Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1564
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SOTALOL (Tablet)
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Dosing and Administration in Adults:<br/>Initiation of Sotalol Hydrochloride Tablets (AF) 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), sotalol hydrochloride tablets (AF) 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)��body weight in kg72��serum creatinine (mg/dL) creatinine clearance (female) = (140-age)��body weight in kg��0.8572��serum creatinine (mg/dL) When serum creatinine is given in��mol/L, divide the value by 88.4 (1 mg/dL = 88.4��mol/L) Step 3. Starting Dose: The starting dose of sotalol hydrochloride tablets (AF) is 80 mg twice daily (BID) if the creatinine clearance is>60 mL/min, and 80 mg once daily (QD) or 40mg twice daily (BID) if the creatinine clearance is 40 to 60 mL/min. If the creatinine clearance is<40 mL/min sotalol hydrochloride tablets (AF) are contraindicated. Step 4. Administer the appropriate daily dose of sotalol hydrochloride tablets (AF) and begin continuous ECG monitoring with QT interval measurements 2 to 4 hours after each dose. Step 5. In patients with a creatinine clearance>60 mL/min, if the 80 mg dose level is tolerated and the QT interval remains<500 msec after at least 3 days, the patient can be discharged. Alternatively, during hospitalization, the dose can be increased to 100 mg or 120 mg BID and the patient followed for 3 days on this dose. In patients with a creatinine clearance of 40 to 60 mL/min, if the 80 mg daily dose (administered as 80 mg QD or 40 mg BID) is tolerated and the QT interval remains<500 msec after 5 or 6 days, the patient can be discharged. Alternatively, during hospitalization, the dose can be increased from 80 mg QD to 100 mg or 120 mg QD, or from 40 mg BID to 60 mg BID and the patient followed for 5 or 6 days on the dose. The steps described above are summarized in the following diagram:<br/>Upward Titration of Dose: In patients with Clcr>60 mL/min, if the 80 mg dose level (given BID) 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 100 mg or 120 mg BID. In patients with Clcr 40-60 mL/min, if the daily dose of 80 mg (given as QD or 40 mg BID) does not reduce the frequency of relapses of AFIB/AFL and is tolerated without excessive QT prolongation (i.e.���520 msec), the dose level may be increased to 100 mg or 120 mg QD or 60 mg BID. 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 sotalol hydrochloride tablets (AF) 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, in patients with Clcr>60 mL/min, the 120 mg BID 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 can be considered. If, in patients with Clcr 40���60 mL/min, the 120 mg QD or 60 mg BID does not reduce the frequency of early relapse of AFIB/AFL and is tolerated without excessive QT interval prolongation (i.e.���520 msec), an increase to 160 mg QD or 80 mg BID can be considered. Steps 2 through 5 used during the initiation of therapy should be used again to introduce such an increase.<br/>Maintenance of Sotalol Hydrochloride Tablets (AF) Therapy: Renal function and QT should be reevaluated regularly if medically warranted. If QT is 520 msec or greater (JT 430 msec or greater if QRS is>100 msec), the dose of sotalol hydrochloride tablets (AF) 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 BID in patients with Clcr>60 mL/min, 80 mg QD or 40 mg BID in patients with Clcr 40���60 mL/min) the drug should be discontinued. If renal function deteriorates, reduce the daily dose in half by administering the drug once daily at the same dose level or twice daily at half the dose as described in Initiation of Sotalol Hydrochloride Tablets (AF) Therapy, Step 3. If the creatinine clearance decreases to<40 mL/min, treatment with sotalol hydrochloride (AF) should be discontinued.<br/>Special Considerations: 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.<br/>Dosing and Administration in Pediatric Patients: 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: individualization regimen as appropriate: gradual increase of doses if required: careful assessment of therapeutic response and tolerability: and frequent monitoring of the QTinterval 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 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/mthree times a day (90 mg/mtotal 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 QT, 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��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��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��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 sotalol hydrochloride should be used with particular caution in children if the QTis greater than 500 msec on therapy and serious consideration should be given to reducing the dose or discontinuing therapy when QT, exceeds 550 msec. The use of sotalol hydrochloride AF 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 QTis more important and it will take much longer to reach steady-state with any dose and/or frequency of administration.<br/>Transfer to Sotalol Hydrochloride Tablets (AF) from Sotalol Hydrochloride: Patients with a history of symptomatic AFIB/AFL who are currently receiving sotalol hydrochloride for the maintenance of normal sinus should be transferred to sotalol hydrochloride tablets (AF) because of the significant differences in labeling (i.e., patient package insert, dosing administration, and safety information).<br/>Transfer to Sotalol Hydrochloride Tablets (AF) from Other Antiarrhythmic Agents: Before starting sotalol hydrochloride tablets (AF), 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 . Treatment has been initiated in some patients receiving I.V. lidocaine without ill effect. After discontinuation of amiodarone, sotalol hydrochloride tablets (AF) should not be initiated until the QT interval is normalized .<br/>Preparation of Extemporaneous Oral Solution: Sotalol Hydrochloride Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1% sodium benzoate (Syrup, NF) available from Humco Laboratories as follows: 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 water-insoluble 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. Stability studies indicate that the suspension is stable when stored at controlled room temperature (15��-30��C/59��-86��F) and ambient humidity for three (3) months.
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Sotalol hydrochloride, is an antiarrhythmic drug with Class II (beta-adrenoreceptor blocking) and Class III (cardiac action potential duration prolongation) properties. It is supplied as a white, capsule-shaped 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 tablets (AF) is d,l-N-[4-[l-hydroxy-2-[(l-methylethyl) amino]ethyl]phenyl]methane-sulfonamide monohydrochloride. The molecular formula is CHNOS���HCl and is represented by the following structural formula: Each tablet contains 80 mg, 120 mg, or 160 mg of sotalol hydrochloride. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, corn starch, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, stearic acid.
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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 tablets (AF) 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 electrophysiological effect can be seen at daily doses of 210 mg/mbody 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/min children.<br/>Electrophysiology: 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 40-100 msec in QT and 10-40 msec in QT. In a study of patients with atrial fibrillation (AFIB)/flutter (AFIB/AFL) receiving three different oral doses of sotalol given q12h (or q24h in patients with a reduced creatinine clearance), mean increases in QT intervals measured from 12-lead ECGs of 25 msec, 40 msec and 54 msec were found in the 80mg, 120 mg and 160 mg dose groups, respectively. (See WARNINGS for description of relationship between QTc 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 2-15 joules) compared to a mean of 16 joules for a non-randomized comparative group primarily receiving amiodarone. In a dose-response trial comparing three dose levels of sotalol hydrochloride tablets (AF), 80 mg, 120 mg, and 160 mg with placebo given q12h (or q24h in patients with a reduced renal creatinine clearance) for the prevention of recurrence of symptomatic atrial fibrillation (AFIB)/flutter (AFL), the mean ventricular rate during recurrence of AFIB/AFL was 125, 107, 110 and 99 beats/min in the placebo, 80 mg, 120 mg and 160 mg dose groups, respectively (p<0.017 for each sotalol dose group versus placebo). In another placebo controlled trial in which sotalol hydrochloride tablets (AF) was titrated to a dose between 160 and 320 mg/day in patients with chronic AFIB, the mean ventricular rate during recurrence of AFIB was 107 and 84 beats/min in the placebo and sotalol hydrochloride tablets (AF) groups, respectively (p<0.001). Twenty-five children in an unblended, 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/mwith dosing every 8 hours for a total of 9 doses. During steady-state, the respective average increases above baseline of the QTinterval, 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 QTinterval, in msec (%) were 23 (+6%), 36 (+9%) and 55 (+14%) msec at the 3 dose levels. The steady-state percent increases in the RR interval were 3, 9 and 12%. The smallest children (BSA<0.33 m) showed a tendency for larger Class III effects (��QT) and an increased frequency of prolongations of the QTinterval as compared with the larger children (BSA���0.33 m). 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.<br/>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 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 non-significant 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 produces significant reductions in both systolic and diastolic blood pressures. Although sotalol is usually well-tolerated hemodynamically, caution should be exercised in patients with marginal cardiac compensation as deterioration in cardiac performance may occur. .<br/>Clinical Studies:<br/>Prolongation of Time to Recurrence of Symptomatic Atrial Fibrillation/Flutter: Sotalol hydrochloride tablets (AF) has been studied in patients with symptomatic AFIB/AFL in two principal studies, one in patients with primarily paroxysmal AFIB/AFL, the other in patients with primarily chronic AFIB. In one study, a U.S. multicenter, randomized, placebo-controlled, double-blind, dose-response trial of patients with symptomatic primarily paroxysmal AFIB/AFL, three fixed dose levels of sotalol hydrochloride tablets (AF) (80 mg, 120 mg and 160 mg) twice daily and placebo were compared in 253 patients. In patients with reduced creatinine clearance (40 to 60 mL/min) the same doses were given once daily. Patients were not randomized for the following reasons: QT>450 msec; creatinine clearance<40 mL/min; intolerance to beta-blockers; bradycardia-tachycardia syndrome in the absence of an implanted pacemaker; AFIB/AFL was asymptomatic or was associated with syncope, embolic CVA or TIA; acute myocardial infarction within the previous 2 months; congestive heart failure; bronchial asthma or other contraindications to beta-blocker therapy; receiving potassium losing diuretics without potassium replacement or without concurrent use of ACE-inhibitors; uncorrected hypokalemia (serum potassium<3.5 meq/L) or hypomagnesemia (serum magnesium<1.5 meq/L); received chronic oral amiodarone therapy for>1 month within previous 12 weeks; congenital or acquired long QT syndromes; history of torsade de pointes with other antiarrhythmic agents which increase the duration of ventricular repolarization; sinus rate<50 bpm during waking hours; unstable angina pectoris; receiving treatment with other drugs that prolong the QT interval; and AFIB/AFL associated with the Wolff-Parkinson-White (WPW) syndrome. If the QT interval increased to���520 msec (or JT���430 msec if QRS>100 msec) the drug was discontinued. The patient population in this trial was 64% male, and the mean age was 62 years. No structural heart disease was present in 43% of the patients. Doses were administered once daily in 20% of the patients because of reduced creatinine clearance. Sotalol hydrochloride tablets (AF) were shown to prolong the time to the first symptomatic, ECG-documented recurrence of AFIB/AFL, as well as to reduce the risk of such recurrence at both 6 and 12 months. The 120 mg dose was more effective than 80 mg, but 160 mg did not appear to have an added benefit. Note that these doses were given twice or once daily, depending on renal function. The results are shown in Figure 1 and Tables 1 and 2. Figure 1Study 1 - Time to First ECG-Documented Recurrence of Symptomatic AFIB/AFL Since Randomization Discontinuation because of adverse events was dose related. In a second multicenter, randomized, placebo-controlled, double-blind study of 6 months duration in 232 patients with chronic AFIB, sotalol hydrochloride tablets (AF) was titrated over a dose range from 80 mg/day to 320 mg/day. The patient population of this trial was 70% male with a mean age of 65 years. Structural heart disease was present in 49% of the patients. All patients had chronic AFIB for>2 weeks but<1 year at entry with a mean duration of 4.1 months. Patients were excluded if they had significant electrolyte imbalance, QT>460 msec, QRS>140 msec, any degree of AV block or functioning pacemaker, uncompensated cardiac failure, asthma, significant renal disease (estimated creatinine clearance<50 mL/min), heart rate<50 bpm, myocardial infarction or open heart surgery in past 2 months, unstable angina, infective endocarditis, active pericarditis or myocarditis,���3 DC cardioversions in the past, medications that prolonged QT interval, and previous amiodarone treatment. After successful cardioversion patients were randomized to receive placebo (n=114) or sotalol hydrochloride tablets (AF) (n=118) at a starting dose of 80 mg twice daily. If the initial dose was not tolerated it was decreased to 80mg once daily, but if it was tolerated it was increased to 160 mg twice daily. During the maintenance period 67% of treated patients received a dose of 160 mg twice daily, and the remainder received doses of 80 mg once daily (17%) and 80 mg twice daily (16%). Figure 2 and Tables 3 and 4 show the results of the trial. There was a longer time to ECG-documented recurrence of AFIB and a reduced risk of recurrence at 6 months compared to placebo. Figure 2Study 2 - Time to First ECG-Documented Recurrence of Symptomatic<br/>Safety in Patients with Structural Heart Disease: In a multicenter double-blind randomized study reported by D. Julian et al, the effect of sotalol 320 mg once daily was compared with that of placebo in 1456 patients (randomized 3:2, sotalol to placebo) surviving an acute myocardial infarction (MI). Treatment was started 5 to 14 days after infarction. Patients were followed for 12 months. The mortality rate was 7.3% in the sotalol group and 8.9% in the placebo group, not a statistically significant difference. Although the results do not show evidence of a benefit of sotalol in this population, they do not show an added risk in post MI patients receiving sotalol.<br/>Pharmacokinetics: In healthy subjects, the oral bioavailability of sotalol 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 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 concentrationswhich are approximately one-half of those at peak. Sotalol does not bind to plasma proteins and is not metabolized. Sotalol shows very little intersubject variability in plasma levels. The pharmacokinetics of the d and l enantiomers of sotalol are essentially identical. Sotalol 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 . Age per se does not significantly alter the pharmacokinetics of sotalol, but impaired renal function in geriatric patients can increase the terminal elimination half-life, resulting in increased drug accumulation. The absorption of sotalol was reduced by approximately 20% compared to fasting when it was administered with a standard meal. Since sotalol is not subject to first-pass metabolism, patients with hepatic impairment show no alteration in clearance of sotalol. The combined analyses of two unblended, 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/mof sotalol was administered in the single dose study and daily doses of 30, 90 and 210 mg/mwere administered q8h 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<0.33 m) 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%.
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Sotalol hydrochloride tablets is contraindicated in patients with sinus bradycardia (<50 bpm during waking hours), sick sinus syndrome or second and third degree AV block (unless a functioning pacemaker is present), congenital or acquired long QT syndromes, baseline QT interval>450 msec, cardiogenic shock, uncontrolled heart failure, hypokalemia (<4 meq/L), creatinine clearance<40 mL/min, bronchial asthma and previous evidence of hypersensitivity to sotalol.
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Sotalol hydrochloride tablets (AF), 80 mg, oval white, scored, debossed MP 518 on one side, the other side plain. Bottles of 30 unit of use NDC 53489-503-07Bottles of 60 unit of use NDC 53489-503-06Bottles of 100 NDC 53489-503-01Bottles of 250 NDC 53489-503-03Bottles of 500 NDC 53489-503-05Bottles of 1000 NDC 53489-503-10 Sotalol hydrochloride tablets (AF), 120 mg, oval white, scored, debossed MP 519 on one side, the other side plain. Bottles of 30 unit of use NDC 53489-504-07Bottles of 60 unit of use NDC 53489-504-06Bottles of 100 NDC 53489-504-01Bottles of 250 NDC 53489-504-03Bottles of 500 NDC 53489-504-05Bottles of 1000 NDC 53489-504-10 Sotalol hydrochloride tablets (AF), 160 mg, oval white, scored, debossed MP 520 on one side, the other side plain. Bottles of 30 unit of use NDC 53489-505-07Bottles of 60 unit of use NDC 53489-505-06Bottles of 100 NDC 53489-505-01Bottles of 250 NDC 53489-505-03Bottles of 500 NDC 53489-505-05Bottles of 1000 NDC 53489-505-10 Store at 20��-25��C (68��-77��F) [See USP Controlled Room Temperature]DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.
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To minimize the risk of induced arrhythmia, patients initiated or re-initiated on sotalol hydrochloride tablets (AF) should be placed for a minimum of three days (on their maintenance dose) in a facility that can provide cardiac resuscitation, continuous electrocardiographic monitoring and calculationsof creatinine clearance. For detailed instructions regarding dose selection and special cautions for people with renal impairment, see DOSAGE AND ADMINISTRATION. Sotalol is also indicated for the treatment of documented life-threatening ventricular arrhythmias and is marketed under the brand name BETAPACE. BETAPACE however, should not be substituted for sotalol hydrochloride tablets (AF) because of significant differences in labeling (i.e. patient package insert, dosing administration and safety information).
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dailymed-ingredient:Anhydrous_lactose,
dailymed-ingredient:colloidal_silicon_dioxide,
dailymed-ingredient:corn_starch,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:pregelatinized_starch,
dailymed-ingredient:sodium_starch_glycolate,
dailymed-ingredient:stearic_acid
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Renal Impairment: Sotalol hydrochloride tablets (AF) is eliminated principally 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 hydrochloride tablets (AF). Guidance for dosing in conditions of renal impairment can be found under "DOSAGE AND ADMINISTRATION."<br/>Information for Patients: Please refer to the patient package insert. Prior to initiation of sotalol hydrochloride tablets (AF) therapy, the patient should be advised to read the patient package insert and reread it each time therapy is renewed. The patient should be fully instructed on the need for compliance with the recommended dosing of sotalol hydrochloride tablets (AF), the potential interactions with drugs that prolong the QT interval and other antiarrhythmics, and the need for periodic monitoring of QT and renal function to minimize the risk of serious abnormal rhythms.<br/>Medications and Supplements: Assessment of patients' medication history should include all over-counter, prescription and herbal/natural preparations with emphasis on preparations that may affect the pharmacodynamics of sotalol hydrochloride tablets (AF) such as other cardiac antiarrhythmic drugs, some phenothiazines, bepridil, tricyclic antidepressants and oral macrolides . Patients should be instructed to notify their health care providers of any change in over-the-counter, prescription or supplement use. If a patientis hospitalized or is prescribed a new medication for any condition, the patient must inform the health care provider of ongoing sotalol hydrochloride tablets (AF) therapy. Patients should also check with their health care provider and/or pharmacist prior to taking a new over-the-counter medicine.<br/>Electrolyte Imbalance: If patients experience symptoms that may be associated with altered electrolyte balance, such as excessive or prolonged diarrhea, sweating, or vomiting, or loss of appetite or thirst, these conditions should be immediately reported to their health care provider.<br/>Dosing Schedule: Patients should be instructed NOT to double the next dose if a dose is missed. The next dose should be taken at the usual time.<br/>Drug Interactions:<br/>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.<br/>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 CHF, a known risk factor for proarrhythmia, in the patients receiving digoxin.<br/>Calcium blocking drugs: Sotalol hydrochloride tablets (AF) 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.<br/>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 hydrochloride tablets (AF) plus a catecholamine depletor should therefore be closely monitored for evidence of hypotension and/or marked bradycardia which may produce syncope.<br/>Insulin and oral antidiabetics: Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment. Symptoms of hypoglycemia may be masked.<br/>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 hydrochloride tablets (AF).<br/>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 hydrochloride tablets (AF).<br/>Other: No pharmacokinetic interactions were observed with hydrochlorothiazide or warfarin.<br/>Antacids: Administration of sotalol hydrochloride tablets (AF) within 2 hours of antacids containing aluminum oxide and magnesium hydroxide should be avoided because it may result in a reduction in Cand 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 hydrochloride tablets (AF) has no effect on the pharmacokinetics or pharmacodynamics of sotalol.<br/>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.<br/>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.<br/>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 HCl. In rabbits, a high dose of sotalol HCl (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 HCl, 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 HCl 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 (AF) should be used during pregnancy only if the potential benefit outweighs the potential risk.<br/>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 hydrochloride tablets (AF), 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.
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Sotalol
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SOTALOL (Tablet)
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Adverse events that are clearly related to sotalol are those which are typical of its Class II (beta-blocking) and Class III (cardiac action potential duration prolongation) effects. The common documented beta-blocking adverse events (bradycardia, dyspnea, and fatigue) and Class III effects (QT interval prolongation) are dose related. In a pooled clinical trial population consisting of four placebo-controlled studies with 275 patients with AFIB/AFL treated with 160 to 320 mg doses of sotalol hydrochloride tablets (AF), the following adverse events were reported at a rate of 2% or more in the 160 to 240 mg treated patients and greater than the rate in placebo patients (see Table 8). The data are presented by incidence of events in the sotalol hydrochloride tablets (AF) and placebogroups by body system and daily dose. No significant irreversible non-cardiac end-organ toxicity was observed. Overall, discontinuation because of unacceptable adverse events was necessary in 17% of the patients, and occurred in 10% of patients less than two weeks after starting treatment. The most common adverse events leading to discontinuation of sotalol hydrochloride tablets (AF) were: fatigue 4.6%, bradycardia 2.4%, proarrhythmia 2.2%, dyspnea 2%, and QT interval prolongation 1.4%. In clinical trials involving 1292 patients with sustained VT/VF, the common adverse events (occurring in���2% of patients) were similar to those described for the AFIB/AFL population. 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. In an unblinded multicenter trial of 25 pediatric patients with SVT and/or VT receiving daily doses of 30, 90 and 210 mg/mwith 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/mdaily, was discontinued because of increased frequency of sinus pauses/bradycardia. Additional cardiovascular AEs were seen at the 90 and 210 mg/mdaily 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/mdaily dose level. Serious adverse events including death, torsades de pointe, other proarrhythmias, high-degree A-V blocks and bradycardia have been reported in infants and/or children.<br/>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 also include rare reports of: emotional lability, slightly clouded sensorium, incoordination, vertigo, paralysis, thrombocytopenia, eosinophilia, leukopenia, photosensitivity reaction, fever, pulmonary edema, hyperlipidemia, myalgia, pruritus, alopecia. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been associated with sotalol hydrochloride tablets (AF) during investigational use and foreign marketing experience.
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Sotalol hydrochloride tablets (AF) are 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 sotalol hydrochloride tablets (AF) can cause life-threatening ventricular arrhythmias, it should be reserved for patients in whom AFIB/AFL is highly symptomatic. Patients with paroxysmal AFIB/AFL that is easily reversed (by Valsalva maneuver, for example) should usually not be given sotalol hydrochloride tablets (AF) . In general, antiarrhythmic therapy for AFIB/AFL aims to prolong the time in normal sinus rhythm. Recurrence is expected in some patients . 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 sotalol hydrochloride tablets (AF) because of significant differences in labeling (i.e. patient package insert, dosing administration and safety information).
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SOTALOL
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