There is no specific antidote for disopyramide. Prostigmine derivatives can be used to treat anticholinergic effects. Symptomatic supportive measures may include : early gastric lavage; administration of a cathartic followed by activated charcoal by mouth or stomach tube; IV administration of isoprenaline, other vasopressors and/or positive inotropic agents; if needed - infusion of lactate and/or magnesium, electro-systolic assistance, cardioversion, insertion of an intra-aortic balloon for counterpulsion and mechanically assisted ventilation. Haemodialysis, haemofiltration or haemoperfusion with activated charcoal has been employed to lower the serum concentration of the drug.
18 months
Hypersensitivity to Disopyramide Phosphate or to any of the excipients.
Disopyramide is contra-indicated in un-paced second or third degree atrioventricular block; bundle-branch block associated with first-degree atrioventricular block; un-paced bifasicular block; pre-existing long QT syndromes; severe sinus node dysfunction; severe heart failure, unless secondary to cardiac arrhythmia; hypersensitivity to disopyramide. It is also contra-indicated in concomitant administration with other anti-arrhythmics or other drugs liable to provoke ventricular arrhythmias, especially Torsade de Pointes. The sustained release formulation is contra-indicated in patients with renal or hepatic impairment.
Not applicable
Glyceryl monostearate
Sucrose
Povidone
Magnesium stearate
Film coating:
Hydroxypropyl methylcellulose
Propylene glycol
Anhydrous glucose
Modified release tablet.
Biconvex tablets and off-white in colour. One side has a break-line and is embossed 013 and E; the other side is embossed with the Roussel logo.
Cardiac: It is accepted that the arrhythmogenic potential of disopyramide is weak. However, as with all antiarrhythmic drugs, disopyramide may worsen or provoke arrhythmias. This proarrhythmic effect is more likely to occur in the presence of hypokalemia with the associated use of antiarrhythmic drugs, in patients with severe structural heart disease with prolongation of the QT interval.
Intra-cardiac conduction abnormalities may occur: QT interval prolongation, widening of the QRS complex, atrioventricular block and bundle-branch block.
Other types of arrhythmia have been reported: Bradycardia, sinus block, ventricular fibrillation, ventricular tachycardia and torsades de pointes.
Episodes of severe heart failure or even cardiogenic shock have also been described particularly in patients with severe structural heart disease. The resulting low cardiac output can cause hypotension, renal insufficiency and/or acute hepatic ischemia.
Other adverse reactions include:
Atropine-like effects (see also section 4.4):
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.
). In some cases, severe hypoglycaemia resulted in coma.
Very rarely: cholestatic jaundice, headache, dizzy sensation, neutropenia.
Rapid infusion may cause profuse sweating.
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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Not applicable.
Properties:
Prevention and control of a wide variety of cardiac arrhythmias, probably by slowing conduction in the his-Purkinje system and by increasing the effective refractory period of the atria and ventricles.
Indications:
1. Maintenance of normal rhythm following conversion by parenteral drugs or electroconversion.
2. Prevention of arrhythmias after myocardial infarction.
3. Treatment of persistent ventricular and atrial extrasystoles, paroxysmal supra ventricular tachycardia, Wolff-Parkinson-White syndrome.
4. Suppression of arrhythmias during surgical procedures.
5. Control of arrhythmias following the use of digitalis or similar glycosides.
Pharmacotherapeutic group: Cardiac therapy; Antiarrhythmias, Class Ia, ATC code: C01BA03
Disopyramide is a Class 1 antiarrhythmic agent with a depressant action on the heart similar to that of quinidine and is used for the prevention and treatment of a wide variety of cardiac arrhythmias.
The dissolution characteristics of Rythmodan Retard are designed to release 250mg disopyramide over 12 hours. The dissolution profile is matched to the drug half-life of 6-8 hours with good therapeutic levels followed by steady release of disopyramide to sustain therapeutic effect. The sustained release mechanism is based on the matrix principle, adapted for disopyramide. Reliable release is achieved by strict control of particle size.
12 June 2014
Rythmodan Retard 250mg Modified Release Tablets
Aventis Pharma Limited
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
or trading as:
Sanofi-aventis or Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
Do not store above 25°C
PVC/PVDC/Aluminium Blister containing 56, 60 or 100 tablets
Not all pack sizes may be marketed.
PL 04425/0647
Pregnancy: Although Rythmodan has undergone animal tests for teratogenicity without evidence of any effect on the developing foetus, its safety in human pregnancy has not been established. Rythmodan has been reported to stimulate contractions of the pregnant uterus. The drug should only be used during pregnancy if benefits clearly outweigh the possible risks to the mother and foetus.
Lactation: No data for Rythmodan Retard, but studies have shown that oral Rythmodan is secreted in breast milk, although no adverse effects to the infant have been noted. However, clinical experience is limited and Rythmodan should only be used in lactation if, in the clinician's judgement, it is essential for the welfare of the patient. The infant should be closely supervised, particularly for anticholinergic effects and drug levels determined if necessary. Ideally, if the drug is considered essential, an alternative method of feeding should be used.
Each tablet contains 322.5mg of the active substance Disopyramide Phosphate (equivalent to 250mg base).
Also contains 30mg of sucrose and 3.529mg of glucose, anhydrous.
Antiarrhythmic drugs belonging to the class 1c (Vaughan Williams Classification) were included in the Cardiac Arrhythmia Suppression Trial (CAST), a long term multicentre randomised, double blind study in patients with asymptomatic non life-threatening ventricular arrhythmia who have had a myocardial infarction more than six days but less than two years previously. A significant increase in mortality and non-fatal cardiac arrest rate was seen in patients treated with class 1c antiarrhythmic drugs when compared with a matched placebo group. The applicability of the CAST results to other antiarrhythmics and other populations (eg. those without recent infarction) is uncertain. At present, it is best to assume that the risk extends to other antiarrhythmic agents for patients with structural heart disease.
There is no evidence that prolonged suppression of ventricular premature contractions with antiarrhythmic drugs prevents sudden death.).
Atropine-like effects: There is a risk of :
- ocular hypertension in patients with narrow-angle glaucoma
- acute urinary retention in patients with prostatic enlargement
- aggravation of myasthenia gravis
- cognitive disorders, especially in elderly patients (see also section 4.8).
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Some adverse reactions may impair the patients' ability to concentrate and react, and hence the ability to drive or operate machinery..
Route of administration
Oral:
Recommended dose for stabilised patients or those receiving Rythmodan for the first time is one to one and a half tablets (250-375mg) twice daily. Tablets should be swallowed and not crushed or chewed.
Children:
There are insufficient data to recommend the use of Rythmodan in children.
Elderly:
A dose reduction due to reduced renal and hepatic function in the elderly (especially elderly non-smokers) should be considered.
No special requirements
Date of first authorisation: 22 December 1980
Date of latest renewal: 4 April 2002
Combination with other antiarrhythmic drugs: Combinations of antiarrhythmic drugs are not well researched and their effect may be unpredictable. Thus, antiarrhythmic combination should be avoided except under certain circumstances, eg. beta-blockers for angina pectoris; digoxin with beta-blocker and/or verapamil for the control of atrial fibrillation, when defined as effective for an individual.
Interaction with drugs associated with risk of Torsade de Pointes, such as
- tricyclic and tetracyclic antidepressants
- all macrolide antibiotics ( e.g. erythromycin, clarithromycin, azithromycin etc)
- astemizole; cisapride; pentamidine; sparfloxacin; terfenadine; pimozide and thioridazine
Phosphodiesterase Type 5 Inhibitors:
There is evidence that phosphodiesterase Type 5 inhibitors may be potentially associated with a risk of QT prolongation. Concomitant administration of disopyramide with such drugs may potentially enhance this QT prolongation effect and is not recommended.
The concomitant use of these medications whilst undergoing treatment with disopyramide increases the chance of cardiac arrhythmia.
There is some evidence that disopyramide is metabolised by hepatic CYP3A.
Concomitant administration of significant inhibitors of this isozyme (e.g. macrolide or azole antifungal antibiotics) may therefore increase the serum levels of disopyramide. On the other hand, inducers of CYP3A (e.g. rifampicin and certain anticonvulsants such as phenytoin, primidone and phenobarbital) may reduce disopyramide and increase MN-disopyramide serum levels. Since the magnitude of such potential effects is not foreseeable, such drug combinations are not recommended.
When prescribing a drug metabolised by CYP3A [such as theophylline, HIV protease inhibitors (e.g. ritonavir, indinavir, saquinavir), ciclosporin A, warfarin] it should be kept in mind that disopyramide is probably also a substrate of this isozyme and thus competitive inhibition of metabolism might occur, possibly increasing serum levels of these drugs.
Interactions with hypokalaemia inducing drugs : Concomitant use with drugs that can induce hypokalaemia such as : diuretics, amphotericin B, tetracosactide (corticotropin analogue), gluco and mineralo-corticoids may reduce the action of the drug, or potentiate proarrhythmic effects. Stimulant laxatives are not recommended to be given concomitantly, due to their potassium lowering potential.
Other drug interactions:
Atropine and other anticholinergic drugs, including phenothiazines, may potentiate the atropine-like effects of disopyramide.
