Disopyramide information from DrugsUpdate
L - Caution when used during lactation
Disopyramide is an antiarrhythmic medication. It is a Class Ia antiarrhythmic (sodium channel blocker) used in the treatment of ventricular tachycardias. It has no effect on alpha or beta adrenergic receptors. It resembles Quinidine but it has a marked anti-muscarinic effect on the heart, for this reason, it is not considered as a drug of 1st choice. It is also used in ventricular arrhythmia and supraventricular arrhythmia that might follow myocardial infarctions.
Disopyramide is a Ia antiarrhythmic agent which acts by decreasing myocardial excitability and conduction velocity. It lengthens the effective refractory period of the atrium. It also possesses antimuscarinic and negative inotropic effects.
Absorption: Readily and almost completely absorbed from the GI tract (oral); peak plasma concentrations after 0.5-3 hr.
Distribution: Crosses the placenta and enters the breast milk. Protein-binding: 50-65%.
Metabolism: Hepatic: Partial metabolism; converted to mono-N-dealkylated disopyramide (also has antiarrhythmic and antimuscarinic properties).
Excretion: Mainly in the kidneys via urine (50% as unchanged, 20% as N-dealkylated metabolite and 10% as other metabolites; via the faeces (10% of the dose). 4-10 hr (elimination half-life); may be increased in cardiac failure, renal and hepatic impairment.
Impotence, constipation, difficulty in micturition, dry mouth, blurred vision, nausea, bloating, abdominal pain, vomiting, diarrhoea, colic. Psychosis, depression, skin rashes, dizziness, fatigue, muscle weakness, headache, cholestatic jaundice, elevated liver enzymes, thrombocytopenia, agranulocytosis, ventricular tachycardia and fibrillation, heart failure, hypotension, conduction disturbances.
Potentially Fatal: Urinary retention, severe cardiovascular depression if given as rapid IV inj. High risk of recurrence of failure in patients with history of congestive cardiac failure. Negative inotropic effect especially prominent in patients with cardiomyopathy, hypertension and uncompensated cardiac failure.
Patients with atrial flutter or fibrillation should be digitalized prior to Disopyramide Phosphate administration to ensure that drug-induced enhancement of AV conduction does not result in an increase of ventricular rate beyond physiologically acceptable limits.
Care should be taken when prescribing Disopyramide Phosphate for patients with sick sinus syndrome (bradycardia-tachycardia syndrome), Wolff-Parkinson-White syndrome (WPW), or bundle branch block. The effect of Disopyramide phosphate in these conditions is uncertain at present.
Patients with myocarditis or other cardiomyopathy may develop significant hypotension in response to the usual dosage of Disopyramide phosphate, probably due to cardiodepressant mechanisms. Therefore, a loading dose of Disopyramide Phosphate should not be given to such patients, and initial dosage and subsequent dosage adjustments should be made under close supervision.
More than 50% of Disopyramide is excreted in the urine unchanged. Therefore Disopyramide Phosphate dosage should be reduced in patients with impaired renal function (see DOSAGE AND ADMINISTRATION). The electrocardiogram should be carefully monitored for prolongation of PR interval, evidence of QRS widening, or other signs of overdosage
Hepatic impairment also causes an increase in the plasma half-life of Disopyramide. Dosage should be reduced for patients with such impairment. The electrocardiogram should be carefully monitored for signs of overdosage
Patients with cardiac dysfunction have a higher potential for hepatic impairment; this should be considered when administering Disopyramide Phosphate.
Antiarrhythmic drugs may be ineffective in patients with hypokalemia, and their toxic effects may be enhanced in patients with hyperkalemia. Therefore, potassium abnormalities should be corrected before starting Disopyramide Phosphate therapy.
Conduction disorders or uncompensated heart failure. Pregnancy and lactation. Renal and hepatic failure. Family history of glaucoma. Correct potassium deficiency.
Avoid other Class I antiarrhythmics and other cardiac depressants including β-blockers except in life-threatening arrhythmias. Risk of worsening of arrhythmias, precipitation of new arrhythmias and ventricular fibrillation when used with other anti-arrhythmics. Reduced efficacy when co-admin with phenytoin.
Potentially Fatal: Enhanced antimuscarinic effects with other antimuscarinic drugs. Potentiates negative chronotropic and inotropic effects of β-blockers and verapamil. Potentiates inhibitory effect on the conduction system produced by digitalis. Potentiates QT interval prolongation produced by TCAs and amiodarone.
Supraventricular and ventricular arrhythmias
Adult: 300-800 mg daily in divided doses (as conventional capsules every 6 hr; as extended-release capsules every 12 hr), adjusted according to patient's response.
Child: 12-18 yr: 6-15 mg/kg daily; 4-12 yr: 10-15 mg/kg daily; 1-4 yr: 10-20 mg/kg daily; <1 yr: 10-30 mg/kg daily.
Hepatic impairment: 400 mg daily in divided doses. Liver cirrhosis: consider a therapeutic range 50% lower than in patients with normal hepatic function.
Supraventricular and ventricular arrhythmias
Adult: 2 mg/kg (max: 150 mg) by slow inj at a rate of ≤30 mg/min, followed by 200 mg by mouth immediately upon completion of inj and every 8 hr for 24 hr. If arrhythmia recurs, repeat IV inj but not exceeding 300 mg in the 1st hr and 800 mg in 24 hr. Alternatively, initial IV inj may be followed by IV infusion of 0.4 mg/kg/hr (or 20-30 mg/hr) Max: 800 mg daily.
Renal impairment: Dose adjustments may be required.
Hepatic impairment: Dose adjustments may be required.
List of Contraindications
Caution when used during pregnancy.
Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Caution when used during lactation
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Disopyramide phosphate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Because of its anticholinergic activity, Disopyramide phosphate should not be used in patients with glaucoma, urinary retention, or benign prostatic hypertrophy (medical conditions commonly associated with the elderly) unless adequate overriding measures are taken (see WARNINGS: Anticholinergic Activity).In the event of increased anticholinergic side effects, plasma levels of Disopyramide should be monitored and the dose of the drug adjusted accordingly. A reduction of the dose by one third, from the recommended 600 mg/day to 400 mg/day, would be reasonable, without changing the dosing interval. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function
Patients with complete heart block; glaucoma; predisposition to urinary retention; myasthenia gravis. Sinus node disease in absence of pacemaker. Cardiomyopathy. Cardiogenic shock. Hypotension. Hypersensitivity. Children.
Intravenous: Store below 30°C.
Oral: Store below 30°C.