

). Both the Class III and beta-blocking effects of sotalol were linearly related with 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 sotalol hydrochloride 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. Pulmonary capillary

wedge pressure increased significantly from 6.4 mmHg to 11.8 mmHg in the 11 patients who completed

the study. One patient was discontinued because of worsening congestive heart failure. Mean arterial

pressure, mean pulmonary artery pressure and stroke work index did not significantly change. Exercise

and isoproterenol induced tachycardia are antagonized by sotalol, and total peripheral resistance

increases by a small amount.

In hypertensive patients, sotalol hydrochloride produces significant reductions in both systolic and

diastolic blood pressures. Although sotalol hydrochloride is usually well-tolerated hemodynamically,

caution should be exercised in patients with marginal cardiac compensation as deterioration in cardiac

performance may occur. (See WARNINGS, Congestive Heart Failure).

Clinical Studies

Sotalol hydrochloride has been studied in life-threatening and less severe arrhythmias. In patients with

frequent premature ventricular complexes (VPC), 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 to 85% of patients having at least a 75%

reduction of VPCs. Sotalol hydrochloride was also superior, at the doses evaluated, to propranolol (40

to 80 mg TID) and similar to quinidine (200 to 400 mg QID) in reducing VPCs. In patients with life-

threatening arrhythmias [sustained ventricular tachycardia/fibrillation (VT/VF)], sotalol hydrochloride

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 sotalol and procainamide given intravenously (total of 2

mg/kg sotalol vs. 19 mg/kg of procainamide over 90 minutes), sotalol 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 sotalol

hydrochloride was compared with 6 other drugs (procainamide, quinidine, mexiletine, propafenone,

imipramine and pirmenol). Overall response, limited to first randomized drug, was 39% for sotalol and

30% for the pooled other drugs. Acute response rate for first drug randomized using suppression of

PES induction was 36% for sotalol 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), sotalol 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), sotalol, 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 to 80%). The most commonly used doses of sotalol hydrochloride 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 sotalol vs. no

pharmacologic treatment (e.g., in patients with implanted defibrillators) whether sotalol response causes

improved survival or identifies a population with a good prognosis.

In a large double-blind, placebo controlled secondary prevention (postinfarction) trial (n=1,456), sotalol

hydrochloride was given as a non-titrated initial dose of 320 mg once daily. Sotalol did not produce a

significant increase in survival (7.3% mortality on sotalol 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 sotalol vs. 2% on placebo). In a second small trial (n=17 randomized to

sotalol) where sotalol was administered at high doses (e.g., 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 sotalol.

Pharmacokinetics

In healthy subjects, the oral bioavailability of sotalol hydrochloride 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 (i.e., after 5 to 6 doses when administered twice daily).

Over the dosage range 160 to 640 mg/day sotalol hydrochloride displays dose proportionality with

respect to plasma concentrations. Distribution occurs to a central (plasma) and to a peripheral

compartment, with a mean elimination half-life of 12 hours. Dosing every 12 hours results in trough

plasma concentrations which are approximately one-half of those at peak.

Sotalol hydrochloride does not bind to plasma proteins and is not metabolized. Sotalol hydrochloride

shows very little intersubject variability in plasma levels. The pharmacokinetics of the d and l

enantiomers of sotalol are essentially identical. Sotalol hydrochloride crosses the blood brain barrier

poorly. Excretion is predominantly via the kidney in the unchanged form, and therefore lower doses are

necessary in conditions of renal impairment (see DOSAGE AND ADMINISTRATION). Age per se

does not significantly alter the pharmacokinetics of sotalol hydrochloride, but impaired renal function in

geriatric patients can increase the terminal elimination half-life, resulting in increased drug

accumulation. The absorption of sotalol hydrochloride was reduced by approximately 20% compared

to fasting when it was administered with a standard meal. Since sotalol hydrochloride is not subject to

first-pass metabolism, patients with hepatic impairment show no alteration in clearance of sotalol.

The combined analysis of two unblinded, multicenter trials (a single dose 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/m

of sotalol was administered in the single dose study and daily doses

of 30, 90 and 210 mg/m

were administered q 8h in the multi-dose 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 was reached after 1 to 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<0.33m

) 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%.

INDICATIONS AND USAGE

Sotalol hydrochloride tablets, USP are indicated for the treatment of documented ventricular

arrhythmias, such as sustained ventricular tachycardia, that in the judgment of the physician are life-

threatening. Because of the proarrhythmic effects of sotalol hydrochloride tablets, USP (see

WARNINGS), including a 1.5 to 2% rate of Torsade de Pointes or new VT/VF in patients with either

NSVT or supraventricular arrhythmias, its use in patients with less severe arrhythmias, even if the

patients are symptomatic, is generally not recommended. Treatment of patients with asymptomatic

ventricular premature contractions should be avoided.

Initiation of sotalol hydrochloride treatment or increasing doses, as with other antiarrhythmic agents

used to treat life-threatening arrhythmias, should be carried out in the hospital. The response to

treatment should then be evaluated by a suitable method (e.g., PES or Holter monitoring) prior to

continuing the patient on chronic therapy. Various approaches have been used to determine the response

to antiarrhythmic therapy, including sotalol hydrochloride tablets, USP.

In the ESVEM Trial, response by Holter monitoring was tentatively defined as 100% suppression of

ventricular tachycardia, 90% suppression of non-sustained VT, 80% suppression of paired VPCs, and

75% suppression of total VPCs in patients who had at least 10 VPCs/hour at baseline; this tentative

response was confirmed if VT lasting 5 or more beats was not observed during treadmill exercise

testing using a standard Bruce protocol. The PES protocol utilized a maximum of three extrastimuli at

three pacing cycle lengths and two right ventricular pacing sites. Response by PES was defined as

prevention of induction of the following: 1) monomorphic VT lasting over 15 seconds; 2) non-sustained

polymorphic VT containing more than 15 beats of monomorphic VT in patients with a history of

monomorphic VT; 3) polymorphic VT or VF greater than 15 beats in patients with VF or a history of

aborted sudden death without monomorphic VT; and 4) two episodes of polymorphic VT or VF of

greater than 15 beats in a patient presenting with monomorphic VT. Sustained VT or NSVT producing

hypotension during the final treadmill test was considered a drug failure.

In a multicenter open-label long-term study of sotalol in patients with life-threatening ventricular

arrhythmias which had proven refractory to other antiarrhythmic medications, response by Holter

monitoring was defined as in ESVEM. Response by PES was defined as non-inducibility of sustained

VT by at least double extrastimuli delivered at a pacing cycle length of 400 msec. Overall survival and

arrhythmia recurrence rates in this study were similar to those seen in ESVEM, although there was no

comparative group to allow a definitive assessment of outcome.

Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.

Sotalol is also indicated for the maintenance of normal sinus rhythm [delay in time to recurrence of atrial

fibrillation/atrial flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus

rhythm and is marketed under the brand name Betapace AF (sotalol hydrochloride, tablets, USP). Sotalol

hydrochloride tablets, USP are not approved for the AFIB/AFL indication and should not be substituted

for Betapace AF because only Betapace AF is distributed with a patient package insert that is

appropriate for patients with AFIB/AFL.

CONTRAINDICATIONS

Sotalol hydrochloride is contraindicated in patients with bronchial asthma, sinus bradycardia, second

and third degree AV block, unless a functioning pacemaker is present, congenital or acquired long QT

syndromes, cardiogenic shock, uncontrolled congestive heart failure, and previous evidence of

hypersensitivity to sotalol.

WARNINGS

Mortality

The National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial I (CAST

I) was a long-term, multi-center, double-blind study in patients with asymptomatic, non-life-

threatening ventricular arrhythmias, 1 to 103 weeks after acute myocardial infarction. Patients in

CAST I were randomized to receive placebo or individually optimized doses of encainide,

flecainide, or moricizine. The Cardiac Arrhythmia Suppression Trial II (CAST II) was similar,

except that the recruited patients had had their index infarction 4 to 90 days before

randomization, patients with left ventricular ejection fractions greater than 40% were not

admitted, and the randomized regimens were limited to placebo and moricizine.

CAST I was discontinued after an average time-on-treatment of 10 months, and CAST II was

discontinued after an average time-on-treatment of 18 months. As compared to placebo

treatment, all three active therapies were associated with increases in short-term (14-day)

mortality, and encainide and flecainide were associated with significant increases in longer-term

mortality as well. The longer-term mortality rate associated with moricizine treatment could not

be statistically distinguished from that associated with placebo.

The applicability of these results to other populations (e.g., those without recent myocardial infarction)

and to other than Class I antiarrhythmic agents is uncertain. Sotalol hydrochloride is devoid of Class I

effects, and in a large (n=1,456) controlled trial in patients with a recent myocardial infarction, who did

not necessarily have ventricular arrhythmias, sotalol did not produce increased mortality at doses up to

320 mg/day (see Clinical Studies). On the other hand, in the large post-infarction study using a non-

titrated initial dose of 320 mg once daily and in a second small randomized trial in high-risk post-

infarction patients treated with high doses (320 mg BID), there have been suggestions of an excess of

early sudden deaths.

Proarrhythmia

Like other antiarrhythmic agents, sotalol can provoke new or worsened ventricular arrhythmias in some

patients, including sustained ventricular tachycardia or ventricular fibrillation, with potentially fatal

consequences. Because of its effect on cardiac repolarization (QT

interval prolongation), Torsade de

Pointes, a polymorphic ventricular tachycardia with prolongation of the QT interval and a shifting

electrical axis is the most common form of proarrhythmia associated with sotalol, occurring in about

4% of high risk (history of sustained VT/VF) patients. The risk of Torsade de Pointes progressively

increases with prolongation of the QT interval, and is worsened also by reduction in heart rate and

reduction in serum potassium (see Electrolyte Disturbances).

Because of the variable temporal recurrence of arrhythmias, it is not always possible to distinguish

between a new or aggravated arrhythmic event and the patient’s underlying rhythm disorder. (Note,

however, that Torsade de Pointes is usually a drug-induced arrhythmia in people with an initially normal

Thus, the incidence of drug-related events cannot be precisely determined, so that the occurrence rates

provided must be considered approximations. Note also that drug-induced arrhythmias may often not be

identified, particularly if they occur long after starting the drug, due to less frequent monitoring. It is

clear from the NIH-sponsored CAST (see WARNINGS, Mortality) that some antiarrhythmic drugs can

cause increased sudden death mortality, presumably due to new arrhythmias or asystole, that do not

appear early in treatment but that represent a sustained increased risk.

Overall in clinical trials with sotalol, 4.3% of 3257 patients experienced a new or worsened ventricular

arrhythmia. Of this 4.3%, there was new or worsened sustained ventricular tachycardia in approximately

1% of patients and Torsade de Pointes in 2.4%. Additionally, in approximately 1% of patients, deaths

were considered possibly drug-related; such cases, although difficult to evaluate, may have been

associated with proarrhythmic events. In patients with a history of sustained ventricular

tachycardia, the incidence of Torsade de Pointes was 4% and worsened VT in about 1%; in

patients with other, less serious, ventricular arrhythmias and supraventricular arrhythmias, the

incidence of Torsade de Pointes was 1% and 1.4%, respectively.

Torsade de Pointes arrhythmias were dose related, as is the prolongation of QT (QT

) interval, as

shown in the table below.

Percent Incidence of Torsade de Pointes and Mean QT

Interval by Dose For Patients With

Sustained VT/VF

Daily Dose (mg)

Incidence of Torsade de Pointes

Mean QT

(msec)

0 (69)

463 (17)

0.5 (832)

467 (181)

1.6 (835)

473 (344)

4.4 (459)

483 (234)

3.7 (324)

490 (185)

> 640

5.8 (103)

512 (62)

In addition to dose and presence of sustained VT, other risk factors for Torsade de Pointes were

gender (females had a higher incidence), excessive prolongation of the QT

interval (see table below)

and history of cardiomegaly or congestive heart failure. Patients with sustained ventricular tachycardia

and a history of congestive heart failure appear to have the highest risk for serious proarrhythmia (7%).

Of the patients experiencing Torsade de Pointes, approximately two-thirds spontaneously reverted to

their baseline rhythm. The others were either converted electrically (D/C cardioversion or overdrive

pacing) or treated with other drugs (see OVERDOSAGE). It is not possible to determine whether some

sudden deaths represented episodes of Torsade de Pointes but in some instances sudden death did

follow a documented episode of Torsade de Pointes. Although sotalol therapy was discontinued in

most patients experiencing Torsade de Pointes, 17% were continued on a lower dose.

Nonetheless, sotalol should be used with particular caution if the QT

is greater than 500 msec on-

therapy and serious consideration should be given to reducing the dose or discontinuing therapy when

c

highest on-therapy value

Number of patients assessed

c

the QT

exceeds 550 msec. Due to the multiple risk-factors associated with Torsade de Pointes,

however, caution should be exercised regardless of the QT

interval. The table below relates the

incidence of Torsade de Pointes to on-therapy QT

and change in QT

from baseline. It should be

noted, however, that the highest on-therapy QT

was in many cases the one obtained at the time of the

Torsade de Pointes event, so that the table overstates the predictive value of a high QT

Relationship Between QT

Interval Prolongation and Torsade de Pointes

( ) Number of patients assessed

On-Therapy QT

Interval (msec)

Incidence of Torsade

de Pointes

Change in QT

Interval From Baseline

(ms ec)

Incidence of Torsade

de Pointes

< 500

1.3% (1787)

< 65

1.6% (1516)

500-525

3.4% (236)

65-80

3.2% (158)

525-550

5.6% (125)

80-100

4.1% (146)

> 550

10.8% (157)

100-130

5.2% (115)

> 130

7.1% (99)

Proarrhythmic events must be anticipated not only on initiating therapy, but with every upward

dose adjustment. Proarrhythmic events most often occur within 7 days of initiating therapy or of an

increase in dose; 75% of serious proarrhythmias (Torsade de Pointes and worsened VT) occurred

within 7 days of initiating sotalol therapy, while 60% of such events occurred within 3 days of initiation

or a dosage change. Initiating therapy at 80 mg BID with gradual upward dose titration and appropriate

evaluations for efficacy (e.g., PES or Holter) and safety (e.g., QT interval, heart rate and electrolytes)

prior to dose escalation, should reduce the risk of proarrhythmia. Avoiding excessive accumulation of

sotalol in patients with diminished renal function, by appropriate dose reduction, should also reduce the

risk of proarrhythmia (see DOSAGE AND ADMINISTRATION).

Congestive Heart Failure

Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and

beta-blockade carries the potential hazard of further depressing myocardial contractility and

precipitating more severe failure. In patients who have congestive heart failure controlled by digitalis

and/or diuretics, sotalol hydrochloride tablets should be administered cautiously. Both digitalis and

sotalol slow AV conduction. As with all beta-blockers, caution is advised when initiating therapy in

patients with any evidence of left ventricular dysfunction. In premarketing studies, new or worsened

congestive heart failure (CHF) occurred in 3.3% (n=3257) of patients and led to discontinuation in

approximately 1% of patients receiving sotalol. The incidence was higher in patients presenting with

sustained ventricular tachycardia/fibrillation (4.6%, n=1363), or a prior history of heart failure (7.3%,

n=696). Based on a life-table analysis, the one-year incidence of new or worsened CHF was 3% in

patients without a prior history and 10% in patients with a prior history of CHF. NYHA Classification

was also closely associated to the incidence of new or worsened heart failure while receiving sotalol

(1.8% in 1395 Class I patients, 4.9% in 1254 Class II patients and 6.1% in 278 Class III or IV patients).

Electrolyte Disturbances

Sotalol should not be used in patients with hypokalemia or hypomagnesemia prior to correction of

imbalance, 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.

Conduction Disturbances

Excessive prolongation of the QT interval (>550 msec) can promote serious arrhythmias and should be

c

c

c

avoided (see Proarrhythmia above). 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%.

Recent Acute MI

Sotalol can be used safely and effectively in the long-term treatment of life-threatening ventricular

arrhythmias following a myocardial infarction. However, experience in the use of sotalol to treat

cardiac arrhythmias in the early phase of recovery from acute MI is limited and at least at high initial

doses is not reassuring (see WARNINGS, Mortality). In the first 2 weeks post-MI caution is advised

and careful dose titration is especially important, particularly in patients with markedly impaired

ventricular function.

The following warnings are related to the beta-blocking activity of sotalol.

Abrupt Withdrawal

Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy.

Occasional cases of exacerbation of angina pectoris, arrhythmias and, in some cases, myocardial

infarction have been reported after abrupt discontinuation of beta-blocker therapy. Therefore, it is

prudent when discontinuing chronically administered sotalol hydrochloride tablets, particularly in

patients with ischemic heart disease, to carefully monitor the patient and consider the temporary use of

an alternate beta-blocker if appropriate. If possible, the dosage of sotalol hydrochloride tablets should

be gradually reduced over a period of one to two weeks. If angina or acute coronary insufficiency

develops, appropriate therapy should be instituted promptly. Patients should be warned against

interruption or discontinuation of therapy without the physician’s advice. Because coronary artery

disease is common and may be unrecognized in patients receiving sotalol hydrochloride tablets, abrupt

discontinuation in patients with arrhythmias may unmask latent coronary insufficiency.

Non-Allergic Bronchospasm (e.g., chronic bronchitis and emphysema)

PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD IN GENERAL NOT RECEIVE

BETA-BLOCKERS. It is prudent, if sotalol hydrochloride tablets are to be administered, to use the

smallest effective dose, so that inhibition of bronchodilation produced by endogenous or exogenous

catecholamine stimulation of beta 2 receptors may be minimized.

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.

Diabetes

In patients with diabetes (especially labile diabetes) or with a history of episodes of spontaneous

hypoglycemia, sotalol hydrochloride tablets should be given with caution since beta-blockade may

mask some important premonitory signs of acute hypoglycemia; e.g., tachycardia.

Sick Sinus Syndrome

Sotalol hydrochloride tablets should be used only with extreme caution in patients with sick sinus

syndrome associated with symptomatic arrhythmias, because it may cause sinus bradycardia, sinus

pauses or sinus arrest.

Thyrotoxicos is

Beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected

of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade

which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm.

PRECAUTIONS

Renal Impairment

Sotalol hydrochloride 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.

Guidance for dosing in conditions of renal impairment can be found under DOSAGE AND

ADMINISTRATION.

Drug Interactions

Drugs undergoing CYP450 metabolism

Sotalol is primarily eliminated by renal excretion; therefore, drugs that are metabolized by CYP450 are

not expected to alter the pharmacokinetics of sotalol. Sotalol is not expected to inhibit or induce any

CYP450 enzymes; therefore, it is not expected to alter the PK of drugs that are metabolized by these

enzymes.

Antiarrhythmics

Class Ia antiarrhythmic drugs, such as disopyramide, quinidine and procainamide and other Class III

drugs (e.g., amiodarone) are not recommended as concomitant therapy with sotalol, because of their

potential to prolong refractoriness (see WARNINGS). There is only limited experience with the

concomitant use of Class Ib or Ic antiarrhythmics. Additive Class II effects would also be anticipated

with the use of other beta-blocking agents concomitantly with sotalol.

Digoxin

Single and multiple doses of sotalol do not substantially affect serum digoxin levels. Proarrhythmic

events were more common in sotalol treated patients also receiving digoxin; it is not clear whether this

represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia, in

the patients receiving digoxin. Both digitalis glycosides and beta-blockers slow atrioventricular

conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Calcium blocking drugs

Sotalol should be administered with caution in conjunction with calcium-blocking drugs because of

possible additive effects on atrioventricular conduction or ventricular function. Additionally,

concomitant use of these drugs may have additive effects on blood pressure, possibly leading to

hypotension.

Catecholamine-depleting agents

Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with a beta-

blocker may produce an excessive reduction of resting sympathetic nervous tone. Patients treated with

sotalol plus a catecholamine depletor should therefore be closely monitored for evidence of

hypotension and/or marked bradycardia which may produce syncope.

Insulin and oral antidiabetics

Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment.

Symptoms of hypoglycemia may be masked.

Beta-2-receptor stimulants

Beta-agonists such as salbutamol, terbutaline and isoprenaline may have to be administered in increased

dosages when used concomitantly with sotalol.

Clonidine

Beta-blocking drugs may potentiate the rebound hypertension sometimes observed after discontinuation

of clonidine; therefore, caution is advised when discontinuing clonidine in patients receiving sotalol.

Other

No pharmacokinetic interactions were observed with hydrochlorothiazide or warfarin.

Antacids

Administration of sotalol within 2 hours of antacids containing aluminum oxide and magnesium

hydroxide should be avoided because it may result in a reduction in C

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 sotalol has no effect on the pharmacokinetics or pharmacodynamics of sotalol.

Drugs prolonging the QT interval

Sotalol should be administered with caution in conjunction with other drugs known to prolong the QT

interval such as Class I and Class III antiarrhythmic agents, phenothiazines, tricyclic antidepressants,

astemizole, bepridil, certain oral macrolides, and certain quinolone antibiotics (see WARNINGS).

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. In screening patients suspected of having a

pheochromocytoma and being treated with sotalol, a specific method, such as a high performance liquid

chromatographic assay with solid phase extraction (e.g., J. Chromatogr. 385:241, 1987) should be

employed in determining levels of catecholamines.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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/m

) 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/m

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 9 times the MRHD as mg/m

) prior to mating, except for a small

reduction in the number of offspring per litter.

Pregnancy Category B

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/m

), respectively, did not reveal any teratogenic potential associated

with sotalol hydrochloride. In rabbits, a high dose of sotalol hydrochloride (160 mg/kg/day) at 16 times

the MRHD as mg/kg (6 times the MRHD as mg/m

) produced a slight increase in fetal death likely due

to maternal toxicity. Eight times the maximum dose (80 mg/kg/day or 3 times the MRHD as mg/m

) did

not result in an increased incidence of fetal deaths. In rats, 1000 mg/kg/day sotalol hydrochloride, 100

times the MRHD (18 times the MRHD as mg/m

), increased the number of early resorptions, while at

14 times the maximum dose (2.5 times the MRHD as mg/m

), no increase in early resorptions was noted.

However, animal reproduction studies are not always predictive of human response.

Although there are no adequate and well-controlled studies in pregnant women, sotalol hydrochloride

has been shown to cross the placenta, and is found in amniotic fluid. There has been a report of

subnormal birth weight with sotalol. Therefore, sotalol hydrochloride tablets should be used during

pregnancy only if the potential benefit outweighs the potential risk.

Nursing Mothers

Sotalol is excreted in the milk of laboratory animals and has been reported to be present in human milk.

Because of the potential for adverse reactions in nursing infants from sotalol, a decision should be

made whether to discontinue nursing or to discontinue the drug, taking into account the importance of

the drug to the mother.

Pediatric Use

The safety and effectiveness of sotalol in children have not been established. However, the Class III

electrophysiologic and beta-blocking effects, the pharmacokinetics, and the relationship between the

effects (QTc interval and resting heart rate) and drug concentrations have been evaluated in children

aged between 3 days and 12 years old (see CLINICAL PHARMACOLOGY).

ADVERSE REACTIONS

During premarketing trials, 3186 patients with cardiac arrhythmias (1363 with sustained ventricular

tachycardia) received oral sotalol, of whom 2451 received the drug for at least two weeks. The most

important adverse effects are Torsade de Pointes and other serious new ventricular arrhythmias (see

WARNINGS), occurring at rates of almost 4% and 1%, respectively, in the VT/VF population. Overall,

discontinuation because of unacceptable side-effects was necessary in 17% of all patients in clinical

trials, and in 13% of patients treated for at least two weeks. The most common adverse reactions leading

to discontinuation of sotalol are as follows: fatigue 4%, bradycardia (less than 50 bpm) 3%, dyspnea

3%, proarrhythmia 3%, asthenia 2%, and dizziness 2%.

Occasional reports of elevated serum liver enzymes have occurred with sotalol therapy but no cause

and effect relationship has been established. One case of peripheral neuropathy which resolved on

discontinuation of sotalol and recurred when the patient was rechallenged with the drug was reported in

an early dose tolerance study. Elevated blood glucose levels and increased insulin requirements can

occur in diabetic patients.

The following table lists as a function of dosage the most common (incidence of 2% or greater)

adverse events, regardless of relationship to therapy and the percent of patients discontinued due to the

event as collected from clinical trials involving 1292 patients with sustained VT/VF

Incidence (%) of Adverse Events and Discontinuations

DAILY DOSE

Body System

160 mg

(n = 832)

240 mg

(n = 263)

320 mg

(n = 835)

480 mg

(n = 459)

640 mg

(n = 324)

Any Dose

(n = 1292)

Body as a whole

infection

< 1

fever

< 1

% Patients

Dis continued

(n = 1292)

localized pain

< 1

Cardiovas cular

dyspnea

bradycardia

chest pain

< 1

palpitation

< 1

edema

ECG abnormal

hypotension

proarrhythmia

< 1

< 1

syncope

heart failure

presyncope

< 1

peripheral vascular

disorder

< 1

cardiovascular

disorder

< 1

< 1

vasodilation

< 1

< 1

AICD discharge

< 1

< 1

hypertension

< 1

< 1

Nervous

fatigue

dizziness

asthenia

light-headed

headache

< 1

sleep problem

< 1

perspiration

< 1

altered

consciousness

< 1

depression

< 1

paresthesia

< 1

anxiety

< 1

mood change

< 1

< 1

< 1

appetite disorder

< 1

stroke

< 1

< 1

< 1

< 1

Diges tive

nausea/vomiting

diarrhea

< 1

dyspepsia

< 1

abdominal pain

< 1

< 1

< 1

colon problem

< 1

< 1

flatulence

< 1

< 1

Res piratory

pulmonary problem

< 1

upper respiratory

tract problem

< 1

asthma

< 1

< 1

Urogenital

genitourinary

disorder

< 1

sexual dysfunction

< 1

< 1

Metabolic

abnormal lab value

< 1

weight change

< 1

< 1

Mus culos keletal

extremity pain

< 1

back pain

< 1

< 1

Skin and Appendages

rash

< 1

Hematologic

bleeding

< 1

< 1

< 1

Special Senses

visual problem

< 1

In an unblinded multicenter trial of 25 patients with SVT and/or VT receiving daily doses of 30, 90 and

210 mg/m

with dosing every 8 hours for a total of 9 doses, no Torsade de Pointes or other serious

new arrhythmias were observed. One (1) patient, receiving 30 mg/m

daily, was discontinued because

of increased frequency of sinus pauses/bradycardia. Additional cardiovascular AEs were seen at the 90

and 210 mg/m

daily dose levels. They included QT prolongations (2 patients), sinus

pauses/bradycardia (1 patient), increased severity of atrial flutter and reported chest pain (1 patient).

Values for QT

≥ 525 msec were seen in 2 patients at the 210 mg/m

daily dose level. Serious adverse

events including death, Torsade de Pointes, other proarrhythmias, high-degree A-V blocks and

bradycardia have been reported in infants and/or children.

Potential Adverse Effects

Foreign marketing experience with sotalol hydrochloride shows an adverse experience profile similar

to that described above from clinical trials. Voluntary reports since introduction include rare reports

(less than one report per 10,000 patients) of: emotional lability, slightly clouded sensorium,

incoordination, vertigo, paralysis, thrombocytopenia, eosinophilia, leukopenia, photosensitivity

reaction, fever, pulmonary edema, hyperlipidemia, myalgia, pruritis, alopecia.

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been associated

with sotalol during investigational use and foreign marketing experience.

OVERDOSAGE

Intentional or accidental overdosage with sotalol hydrochloride has rarely 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

hydrochloride the following clinical findings were seen: hypotension, bradycardia, cardiac asystole,

prolongation of QT interval, Torsade de Pointes, ventricular tachycardia, and premature ventricular

complexes. If overdosage occurs, therapy with sotalol should be discontinued and the patient 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

Because patients are counted at each dose level tested, the Any Dose column cannot be determined by adding

across the doses.

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 or norepinephrine may be

useful.

Bronchospasm

Aminophylline or aerosol beta-2-receptor stimulant.

Torsade de Pointes

DC cardioversion, transvenous cardiac pacing, epinephrine, magnesium sulfate.

DOSAGE AND ADMINISTRATION

As with other antiarrhythmic agents, sotalol hydrochloride tablets, USP should be initiated and doses

increased in a hospital with facilities for cardiac rhythm monitoring and assessment (see

INDICATIONS AND USAGE). Sotalol hydrochloride tablets, USP should be administered only after

appropriate clinical assessment (see INDICATIONS AND USAGE), and the dosage of sotalol

hydrochloride tablets, USP must be individualized for each patient on the basis of therapeutic response

and tolerance. Proarrhythmic events can occur not only at initiation of therapy, but also with each

upward dosage adjustment.

Adults

Dosage of sotalol hydrochloride tablets, USP should be adjusted gradually, allowing 3 days between

dosing increments in order to attain steady-state plasma concentrations, and to allow monitoring of QT

intervals. Graded dose adjustment will help prevent the usage of doses which are higher than necessary

to control the arrhythmia. The recommended initial dose is 80 mg twice daily. This dose may be

increased, if necessary, after appropriate evaluation to 240 or 320 mg/day (120 to 160 mg twice daily).

In most patients, a therapeutic response is obtained at a total daily dose of 160 to 320 mg/day, given in

two or three divided doses. Some patients with life-threatening refractory ventricular arrhythmias may

require doses as high as 480 to 640 mg/day; however, these doses should only be prescribed when the

potential benefit outweighs the increased risk of adverse events, in particular proarrhythmia. Because

of the long terminal elimination half-life of sotalol, dosing on more than a BID regimen is usually not

necessary.

Children

As in adults the following precautionary measures should be considered when initiating sotalol

treatment in children: initiation of treatment in the hospital after appropriate clinical assessment;

individualized regimen as appropriate; gradual increase of doses if required; careful assessment of

therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.

For children aged about 2 years and greater

For children aged about 2 years and greater, with normal renal function, doses normalized for body

surface area are appropriate for both initial and incremental dosing. Since the Class III potency in

children (see CLINICAL PHARMACOLOGY) is not very different from that in adults, reaching

plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric

pharmacokinetic data the following is recommended.

For initiation of treatment, 30 mg/m

three times a day (90 mg/m

total daily dose) is approximately

equivalent to the initial 160 mg total daily dose for adults. Subsequent titration to a maximum of 60 mg/m

(approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be

guided by clinical response, heart rate and QTc, with increased dosing being preferably carried out in-

hospital. At least 36 hours should be allowed between dose increments to attain steadystate plasma

concentrations of sotalol in patients with age-adjusted normal renal function.

For children aged about 2 years or younger

For children aged about 2 years or younger, the above pediatric dosage should be reduced by a factor

that depends heavily upon age, as shown in the following graph, age plotted on a logarithmic scale in

months.

For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years

or greater should be multiplied by about 0.97; the initial starting dose would be (30 X 0.97)=29.1 mg/m

, administered three times daily. For a child aged 1 month, the starting dose should be multiplied by

0.68; the initial starting dose would be (30 X 0.68)=20 mg/m

, administered three times daily. For a

child aged about 1 week, the initial starting dose should be multiplied by 0.3; the starting dose would be

(30 X 0.3)=9 mg/m

. Similar calculations should be made for increased doses as titration proceeds.

Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state

will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.

In all children, individualization of dosage is required. As in adults Betapace (sotalol hydrochloride)

should be used with particular caution in children if the QTc is greater than 500 msec on therapy, and

serious consideration should be given to reducing the dose or discontinuing therapy when QTc

exceeds 550 msec.

Dosage in Renal Impairment

Adults

Because sotalol is excreted predominantly in urine and its terminal elimination half-life is prolonged in

conditions of renal impairment, the dosing interval (time between divided doses) of sotalol should be

modified (when creatinine clearance is lower than 60 mL/min) according to the following table.

Creatinine Clearance

mL/min

Dosing

Interval

(hours)

>60

30-59

10-29

36-48

<10

Dose should be individualized

Since the terminal elimination half-life of sotalol hydrochloride is increased in patients with renal

impairment, a longer duration of dosing is required to reach steady-state. Dose escalations in renal

impairment should be done after administration of at least 5 to 6 doses at appropriate intervals (see table

above). Extreme caution should be exercised in the use of sotalol in patients with renal failure

undergoing hemodialysis. The half-life of sotalol is prolonged (up to 69 hours) in anuric patients.

Sotalol, however, can be partly removed by dialysis with subsequent partial rebound in concentrations

when dialysis is completed. Both safety (heart rate, QT interval) and efficacy (arrhythmia control) must

be closely monitored.

Children

The use of sotalol hydrochloride in children with renal impairment has not been investigated. Sotalol

elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with

decreased renal function should be at lower doses or at increased intervals between doses. Monitoring

of heart rate and QT

is more important and it will take much longer to reach steady-state with any dose

and/or frequency of administration.

Transfer to Sotalol Hydrochloride Tablets, USP

Before starting sotalol hydrochloride tablets, USP, previous antiarrhythmic therapy should generally be

withdrawn under careful monitoring for a minimum of 2 to 3 plasma half-lives if the patient's clinical

condition permits (see Drug Interactions). Treatment has been initiated in some patients receiving I.V.

lidocaine without ill effect. After discontinuation of amiodarone, sotalol hydrochloride tablets, USP

should not be initiated until the QT interval is normalized (see WARNINGS).

Preparation of Extemporaneous Oral Solution

Information relating to the preparation of an extemporaneous oral solution of sotalol is approved for

Berlex Laboratories’ sotalol hydrochloride tablets. However, due to Berlex’s marketing exclusivity

rights, this drug product is not labeled with that information.

Transfer to Betapace AF from Sotalol Hydrochloride Tablets, USP

Patients with a history of symptomatic AFIB/AFL who are currently receiving sotalol hydrochloride

tablets, USP for the maintenance of normal sinus rhythm should be transferred to Betapace AF because

of the significant differences in labeling (i.e., patient package insert for Betapace AF, dosing

administration, and safety information).

HOW SUPPLIED

Sotalol Hydrochloride Tablets, USP 80 mg are available for oral administration as white to off-white

capsule shaped, scored tablets, imprinted “APO” on one side and “SO” bisect “80” on the other side;

Available:

Overbagged with 10 tablets per bag, NDC 55154-8179-0

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP

The initial dose of 80 mg and subsequent doses should be administered at these intervals. See following paragraph

for dosage escalations.

Controlled Room Temperature].

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

Betapace AF

is a trademark of Berlex.

Distributed by:

American Health Packaging

Columbus, OH 43217

Distributed by:

Cardinal Health

Dublin, OH 43017

8265401/0116

L55203900319

Package/Label Display Panel

Sotalol Hydrochloride Tablets, USP

80 mg

10 Tablets

SOTALOL HYDROCHLORIDE

sotalol hydrochloride tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:55154-8 179 (NDC:6 8 0 8 4-6 54)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

SO TALO L HYDRO CHLO RIDE (UNII: HEC37C70 XX) (SOTALOL - UNII:A6 D9 7U29 4I)

SOTALOL HYDROCHLORIDE

8 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

Product Characteristics

Color

white

S core

2 pieces

S hap e

OVAL (capsule shaped)

S iz e

10 mm

Flavor

Imprint Code

APO;SO;8 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:55154-8 179 -0

10 in 1 BAG

0 3/11/20 14

1

1 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 76 140

0 3/11/20 14

Cardinal Health

Labeler -

Cardinal Health (603638201)

Revised: 7/2019

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