Disopyramide

Oral
Supraventricular arrhythmias, Ventricular arrhythmias

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.

As conventional cap: 100 mg 6 hrly. As modified-release tab: 200 mg 12 hrly.

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).

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.

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.

PO: C

May impair ability to drive or operate machinery.

Monitor ECG, BP, disopyramide drug level, and serum K and blood sugar levels.

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.

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.

Description:
Mechanism of Action: 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.

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

Store between 20-25°C.

Cardiac Drugs

C01BA03 - disopyramide ; Belongs to class Ia antiarrhythmics.

Anon. Disopyramide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/10/2016.

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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.