Sorine (Sotalol Hydrochloride) - Indications and Dosage

INDICATIONS AND USAGE

Oral Sorine^® (Sotalol HCl) Tablets 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 (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 Sorine^® (Sotalol HCl) Tablets 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.

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 to 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 multi-center 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^™. Sorine^® is 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.

DOSAGE AND ADMINISTRATION

As with other antiarrhythmic agents, Sorine^® (Sotalol HCl) Tablets should be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment (see INDICATIONS AND USAGE). Sorine^® should be administered only after appropriate clinical assessment (see INDICATIONS AND USAGE), and the dosage of Sorine^® 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 Sorine^® 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.

Pediatrics: Pediatric dosing information for sotalol hydrochloride tablets is approved for Berlex Laboratories' sotalol hydrochloride tablets. However, due to Berlex's marketing exclusivity rights, this drug product is not labeled for pediatric use.

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 Sorine^® (Sotalol HCl) Tablets should be modified (when creatinine clearance is lower than 60 mL/min) according to the following table.

*The initial dose of 80 mg and subsequent doses should be administered at these intervals. See following paragraph for dosage escalations.
Creatinine Clearance	Dosing* Interval
mL/min	(hours)
>60	12
30-59	24
10-29	36-48
<10	Dose should be individualized

Since the terminal elimination half-life of sotalol 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 5-6 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.

Pediatrics: The use of sotalol in pediatric patients 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_c is more important and it will take much longer to reach steady-state with any dose and/or frequency of administration.

Transfer to SORINE^®

Before starting Sorine^® (Sotalol HCl) Tablets, previous antiarrhythmic therapy should generally be withdrawn under careful monitoring for a minimum of 2-3 plasma half-lives if the patient's clinical condition permits (see PRECAUTIONS, Drug Interactions). Treatment has been initiated in some patients receiving I.V. lidocaine without ill effect. After discontinuation of amiodarone, Sorine^® 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 Sorine^®

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

Sorine^® (Sotalol HCl) Tablets are white, capsule-shaped, scored tablets with the following tablet deboss, respectively:

80 mg	“US” to the left and “12” to the right of the score,
	“80” strength on the unscored side
120 mg	“US” to the left and “13” to the right of the score,
	“120” strength on the unscored side
160 mg	“US” to the left and “14” to the right of the score,
	“160” strength on the unscored side
240 mg	“US” to the left and “15” to the right of the score,
	“240” strength on the unscored side

Sorine^® (Sotalol HCl) Tablets are available as follows:

80 mg	NDC 0245-0012-11, bottle of 100 tablets
	NDC 0245-0012-01, carton of 100 unit dose tablets
120 mg	NDC 0245-0013-11, bottle of 100 tablets
	NDC 0245-0013-01, carton of 100 unit dose tablets
160 mg	NDC 0245-0014-11, bottle of 100 tablets
	NDC 0245-0014-01, carton of 100 unit dose tablets
240 mg	NDC 0245-0015-11, bottle of 100 tablets
	NDC 0245-0015-01, carton of 100 unit dose tablets

Store at controlled room temperature, between 15°-30°C (59°-86°F) (see USP).

Dispense in a well-closed container (USP).

BETAPACE AF is a registered trademark of Berlex Laboratories, Inc.

Manufactured by
UPSHER-SMITH LABORATORIES, INC., Minneapolis, MN 55447

Rev. 0203