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RYTHMODAN is a brand name for Disopyramide, supplied as a capsule. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AND CLINICAL USE ...................................................................................... 4 4 CONTRAINDICATIONS ........................................................................................................... 4 5 WARNINGS…
Verbatim from this product's HC label. Tap a section to expand.
The dosage of RYTHMODAN® should be individualized for each patient, based upon response and tolerance and patient weight. Capsules The usual daily dose of RYTHMODAN® is 400-800 mg given in 4 divided doses. Rarely, control may be maintained on daily doses of less than 400 mg.
If rapid control of arrhythmia is essential, an initial dosage schedule for most adults is a single loading dose of 300 mg followed by 100 mg every 6 hours. If satisfactory control of the arrhythmias not obtained with the maintenance dose of 100 mg q 6 hours, increase to 150 mg or subsequently to 200 mg q 6 hours if necessary.
For patients with cardiomyopathy or possible cardiac decompensation, loading doses should not be given, an initial dosage should be limited to 100 mg of RYTHMODAN® every 6 hours. Subsequent dosage adjustments should be made gradually with close monitoring for possible development of hypotension and/ or congestive heart failure (see WARNINGS).
For patients of small stature (body weight less than 50 kg or 110 lbs) and for patients with mild hepatic or renal insufficiency (creatinine clearance above 60 mL/minute), a loading dose of 200 mg is recommended, followed by 100 mg every 6 hours.
The recommended maintenance dose of these patients is 400 mg per day given in doses of 100 mg every 6 hours. In patients with severe hepatic or renal insufficiency (creatinine clearance below 50 mL/minute), an initial loading dose of 100 mg is recommended.
These patients are best managed with repeated plasma disopyramide determinations and subsequent dosage and frequency of administration should be based on the results of these determinations (see PRECAUTIONS). RYTHMODAN® Capsules Dosage Interval for Patients With Renal Insufficiency Creatinine clearance (mL/minute) 40 - 30 30 - 15 <15 Approximate maintenance-dosing interval q 8 h q 12 h q 24 h No loading dose should be given to patients who are being transferred from other oral antiarrhythmic agents such as quinidine or procainamide (see PRECAUTIONS - DRUG INTERACTIONS).
5 Chemical Name: 4-diisopropylamino-2-phenyl-2-(2-pyridyl) butyramide.
Description:
Disopyramide is a stable white powder, insoluble in water but soluble in dilute acid or organic solvents. 5. It is soluble in water. 11 AVAILABILITY OF DOSAGE FORMS RYTHMODAN® 100 mg capsules are presented in green/yellow, hard gelatin capsules marked RY RL.
Rare occurrence of congestive heart failure (CHF), hypotension, widening QRS, sinus arrest, nodal rhythm dissociation, cardiac arrest and cardiovascular collapse have been reported. An occasional paradoxical ventricular tachycardia, evolving sometimes to fibrillation has been observed.
A definite relationship to the drug was not always established in the above cardiovascular effects.
Intra-cardiac conduction abnormalities may occur:
QT interval prolongation, atrioventricular block and bundle-branch block. Other types of arrhythmia have been reported: bradycardia, sinus block. Pr RYTHMODAN® Page 13 of 22 The most common adverse reactions which are dose dependent are associated with the anticholinergic properties of the drug.
These may be transitory, but may be persistent and can be severe. Urinary retention is the most serious anticholinergic effect.
The following reactions were reported in more than 10% of patients:
Anticholinergic: dry mouth (16-30%), urinary retention (7-13%), constipation. Gastrointestinal: nausea, indigestion, vomiting, diarrhea, flatulence, bad taste in the mouth, anorexia.
The following reactions were reported in 1 to 10% of patients:
Anticholinergic: blurred vision, dry eyes/nose/throat. Cardiovascular: hypotension with or without CHF, increased CHF, cardiac conduction disturbances, proarrhythmic effects (6%), œdema, dyspnea, cyanosis, chest pain. Dermatologic: skin reactions including pruritus, urticaria, morbilliform eruption, abdominal rash, photosensitization.
General: dizziness, vertigo, drowsiness, profuse sweating. Genitourinary: urinary hesitancy and frequency. Other: raised SGOT levels. The following were reported in less than 1% of patients: dysuria, headache, feeling of warmth, pallor, peripheral paresthesia, fatigue, malaise, insomnia, confusion, transitory psychosis, elevated BUN, elevated creatinine, decreased hemoglobin/hematocrit, hypoglycemia (sometimes severe, associated with the risk of occurrence of consciousness disorder including hypoglycemic coma), neutropenia, idiosyncratic reaction to drug.
e. bundle-branch block associated with first-degree atrioventricular block, double block [left posterior or anterior hemiblock and right bundle-branch Pr RYTHMODAN® Page 5 of 22 block]), pre-existing second and third degree A-V block (if no pacemaker is present), known hypersensitivity to the drug or to any ingredient in the formulation (for a complete list, see AVAILABILITY OF DOSAGE FORMS).
RYTHMODAN® is contraindicated in patients with a pre-existing long QT (see WARNINGS - OTHER CARDIAC EFFECTS, Q-T Prolongation). RYTHMODAN® is contraindicated in patients with severe sinus node dysfunction (see PRECAUTIONS - PATIENTS WITH SPECIAL DISEASE OR CONDITIONS, Conductions Abnormalities).
RYTHMODAN® should not be used in the presence of uncompensated or inadequately compensated congestive heart failure (see WARNINGS). RYTHMODAN® is contraindicated in most patients with extensive myocardial disease, but may on occasion be used in these patients under the close supervision of a cardiologist if in their opinion the patient’s condition justifies it.
When used in these patients continuous ECG monitoring in a CCU facility is mandatory. Due to its anticholinergic activity, RYTHMODAN® is contraindicated in patients with glaucoma or in patients in whom urinary retention is present (see PRECAUTIONS).
Concomitant administration of RYTHMODAN® with other antiarrhythmics or other drugs liable to provoke ventricular arrhythmias and especially torsade de pointes is contraindicated (see PRECAUTIONS - DRUG INTERACTIONS, Concomitant Antiarrhythmic Therapy and Drugs Associated with Risk of «torsade de pointes»).
5 WARNINGS GENERAL All antiarrhythmic drugs can produce unwanted effects when they are used to treat symptomatic but not life threatening arrhythmia; the expected benefit should be balanced against their risks. Proarrhythmia and cardiac decompensation are special risks associated with the use of antiarrhythmic drugs in patients with structural heart disease.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Each capsule contains 100 mg disopyramide. The capsules are available in blister packs of 84 (6 x 14).
Non-medicinal ingredients:
Corn starch, magnesium stearate, pregelatinized starch, talc.
Capsule Body and Head:
FD&C Blue #2, gelatin, titanium dioxide, yellow iron oxide. v. ) in anesthetized dogs. A weak, negative inotropic effect on isolated heart preparations and a reduction in the contractile force of the heart in situ. v. Local anesthetic activity approximately equivalent to lignocaine but of longer duration in guinea- pig (wheal) and mouse (nerve conduction) tests.
Electrophysiology A decrease in conduction velocity through the atria, A-V node and His-Purkinje system was seen in dog heart in situ. Isolated preparations revealed an increase in the duration of the action potential, accompanied by a decreased amplitude and rate of rise of the phase 0 of the action potential.
Membrane responsiveness was decreased and the effective refractory period increased with consequent increased diastolic thresholds and reduced cardiac excitability. In man disopyramide prolongs the effective refractory period of the atria and the ventricles.
The effective refractory period of the A-V node is either slightly shortened or unchanged. The relative refractory period of the His-Purkinje system is prolonged. A-V nodal conduction time is unchanged by disopyramide. Conduction through the His-Purkinje system is unchanged, or slightly delayed.
Hemodynamics The main hemodynamic changes induced in patients by disopyramide are: 1. Heart rate unchanged or slightly increased. 2. Cardiac output unchanged or lowered by 10-25%. 3. Peripheral resistance increased or unchanged. 4. Effects on blood pressure were inconsistent but usually there was a slight fall.
5. Left ventricular end diastolic pressure unchanged or increased. 6. Negative inotropic effect which can be marked in patients with depressed left ventricular function. 5 hours. Steady state was achieved after 4 days of dosing. 2 hours.
The half-life was shown to be longer in hospitalized patients. There was no evidence of accumulation following oral treatment with 250 mg bid of long-acting disopyramide for 30 days in patients previously taking 2 x 100 mg tid of regular disopyramide.
Metabolism In man, disopyramide is metabolized by N-dealkylation. After an oral dose of approximately 6 mg/kg disopyramide phosphate to normal healthy volunteers, […]
In a few instances cholestatic jaundice has been reported. A definite causal relationship has not been established. A high plasma concentration has been associated with impotence. Other atropine-like ocular adverse reactions were reported: disorders of accommodation, diplopia.
Other atropine-like effects were reported: cognitive disorders, psychiatric disorders. Epigastralgia has been also reported. g. angioedema) possibly culminating in shock (essentially reported in association with the injectable formulation).
Post-Market Adverse Drug Reactions Blood and lymphatic system disorders Agranulocytosis Pr RYTHMODAN® Page 14 of 22 8 SYMPTOMS AND TREATMENT OF OVERDOSAGE Symptoms Patients who took deliberate overdoses of oral disopyramide presented with an early loss of consciousness after an apneic period, cardiac arrhythmias and loss of spontaneous respiration, leading to death.
Serum levels in these patients were as high as 114 mg/L taken at various times after ingestion, including post-mortem. The clinical signs of overdose may also include: paralytic ileus, bilateral mydriasis (suggestive of overdose); syncope, hypotension or shock; cardiac arrest due to intraventricular block or asystole; respiratory symptoms; coma (with bilateral mydriasis) in cases of massive intoxication.
Toxic plasma levels of disopyramide produce excessive widening of QRS complex and QT interval as a premonitory sign of other arrhythmias, in particular torsade de pointes which can result in repeated syncopes, worsening of CHF, hypotension, varying kinds and degrees of conduction disturbance, bradycardia and finally asystole.
Obvious anticholinergic effects are also observed. Treatment Discontinue drug and initiate gastric lavage; no specific antidote has been identified; treatment of overdosage should be symptomatic and may include the administration of isoproterenol, dopamine, intra-aortic balloon counterpulsation, mechanically assisted respiration and hemoperfusion with charcoal.
Hemodialysis may be employed to rapidly lower serum concentration of drug. In vitro studies with human blood have demonstrated good dialyzability. Its clearance was 33 mL/minute at a blood flow of 250 mL/ minute when an initial plasma concentration of 22 mcg/mL was dialysed using an artificial kidney (Cordis-DOW-4).
The ECG should be monitored and supportive therapy with vasopressors, sympathomimetics, cardiac glycosides and diuretics should be given, as required. Should progressive heart block develop, endocardial pacing should be implemented.
In case of any impaired renal function, measures to increase glomerular filtration rate may reduce the toxicity (disopyramide is excreted primarily by the kidney). Altering the urinary pH in man does not affect plasma half-life or the amount of disopyramide excreted in urine.
The anticholinergic effects could be reversed with neostigmine, at the discretion of the physician. For management of a suspected drug overdose, contact your regional Poison Control Centre. Pr RYTHMODAN® Page 15 of 22 9 DOSAGE AND ADMINISTRATION The dosage of RYTHMODAN® should be individualized for each patient, based upon response and tolerance and patient weight.
Capsules The usual daily dose of RYTHMODAN® is 400-800 mg given in 4 divided doses. Rarely, control may be maintained on daily doses of less than 400 mg. If rapid control of arrhythmia is essential, an initial dosage schedule for most adults is a single loading dose of 300 mg followed by 100 mg every 6 hours.
If satisfactory control of the arrhythmias not obtained with the maintenance dose of 100 mg q 6 hours, increase to 150 mg or subsequently to 200 mg q 6 hours if necessary. For patients with cardiomyopathy or possible cardiac decompensation, loading doses should not be given, an initial dosage should be limited to 100 mg of RYTHMODAN® every […]
Special caution should be exercised when prescribing in this context (see PRECAUTIONS - DRUG INTERACTIONS, Concomitant Antiarrhythmic Therapy). Life threatening and hemodynamically significant arrhythmia are difficult to treat and affected patients are at high risk.
Treatment of these arrhythmias, whatever modality, must be initiated in the hospital. Pr RYTHMODAN® Page 6 of 22 MORTALITY The results of the Cardiac Arrhythmia Suppression Trial (CAST) in post-myocardial infarction patients with asymptomatic ventricular arrhythmias showed a significant increase in mortality and in non-fatal cardiac arrest rate in patients treated with encainide or flecainide compared with a matched placebo-treated group.
CAST was continued using a revised protocol with the moricizine and placebo arms only. The trial was prematurely terminated because of a trend towards an increase in mortality in the moricizine treated group. The applicability of these results to other populations or other antiarrhythmic agents is uncertain, but at present it is prudent to consider these results when using any antiarrhythmic agent.
NEGATIVE INOTROPIC PROPERTIES Heart Failure Because of its negative inotropic effect disopyramide may cause or worsen congestive heart failure. Therefore, this drug should not be used in patients with heart failure, and should be especially avoided in patients with a previous history of heart failure except in the very special circumstances described below: In patients in whom the failure is exacerbated or caused by an arrhythmia, RYTHMODAN® may be used to suppress the ectopy but it must be borne in mind that any such benefit on cardiac function may be overcome by the depressant effect on cardiac output, and thereby result in even worse failure even though routine methods of anti-failure therapy including optimal digitalization are attempted.
Careful monitoring is essential under these circumstances. Patients with compensated heart failure may be treated with RYTHMODAN®, but careful attention must be given to the maintenance of cardiac function including optimal digitalization.
Close observation is mandatory, as any benefit of RYTHMODAN® either therapeutic or prophylactic could be accompanied by an unacceptable lowering of cardiac output. For most patients the encroachment on their cardiac reserve may be of minimal clinical consequence, but in patients with a limited reserve as a result of pump dysfunction and/or imbalanced work load, even a minor encroachment on reserve can precipitate clinically evident failure or make its control more difficult, and even result in a gross low output congestive cardiac failure state.
Hypotension On rare occasions RYTHMODAN® has caused syncope with sudden loss of consciousness. In the cases reported, this was believed to be due to an excessive hypotensive action of the drug or, in some cases, due to concomitant use with other hypotensive or negative inotropic agents.
, beta-adrenergic blockers or verapamil. An oral Pr RYTHMODAN® Page 7 of 22 loading dose of RYTHMODAN® should not be given to such patients; initial dosage and subsequent dosage adjustments should be made under close supervision. If severe hypotension develops, RYTHMODAN® should be discontinued promptly (see DRUG INTERACTIONS).
OTHER CARDIAC EFFECTS QRS Widening Significant widening (greater than 25%) of the QRS complex may occur during RYTHMODAN® administration; in such cases RYTHMODAN® should be discontinued. Q-T Prolongation As with other quinidine-like antiarrhythmic drugs, prolongation of the Q-T interval […]