Sotoger 80 mg Tablets

(ref: DK/H/0103/IA/051/G) Addition of a manufacturer responsible for batch release – Mylan Hungary Kft (Komarom, HU).

4.2  Posology and method of administration

Patients with renal impairment

Because Sotoger sotalol 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:

Paediatric population

The safety and effectiveness of Sogoter in children under 18 has not been established. No data are available.
There is no relevant use of sotalol in the paediatric population.Sotoger are not intended for administration to children.
4.4 Special warnings and precautions for use 

4.4 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Abrupt Withdrawal: Hypersensitivity to catecholamines is observed in patients withdrawn from beta-blocker therapy.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 Sotoger sotalol, particularly those with ischaemic heart disease. If possible the dosage should be gradually reduced over a period of one to two weeks, if necessary at the same time initiating replacement therapy. Because coronary artery disease is common and may be unrecognised in patients receiving sotalol, Abrupt abrupt discontinuation in patients with arrhythmias may unmask latent coronary insufficiency. In addition, hypertension may develop.

Proarrhythmias: The most dangerous adverse effect of Class III antiarrhythmic drugs 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. Experience to date indicates that the risk of torsades de pointes is associated with the prolongation of the QT-interval, reduction of the heart rate, reduction in serum potassium and magnesium, (e.g. as a consequence of diuretic use), high plasma sotalol concentrations (e.g. as a consequence of overdosage or renal insufficiency), and with the concomitant use of sotalol and other medications such as antidepressants and Class I antiarrhythmics which have been associated with torsades de pointes (see section 4.5). Females may be at increased risk of developing torsades de pointes.

ECG monitoring immediately prior to or following the episodes usually reveals a significantly prolonged QT interval and a significantly prolonged QTc interval. In clinical trials sotalol generally has not been initiated to patients whose pretreatment QTc interval exceeded 450 msec. Sotalol should be titrated very cautiously in patients with prolonged QT intervals.

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 terminates spontaneously in the majority of patients. Although most episodes of torsades de pointes are self-limited or associated with symptoms (e.g. syncope), they can progress to ventricular fibrillation.

Clinical studies for arrhythmia: During clinical trials, 4.3% of 3257 patients with arrhythmias experienced a new or worsened ventricular arrhythmia, including sustained ventricular tachycardia (approximately 1%) and torsade de pointes (2.4%). In addition, in approximately 1% of patients, deaths were considered possibly drug-related. In patients with other, less serious, ventricular arrhythmias and supraventricular arrhythmias, the incidence of torsade de pointes was 1% and 1.4%, respectively.

Serious proarrhythmias including torsade de pointes were dose related as indicated below:

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 320 mg. 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; events tend to occur within 7 days of initiating therapy or with an increase in dose. Initiating therapy at 80 mg with gradual upward dose titration thereafter reduces the risk of proarrhythmia. Sotoger should be used with caution if the QTC is greater than 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: Sotoger 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. Caution is advised when initiating therapy in patients with left ventricular dysfunction controlled by therapy (i.e. ACE Inhibitors, diuretics, digitalis, etc); a low initial dose and careful dose titration is appropriate.

Recent MI: 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. The adverse results of clinical trials involving antiarrhythmic drugs (i.e. apparent increase in mortality) suggest that Sotoger 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 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 the allergic reaction.

Anaesthesia: As with other beta-blocking agents, Sotoger should be used with caution in patients undergoing surgery and in association with anaesthetics that cause myocardial depression, such as cyclopropane or trichloroethylene.

Sotalol can be administered with caution to patients with obstructive respiratory disorders provided that adequate supervision is maintained. If increased airways resistance develops consideration must be given to discontinuation of the beta-blocker, depending on the degree of airways resistance and the benefit derived from beta-blockade.

Diabetes Mellitus: Sotoger should be used with caution in patients with diabetes (especially labile diabetes) or with a history of episodes of spontaneous hypoglycaemia, since beta-blockade may mask some important signs of the onset of acute hypoglycaemia, e.g. tachycardia.

Thyrotoxicosis: Beta-blockade may mask certain clinical signs of hyperthyroidism (e.g., tachycardia). Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm.

Hepatic Impairment: Since sotalol is not subject to first-pass metabolism, patients with hepatic impairment show no alteration in clearance of sotalol.

Renal Impairment: As sSotalol is mainly eliminated via the kidneys through glomerular filtration and to a small degree by tubular secretion. Serum creatinine or creatinine clearance is not necessarily a reliable indicator of kidney function however there There is a direct relationship between renal function, as measured by serum creatinine or creatinine clearance, and the elimination half- life of sotalol and its urinary excretion. the The dose should be adjusted in patients with renal impairment (see section 4.2).

Psoriasis: Beta-blocking drugs have been reported rarely to exacerbate the symptoms of psoriasis vulgaris.

4.5 Interaction with other medicinal products and other forms of interaction

Antiarrhythmics: Class 1a antiarrhythmic drugs, such as disopyramide, quinidine, procainamide and flecainide and other Class III antiarrhythmic drugs such as amiodarone and bepridil are not recommended as concomitant therapy with Sotoger, because of their potential to prolong refractoriness (see section 4.4). The concomitant use of other beta-blocking agents with Sotoger Tablets may result in additive Class II effects.

Digitalis glycosides: Single and multiple doses of Sotoger sotalol do not significantly affect serum digoxin levels. Proarrhythmic events were more common in sotalol treated patients also receiving digitalis glycosides; however, this may be related to the presence of CHF, a known risk factor for proarrhythmia, in patients receiving digitalis glycosides. Association of digitalis glycosides with beta-blockers may increase auriculo-ventricular conduction time.

Beta-2-receptor stimulants: Patients in need of beta-agonists should not normally receive sotalol. However if concomitant therapy is necessary beta-agonists (such as salbutamol, terbutaline and isoprenaline) may have to be administered in increased dosages.

4.8  Undesirable effects

Sotoger Sotalol is well tolerated in the majority with the most frequent adverse effects arising from 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. The most significant adverse effects, however, are those due to proarrhythmia, including torsades de pointes (see section 4.4).

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), not known (cannot be estimated from the available data).

The following are adverse events considered related to therapy with Sotoger sotalol:

Cardiac disorders
Common: Bradycardia, dyspnoea, chest pain, palpitations, oedema, ECG abnormalities, proarrhythmia, syncope, heart failure, presyncope

Musculoskeletal and connective tissue disorders
Common: Muscle spasmsCramps

In clinical trials, 32563257 patients with cardiac arrhythmias (1363 with sustained ventricular tachycardia) received oral sotalol, of whom 2451 received the drug for at least two weeks. The most significant adverse events were torsade de pointes and other serious new ventricular arrhythmias (see section 4.4), which occurred at the following rates:

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:

In trials of patients with cardiac arrhythmia, the most common adverse events leading to discontinuation of Sotoger are listed in the table below:

4.9 Overdose

Intentional or accidental overdosage with Sotoger sotalol has rarely resulted in death. Haemodialysis results in a large reduction of plasma levels of sotalol.

Symptoms and treatment of overdosage: The most common signs to be expected are bradycardia, congestive heart failure, hypotension, bronchospasm and hypoglycaemia. In cases of massive intentional overdosage (2-16 g) of Sotalol Tablets sotalol the following clinical findings were seen: hypotension, bradycardia, prolongation of QT-interval, premature ventricular complexes, ventricular tachycardia, torsades de pointes.

8. MARKETING AUTHORISATION NUMBER(S)

 PA0577/021/002 

1. NAME OF THE MEDICINAL PRODUCT

 Sotoger Tablets 80mg 80mg Tablets
 Sotoger Tablets 160mg 160mg Tablets

2. QUALITATIVE AND QUANTITIVE COMPOSITION

Sotalol Hydrochloride BP 80.0mg Each tablets contains Sotalol Hydrochloride 80mg
Sotalol Hydrochloride BP 160.0mg Each tablets contains Sotalol Hydrochloride 160mg

For list of excipients, see section 6.1 For a full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM

Tablets

White flat bevel-edged tablet with “SL” breakline “80” on one side and blank on the reverse, approximately 7mm in diameter.
White flat bevel-edged tablet with “SL” breakline “160” on one side and blank on the reverse, approximately 9.5mm in diameter.

The breakline allows the tablet to be divided into two equal halves.

4.3 Contra-indications

5.1 Pharmacodynamic Properties

Therapeutic classification
C 07 AA 07. Group of Beta blocking agents, non-selective

Sotoger belongs to the group of non-selective beta receptor blocking agents.  It counteracts the sympathetic neurotransmitters by competitive dislocation around the sympathetic nerve endings.  This causes a decrease in the contractile strength of the heart muscle and the heart rate.  Sotoger does not have any Intrinsic Sympathomimetic Activity (ISA) or local anaesthetic effect but it does have Class III anti-arrhythmic activity.

6.4 Special precautions for Storage
Polypropylene Containers
Store in the original container in order to protect from light.
Blister Packs
Keep the container in the outer carton in order to protect from light.

6.6 Special precautions for disposal and other handling
None. No special requirements.