Sotylize (sotalol hydrochloride)

WARNING

LIFE THREATENING PROARRHYTHMIA

To minimize the risk of induced arrhythmia, patients initiated or re-initiated on oral sotalol, and patients who are converted from intravenous sotalol to oral administration should be hospitalized in a facility that can provide cardiac resuscitation, continuous electrocardiographic monitoring and calculations of creatinine clearance.

• Sotalol can cause life threatening ventricular tachycardia associated with QT interval prolongation
• Do not initiate sotalol therapy if the baseline QTc is longer than 450 ms. If the QT interval prolongs to 500 ms or greater, the dose must be reduced, the interval between doses prolonged, or the drug discontinued.
• Adjust the dosing interval based on creatinine clearance.

Sotylize can cause serious side effects, including:

• Slow heartbeat (bradycardia) is common with Sotylize. A slow heartbeat increases your risk of developing a serious abnormal heartbeat. Your doctor will check you for this problem, especially if you take the medicine digoxin.
• New or worsening heart failure can happen in people who take Sotylize. Symptoms of worsening heart failure include shortness of breath and fatigue. If these occur, contact your doctor.
• If you have diabetes, Sotylize can make it more difficult for you to tell if you have low blood sugar (hypoglycemia). Certain important signs of low blood sugar, such as a fast heartbeat, may be hidden.
• If you have an overactive thyroid gland (hyperthyroidism), Sotylize can make it more difficult for you to tell if you are having symptoms of too much thyroid hormone in your blood. Certain signs of having too much thyroid hormone in your blood, such as a fast heartbeat, may be hidden. If you stop taking Sotylize suddenly, your symptoms of having too much thyroid hormone in your blood may become much worse, and could be life-threatening.
• Severe allergic reactions. People who have had severe allergic reactions in the past to other things may have a more severe allergic reaction when taking medicines like Sotylize.
• Possible side effects to anesthesia. Sotylize may cause severe low blood pressure and heart rhythm problems in people who receive anesthesia for major surgery. Tell your doctor that you are taking Sotylize if you need to have surgery during treatment with Sotylize.

The most common side effects of Sotylize include:

• tiredness
• slow heart rate
• dizziness
• headache

Changes in the level of body salts (electrolytes) in your blood can lead to serious side effects during treatment with Sotylize. Call your doctor if you have any of the following symptoms:

• severe diarrhea
• unusual sweating
• vomiting
• less appetite than normal
• increased thirst (drinking more than normal)

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Sotylize. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General Rules And Safety Measures Of Oral Sotalol Therapy

• To minimize the risk of induced arrhythmia, patients initiated or re-initiated on sotalol should be hospitalized 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 trained in the management of serious ventricular arrhythmias.
• Perform a baseline ECG to determine the QT interval and measure and normalize serum potassium and magnesium levels before initiating therapy with sotalol.
• Measure serum creatinine and calculate an estimated creatinine clearance in order to establish the appropriate dosing interval for sotalol.
• Start sotalol therapy only if the baseline QT_c interval is <450 msec. During initiation and titration, monitor the QT interval after each dose. If the QT_c interval prolongs to 500 msec or greater, reduce the dose, increase the interval between doses, or discontinue the drug.
• Administer sotalol twice daily in patients with a creatinine clearance >60 mL/min or once daily in patients with creatinine clearance between 40 and 60 mL/min. Sotalol is not recommended in patients with a creatinine clearance <40 mL/min. The recommended initial oral dose of sotalol is 80 mg (once or twice daily) and is initiated and titrated as described below.
• Patients to be discharged on Sotylize therapy from an in-patient setting should have an adequate supply of Sotylize, to allow uninterrupted therapy until the patient can fill a Sotylize prescription.
• Advise patients who miss a dose to take just the next dose at the usual time.
• For patients discharged and taking compounded sotalol oral solution filled by the pharmacy, consider switching to Sotylize while in an outpatient setting.
• Table 1 shows the appropriate volume of Sotylize solution for typical doses.

Table 1: Sotylize Dose Volume

Ventricular Arrhythmia

The recommended initial dose of oral sotalol for the treatment of ventricular arrhythmia is 80 mg, once or twice daily based on creatinine clearance [see General Rules And Safety Measures Of Oral Sotalol Therapy above]. The dose may be increased in increments of 80 mg per day every 3 days as needed, provided QT_c < 500 msec. The usual therapeutic effect is observed with oral doses of 80 to 160 mg once or twice a day. Oral doses as high as 240-320 mg once or twice a day have been utilized in patients with refractory life-threatening arrhythmias.

Pediatrics

• As in adults, initiate in the hospital after appropriate clinical assessment, gradually increase dose as required, and monitor QT and heart rate.
• For children aged 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing.
• 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. Allow at least 36 hours between dose increments to attain steady-state plasma concentrations of sotalol in patients with normal renal function.
• For children aged 2 years or younger, reduce the dose.
  • For a child with normal renal function aged 1 month, the initial starting dose would be (30 × 0.7) = 21 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 × 0.3) = 9 mg/m². Use similar calculations for dose titration.
  • Since the half-life of sotalol increases below about 2 years, time to steady-state will also increase. Thus, in neonates the time to steady-state may be a week or longer.

Symptomatic AFIB/AFL

• The recommended initial dose of oral sotalol for the treatment of symptomatic AFIB/AFL is 80 mg, once or twice daily based on creatinine clearance [see General Rules And Safety Measures Of Oral Sotalol Therapy above].
• If that dose level at steady-state does not acceptably reduce the time to recurrence of arrhythmia and is tolerated with QT_c <520 msec, increase the dose to 160 mg orally once or twice a day every three days.
• In the U.S. multicenter dose-response study, 120 mg orally once or twice a day was found to be the most effective dose in prolonging the time to ECG-documented symptomatic recurrence of AFIB/AFL.

Considerations In Renal Impairment

• 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 most important and it will take much longer to reach steady-state with any dose and/or frequency of administration.

Digoxin

• 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 heart failure, a known risk factor for proarrhythmia, in the patients receiving digoxin.

Calcium-Blocking Drugs

• Sotalol and calcium blocking drugs can be expected to have additive effects on atrioventricular conduction, ventricular function, and blood pressure.

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. Monitor such patients for hypotension and marked bradycardia which may produce syncope.

Insulin And Oral Antidiabetic Agents

• 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 albuterol, terbutaline and isoproterenol 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.

Drugs That Prolong QT Interval And Antiarrhythmic Agents

• Sotalol has not been studied with other drugs that prolong the QT interval such as antiarrhythmics, some phenothiazines, tricyclic antidepressants, certain oral macrolides and certain quinolone antibiotics.
• Class I or Class III antiarrhythmic agents should be withheld for at least three half-lives prior to dosing with sotalol. In clinical trials, sotalol was not administered to patients previously treated with oral amiodarone for >1 month in the previous three months.
• 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.
• There is only limited experience with the concomitant use of Class Ib or Ic antiarrhythmics.

Antacids

• Administration of oral sotalol within 2 hours of antacids containing aluminum oxide and magnesium hydroxide should be avoided because it may result in a reduction in Cmax 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 oral sotalol has no effect on the pharmacokinetics or pharmacodynamics of sotalol.

• There are no adequate and well-controlled studies in pregnant women. Sotalol crosses the placenta.
• Sotalol is excreted in the milk of laboratory animals and has been reported to be present in human milk. Discontinue nursing or Sotylize.