Sotalol adverse effects

Sotalol is rapidly and almost completely (>90%) absorbed. Bioavahabhity of absorbed dmg is 89—100%. Peak plasma levels are achieved in 2—4 h. Sotalol is 50% bound to plasma proteins. Plasma half-life of the compound is about 5.2 h. No metabolites of sotalol have been identified indicating littie metabolism. The dmg is excreted mainly by the kidneys (80—90%) and about 10% is eliminated in the feces. The plasma half-life is prolonged in patients having renal failure. Kinetics of the compound are not affected by changes in liver function (1,2). Sotalol has ah the adverse effects of -adrenoceptor blockers including myocardial depression, bradycardia, transient hypotension, and proarrhythmic effects (1,2). 

Side effects of sotalol include those attributed to both P-adrenoceptor blockade and proarrhythmic effects. This arrhythmia is a serious threat, as it may lead to ventricular fibrillation. Adverse effects attributable to its p-blocker activity include fatigue, dyspnea, chest pain, headache, nausea, and vomiting. 

Sotalol is well absorbed orally with bioavailability of approximately 100%. It is not metabolized in the liver and is not bound to plasma proteins. Excretion is predominantly by the kidneys in the unchanged form with a half-life of approximately 12 hours. Because of its relatively simple pharmacokinetics, solatol exhibits few direct drug interactions. Its most significant cardiac adverse effect is an extension of its pharmacologic action a dose-related incidence of torsade de pointes that approaches 6% at the highest recommended daily dose. Patients with overt heart failure may experience further depression of left ventricular function during treatment with sotalol. 

Amiodarone has a higher incidence of side effects than sotalol. Seventy-five percent of patients report side effects over 5 years with 15-35 percent requiring discontinuance of the drug. Severe adverse effects, including pulmonary fibrosis, can occur with usual doses of amiodarone and may be lethal or irreversible or persist for months after treatment is stopped. 

In 186 patients randomized equally to amiodarone 200 mg/day, sotalol 160-480 mg/day, or placebo, the incidence of atrial fibrillation after 6 months was higher in those taking placebo compared with amiodarone and sotalol and higher in those taking sotalol compared with amiodarone (19). Of the 65 patients who took amiodarone, 15 had significant adverse effects after an average of... 

In a comparison of amiodarone (n = 23) with sotalol (n = 22) in patients with spontaneous sustained ventricular tachydysrhythmias secondary to myocardial infarction, sotalol was much more effective, 75% of those taking it remaining free of dysrhythmias compared with 38% of those taking amiodarone (34). Adverse effects requiring withdrawal occurred in 17% of those taking amiodarone at a median time of 3.5 months. The adverse effects included malaise, rash, headaches, flushing, and dyspnea due to pulmonary fibrosis. 

Antidysrhythmic dmgs can themselves cause cardiac dysrhythmias, their major adverse effect. The risk of antidysrhythmic-induced cardiac dysrhythmias (prodys-rhythmic effects) has been estimated at about 11-13% in non-invasive studies (18,19) and at up to 20% in invasive electrophysiological studies. However, the risk varies from dmg to drug and is particularly low with class III drugs. In one study the quoted risks of dysrhythmias were flecainide 30%, quinidine 18%, propafenone 7%, sotalol 6%, and amiodar-one 0% (20). However, amiodarone does cause dysrhythmias, especially when the QT interval is over 600 ms. 

All beta-blockers cause an increase in atrioventricular conduction time this is most pronounced with drugs that have potent membrane-depressant properties and no partial agonist activity. Sotalol differs from other beta-blockers in that it increases the duration of the action potential in the cardiac Purkinje fibers and ventricular muscle at therapeutic doses. This is a class III antidysr-hythmic effect, and because of this, sotalol has been used to treat ventricular (54-56) and supraventricular dysrhythmias (57). The main serious adverse effect of sotalol is that it is prodysrhythmic in certain circumstances, and can cause torsade de pointes (58,59). 

In a randomized, double-blind, placebo-controlled comparison of propafenone (mean dose 13 mg/kg/day n = 102) and sotalol (mean dose 3 mg/kg/day n = 106) in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation in 300 patients, efficacy was comparable (13). Tolerable adverse effects in those who took propafenone were gastrointestinal discomfort (n — 15), neurological disturbances (n = 9), a metallic taste (n = 4), and generalized weakness (n = 1) nine patients withdrew owing to adverse effects, four with gastrointestinal disorders, three with dizziness, and two with headache there were no prodysrhythmias. 

Propafenone 450 mg/day and sotalol 240 mg/day have been compared in a placebo-controlled study of 300 patients with atrial fibrillation (14). The two drugs had similar efficacy. There were adverse events in 38 of the patients who took propafenone, compared with 12 of those who took placebo. These included gastrointestinal discomfort, neurological disturbances, asymptomatic bradycardia, a metallic taste, and general weakness. In nine patients the adverse effects were sufficient to cause withdrawal of propafenone. 

Retrospective analysis of a large multinational study in patients given terazosin 5 or 10 mg daily found that terazosin only affected the blood pressure of patients taking beta blockers (atenolol, labetalol, metoprolol, sotalol, and timolol) if the blood pressure was uncontrolled. No change in blood pressure was seen in those with normal blood pressure (i.e. those without hypertension and those with hypertension controlled by beta blockers). The most common adverse effect in the 10-week terazosin phase was dizziness, and the incidence of this appeared to be lower in those taking antihypertensives (13 to 16%) than those not (21 to 25%)."... 

Figure 3 Promiscuous HERG channels are blocked by structurally diverse molecules [from (122)]. In addition to compounds developed for K+ channel blockade (Dofetilide and Sotalol), a wide range of compounds, from antihistamines (Terfenadine) to antibiotics (Erythromycin), block HERG as an adverse side effect.

The serum levels of talinolol and possibly nadolol are increased by erythromycin, but the clinical importance of this is uncertain. Te-lithromycin does not appear to adversely affect sotalol-induced QT prolongation. However, the combined use of sotalol and intravenous erythromycin should generally be avoided because of the possible additive effects on QT interval prolongation. 

In an analysis of cases of torsade de pointes associated with fluoroquinolones on the FDA Adverse Events Reporting System database, two cases of torsade de pointes were noted in patients taking a fluoroquinolone with sotalol (there were 37 cases identified, and 19 occurred in patients also taking other drugs known to prolong the QT interval). Sotalol has class III antiarrhythmic effects and prolongs the QT interval, and this could be additive with the effects of quinolones that prolong the QT interval (e.g. gat-ifloxacin, moxifloxacin, sparfloxacin, see Table 9.2 , (p.257)). The... 

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