Disopyramide


Concise Prescribing Info
Indications/Uses
Supraventricular and ventricular arrhythmias.
Dosage/Direction for Use
Adult : PO As conventional cap: 300-800 mg/day in divided doses. As modified-release tab: 250-375 mg bid.
Dosage Details
Oral
Supraventricular arrhythmias, Ventricular arrhythmias
Adult: As conventional cap: 300-800 mg daily in divided doses. As modified-release tab: 250-375 mg bid.
Elderly: Start at the lower end of dosing range.
Renal Impairment
CrCl (mL/min) Dosage
<15 As conventional cap: 100 mg 24 hrly. 
15-30 As conventional cap: 100 mg 12 hrly. 
30-40  As conventional cap: 100 mg 8 hrly.
>40  As conventional cap: 100 mg 6 hrly.
≤40  As modified-release tab: Contraindicated.
>40  As modified-release tab: 200 mg 12 hrly.
Hepatic Impairment
As conventional cap: 100 mg 6 hrly. As modified-release tab: 200 mg 12 hrly.
Contraindications
Cardiogenic shock, pre-existing 2nd- or 3rd-degree heart block w/o pacemaker, bundle branch block associated w/ 1st-degree AV block, congenital QT prolongation, severe sick sinus syndrome. Concomitant use w/ TCAs, tetracyclic antidepressants, macrolide antibiotics, and other drugs that may increase risk of torsade de pointes. Renal (CrCl ≤40 mL/min) impairment (modified-release).
Special Precautions
Patient w/ AF/flutter, benign prostatic hyperplasia, electrolyte imbalance (i.e. hypokalaemia, hypomagnesaemia), glaucoma, uncompensated CHF (unless secondary to cardiac arrhythmia), cardiomyopathy, myasthenia gravis, Wolff-Parkinson-White syndrome. Elderly. Renal and hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: QT interval prolongation, QRS complex widening, AV bock, bundle branch block, hypotension, severe heart failure, cardiogenic shock.
Nervous: Nervousness, headache, dizziness.
CV: Oedema, chest pain, bradycardia, sinus block, ventricular fibrillation, ventricular tachycardia.
GI: Dry mouth, abdominal pain, nausea, vomiting, anorexia, diarrhoea, constipation.
Resp: Dyspnoea.
Hepatic: Cholestatic jaundice, elevated liver enzymes.
Genitourinary: Dysuria, acute urinary retention, frequency, and urgency.
Endocrine: Hypoglycaemia.
Haematologic: Thrombocytopenia, agranulocytosis, neutropenia.
Ophthalmologic: Diplopia.
Otic: Blurred vision.
Dermatologic: Rash.
Others: Wt gain.
Potentially Fatal: Torsades de pointes.
Patient Counseling Information
May impair ability to drive or operate machinery.
MonitoringParameters
Monitor ECG, BP, disopyramide drug level, and serum K and blood sugar levels.
Overdosage
Symptoms: Anticholinergic effects, loss of consciousness, hypotension, resp arrest, apnoea, cardiac conduction disturbances, arrhythmias, QT interval prolongation, QRS complex widening, bradycardia, CHF, asystole, and seizures. Management: Symptomatic and supportive treatment. Perform gastric lavage or induce emesis. Monitor ECG. Administer cardiac glycoside, diuretics, vasopressors and sympathomimetics (e.g. isoproterenol, dopamine) if necessary. Treat anticholinergic effects w/ neostigmine. Employ intra-aortic balloon counterpulsation or mechanical ventilation if necessary. For progressive AV block, institute endocardial pacing.
Drug Interactions
Enhanced QT prolongation effect w/ phosphodiesterase type 5 inhibitors. Increased serum levels if concomitantly used w/ CYP3A4 enzyme inhibitors (e.g. azole antifungals). Reduced serum levels w/ CYP3A4 enzyme inducers (e.g. rifampicin, phenytoin). May cause competitive inhibition of metabolism w/ HIV protease inhibitors (e.g. ritonavir, indinavir, saquinavir), ciclosporin, warfarin, and theophylline. May induce hypokalaemia or potentiate proarrhythmic effects when used w/ diuretics, amphotericin B, gluco- and mineralo-corticoids, laxatives. Potentiate atropine-like effects when used w/ atropine and other anticholinergic agents (e.g. phenothiazines).
Potentially Fatal: May potentiate torsades de pointes when used w/ TCAs, tetracyclic antidepressants, macrolide antibiotics (e.g. clarithromycin, erythromycin), astemizole, cisapride, pentamidine, pimozide, terfenadine, thioridazine.
Action
Description: Disopyramide, a Class Ia antiarrhythmic agent, is a Na channel blocker w/ membrane stabilising effect. It depresses the myocardial excitability and conduction velocity, and reduces disparity in refractory between normal and infarcted myocardium. It also possesses anticholinergic, peripheral vasoconstrictive, and negative inotropic effects.
Onset: 0.5-3.5 hr.
Duration: 1.5-8.5 hr (conventional).
Pharmacokinetics:
Absorption: Rapidly absorbed from the GI tract. Bioavailability: 80-90%. Time to peak plasma concentration: W/in 2 hr (conventional); 4-7 hr (modified-release).
Distribution: Crosses the placenta and enters breast milk. Volume of distribution: 0.8-2 L/kg. Plasma protein binding: 20-60%.
Metabolism: Undergoes partial hepatic metabolism by CYP3A4 enzyme via N-dealkylation to the active metabolite, N-despropyldisopyramide, and other inactive metabolites.
Excretion: Via urine (approx 50% as unchanged drug, approx 20% as N-despropyldisopyramide, 10% as other metabolites); faeces (10-15%). Elimination half-life: 4-10 hr.
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Disopyramide, CID=3114, https://pubchem.ncbi.nlm.nih.gov/compound/Disopyramide (accessed on Jan. 21, 2020)

Storage
Store between 20-25°C.
MIMS Class
ATC Classification
C01BA03 - disopyramide ; Belongs to class Ia antiarrhythmics.
References
Anon. Disopyramide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/10/2016.

Buckingham R (ed). Disopyramide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/10/2016.

Disopyramide Phosphate Capsule (Mayne Pharma Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 20/10/2016.

Joint Formulary Committee. Disopyramide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/10/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Disopyramide Phosphate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 20/10/2016.

Sanofi-Aventis New Zealand Limited. Rythmodan Capsules data sheet 11 July 2016. Medsafe. http://www.medsafe.govt.nz/. Accessed 20/10/2016.

Disclaimer: This information is independently developed by MIMS based on Disopyramide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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