sotalol hydrochloride 80 MG Oral Tablet [Sorine]

INDICATIONS AND USAGE Sotalol hydrochloride tablets, USP 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 hydrochloride tablets, USP (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 sotalol hydrochloride 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 hydrochloride tablets, USP. In the ESVEM Trial, response by Holter monitoring was tentatively defined as 100% suppression of ventricular tachycardia, 90% suppression of nonsustained 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 by 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 multicenter 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 (sotalol hydrochloride, tablets, USP). Sotalol hydrochloride tablets, USP 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 Dosing and Administration in Adults Therapy with sotalol hydrochloride tablets (AF) 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 sotalol hydrochloride tablet (AF) treatment and for monitoring safety during treatment. The baseline QT interval must be ≤450 msec in order for a patient to be started on sotalol hydrochloride tablet (AF) therapy. During initiation and titration, the QT interval should be monitored 2 to 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 Sotalol Hydrochloride Tablets, USP (AF) must be individualized according to calculated creatinine clearance. In patients with a creatinine clearance >60 mL/min Sotalol Hydrochloride Tablets, USP (AF) is administered twice daily (BID) while in those with a creatinine clearance between 40 and 60 mL/min, the dose is administered once daily (QD). In patients with a creatinine clearance less than 40 mL/min Sotalol Hydrochloride Tablets, USP (AF) is contraindicated. The recommended initial dose of Sotalol Hydrochloride Tablets, USP (AF) is 80 mg and is initiated as shown in the dosing algorithm described below. The 80 mg dose can be titrated upward to 100mg or 120mg during initial hospitalization 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 anticoagulated according to usual medical practice. Hypokalemia should be corrected before initiation of sotalol hydrochloride tablet (AF) therapy (see WARNINGS , Ventricular Arrhythmia ). Patients to be discharged on sotalol hydrochloride tablet (AF) therapy from an in-patient setting should have an adequate supply of sotalol hydrochloride tablets (AF), to allow uninterrupted therapy until the patient can fill a sotalol hydrochloride tablets (AF) prescription. Initiation of Sotalol Hydrochloride Tablets, USP (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) are 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 mcmol/L, divide the value by 88.4 (1 mg/dL= 88.4 mcmol/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) 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 . 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 100 mg or 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: Place Patient on Telemetry Check Baseline QT If QT >450 msec Sotalol hydrochloride tablets (AF) are CONTRAINDICATED If QT ≤450 msec, proceed Calculate Creatine Clearance (Clcr) If Clcr is <40 mL/min sotalol hydrochloride tablets (AF) are CONTRAINDICATED If Clcr is 40 to 60 mL/min start sotalol hydrochloride tablets (AF) 80 mg QD If Clcr is >60 mL/min start sotalol hydrochloride tablets (AF) 80 mg BID Monitor QT 2 to 4 hours after each dose. If QT ≥500 msec discontinue sotalol hydrochloride tablets (AF). If QT <500 msec after 3 days (after 5 th or 6 th dose if patient receiving QD dosing) discharge patient on current treatment. 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). 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 sotalol hydrochloride tablet (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 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 Sotalol Hydrochloride Tablets, USP (AF) 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 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) 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 sotalol hydrochloride tablets (AF) Therapy, Step 3 . 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. 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 QT c 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 with

WARNINGS Mortality The National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial I (CAST I) was a long-term, multi-center, double-blind study in patients with asymptomatic, non-life-threatening ventricular arrhythmias, 1 to 103 weeks after acute myocardial infarction. Patients in CAST I were randomized to receive placebo or individually optimized doses of encainide, flecainide, or moricizine. The Cardiac Arrhythmia Suppression Trial II (CAST II) was similar, except that the recruited patients had had their index infarction 4 to 90 days before randomization, patients with left ventricular ejection fractions greater than 40% were not admitted, and the randomized regimens were limited to placebo and moricizine. CAST I was discontinued after an average time-on-treatment of 10 months, and CAST II was discontinued after an average time-on-treatment of 18 months. As compared to placebo treatment, all three active therapies were associated with increases in short-term (14-day) mortality, and encainide and flecainide were associated with significant increases in longer-term mortality as well. The longer-term mortality rate associated with moricizine treatment could not be statistically distinguished from that associated with placebo. The applicability of these results to other populations (e.g., those without recent myocardial infarction) and to other than Class I antiarrhythmic agents is uncertain. Sotalol hydrochloride is devoid of Class I effects, and in a large (n=1,456) controlled trial in patients with a recent myocardial infarction, who did not necessarily have ventricular arrhythmias, sotalol did not produce increased mortality at doses up to 320 mg/day (see Clinical Studies ). On the other hand, in the large postinfarction study using a non-titrated initial dose of 320 mg once daily and in a second small randomized trial in high-risk post-infarction patients treated with high doses (320 mg BID), there have been suggestions of an excess of early sudden deaths. Proarrhythmia Like other antiarrhythmic agents, sotalol can provoke new or worsened ventricular arrhythmias in some patients, including sustained ventricular tachycardia or ventricular fibrillation, with potentially fatal consequences. Because of its effect on cardiac repolarization (QTc interval prolongation), Torsade de Pointes, a polymorphic ventricular tachycardia with prolongation of the QT interval and a shifting electrical axis is the most common form of proarrhythmia associated with sotalol, occurring in about 4% of high risk (history of sustained VT/VF) patients. The risk of Torsade de Pointes progressively increases with prolongation of the QT interval, and is worsened also by reduction in heart rate and reduction in serum potassium (see Electrolyte Disturbances ). Because of the variable temporal recurrence of arrhythmias, it is not always possible to distinguish between a new or aggravated arrhythmic event and the patient’s underlying rhythm disorder. (Note, however, that Torsade de Pointes is usually a drug-induced arrhythmia in people with an initially normal QTc.) Thus, the incidence of drug-related events cannot be precisely determined, so that the occurrence rates provided must be considered approximations. Note also that drug-induced arrhythmias may often not be identified, particularly if they occur long after starting the drug, due to less frequent monitoring. It is clear from the NIH-sponsored CAST (see WARNINGS, Mortality ) that some antiarrhythmic drugs can cause increased sudden death mortality, presumably due to new arrhythmias or asystole, that do not appear early in treatment but that represent a sustained increased risk. Overall in clinical trials with sotalol, 4.3% of 3257 patients experienced a new or worsened ventricular arrhythmia. Of this 4.3%, there was new or worsened sustained ventricular tachycardia in approximately 1% of patients and Torsade de Pointes in 2.4%. Additionally, in approximately 1% of patients, deaths were considered possibly drug-related; such cases, although difficult to evaluate, may have been associated with proarrhythmic events. In patients with a history of sustained ventricular tachycardia, the incidence of Torsade de Pointes was 4% and worsened VT in about 1%; in patients with other, less serious, ventricular arrhythmias and supraventricular arrhythmias, the incidence of Torsade de Pointes was 1% and 1.4%, respectively. Torsade de Pointes arrhythmias were dose related, as is the prolongation of QT (QTc) interval, as shown in the table below. Percent Incidence of Torsade de Pointes and Mean QTc Interval by Dose For Patients With Sustained VT/VF Daily Dose (mg) Incidence of Torsade de Pointes Mean QTc a (msec) 80 0 (69) b 463 (17) 160 0.5 (832) 467 (181) 320 1.6 (835) 473 (344) 480 4.4 (459) 483 (234) 640 3.7 (324) 490 (185) >640 5.8 (103) 512 (62) a) highest on-therapy value In addition to dose and presence of sustained VT, other risk factors for Torsade de Pointes were gender (females had a higher incidence), excessive prolongation of the QT c interval (see table below) and history of cardiomegaly or congestive heart failure. Patients with sustained ventricular tachycardia and a history of congestive heart failure appear to have the highest risk for serious proarrhythmia (7%). Of the patients experiencing Torsade de Pointes, approximately two-thirds spontaneously reverted to their baseline rhythm. The others were either converted electrically (D/C cardioversion or overdrive pacing) or treated with other drugs (see OVERDOSAGE ). It is not possible to determine whether some sudden deaths represented episodes of Torsade de Pointes, but in some instances sudden death did follow a documented episode of Torsade de Pointes. Although sotalol therapy was discontinued in most patients experiencing Torsade de Pointes, 17% were continued on a lower dose. Nonetheless, sotalol should be used with particular caution if the QT c is greater than 500 msec on-therapy and serious consideration should be given to reducing the dose or discontinuing therapy when the QT c exceeds 550 msec. Due to the multiple risk factors associated with Torsade de Pointes, however, caution should be exercised regardless of the QT c interval. The table below relates the incidence of Torsade de Pointes to on-therapy QT c and change in QTc from baseline. It should be noted, however, that the highest on-therapy QT c was in many cases the one obtained at the time of the Torsade de Pointes event, so that the table overstates the predictive value of a high QT c . Relationship Between QTc Interval Prolongation and Torsade de Pointes ( ) Number of patients assessed On-Therapy QTc Interval (msec) Incidence of Torsade de Pointes Change in QTc Interval From Baseline (msec) Incidence of Torsade de Pointes < 500 1.3% (1787) < 65 1.6% (1516) 500-525 3.4% (236) 65-80 3.2% (158) 525-550 5.6% (125) 80-100 4.1% (146) >550 10.8% (157) 100-130 5.2% (115) > 130 7.1% (99) Proarrhythmic events must be anticipated not only on initiating therapy, but with every upward dose adjustment. Proarrhythmic events most often occur within 7 days of initiating therapy or of an increase in dose; 75% of serious proarrhythmias (Torsade de Pointes and worsened VT) occurred within 7 days of initiating sotalol therapy, while 60% of such events occurred within 3 days of initiation or a dosage change. Initiating therapy at 80 mg BID with gradual upward dose titration and appropriate evaluations for efficacy (e.g., PES or Holter) and safety (e.g., QT interval, heart rate and electrolytes) prior to dose escalation, should reduce the risk of proarrhythmia. Avoiding excessive accumulation of sotalol in patients with diminished renal function, by appropriate dose reduction, should also reduce the risk of proarrhythmia (see DOSAGE AND ADMINISTRATION ). Congestive Heart Failure Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and beta-blockade carries

CONTRAINDICATIONS Sotalol hydrochloride tablets are contraindicated in patients with: • Sinus bradycardia, sick sinus syndrome, second and third degree AV block, unless a functioning pacemaker is present • Congenital or acquired long QT syndromes • Cardiogenic shock or decompensated heart failure • Serum potassium <4 mEq/L • Bronchial asthma or related bronchospastic conditions • Hypersensitivity to sotalol For the treatment of AFIB/AFL, sotalol hydrochloride tablets are also contraindicated in patients with: • Baseline QT interval >450 ms • Creatinine clearance <40 mL/min For the treatment of AFIB/AFL or ventricular arrhythmias • Sinus bradycardia, 2 nd or 3 rd degree AV block, sick sinus syndrome ( 4 ) • Congenital or acquired long QT syndrome, ( 4 ) • Serum potassium <4 mEq/L ( 4 ) • Cardiogenic shock, decompensated heart failure ( 4 ) • Bronchial asthma or related bronchospastic conditions ( 4 ) • Hypersensitivity to sotalol ( 4 ) For the treatment of AFIB/AFL also contraindicated for: • QT interval >450 ms ( 4 ) • Creatine clearance <40 ml/min ( 4 )

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Sotalol has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. The two isomers of sotalol 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 electrophysiologic effect can be seen at daily doses of 210 mg/m 2 body 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/m 2 in children. 12.2 Pharmacodynamics Cardiac Electrophysiological Effects 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 to 100 msec in QT and 10 to 40 msec in QTc [see Warnings and Precautions (5.1) ] . No significant alteration in QRS interval is observed. In a small study (n=25) of patients with implanted defibrillators treated concurrently with sotalol hydrochloride, the average defibrillatory threshold was 6 joules (range 2 to 15 joules) compared to a mean of 16 joules for a nonrandomized comparative group primarily receiving amiodarone. Twenty-five children in an unblinded, multicenter trial with SVT and/or ventricular 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/m 2 with dosing every 8 hours for a total 9 doses. During steady-state, the respective average increases above baseline of the QTc interval were 2, 14, and 29 msec at the 3 dose levels. The respective mean maximum increases above baseline of the QTc interval were 23, 36, and 55 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 2 ) showed a tendency for larger Class III effects (ΔQTc) and an increased frequency of prolongations of the QTc interval as compared with larger children (BSA ≥0.33 m 2 ). The beta-blocking effects also tended to be greater in the smaller children (BSA <0.33 m 2 ). Both the Class III and beta-blocking effects of sotalol were linearly related to the plasma concentrations. 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 hydrochloride 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 nonsignificant increases of 25% and 8%, respectively. One patient was discontinued because of worsening congestive heart failure. Pulmonary capillary wedge pressure increased significantly from 6.4 to 11.8 mmHg in the 11 patients who completed the study. Mean arterial pressure, mean pulmonary artery pressure and stroke work index did not significantly change. Exercise and isoproterenol induced tachycardia are antagonized by sotalol hydrochloride, 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, deterioration in cardiac performance may occur in patients with marginal cardiac compensation [see Warnings and Precautions (5.3) ]. 12.3 Pharmacokinetics The pharmacokinetics of the d- and l-enantiomers of sotalol are essentially identical. Absorption 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 (that is, 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. When administered with a standard meal, the absorption of sotalol was reduced by approximately 20% compared to administration in fasting state. Distribution Sotalol does not bind to plasma proteins. Distribution occurs to a central (plasma) and to a peripheral compartment. Sotalol crosses the blood brain barrier poorly. Metabolism Sotalol is not metabolized and is not expected to inhibit or induce any CYP450 enzymes. Excretion Excretion of sotalol is predominantly via the kidney in the unchanged form, and therefore, lower doses are necessary in conditions of renal impairment [see Dosage and Administration (2.5) ] . The mean elimination half-life of sotalol is 12 hours. Dosing every 12 hours results in trough plasma concentrations which are approximately one-half of those at peak. Specific Populations Pediatric: The combined analysis of a single-dose study 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/m 2 of sotalol was administered in the single dose study and daily doses of 30, 90, and 210 mg/m 2 were administered every 8 hours in the multidose 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. Body surface area was the most important covariate and more relevant than age for the pharmacokinetics of sotalol. The smallest children (BSA <0.33 m 2 ) 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%. Geriatric: Age does not significantly alter the pharmacokinetics of sotalol hydrochloride, but impaired renal function in geriatric patients can increase the terminal elimination half-life, resulting in increased drug accumulation. Renal Impairment: Sotalol is mainly eliminated 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. The half-life of sotalol is prolonged (up to 69 hours) in anuric patients. Adjust doses or dosing intervals based on creatinine clearance [see Dosage and Administration (2.5) ]. Hepatic Impairment: Patients with hepatic impairment show no alteration in clearance of sotalol. Drug-Drug Interactions Antacids : Administration of oral sotalol within 2 hours of antacids may result in a reduction in C max and AUC of