Disopyramide

Dose reduction may be required. Dosing and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).

Dose reduction may be required. Dosing and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).

Cardiogenic shock, pre-existing 2nd- or 3rd-degree AV block or bifascicular block (except in those with a functioning artificial pacemaker); congenital long QT syndrome, bundle branch block (associated with 1st-degree AV block), severe sinus node dysfunction, severe heart failure (unless secondary to arrhythmia). Concomitant use with other antiarrhythmics or other drugs capable of provoking ventricular arrhythmias (particularly torsades de pointes).

Patient with history of heart failure; structural heart disease, atrial flutter or atrial tachycardia with block, Wolff-Parkinson-White syndrome, cardiomyopathy, electrolyte imbalance (particularly hypokalaemia or hypomagnesaemia), glaucoma or family history of glaucoma, benign prostatic hyperplasia, urinary retention, myasthenia gravis. Renal and hepatic impairment. Elderly. Pregnancy and lactation.

Significant: Hypotension; prolonged QT interval resulting in torsades de pointes; significant widening of QRS complex; ventricular tachycardia, ventricular fibrillation. Rarely, hypoglycaemia.
Cardiac disorders: Chest pain.
Eye disorders: Blurred vision, dry eyes.
Gastrointestinal disorders: Dry mouth, nausea, vomiting, diarrhoea, constipation, bloating, flatulence.
General disorders and administration site conditions: Fatigue, oedema.
Metabolism and nutrition disorders: Anorexia.
Psychiatric disorders: Nervousness.
Renal and urinary disorders: Urinary retention, urinary hesitancy.
Reproductive system and breast disorders: Impotence.
Respiratory, thoracic and mediastinal disorders: Dry throat, dyspnoea.
Skin and subcutaneous tissue disorders: Rash, pruritus.

PO: C

Monitor ECG, blood pressure, blood sugar and serum K. Assess for signs and symptoms of heart failure and CNS anticholinergic effects.

Symptoms: ECG abnormalities (e.g. marked QT interval prolongation, QRS complex widening, variable degrees of AV block), apnoea, bradycardia, worsening of CHF, bilateral mydriasis, syncope, hypotension, shock, loss of spontaneous respiration, coma, asystole leading to cardiac arrest. Management: Symptomatic and supportive treatment. Perform gastric lavage or induce emesis. May administer a cathartic followed by activated charcoal orally or via stomach tube. May give IV isoprenaline or other vasopressors as needed. May perform cardioversion, intra-aortic balloon insertion for counterpulsation or mechanical ventilation; haemodialysis, haemofiltration or haemoperfusion if necessary. Monitor ECG and vital signs.

Concomitant use with other antiarrhythmic drugs (e.g. quinidine, procainamide, lidocaine, propranolol) may result in excessive widening of QRS complex and/or prolongation of QT interval. Increased risk of torsades de pointes with TCAs, tetracyclic antidepressants, macrolide antibiotics (e.g. erythromycin, clarithromycin, azithromycin), astemizole, cisapride, pentamidine, pimozide, terfenadine, thioridazine. Increased risk of QT prolongation with phosphodiesterase type 5 inhibitors. May increase serum levels with CYP3A inhibitors (e.g. azole antifungals). May decrease serum levels with CYP3A inducers (e.g. rifampicin, phenytoin, primidone, phenobarbital). May increase the serum levels of theophylline, HIV protease inhibitors (e.g. ritonavir, indinavir, saquinavir), ciclosporin, warfarin. May induce hypokalaemia with diuretics, amphotericin B, tetracosactide, glucocorticoids, mineralocorticoids, stimulant laxatives. May potentiate the atropine-like effects with atropine and other anticholinergic drugs (e.g. phenothiazine).

Description:
Mechanism of Action: Disopyramide is a class Ia antiarrhythmic agent. It decreases myocardial excitability and conduction velocity and reduces disparity in refractory between normal and infarcted myocardium. Additionally, it has anticholinergic, peripheral vasoconstrictive and negative inotropic effects.
Onset: 0.5-3.5 hours.
Duration: 1.5-8.5 hours (conventional cap).
Pharmacokinetics:
Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: Within 2 hours (conventional cap); 4-7 hours (modified-release tab).
Distribution: Crosses the placenta and enters breast milk. Volume of distribution: 0.8-2 L/kg. Plasma protein binding: 50-65%.
Metabolism: Partially metabolised in the liver by CYP3A4 isoenzyme via N-dealkylation to form N-despropyldisopyramide (active metabolite) 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 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3114, Disopyramide. https://pubchem.ncbi.nlm.nih.gov/compound/Disopyramide. Accessed Sept. 24, 2024.

Store below 25°C.

Cardiac Drugs

C01BA03 - disopyramide ; Belongs to class Ia antiarrhythmics.

Anon. Disopyramide Phosphate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 29/05/2024.

Buckingham R (ed). Disopyramide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/05/2024.

Disopyramide. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 29/05/2024.

Joint Formulary Committee. Disopyramide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/05/2024.

Norpace Capsule, Gelatin Coated; Norpace CR Capsule, Extended Release (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 29/05/2024.

Rythmodan 100 mg Capsules (Neon Healthcare Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 29/05/2024.

Rythmodan Retard 250 mg Modified Release Tablets (Neon Healthcare Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 29/05/2024.