Intentional or accidental overdose with Sotalex has rarely resulted in death. Haemodialysis results in a large reduction of plasma levels of Sotalex.
Symptoms and treatment of overdose: The most common signs to be expected are bradycardia, congestive heart failure, hypotension, bronchospasm and hypoglycaemia. In cases of massive intentional overdose (2-16 g) of Sotalex the following clinical findings were seen: hypotension, bradycardia, prolongation of QT-interval, premature ventricular complexes, ventricular tachycardia, torsades de pointes.
If overdose occurs, therapy with Sotalex should be discontinued and the patient observed closely. In addition, if required, the following therapeutic measures are suggested:
Bradycardia
Atropine (0.5 to 2 mg IV), another anticholinergic drug, a beta-adrenergic agonist (isoprenaline, 5 microgram per minute, up to 25 microgram, by slow IV injection) or transvenous cardiac pacing
Heart Block (second and third degree)
Transvenous cardiac pacing
Hypotension
Adrenaline rather than isoprenaline or noradrenaline may be useful, depending on associated factors
Bronchospasm
Aminophylline or aerosol beta-2-receptor stimulant
Torsades de pointes
DC cardioversion, transvenous cardiac pacing, adrenaline, and/or magnesium sulphate
Sotalex 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 Sotalex, other betablockers or any of the excipients in the formulation.
- metabolic acidosis
- renal failure (creatinine clearance < 10 ml/min).
- Contraindicated Combination: Sotalex should not be administered in combination with drugs like class Ia antiarrhythmics, class II antiarrhythmics such as amiodarone, dofetilide, Ibutilide etc; neuroleptics such as trimipramine, phenobarbitone, chlorpromazine etc; and antibiotics such as erythromycin IV and moxifloxacin.
Not applicable
The most frequent adverse effects of Sotalex arise from its beta-blockade properties. Adverse effects are usually transient in nature and rarely necessitate interruption of, or withdrawal from treatment. If they do occur, they usually disappear when the dosage is reduced. The most significant adverse effects, however, are those due to proarrhythmia, including torsades de pointes (see Warnings).
The following are adverse events considered related to therapy, occurring in 1% or more of patients treated with Sotalex.
Cardiovascular
Bradycardia, dyspnoea, chest pain, palpitations, oedema, ECG abnormalities, hypotension, proarrhythmia, syncope, heart failure, presyncope
Dermatologic
Rash
Gastro-intestinal
Nausea/vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence
Musculoskeletal
Cramps
Nervous/psychiatric
Fatigue, dizziness, asthenia, lightheadedness, headache, sleep disturbances, depression, paresthesia, mood changes, anxiety
Urogenital
Sexual dysfunction
Special Senses
Visual disturbances, taste abnormalities, hearing disturbances
Body as a whole
Fever
In trials of patients with cardiac arrhythmia, the most common adverse events leading to discontinuation of Sotalex were fatigue 4%, bradycardia (<50 bpm) 3%, dyspnoea 3%, proarrhythmia 2%, asthenia 2%, and 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 products is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
No further particulars.
Sotalex 40mg Tablets are indicated for:
1. Ventricular arrhythmias:
- Treatment of life-threatening ventricular tachyarrhythmias;
- Treatment of symptomatic non-sustained ventricular tachyarrhythmias
2. Supraventricular arrhythmias:
- Prophylaxis of paroxysmal atrial tachycardia, paroxysmal atrial fibrillation, paroxysmal A-V nodal re-entrant tachycardia, paroxysmal A-V re-entrant tachycardia using accessory pathways, and paroxysmal supraventricular tachycardia after cardiac surgery;
- Maintenance of normal sinus rhythm following conversion of atrial fibrillation or atrial flutter
ATC Code - C70A A07
D,l-Sotalex is a non-selective hydrophilic β-adrenergic receptor blocking agent, devoid of intrinsic sympathomimetic activity or membrane stabilizing activity.
Sotalex has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. Sotalex has no known effect on the upstroke velocity and therefore no effect on the depolarisation phase.
Sotalex uniformly prolongs the action potential duration in cardiac tissues by delaying the repolarisation phase. Its major effects are prolongation of the atrial, ventricular and accessory pathway effective refractory periods.
The Class II and III properties may be reflected on the surface electrocardiogram by a lengthening of the PR, QT and QTc (QT corrected for heart rate) intervals with no significant alteration in the QRS duration.
The d- and l-isomers of Sotalex have similar Class III antiarrhythmic effects while the l-isomer is responsible for virtually all of the beta-blocking activity. Although significant beta-blockade may occur at oral doses as low as 25 mg, Class III effects are usually seen at daily doses of greater than 160 mg.
Its β-adrenergic blocking activity causes a reduction in heart rate (negative chronotropic effect) and a limited reduction in the force of contraction (negative inotropic effect). These cardiac changes reduce myocardial oxygen consumption and cardiac work. Like other β-blockers, Sotalex inhibits renin release. The renin-suppressive effect of Sotalex is significant both at rest and during exercise. Like other beta adrenergic blocking agents, Sotalex produces a gradual but significant reduction in both systolic and diastolic blood pressures in hypertensive patients. Twenty-four-hour control of blood pressure is maintained both in the supine and upright positions with a single daily dose.
The bioavailability of oral Sotalex is essentially complete (greater than 90%). After oral administration, peak levels are reached in 2.5 to 4 hours, and steady-state plasma levels are attained within 2-3 days. The absorption is reduced by approximately 20% when administered with a standard meal, in comparison to fasting conditions. Over the dosage range 40-640 mg/day Sotalex displays dose proportionality with respect to plasma levels. Distribution occurs to a central (plasma) and a peripheral compartment, with an elimination half-life of 10-20 hours. Sotalex does not bind to plasma proteins and is not metabolised. There is very little inter-subject variability in plasma levels. Sotalex crosses the blood brain barrier poorly, with cerebrospinal fluid concentrations only 10% of those in plasma. The primary route of elimination is renal excretion. Approximately 80 to 90% of a dose is excreted unchanged in the urine, while the remainder is excreted in the faeces. Lower doses are necessary in conditions of renal impairment (see Dosage and Administration in patients with renal dysfunction). Age does not significantly alter the pharmacokinetics, although impaired renal function in geriatric patients can decrease the excretion rate, resulting in increased drug accumulation.
Abrupt Withdrawal
Hypersensitivity to catecholamines is observed in patients withdrawn from beta-blocker therapy.).
Psoriasis
Beta-blocking drugs have been reported rarely to exacerbate the symptoms of psoriasis vulgaris.
There are no data available, but the occasional occurrence of side effects such as dizziness and fatigue should be taken into account (see
Oral administration in adults:
As with other antiarrhythmic agents, it is recommended that Sotalex 40mg Tablets 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.
In view of its β-adrenergic blocking properties, treatment with Sotalex 40mg Tablets should not be discontinued suddenly, especially in patients with ischaemic heart disease (angina pectoris, prior acute myocardial infarction) or hypertension, to prevent exacerbation of the disease (see 4.4 Warnings).
The initiation of treatment or changes in dosage with Sotalex 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 4.4 Warnings and precautions).
The following dosing schedule can be recommended:
The initial dose is 80 mg, administered either singly or as two divided doses.
Oral dosage of Sotalex 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 respond to a daily dose of 160 to 320 mg 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. These doses should be used under specialist supervision and should only be prescribed when the potential benefit outweighs the increased risk of adverse events, particularly proarrhythmias (see 4.4 Warnings).
Children
Sotalex is not intended for administration to children.
Dosage in renally impaired patients
Because Sotalex is excreted mainly in urine, the dosage should be reduced when the creatinine clearance is less than 60 ml/min according to the following table:
Creatinine clearance (ml/min)
Adjusted doses
| > 60 | Recommended Dose |
| 30-60 | ½ recommended Dose |
| 10-30 | ¼ recommended Dose |
| < 10 | Avoid Sotalex |
The creatinine clearance can be estimated from serum creatinine by the Cockroft and Gault formula:
| Men: | (140 - age) x weight (kg) / 72 x serum creatinine (mg/dl) |
| Women: | idem x 0.85 |
When serum creatinine is given in μmol/l, divide the value by 88.4 (1mg/dl = 88.4 μmol/l).
Dosage in hepatically impaired patients
No dosage adjustment is required in hepatically impaired patients.
None
