SOTALOL HYDROCHLORIDE

Posology:

Paediatric population There is no relevant use of Sotalol in the paediatric population. The initiation of treatment or changes in dosage with Sotalol hydrochloride should follow an appropriate medical evaluation including ECG control with measurement of the corrected QT interval, and assessment of renal function, electrolyte balance, and concomitant medications (see

). 8 Undesirable effects Sotalol is well tolerated in the majority of patients, with the most frequent adverse effects arising from its beta-blockade properties. Adverse effects are usually transient in nature and rarely necessitate interruption of, or withdrawal from treatment.

These include dyspnea, fatigue, dizziness, headache, fever, excessive bradycardia and/or hypotension. If they do occur, they usually disappear when the dosage is reduced. 4). Frequency is defined using the following convention: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000) including isolated reports.

The following are adverse events considered related to therapy with Sotalol:

System Organ Class Common Cardiac disorders Bradycardia Dyspnoea Chest pain Palpitations Oedema Electrocardiogram abnormal Hypotension Arrhythmia Syncope Presyncope Cardiac failure Skin and subcutaneous tissue disorder Rash Gastrointestinal disorder Nausea Vomiting Diarrhoea Dyspepsia Abdominal pain Flatulence Musculoskeletal, connective tissue and bone disorders Muscle spasms Nervous system disorders Headache Dizziness Fatigue Asthenia Lightheadedness Paraesthesia Dysgeusia Psychiatric disorders Sleep disorder Mood altered Depression Anxiety Reproductive system and breast disorders Sexual dysfunction Eye disorders Visual disturbance Ear and labyrinth disorders Hearing disturbances General disorders and administration site conditions Pyrexia In clinical trials, 3256 patients with cardiac arrhythmias (1363 with sustained ventricular tachycardia) received oral Sotalol, of whom 2451 received the drug for at least two weeks.

3% VT = ventricular tachycardia; VF = ventricular fibrillation; NSVT = non sustained ventricular tachycardia; PVC = premature ventricular contraction; SVA = supraventricular arrhythmia. Overall, discontinuation because of unacceptable adverse events was necessary in 18% of all patients in cardiac arrhythmia trials.

The most common adverse events leading to discontinuation of Sotalol are listed in the table below: - fatigue 4% - bradycardia(<50 bpm) 3% - dyspnoea 3% - proarrythmia 2% - asthenia 2% - dizziness 2% Cold and cyanotic extremities, Raynaud’s phenomenon, increase in existing intermittent claudication and dry eyes have been seen in association with other beta- blockers.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4 Warnings and precautions). As with other antiarrhythmic agents, it is recommended that Sotalol hydrochloride be initiated and doses increased in a facility capable of monitoring and assessing cardiac rhythm. The dosage must be individualized and based on the patient’s response.

Proarrhytbmic events can occur not only at initiation of therapy, but also with each upward dosage adjustment. 4).

Method of administration The following dosing schedule can be recommended:

The initial dose is 80mg, administered in either one or two divided doses. Oral dosage of Sotalol Hydrochloride 40mg Tablets should be adjusted gradually allowing 2-3 days between dosing increments in order to attain steady state and to allow monitoring of QT intervals.

Most patients will respond to a daily dose of 160 – 320mg administered in two divided doses at approximately 12 hour intervals. Some patients with life- threatening refractory ventricular arrhythmias may require doses as high as 480 - 640 mg/day.

4 Warnings). 4 μ mol/l). Dosage in hepatically impaired patients Since Sotalol is not subject to first-pass metabolism, patients with hepatic impairment show no alteration in clearance of Sotalol. No dosage adjustment is required in hepatically impaired patients.

1. Sotalol should not be used where there is evidence of sick sinus syndrome; second and third degree AV heart block unless a functioning pacemaker is present; congenital or acquired long QT syndromes; torsades de pointes; symptomatic sinus bradycardia; uncontrolled congestive heart failure; cardiogenic shock; anaesthesia that produces myocardial depression; untreated phaeochromocytoma; hypotension (except due to arrhythmia); Raynaud's phenomenon and severe peripheral circulatory disturbances; history of chronic obstructive airway disease or bronchial asthma; hypersensitivity to any of the components of the formulation; metabolic acidosis; renal failure (creatinine clearance < 10 ml/min).

4 Special warnings and precautions for use Abrupt withdrawal Hypersensitivity to catecholamines is observed in patients withdrawn from beta- blocker therapy. Occasional cases of exacerbation of angina pectoris, arrhythmias, and in some cases, myocardial infarction have been reported after abrupt discontinuation of beta-blocker therapy.

Patients should be carefully monitored when discontinuing chronically administered Sotalol, particularly those with ischaemic heart disease. If possible the dosage should be gradually reduced over a period of one to two weeks. Because coronary artery disease is common and may be unrecognised in patients receiving Sotalol, abrupt discontinuation in patients with arrhythmias may unmask latent coronary insufficiency.

In addition, hypertension may develop. Proarrhythmias The most dangerous adverse effect of Class I and Class III antiarrhythmic drugs (such as sotalol hydrochloride) is the aggravation of pre-existing arrhythmias or the provocation of new arrhythmias.

Drugs that prolong the QT-interval may cause torsades de pointes, a polymorphic ventricular tachycardia associated with prolongation of the QT-interval. ) Females may be at increased risk of developing torsades de pointes. The incidence of torsades de pointes is dose dependent.

Torsades de pointes, usually occurs early after initiating therapy or escalation of the dose and can progress to ventricular fibrillation. In clinical trials of patients with sustained VT/VF the incidence of severe proarrhythmia (torsades de pointes or new sustained VT/VF) was <2% at doses up to 320mg.

The incidence more than doubled at higher doses. Other risk factors for torsades de pointes were excessive prolongation of the QTc and history of cardiomegaly or congestive heart failure. Patients with substandard ventricular tachycardia and a history of congestive heart failure have the highest risk of serious proarrhythmia (7%).

Proarrhythmic events must be anticipated not only on initiating therapy but with every upward dose adjustment. Initiating therapy at 80mg with gradual upward dose titration thereafter reduces the risk of proarrthymia. In patients already receiving sotalol hydrochloride caution should be used if the QTc exceeds 500msec whilst on therapy, and serious consideration should be given to dose reduction or discontinuation of therapy when the QTc –interval […]

1. Sotalol should not be used where there is evidence of sick sinus syndrome; second and third degree AV heart block unless a functioning pacemaker is present; congenital or acquired long QT syndromes; torsades de pointes; symptomatic sinus bradycardia; uncontrolled congestive heart failure; cardiogenic shock; anaesthesia that produces myocardial depression; untreated phaeochromocytoma; hypotension (except due to arrhythmia); Raynaud's phenomenon and severe peripheral circulatory disturbances; history of chronic obstructive airway disease or bronchial asthma; hypersensitivity to any of the components of the formulation; metabolic acidosis; renal failure (creatinine clearance < 10 ml/min).