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 BETAPACE® 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 BETAPACE®, and total peripheral resistance increases by a small amount.

In hypertensive patients, BETAPACE® (sotalolhydro chloride) produces significant reductions in both systolic and diastolic blood pressures. Although BETAPACE® (sotalolhydro chloride) is usually well-tolerated hemodynamically, caution should be exercised in patients with marginal cardiac compensation as deterioration in cardiac performance may occur. (See WARNINGS: Congestive Heart Failure.)

Clinical Actions

BETAPACE® (sotalol hydrochloride) has been studied in life-threatening and less severe arrhythmias. In patients with frequent premature ventricular complexes (VPC), BETAPACE® (sotalolhydro chloride) was significantly superior to placebo in reducing VPCs, paired VPCs and non-sustained ventricular tachycardia (NSVT); the response was dose-related through 640 mg/day with 80-85% of patients having at least a 75% reduction of VPCs. BETAPACE® (sotalolhydro chloride) was also superior, at the doses evaluated, to propranolol (40-80 mg TID) and similar to quinidine (200-400 mg QID) in reducing VPCs. In patients with life-threatening arrhythmias [sustained ventricular tachycardia/fibrillation (VT/VF)], BETAPACE® (sotalolhydro chloride) was studied acutely [by suppression of programmed electrical stimulation (PES) induced VT and by suppression of Holter monitor evidence of sustained VT] and in acute responders, chronically.

In a double-blind, randomized comparison of BETAPACE® and procainamide given intravenously (total of 2 mg/kg BETAPACE® vs. 19 mg/kg of procainamide over 90 minutes), BETAPACE® suppressed PES induction in 30% of patients vs. 20% for procainamide (p=0.2).

In a randomized clinical trial [Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) Trial] comparing choice of antiarrhythmic therapy by PES suppression vs. Holter monitor selection (in each case followed by treadmill exercise testing) in patients with a history of sustained VT/VF who were also inducible by PES, the effectiveness acutely and chronically of BETAPACE® (sotalolhydro chloride) was compared with 6 other drugs (procainamide, quinidine, mexiletine, propafenone, imipramine and pirmenol). Overall response, limited to first randomized drug, was 39% for sotalol and 30% for the pooled other drugs. Acute response rate for first drug randomized using suppression of PES induction was 36% for BETAPACE® vs. a mean of 13% for the other drugs. Using the Holter monitoring endpoint (complete suppression of sustained VT, 90% suppression of NSVT, 80% suppression of VPC pairs, and at least 70% suppression of VPCs), BETAPACE® yielded 41% response vs. 45% for the other drugs combined. Among responders placed on long-term therapy identified acutely as effective (by either PES or Holter), BETAPACE® when compared to the p.o. of other drugs, had the lowest two-year mortality (13% vs. 22%), the lowest two-year VT recurrence rate (30% vs. 60%), and the lowest withdrawal rate (38% vs. about 75-80%). The most commonly used doses of BETAPACE® (sotalolhydro chloride) in this trial were 320-480 mg/day (66% of patients), with 16% receiving 240 mg/day or less and 18% receiving 640 mg or more.

It cannot be determined, however, in the absence of a controlled comparison of BETAPACE® vs. no pharmacologic treatment (e.g., in patients with implanted defibrillators) whether BETAPACE® response causes improved survival or identifies a population with a good prognosis.

In a large double-blind, placebo controlled secondary prevention (post-infarction) trial (n=1,456), BETAPACE® (sotalolhydro chloride) was given as a non-titrated initial dose of 320 mg once daily. BETAPACE® did not produce a significant increase in survival (7.3% mortality on BETAPACE® vs. 8.9% on placebo, p=0.3), but overall did not suggest an adverse effect on survival. There was, however, a suggestion of an early (i.e., first 10 days) excess mortality (3% on sotalolvs. 2% on placebo). In a second small trial (n=17 randomized to sotalol) where sotalolwas administered at high doses (e.g., 320 mg twice daily) to high-risk post-infarction patients (ejection fraction <40% and either >10 VPC/hr or VT on Holter), there were 4 fatalities and 3 serious hemodynamic/electrical adverse events within two weeks of initiating sotalol.

Pharmacokinetics

Bookmark this page: