"May 31, 2013 -- More than 2 million Americans have an abnormal heart rhythm known as atrial fibrillation, raising their risk of blood clots leading to stroke. For many years, the blood thinner Coumadin (warfarin) was the only game in town to help"...
BETAPACE AF (sotalol hcl) is 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. Because BETAPACE AF can cause lifethreatening ventricular arrhythmias, it should be reserved for patients in whom AFIB/AFL is highly symptomatic. Patients with paroxysmal AFIB whose AFIB/AFL that is easily reversed (by Valsalva maneuver, for example) should usually not be given BETAPACE AF (see WARNINGS).
Sotalol is also indicated for the treatment of documented life- threatening ventricular arrhythmias and is marketed under the brand name BETAPACE (sotalol hydrochloride). BETAPACE, however, must not be substituted for BETAPACE AF because of significant differences in labeling (i.e., patient package insert, dosing administration and safety information).
DOSAGE AND ADMINISTRATION
Dosing and Administration in Adults
- Therapy with BETAPACE AF (sotalol hcl) must be initiated (and, if necessary, titrated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Patients should continue to be monitored in this way for a minimum of 3 days on the maintenance dose. In addition, patients should not be discharged within 12 hours of electrical or pharmacological conversion to normal sinus rhythm.
- The QT interval is used to determine patient eligibility for BETAPACE AF (sotalol hcl) treatment and for monitoring safety during treatment. The baseline QT interval must be ≤ 450 msec in order for a patient to be started on BETAPACE AF (sotalol hcl) therapy. During initiation and titration, the QT interval should be monitored 2-4 hours after each dose. If the QT interval prolongs to 500 msec or greater, the dose must be reduced or the drug discontinued.
- The dose of BETAPACE AF (sotalol hcl) must be individualized according o t calculated creati nine clearance. In patients with a creatinine clearance > 60 mL/min BETAPACE AF (sotalol hcl) is administered twice daily (BID) while in those with a creatinine clearance between 40 and 60 mL/m in, the dose is administered once daily Q(D). In patients with a creatinine clearance less than 40 mL/min BETAPACE AF is contraindicated. The recommended initial dose of BETAPACE AF (sotalol hcl) is 80 mg and is initiated as shown in the dosing algorithm described below. The 80 mg dose can be titrated upward to 120 mg during initial hospitailzation or after discharge on 80 mg in the event of recurrence, by rehospitalization and repeating the same steps used during the initiation of therapy (see Upward Titration of Dose).
- Patients with atrial fibrillation should be anticoagulate d according to usual medical practice. Hypokalemia should be corrected before intiaition of BETAPACE AF therapy (see WARNINGS, Ventricular Arrhythmia).
- Patients to be discharged on BETAPACE AF (sotalol hcl) therapy from an in-patient setting should have an adequate supply of BETAPACE AF (sotalol hcl) , to allow uninterrupted therapy until the patient can fill a BETAPACE AF (sotalol hcl) prescription.
Initiation of BETAPACE AF (sotalol hcl) Therapy
Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QT interval must be determined using an average of 5 beats. If the baseline QT is greater than 450 msec (JT ≥ 330 msec if QRS over 100 msec), BETAPACE AF (sotalol hcl) is contraindicated.
Step 2. Calculation of creatinine clearance: Prior to the administration of the first dose, the patient's creatinine clearance should be calculated using the following formula:
|creatinine clearance (male) =||(140-age) x body weight in kg|
|72 x serum creatinine (mg/dL)|
|creatinine clearance (female) =||(140-age) x body weight in kg x 0.85|
|72 x serum creatinine (mg/dL)|
When serum creatinine is given in µmol/L, divide the value by 88.4 (1 mg/dL = 88.4 µmol/L).
Step 3. Starting Dose: The starting dose of BETAPACE AF (sotalol hcl) is 80 mg twice daily (BID) if the creatinine clearance is > 60 mL/min, and 80 mg once daily (QD) if the creatinine clearance is 40-60 mL/min. If the creatinine clearance is < 40 mL/min BETAPACE AF (sotalol hcl) is contraindicated.
Step 4. Administer the appropriate daily dose of BETAPACE AF (sotalol hcl) and begin continuous ECG monitoring with QT interval measurements 2-4 hours after each dose.
Step 5. If the 80 mg dose level is tolerated and the QT interval remains < 500 msec after at least 3 days (after 5 or 6 doses if patient receiving QD dosing), the patient can be discharged. Alternatively, during hospitalization, the dose can be increased to 120 mg bid and the patient followed for 3 days on this dose (followed for 5 or 6 doses if patient receiving QD doses).
The steps described above are summarized in the following diagram:
Upward Titration of Dose
If the 80 mg dose level (given BID or QD depending upon the creatinine clearance) does not reduce the frequency of relapses of AFIB/AFL and is tolerated without excessive QT interval prolongation (i.e., ≥ 520 msec), the dose level may be increased to 120 mg (BID or QD depending upon the creatinine clearance). As proarrhythmic events can occur not only at initiation of therapy, but also with each upward dosage adjustment, Steps 2 through 5 used during initiation of BETAPACE AF (sotalol hcl) therapy should be followed when increasing the dose level. In the U.S. multicenter dose-response study, the 120 mg dose (BID or QD) was found to be the most effective in prolonging the time to ECG documented symptomatic recurrence of AFIB/AFL. If the 120 mg dose does not reduce the frequency of early relapse of AFIB/AFL and is tolerated without excessive QT interval prolongation ( ≥ 520 msec), an increase to 160 mg (BID or QD depending upon the creatinine clearance), can be considered. Steps 2 through 5 used during the initiation of therapy should be used again to introduce such an increase.
Maintenance of BETAPACE AF (sotalol hcl) Therapy
Renal function and QT should be re-evaluated regularly if medically warranted. If QT is 520 msec or greater (JT 430 msec or greater if QRS is > 100 msec), the dose of BETAPACE AF (sotalol hcl) therapy should be reduced and patients should be carefully monitored until QT returns to less than 520 msec. If the QT interval is ≥ 520 msec while on the lowest maintenance dose level (80 mg) the drug should be discontinued. If renal function deteriorates, reduce the daily dose in half by administering the drug once daily as described in Initiation of BETAPACE AF (sotalol hcl) Therapy, Step 3.
The maximum recommended dose in patients with a calculated creatinine clearance greater than 60 mL/min is 160 mg BID, doses greater than 160 mg BID have been associated with an increased incidence of Torsade de Pointes and are not recommended.
A patient who misses a dose should NOT double the next dose. The next dose should be taken at the usual time.
Dosing and Administration in 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, 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/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being preferably carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steady-state plasma concentrations of sotalol in patients with age-adjusted normal renal function.
For children aged about 2 years or younger 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/m2, administered three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 X 0.68)=20 mg/m2, administered three times daily. For a child aged about 1 week, the initial starting dose should be multiplied by 0.3; the starting dose would be (30 X 0.3)=9 mg/m2. 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 AF (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 550msec.
The use of BETAPACE AF (sotalol hcl) (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 QTc is more important and it will take much longer to reach steady-state with any dose and/or frequency of administration.
Transfer to BETAPACE AF (sotalol hcl) from BETAPACE
Patients with a history of symptomatic AFIB/AFL who are currently receiving BETAPACE for the maintenance of normal sinus should be transferred to BETAPACE AF because of the significant differences in labeling (i.e., patient package insert, dosing administration, and safety information).
Transfer to BETAPACE AF (sotalol hcl) from Other Antiarrhythmic Agents
Before starting BETAPACE AF (sotalol hcl) , 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 DRUG INTERACTIONS). Treatment has been initiated in some patients receiving I.V. lidocaine without ill effect. After discontinuation of amiodarone, BETAPACE AF should not be initiated until the QT interval is normalized (see WARNINGS).
Preparation of Extemporaneous Oral Solution
BETAPACE AF (sotalol hcl) Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1% sodium benzoate (Syrup, NF) available from Humco Laboratories as follows:
- Measure 120mL of Simple Syrup
- Transfer the syrup to a 6-ounce amber plastic (polyethylene terephthalate [PET]) prescription bottle. NOTE: An oversized bottle is used to allow for a headspace, so that there will be more effective mixing during shaking of the bottle.
- Add five (5) BETAPACE AF (sotalol hcl) 120 mg tablets to the bottle. These tablets are added intact; it is not necessary to crush the tablets. NOTE: The addition of the tablets can also be done first. The tablets can also be crushed if preferred. If the tablets are crushed, care should be taken to transfer the entire quantity of tablet powder into the bottle containing the syrup.
- Shake the bottle to wet the entire surface of the tablets. If the tablets have been crushed, shake the bottle until the endpoint is achieved.
- Allow the tablets to hydrate for approximately two hours.
- After at least two hours have elapsed, shake the bottle intermittently over the course of at least another two hours until the tablets are completely disintegrated. NOTE: The tablets can be allowed to hydrate overnight to simplify the disintegration process.
The endpoint is achieved when a dispersion of fine particles in the syrup is obtained.
This compounding procedure results in a solution containing 5 mg/mL of sotalol HCl. The fine solid particles are the waterinsoluble inactive ingredients of the tablets.
This extemporaneously prepared oral solution of sotalol HCl (with suspended inactive particles) must be shaken well prior to administration. This is to ensure that the amount of inactive solid particles per dose remains constant throughout the duration of use.
BETAPACE AF (sotalol hcl) (sotalol hydrochloride); capsule-shaped white scored tablets imprinted with the strength are available as follows:
NDC 50419-115-06 80 mg strength, bottle of 60 in unit use package
NDC 50419-119-06 120 mg strength, bottle of 60 in unit use package
NDC 50419-116-06 160 mg strength, bottle of 60 in unit use package
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature].
Manufactured for: Bayer HealthCare Pharmaceuticals Inc. Wayne, NJ 07470. Manufactured in Finland. Rev. April 2007. FDA Rev date: 4/2/2003
Last reviewed on RxList: 12/29/2008
This monograph has been modified to include the generic and brand name in many instances.
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