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 2 three times a day (90 mg/m 2 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 2 (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 2, 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 2, 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 2. 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. Figure1.jpg 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 The initial dose of 80 mg and subsequent doses should be administered at these intervals. See following paragraph for dosage escalations. Interval (hours) >60 12 30-59 24 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 c 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).