Disopyramide

Disopyramide is a class IA antiarrhythmic with strong anticholinergic and negative inotropic effects. It is used for vagally mediated atrial fibrillation and, in specialist centres, to reduce the left ventricular outflow gradient in hypertrophic obstructive cardiomyopathy. It is avoided in heart failure and in patients with glaucoma or prostate disease. It is rarely available in East Africa.

Classification. Class IA antiarrhythmic (sodium channel blocker with potassium channel block and anticholinergic effect).

Mechanism. Blocks the fast sodium channel (slowing conduction) and prolongs the action potential and QT interval. It has muscarinic receptor blocking effects and is a negative inotrope, which reduces contractility and the outflow tract gradient.

Pharmacodynamics. Oral onset within 30 to 60 minutes, peak at 1 to 2 hours (immediate release). Prolongs QRS and QT; raises atrioventricular conduction through vagal block; lowers outflow tract gradient by 40 to 50% in obstructive cardiomyopathy.

Pharmacokinetics. Oral bioavailability 60 to 83%. Half life 6 to 8 hours (longer in kidney impairment and older adults). Protein binding is concentration dependent. About 50% excreted unchanged in urine; the rest is metabolised to an active mono dealkylated metabolite with greater anticholinergic effect.

Ventricular arrhythmias and atrial fibrillation (vagal), adult.

• Immediate release: 100 to 200 mg every 6 hours (400 to 800 mg daily).

• Modified release: 250 to 300 mg every 12 hours.

• Maximum 800 mg daily; under 50 kg: maximum 400 mg daily in divided doses.

Obstructive hypertrophic cardiomyopathy (specialist), adult. Start 250 mg modified release twice daily; titrate every 3 to 7 days to 400 to 800 mg daily in divided doses; maximum 800 mg daily. Give a beta blocker or nodal blocker first.

Children (specialist). 10 to 30 mg/kg daily in 3 to 4 divided doses (lower end under 1 year; maximum 800 mg daily).

Contraindications. Second or third degree atrioventricular block without a pacemaker; cardiogenic shock; uncontrolled heart failure; long QT syndrome or torsades; closed angle glaucoma; urinary retention or prostatic hypertrophy; myasthenia gravis; sick sinus syndrome without a pacemaker; hypersensitivity.

Warnings. Negative inotropy (may cause heart failure); proarrhythmia; anticholinergic effects (dry mouth, constipation, blurred vision, urinary retention, glaucoma); hypoglycaemia (in diabetes, older adults, renal impairment); hypotension; QT prolongation; hepatic cholestasis (rare). Correct potassium before starting.

Adverse effects. Dry mouth, constipation, urinary hesitancy, blurred vision, dizziness, hypotension, heart failure, hypoglycaemia, nausea, QT prolongation.

Interactions. Clarithromycin and erythromycin: raised levels and torsades. Rifampicin, phenytoin: lower levels. Beta blockers, verapamil: additive negative inotropy and bradycardia. Other antiarrhythmics and QT prolonging drugs (antimalarials, antipsychotics, fluoroquinolones): torsades. Anticholinergics: additive effect. Antidiabetic drugs: hypoglycaemia.

Special groups.

• Pregnancy: avoid unless essential; may cause uterine contractions.

• Breastfeeding: excreted in milk; avoid.

• Patients of African ancestry: no dose change.

• Older adults: lower doses; high risk of urinary retention, hypoglycaemia and confusion.

• Kidney impairment: reduce the dose and extend the interval; creatinine clearance 15 to 40 mL/min: 100 mg every 12 hours (immediate release); below 15 mL/min: 100 mg every 24 hours.

• Liver impairment: maximum 400 mg daily (immediate release).

Formulations. Capsules 100 and 150 mg; modified release tablets 250 mg.

Administration. Oral at regular intervals; swallow modified release tablets whole.

Baseline. ECG (QTc), potassium, magnesium, creatinine, glucose, prostate or urinary symptoms, intraocular pressure history.

Monitoring. ECG after each dose change and every 6 months; stop if QTc exceeds 500 ms. Blood glucose in diabetes and older adults. Urine flow and bowel habit. Heart failure signs.

Stopping. Taper over days to weeks where possible.

Common prescribing errors. Using it in heart failure or glaucoma; combining with clarithromycin; omitting the renal dose reduction; ignoring hypoglycaemia; giving without a nodal blocker in atrial flutter.