Procainamide

Procainamide is a class IA antiarrhythmic given intravenously for stable wide complex tachycardia, ventricular tachycardia and atrial fibrillation with a rapid ventricular rate in Wolff Parkinson White syndrome. Oral procainamide is no longer made in most places because of lupus like syndrome and blood toxicity. It has a shorter effect than amiodarone. It is rarely available in East Africa.

Classification. Class IA antiarrhythmic (sodium and potassium channel blocker); amide derivative of procaine.

Mechanism. Blocks fast sodium channels and potassium channels, slowing conduction in atrial, ventricular and accessory tract tissue and prolonging the action potential and refractoriness. Its active metabolite N acetylprocainamide (NAPA) is a pure class III agent.

Pharmacodynamics. IV onset within 5 to 10 minutes. Prolongs PR, QRS and QT intervals. Causes hypotension through ganglionic blockade when given quickly.

Pharmacokinetics. Half life 2.5 to 4.7 hours for procainamide and 6 to 8 hours for NAPA (both longer in kidney impairment). About 50% excreted unchanged in urine; acetylation to NAPA is fast or slow depending on genes. Therapeutic level: procainamide 4 to 10 mg/L; combined with NAPA below 30 mg/L.

Stable monomorphic ventricular tachycardia, wide complex tachycardia of unknown origin, or atrial fibrillation with an accessory tract, adult (IV).

• Give 20 to 50 mg/minute (or 100 mg every 5 minutes) by slow infusion with continuous ECG and blood pressure monitoring.

• Stop when the arrhythmia ends, hypotension occurs, the QRS widens by more than 50% from baseline, or a total of 17 mg/kg (about 1 g) has been given.

• Maintenance infusion 1 to 4 mg/minute (reduce to 1 to 2 mg/minute in kidney or heart failure).

Children (specialist). Loading 15 mg/kg IV over 30 to 60 minutes; maintenance infusion 20 to 80 micrograms/kg/minute (maximum 2 g daily).

Contraindications. Second or third degree atrioventricular block without a pacemaker; torsades de pointes; systemic lupus erythematosus; known hypersensitivity to procaine or similar anaesthetics; marked QT prolongation; severe heart failure; myasthenia gravis.

Warnings. Hypotension with rapid infusion; proarrhythmia (torsades de pointes); agranulocytosis and other blood dyscrasias (fever, sore throat, mouth ulcers: stop and test); drug induced lupus (positive antinuclear antibodies in most patients on long term therapy); accumulation of NAPA in kidney impairment; heart block; use in atrial fibrillation with a rapid rate can speed ventricular rate if nodal conduction improves.

Adverse effects. Hypotension, nausea, vomiting, flushing, dizziness, confusion, lupus like syndrome, rash, neutropenia, QT prolongation.

Interactions. Amiodarone, other class I and III antiarrhythmics, antimalarials, macrolides, fluoroquinolones: QT prolongation. Trimethoprim and cimetidine: raised procainamide levels. Neuromuscular blockers: prolonged block. Anticholinergics: additive effect. Antihypertensives: additive hypotension.

Special groups.

• Pregnancy: avoid unless essential; used for foetal tachycardia in specialist care.

• Breastfeeding: excreted in milk; avoid.

• Patients of African ancestry: no dose change.

• Older adults: lower infusion rates; accumulation of NAPA is more likely.

• Kidney impairment: reduce the maintenance infusion to 1 to 2 mg/minute; monitor levels.

• Liver impairment: reduce the dose.

Formulations. Injection 100 mg/mL and 500 mg/mL; oral tablets and capsules not widely available.

Administration. IV only in monitored settings. Dilute to 20 mg/mL or less in 5% glucose or 0.9% sodium chloride; infuse by pump. Keep the patient supine during infusion.

Baseline. ECG (QRS, QTc), blood pressure, antinuclear antibodies if long therapy is planned, full blood count, creatinine, potassium, magnesium.

Monitoring. Continuous ECG and blood pressure. Stop at QRS widening of 50% or more, hypotension, or arrhythmia end. Procainamide and NAPA levels during long infusions. Full blood count weekly for the first 3 months of any oral therapy and if infection occurs.

Stopping. Stop the infusion once rhythm is restored; no taper.

Common prescribing errors. Fast infusion causing hypotension; adding to amiodarone; exceeding 17 mg/kg; failing to reduce the maintenance dose in kidney impairment; long term use without antinuclear antibody and blood count checks.