Procainamide

Why this drug is interesting

Procainamide is the clearest current example of a gap between the national algorithm and what is physically in the resus room cupboard. The RCUK 2025 adult tachyarrhythmia algorithm names it first for stable broad-complex regular tachycardia, and offers amiodarone only if procainamide is not available or contraindicated.³

The evidence supporting procainamide over amiodarone in this setting is genuinely good — but a drug you cannot obtain within twenty minutes is not a treatment option, and knowing whether your department holds it is more useful than knowing the dose.

Pharmacology

Mechanism

Procainamide is a class Ia antiarrhythmic: it blocks fast sodium channels with intermediate association-dissociation kinetics, slowing phase 0 depolarisation and conduction velocity while prolonging the action potential duration and refractory period. On the ECG this appears as QRS widening and QT prolongation.

Critically for emergency use, it slows conduction in accessory pathways as well as in ventricular myocardium — which is why it, rather than an AV nodal blocking agent, is the drug for pre-excited atrial fibrillation.

The metabolite matters

Procainamide is acetylated in the liver to N-acetylprocainamide (NAPA), which is itself active but behaves as a class III agent — potassium channel blockade, further QT prolongation. NAPA is renally cleared and has a longer half-life than the parent drug, so it accumulates in renal impairment and in slow acetylators.

Procainamide half-life

Approximately 3 hours

NAPA half-life

Approximately 6–8 hours, longer in renal impairment

Elimination

Both hepatic (acetylation) and renal; NAPA predominantly renal

Practical consequence

Reduce dose and monitor closely in renal impairment — the class III effect outlasts the class I one

Dosing and monitoring

RCUK 2025 adult tachyarrhythmia algorithm

Practical administration

• Continuous ECG and blood pressure monitoring throughout — this is a resus room drug
• Infuse over the full 20 minutes; the hypotension is largely rate-dependent, so slowing the infusion often manages it without abandoning the drug
• Print or record a rhythm strip before and during administration — the QRS comparison requires a baseline
• Have defibrillation immediately available; procainamide is being given to a patient in a rhythm that may deteriorate

Why the algorithm changed — PROCAMIO

The reordering of procainamide ahead of amiodarone rests substantially on PROCAMIO, a randomised comparison of intravenous procainamide against intravenous amiodarone for tolerated wide-QRS tachycardia.⁴

Procainamide performed better on both efficacy and safety: higher rates of tachycardia termination and substantially fewer major cardiac adverse events — the adverse event difference being the more striking of the two findings. Amiodarone, given as a rapid intravenous load to a patient in sustained VT, produced more hypotension and more clinical deterioration than its reputation implies.

It is worth noting what has not changed: electrical cardioversion remains the treatment of choice for the unstable patient, and drugs are what you reach for when sedation or anaesthesia carries too much risk, or when shocks have already failed.

Pre-excited atrial fibrillation

This is procainamide's other distinctive niche, and the RCUK 2025 algorithm is explicit: for atrial fibrillation with pre-excitation, the options are procainamide or cardioversion.³

The recognition point is an irregular, broad-complex, very fast tachycardia with varying QRS morphology. Irregularity is the clue. See Adenosine for the same hazard from the other direction.

Contraindications and adverse effects

Avoid or use with great caution in

• Prolonged QT or known long QT syndrome — procainamide and NAPA both prolong it further
• Torsades de pointes and polymorphic VT with QT prolongation — as with amiodarone, this is the wrong drug; give magnesium
• Second- or third-degree AV block without pacing
• Severe heart failure or cardiogenic shock — negative inotropy and vasodilatation are poorly tolerated
• Myasthenia gravis — may worsen weakness
• Significant renal impairment — NAPA accumulation
• Known hypersensitivity, including to procaine and related agents

Acute adverse effects

• Hypotension — the commonest, largely infusion-rate-dependent
• QRS widening and QT prolongation
• Proarrhythmia, including torsades de pointes
• Bradycardia and AV block
• Nausea, and a bitter taste

Chronic toxicity

That history is the likely reason procainamide vanished from UK emergency stock in the first place: its chronic toxicity ended its oral use, and the intravenous preparation disappeared alongside it, despite the acute indication being unaffected by either problem.

Critical appraisal

1. The evidence base is smaller than the guideline promotion implies. PROCAMIO is the pivotal trial and it is modest in size and stopped early. The recommendation is directionally well supported but not built on the kind of large trial that underpins, say, tranexamic acid in trauma.
2. Availability is the binding constraint in UK practice, and the algorithm concedes it by writing in an amiodarone fallback. A recommendation whose first-line agent is frequently absent will be followed inconsistently, and that inconsistency is a system problem rather than a clinical one.
3. Familiarity is a genuine safety consideration. A drug requiring weight-based dosing, a 20-minute titrated infusion and active monitoring of QRS width is harder to give safely for the first time under pressure than a 300 mg amiodarone load. That argues for departmental preparation — a pre-written prescription and a stocked location — rather than against the drug.
4. Its resurgence is partly a re-evaluation of amiodarone, not solely enthusiasm for procainamide. PROCAMIO's most uncomfortable finding was how poorly rapid intravenous amiodarone performed on adverse events in this population.
5. None of this displaces electricity. For the unstable patient, synchronised cardioversion remains first-line, and the drug discussion applies to the stable patient or after shocks have failed.

References

1. 1
   electronic Medicines Compendium — searched 21 Aug 2026: no procainamide product is listed. There is no current UK marketing authorisation for an intravenous preparation. Where supply exists it is via an imported or unlicensed product, and the accompanying product information governs.
2. 2
   Procainamide hydrochloride — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk Confirm local availability and supply route with pharmacy before relying on it.
3. 3
   Resuscitation Council UK. Adult tachyarrhythmia algorithm, 2025. resus.org.uk — mirrored at lifesupport.resusdoc.uk. Lists procainamide 10–15 mg/kg over 20 min ahead of amiodarone for stable broad-complex regular tachycardia, and as an option after failed shocks in the unstable patient; names procainamide or cardioversion for AF with pre-excitation.
4. 4
   Ortiz M, Martín A, Arribas F, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia (PROCAMIO). Eur Heart J 2017;38(17):1329–35.
5. 5
   Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardia. Eur Heart J 2020;41(5):655–720.