DISOPYRAMIDE PHOSPHATE

Adults 300-800mg in divided doses adjusted according to the response of the patient. Heart Failure In determining the intervals between administration of Disopyramide capsules it should be borne in mind that whilst the elimination half-life in normal volunteers is approximately seven hours, in patients with heart failure, half-life values of 12 hours or more have been recorded.

4). A reduced dosage, preferably accompanied by assay of Disopyramide plasma levels in cases of severe renal failure (creatinine clearance <8ml/min) is recommended. The following table may be helpful as a guide. Creatinine Clearance (ml/min) Dosage 100 or 150mg capsules Normal Normal Dosage 20 - 60 100mg 8 hourly or 150mg 12 hourly 8 - 20 100mg 12 hourly < 8 150mg daily Paediatric population The safety and efficacy of disopyramide in children less than 18 years has not been established.

2. Posology For oral administration only. The capsules should be swallowed whole and not chewed or opened.

Disopyramide is usually well tolerated, however the following undesirable effects may occur. Cardiac There have been reports of ventricular tachycardia, ventricular fibrillation or Torsade de Pointes in patients receiving Disopyramide.

These have been usually, but not always, associated with significant widening of the QRS complex, prolonged QT interval or other inter-cardiac conduction abnormalities such as atrioventricular and bunch bundle block. Bradycardia and sinus block have also been reported.

The occurrence of hypotension following Disopyramide administration, which has been observed especially in patients with cardiomyopathy or inadequately compensated congestive heart failure, requires prompt discontinuation of the drug.

Any resumption of therapy should be at a lower dose with close patient monitoring. As with all antiarrhythmic drugs, there is a small possibility that Disopyramide may worsen or even provoke arrhythmia. This risk is increased in the presence of hypokalaemia, with the concomitant use of other antiarrhythmic drugs, in patients with severe structural heart disease or prolongation of the QT interval.

Episodes of severe heart failure or cardiogenic shock have also been described in patients with severe structural heart disease. The resulting low cardiac output can cause hypotension, renal insufficiency and/or acute hepatic ischaemia.

4): • Urinary: dysuria; acute urinary retention, especially in prostatism. • Ocular: disorders of accommodation; diplopia. • Gastrointestinal: dry mouth; abdominal pain; nausea, vomiting, anorexia, diarrhoea; constipation. • Impotence.

• Cognitive disorders. • Psychiatric disorders. • Skin reactions: very rarely, rashes. 4). In some cases, severe hypoglycaemia resulted in coma. • Very rarely: cholestatic jaundice, headache, dizzy sensation, neutropenia. • Agranulocytosis.

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.

There is no evidence that prolonged suppression of ventricular premature contractions with antiarrhythmic drugs prevents sudden death. For this reason, antiarrhythmic drugs should not be prescribed for the treatment of patients with asymptomatic ventricular premature contractions.

All antiarrhythmic drugs can produce unwanted effects when they are used to treat symptomatic but non life-threatening arrhythmia; the expected benefits should be balanced against the risks. In patients with structural heart disease, proarrhythmia and cardiac decompensation are special risks associated with antiarrhythmic drugs.

Special caution should be exercised when prescribing in this context. Disopyramide should not be used in patients with uncompensated congestive heart failure unless this is secondary to cardiac arrhythmia. If dispoyramide is to be given under these circumstances, special care and monitoring are essential.

Life threatening and haemodynamically significant arrhythmias are difficult to treat and affected patients have a high mortality risk. Treatment of these arrhythmias, by whatever modality, must be initiated in hospital. Disopyramide phosphate should be avoided in patients with glaucoma.

In patients with a history or family history of glaucoma, intraocular pressure should be measured before initiating treatment. There have been reports of ventricular tachycardia or ventricular fibrillation or torsade de pointes in patients receiving Disopyramide.

These have been usually, but not always, associated with significant widening of the QRS complex or prolonged QT interval. The QT interval and QRS duration must be monitored and Disopyramide should be stopped if these are increased by more than 25 %.

If these ECG changes or arrhythmias develop the drug should be discontinued. Disopyramide should be used only with caution in patients with atrial flutter or atrial tachycardia with block as conversion of a partial AV block to a 1:1 response may occur, leading to a potentially more serious tachyarrhythmia.

Accordingly the need for prior digitalisation should be considered. Owing to its negative inotrophic effect, Disopyramide should be used with caution in patients suffering from significant cardiac failure. This group may be especially sensitive to the negative inotropic properties of Disopyramide.

Such patients should be fully digitalised or controlled with other therapy before initiating treatment with Disopyramide. Aggravation of existing arrhythmia, or emergence of a new type of arrhythmia, demands urgent review of Disopyramide treatment.

Similarly, if an atrioventricular block or a bifascicular occurs during treatment, the use of Disopyramide should be reviewed. The occurrence of hypotension following Disopyramide administration, which has been observed especially in patients with cardiomyopathy or inadequately compensated congestive heart failure, requires prompt discontinuation of the drug.

Any resumption of therapy should be a lower dose with close patient monitoring. Disopyramide should be used with caution in treatment of digitalis intoxication. Care should be taken when prescribing Disopyramide with bundle branch block as the effect of Disopyramide in this condition is unpredictable.

If first degree heart block develops in a patient receiving Disopyramide, dosage should be reduced and may require discontinuation if the block persists. Since Disopyramide is eliminated predominantly by glomerular filtration the dose administered to patients with significant renal impairment may require adjustment.

Hepatic insufficiency Hepatic impairment causes an increase in the plasma half-life of Disopyramide and a reduced dosage may be required. Potassium imbalance Antiarrhythmic drugs may be hazardous in patients with potassium imbalance, as potassium abnormalities can induce arrhythmia.

Disopyramide should be used with caution in patients receiving concurrent therapy with diuretics or stimulant laxatives, as these are likely to give rise to hypokalaemia. Potassium levels should be checked regularly. Renal insufficiency In renal insufficiency, the dosage of Disopyramide should be reduced by adjusting the interval between administrations.

8). These targets of patients may be unsuitable for Disopyramide therapy. Hypoglycaemia Hypoglycaemia, sometimes severe, has been reported in association with Disopyramide administration, particularly in elderly and malnourished patients, in patients with impaired renal or hepatic function, cardiac failure or other conditions predisposing to disturbance of gluco-regulatory mechanisms.

Blood sugar levels should be monitored in all patients and strict adherence to the dosing recommendations is advised. Treatment with Disopyramide should be discontinued if hypoglycaemia occurs. 5). Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Paediatric population Paediatric patients with hepatic insufficiency may be at risk for increased exposures.

1. Disopyramide is contra-indicated in patients with un-paced second or third degree atrioventricular block, bundle-branch block associated with first degree atrioventricular block; un-paced bifascicular block, and severe sinus node disease if no pacemaker is present, cardiogenic shock and severe uncompensated heart failure, unless of secondary to cardiac arrhythmia.

Disopyramide is also contra-indicated in patients with pre-existing long QT syndromes. 5).