SOTALOL HYDROCHLORIDE

Posology Paediatric population There is no relevant use of sotalol hydrochloride in the paediatric population. 4). 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. Proarrhythmic 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 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 to 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 - 640mg/day.

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

Sotalol hydrochloride 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 dyspnoea, 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 hydrochloride: Cardiac disorders: Common: Bradycardia, dyspnoea, chest pain, palpitations, oedema, Electrocardiogram (ECG) abnormal, hypotension, arrhythmia, syncope, presyncope, cardiac failure Skin and subcutaneous tissue disorders: Common: Rash Frequency unknown: Alopecia, hyperhidrosis Gastrointestinal disorders: Common: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence Musculoskeletal, connective tissue and bone disorders: Common: Muscle spasms Nervous system disorders: Common: Headache, dizziness, fatigue, asthenia, lightheadedness, paraesthesia, dysgeusia Psychiatric disorders: Common: Sleep disorder, mood altered, depression, anxiety Reproductive system and breast disorders: Common: Sexual dysfunction Eye disorders: Common: Visual disturbances Ear and labyrinth disorders Common: Hearing disturbances General disorders and administration site conditions Common: Pyrexia Blood and lymphatic system disorders: Frequency unknown: Thrombocytopenia In clinical trials, 3256 patients with cardiac arrhythmias (1363 with sustained ventricular tachycardia) received oral sotalol hydrochloride, 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 hydrochloride are listed below: - fatigue 4% - bradycardia (<50 bpm) 3% - dyspnoea 3% - proarrhythmia 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.

Abrupt withdrawal Hypersensitivity to catecholamines is observed in patients withdrawn from beta- blocker therapy.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

Patients should be carefully monitored when discontinuing chronically administered sotalol hydrochloride, particularly those with ischaemic heart disease. If possible, the dosage should be gradually reduced over a period of one or two weeks.

Because coronary artery disease is common and may be unrecognised in patients receiving sotalol hydrochloride, abrupt discontinuation in patients with arrhythmias may unmask latent coronary insufficiency. In addition, hypertension may develop.

Proarrhythmia 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.

5). 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 within 7 days of 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 sustained 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 500 msec whilst on therapy, and serious consideration should be given to reducing the dose or discontinuing therapy when the QTc –interval exceeds 550 msec.

Due to the multiple risk factors associated with torsades de pointes however, caution should be exercised regardless of the QTc-interval. Electrolyte disturbances Sotalol hydrochloride should not be used in patients with hypokalaemia or hypomagnesaemia prior to correction of imbalance; these conditions can exaggerate the degree of QT prolongation and increase the potential for torsades de pointes.

Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhoea, or patients receiving concomitant magnesium- and/or potassium-depleting drugs. Congestive heart failure Beta-blockade may further depress myocardial contractility and precipitate more severe heart failure.

e. ACE inhibitors, diuretics, digitalis etc); a low initial dose and careful dose titration is appropriate. Recent myocardial infarction In post-infarction patients with impaired left ventricular function, the risk-versus- benefit of sotalol administration must be considered.

Careful monitoring and dose titration are critical during initiation and follow-up of therapy. e. apparent increase in mortality) suggest that sotalol hydrochloride should be avoided in patients with left ventricular ejection fractions < 40% without serious ventricular arrhythmias.

Electrocardiographic changes Excessive prolongation of the QT-interval, >500 msec, can be a sign of toxicity and should be avoided (see ‘Proarrhythmias’ section above). Sinus bradycardia has been observed very commonly in arrhythmia patients receiving sotalol in clinical trials.

Bradycardia increases the risk of torsades de pointes. Sinus pause, sinus arrest and sinus node dysfunction occur in less than 1% of patients. The incidence of 2nd- or 3rd-degree AV block is approximately 1%. Anaphylaxis Patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge while taking beta blockers.

Such patients may be unresponsive to the usual doses of adrenaline used to treat allergic reaction. Anaesthesia As with other beta-blocking agents sotalol hydrochloride should be used with caution in patients undergoing surgery, and in association with anaesthetics that cause myocardial depression, such as cyclopropane or trichloroethylene.

g. tachycardia. g. tachycardia). Patients suspected of developing thyrotoxicosis should be carefully managed to avoid abrupt withdrawal of beta-blockade which might be followed by the exacerbation of symptoms of hyperthyroidism, including thyroid storm.

2). Psoriasis Beta-blocking drugs have been […]

1. Sotalol hydrochloride tablets are contraindicated in the following: - 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).