INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo RYTHMODAN 100 mg CAPSULES
RYTHMODAN 150 mg CAPSULES
RYTHMODAN RETARD TABLETS
RYTHMODAN INJECTION 50 mg/5 mL

SCHEDULING STATUS
S4

PROPRIETARY NAME
(and dosage form)

RYTHMODAN 100 mg CAPSULES
RYTHMODAN 150 mg CAPSULES
RYTHMODAN RETARD TABLETS
RYTHMODAN INJECTION 50 mg/5 mL

COMPOSITION
Oral: Disopyramide 100 mg; Disopyramide 150 mg
Retard: Each tablet contains 322,5 mg disopyramide phosphate equivalent to 250 mg of the base in a sustained release formulation.
i.v.: Each 5 ml ampoule contains 64,4 mg disopyramide phosphate equivalent to 50 mg disopyramide. Benzyl alcohol 1%.

PHARMACOLOGICAL CLASSIFICATION
A. 6.2 cardiac depressants.

PHARMACOLOGICAL ACTION
Rythmodan slows conduction in the myocardium and in the Purkinje system. Clinically a variable effect is found on the A-V node. Usage has confirmed the characteristic electrocardiographic findings found in animals of widening of the QRS complex and prolongation of the QT interval. Rythmodan is negatively inotropic and possesses anti-cholinergic properties. Cardiac output and blood pressure are usually little affected.

INDICATIONS
Prevention and treatment of the following arrhythmias:
1. Unifocal and multifocal premature ventricular contractions.
2. Premature atrial contractions.
3. Paroxysmal atrial tachycardia.

Rythmodan may be used in the following conditions when complicated by the above arrhythmias.
1. During or after surgical procedures e.g. cardiac catheterization.
2. Following the use of digitalis or similar glycosides.

CONTRA-INDICATIONS
Rythmodan is contra-indicated in the presence of complete heart block. The drug should be used with caution in patients with partial heart block and in patients being concurrently treated with a potent diuretic which could give rise to hypokalaemia, which may reduce patient response to Rythmodan and increase side-effects. Owing to the drug’s negative inotropic effect, patients suffering from any degree of heart failure, latent or overt, should be digitalised prior to Rythmodan therapy. The administration of disopyramide is contra-indicated in patients with congestive cardiac failure, irrespective of whether the patient is digitalised. Due to its anti-cholinergic properties, patients with glaucoma or a tendency to urinary retention may be unsuitable for Rythmodan therapy. Exceptionally, individual sensitivity to Rythmodan may be found.
Safety in pregnancy has not been established.
In the presence of impaired renal function plasma levels may rise and the half-life will be prolonged. Caution must be observed in these patients with continuous monitoring of effects.
Intravenous Rythmodan is contra-indicated in established cardiac insufficiency and complex cardiopathies.

WARNING
Rythmodan must be used with caution in post-myocardial infarction patients as it can precipitate cardiac failure.

DOSAGE AND DIRECTIONS FOR USE
Capsules
The recommended initial adult oral dosage is 300 - 800 mg per day, given as 100 mg capsule every 6 hours or 150 mg capsule every 8 hours. The dose should be adjusted according to the response of the patient. Most patients respond to 100 mg 6 hourly.

Retard
The recommended dose for stabilised patients or those receiving Rythmodan for the first time, is 1 - 1½ (250 - 375 mg) Retard tablets twice daily. Patients being transferred from intravenous therapy with Rythmodan should be stabilised on conventional Rythmodan capsules for the first 24 hours before starting therapy with the Retard formula.

Ampoules
Rythmodan injectable may be given:
1. Either by slow direct intravenous injection followed by:
  a) oral administration
  b) or slow infusion and oral administration
2. Or by slow intravenous infusion followed by oral administration.

Details for the above routes of administration are given hereafter:
1. Slow direct intravenous injection: 0,75 mg/kg body mass over 2 minutes and repeated at 5 minute intervals until the arrhythmia is controlled - but not exceeding 4 mg/kg body mass in the first hour.
Subsequent i.v. regimen 0,4 mg/kg body mass/hour by infusion, but it is preferable to convert to oral dosing as soon as possible.
Transition from i.v. to oral route: The patient should be transferred to the oral dosage form as soon as possible.
2. Slow intravenous infusion: May be given at a rate of 50 mg per hour up to a total dose of 300 mg followed by oral administration as given below -
  - one 100 mg capsule one hour before end of the infusion
  - two more capsules 4 hours after the end of the infusion
  - and then one capsule every 4 to 8 hours without exceeding a total of 800 mg per 24 hours.
  In determining the intervals between administration of Rythmodan it should be borne in mind that its elimination half life in normal volunteers is approximately 7 hours and in patients with heart failure approximately 12 hours. If the clinician wishes to use more than 800 mg daily, the possible increase in the therapeutic efficiency must be weighed against the probable side-effects and close monitoring of the patient should be undertaken in an intensive care unit.

Insufficient data exists for recommendations to be made for paediatric dosage.

PHARMACEUTICAL PRECAUTIONS
Rythmodan has been found to be physically compatible with the following:
  Sodium chloride injection B.P.,
  Dextrose injection B.P.,
  Compound sodium chloride injection B.P.,
  Compound sodium lactate injection B.P.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Most common side-effects (dry mouth, blurred vision, urinary hesitancy) are attributable to anticholinergic action. The administration of disopyramide may precipitate cardiac failure when administered to patients with congestive failure, who have been stabilised.
Gastro-intestinal irritation may also occur. Hypoglycaemia has been observed and is a risk in individuals with cardiac decompensation, diabetes mellitus, liver dysfunction and patients using alcohol or betablockers. Blood sugar monitoring is advisable in these patients.
Cholestatic jaundice has been reported.
Myocardial depression can occur. Hypotension, syncope, tinnitus, sleeplessness and maculopapular or erythematous skin rash may occur.
Side-effects disappear rapidly with either reduction of dosage or cessation of therapy. Disopyramide may cause ventricular dysrhythmias including ventricular tachycardia and fibrillation.
Profuse sweating may occur in case of too rapid intravenous injection.
In view of the serious nature of many of the conditions being treated, it is suggested that Rythmodan injectable should be used only when facilities exist for cardiac monitoring or defibrillation, if the need should arise.
Patients with atrial flutter or atrial fibrillation must also be digitalised prior to the administration of Rythmodan.
Plasma-disopyramide concentrations should be measured periodically in all patients on long-term therapy, especially those with renal impairment.
Impaired renal function: A reduced dosage, preferably accompanied by assay of disopyramide plasma evels in cases of severe renal failure (creatinine clearance < 8 ml/min) is recommended.
The following table may be helpful as a guide:-

CREATININE CLEARANCE
(ML/MIN)
DOSAGE
Normal 100 mg 6 hourly
20 - 60 100 mg 8 hourly or
  150 mg 12 hourly
8 - 20 100 mg 12 hourly
< 8 150 mg daily

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Animal studies indicated that overdosage may lead to cardiac arrest or atrio-ventricular block or to disorders of ventricular excitability leading to terminal ventricular fibrillation. Intracardiac conduction defects and ventricular hyperexcitability may be controlled by general intensive supportive therapy.

CONDITIONS OF REGISTRATION
To be advertised to the professions only.

IDENTIFICATION
Oral 100 mg: Size no. 2, two-coloured, hard gelatin capsules containing a white powder. The cap is opaque green and the body is opaque beige.
The capsule is overprinted with RY RL.
Oral 150 mg: Size no. 2, white opaque, hard gelatin capsules containing a white powder.
The capsule is overprinted with RY 150.
Retard: White, circular, biconvex tablets, 12 mm in diameter, film coated with a break-line. Tablets are marked RY above R on one side and the Roussel logo on the reverse.
I.V.: Clear neutral glass 5 ml ampoule containing aqueous clear solution without any specific odour, miscible with water.

PRESENTATION
Oral 100 mg : Blister packs of 100 capsules
150 mg : Blister packs of 100 capsules
Retard : Blister packs of 60 tablets
i.v. : 5 x 5 ml clear glass ampoules

STORAGE INSTRUCTIONS
Store in a cool dry place, below 25°C, protected from light.
Keep out of reach of children.

REGISTRATION NUMBER
Oral 100 mg : E/6.2/163
150 mg : K/6.2/276
Retard 250 mg : P/6.2/51
i.v. 50 mg/5 mL : H/6.2/265

NAME AND BUSINESS ADDRESS OF APPLICANT
Roussel Laboratories (Pty) Limited
REG. NO. 66/01057/07
5th Street
Marlboro Extension 1
SANDTON
2199

DATE OF PUBLICATION OF THIS PACKAGE INSERT
January 1984

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