Procainamide (Pronestyl) | Medication Reference

Bedside Snapshot

Drug Class: Class Ia antiarrhythmic (sodium-channel blocker with action potential prolongation)
Primary Uses: Stable monomorphic VT, atrial fibrillation/flutter with pre-excitation (e.g., WPW), wide-complex tachycardia in hemodynamically stable patients
Mechanism: Blocks fast Na⁺ channels, slows conduction, and prolongs repolarization via K⁺-current effects (including active metabolite NAPA). Result: QRS and QT prolongation with suppression of re-entrant tachycardias
Adult IV Dosing (ACLS 2025): Infuse 20–50 mg/min until arrhythmia suppressed, hypotension occurs, QRS widens ≥50%, or total 17 mg/kg (~1 g) reached; then maintenance 1–4 mg/min
Alternative Regimen: 100 mg IV q5 min (max 17 mg/kg or 1 g) for prehospital/ED settings
Onset: 10–30 minutes as therapeutic levels reached with IV infusion; distribution relatively rapid, elimination primarily renal
Key Acute Risks: Hypotension, QRS widening, QT prolongation/torsades risk, bradycardia/AV block, heart failure exacerbation (especially with renal impairment or concurrent QT-prolonging drugs)
Key Chronic Risks: Drug-induced lupus-like syndrome, agranulocytosis/pancytopenia, chronic QT prolongation with proarrhythmia
Critical Rule: Stop infusion if QRS widens ≥50% from baseline or significant hypotension develops
Special Note: Not for VF/pulseless VT (requires time to load); positioned for stable tachyarrhythmias only. When in doubt, electricity (cardioversion) is faster and safer

Brand & Generic Names

Generic Name: Procainamide
Brand Names: Pronestyl (historical), Procanbid (discontinued), now primarily available as multiple generics; availability is institution- and region-specific

Medication Class

Class Ia antiarrhythmic agent (sodium-channel blocker with action potential prolongation)

Pharmacology

Mechanism of Action:

Class Ia sodium-channel blocker: Binds fast Na⁺ channels in open state, slows phase 0 depolarization, and decreases conduction velocity in atrial, ventricular, and His–Purkinje tissue
Prolongs effective refractory period and action potential duration in atrial and ventricular myocardium and accessory pathway tissue, chiefly via K⁺-current blockade and effects of N-acetylprocainamide (NAPA), which behaves like Class III agent
Net electrophysiologic effects: Slowed conduction (widened QRS), prolonged repolarization (prolonged QT), decreased automaticity, and interruption of re-entrant circuits in both atrial and ventricular tissue
Compared with lidocaine (Class Ib), procainamide has more prominent effects on conduction and repolarization in normal myocardium, improving efficacy in wider range of arrhythmias but increasing proarrhythmic potential
Negative inotrope and mild vasodilator: May reduce contractility and systemic vascular resistance; hypotension and worsening heart failure are key risks, especially with faster infusion rates or in LV dysfunction

Pharmacokinetics:

Routes: IV for acute arrhythmia management; oral immediate- and sustained-release historically used for chronic suppression but now uncommon due to toxicity and availability of alternatives
Onset (IV): Arrhythmia suppression typically begins as cumulative loading dose approaches 10–17 mg/kg, usually within 10–30 minutes when infused at 20–50 mg/min
Distribution: Relatively rapid initial distribution phase with early half-life on order of tens of minutes; apparent volume of distribution moderate (~2 L/kg)
Metabolism: Hepatic acetylation to N-acetylprocainamide (NAPA), which has Class III–like potassium-channel–blocking properties and contributes substantially to total antiarrhythmic effect
Elimination: Both procainamide and NAPA cleared predominantly by kidneys. Elimination half-life of procainamide roughly 2.5–5 hours in normal renal function; NAPA's half-life longer (about 4–15 hours)
Chronic kidney disease: Both parent and metabolite accumulate; dosage reductions and longer dosing intervals (or lower infusion rates) are mandatory. Serum levels (if available) are useful
Hepatic impairment and slow acetylator status: Reduce conversion to NAPA but also reduce overall clearance; lower dosing and careful monitoring of QRS/QT intervals and blood pressure required
Dialysis: Procainamide not dialyzable in clinically meaningful way during routine hemodialysis; CRRT can remove some drug and metabolite but dose adjustment formulas are institution-specific

Indications

Stable monomorphic wide-complex tachycardia (presumed VT) when synchronized cardioversion not immediately required or as adjunct after cardioversion, per ACLS tachycardia algorithms
Atrial fibrillation/flutter with pre-excitation (e.g., WPW) in hemodynamically stable patients when electrical cardioversion not immediately required; avoids AV-node–only blockade which can worsen conduction over accessory pathway
Other supraventricular tachycardias (e.g., AVRT/AVNRT) when first-line agents such as adenosine or AV nodal blockers are contraindicated or ineffective and expert consultation available
Short-term suppression of recurrent VT episodes or VT storm in ICU as continuous infusion, particularly when amiodarone is ineffective, poorly tolerated, or relatively contraindicated
Historically: chronic oral suppression of atrial and ventricular arrhythmias, now mostly reserved for selected patients under electrophysiology guidance due to toxicity

Dosing & Administration

Available Forms:

IV vials or ampoules: Typically 100 mg/mL or 50 mg/mL procainamide hydrochloride for dilution and infusion (check your formulary)
Premixed IV bags (varies by institution): e.g., 1 g in 250 mL D5W (4 mg/mL) or similar standard concentrations for loading/maintenance infusions
Oral forms (less commonly stocked): Immediate-release capsules or tablets and extended-release tablets (e.g., 250 mg, 500 mg, 750 mg, 1 g) where available, mainly for legacy outpatient usage

Standard IV Dosing (Always Follow Local Protocols and ACLS/Arrhythmia Guidelines):

Indication / Population	Initial IV Loading	Repeat / Infusion	Typical Maximum (First 24 h)
Adult stable monomorphic wide-complex tachycardia (presumed VT)	Infuse 20–50 mg/min IV until arrhythmia suppressed, hypotension occurs, QRS widens ≥50%, or total 17 mg/kg (≈1 g) reached	Start maintenance infusion 1–4 mg/min once loading complete and rhythm controlled	Total loading generally limited to 17 mg/kg or about 1 g
Adult AF/flutter with pre-excitation (WPW) or other SVT (hemodynamically stable)	10–17 mg/kg IV (not faster than 50 mg/min), often via 20–50 mg/min infusion over 20–60 min	Then 1–4 mg/min maintenance infusion with continuous ECG and BP monitoring	Same 17 mg/kg (≈1 g) loading limit; avoid in prolonged QT or decompensated HF
Pediatric stable wide-complex tachycardia or SVT (specialist use)	10–15 mg/kg IV over 30–60 min (max rate 50 mg/min)	Maintenance infusion 20–50 mcg/kg/min titrated to effect	Total loading typically ≤15–17 mg/kg
Adult alternative bolus regimen (field/ED)	100 mg IV over 5 minutes, repeated q5 min as needed	Stop when arrhythmia terminates, QRS widens ≥50%, hypotension occurs, or total 17 mg/kg (~1 g) reached; then begin 1–4 mg/min infusion	Total loading limited to 17 mg/kg or ~1 g

Critical Monitoring: Monitor ECG continuously during loading and infusion. Stop or slow infusion if QRS widens by ≥50% from baseline, QTc becomes markedly prolonged, or significant hypotension develops.

Important Notes: Avoid combining procainamide with other QT-prolonging drugs (e.g., amiodarone, sotalol) unless under electrophysiology guidance—combination markedly increases proarrhythmic risk. In heart failure or reduced EF, procainamide can worsen hemodynamics; amiodarone or electrical cardioversion often preferred if available. In renal impairment, reduce loading dose and especially maintenance infusion rate; consider therapeutic drug monitoring (combined procainamide + NAPA levels) when available.

Special Considerations:

Because loading takes time, procainamide is not recommended for ongoing VF/pulseless VT; for cardiac arrest, focus on defibrillation, high-quality CPR, and agents like amiodarone or lidocaine per current ACLS guidance
Therapeutic drug monitoring (where available): typical combined therapeutic range for procainamide + NAPA is roughly 10–30 mcg/mL; toxicity risk rises as QRS/QTc prolong beyond 50% of baseline

Contraindications

Absolute or Major Contraindications:

Documented hypersensitivity to procainamide or related compounds
Second- or third-degree AV block, marked bundle-branch block, or severe intraventricular conduction disturbance without a functioning pacemaker
Known prolonged QT interval or history of torsades de pointes
Overt decompensated heart failure or cardiogenic shock where negative inotropy and vasodilation would be poorly tolerated
Myasthenia gravis (can worsen neuromuscular weakness)

Major Precautions:

Heart failure with reduced ejection fraction: Use extreme caution; hypotension and further reduction in cardiac output are common at higher infusion rates
Chronic kidney disease or acute kidney injury: Procainamide and NAPA accumulate; reduce loading and maintenance dosing and consider level monitoring
Hepatic impairment or slow acetylator status: Impaired metabolism to NAPA can alter kinetics and increase parent-drug accumulation; monitor QRS/QT and hemodynamics closely
Electrolyte disturbances (hypokalemia, hypomagnesemia): Correct before and during therapy to reduce risk of torsades and other ventricular arrhythmias
Concomitant use of other QT-prolonging agents: (e.g., amiodarone, sotalol, macrolide antibiotics, certain antipsychotics) significantly increases proarrhythmic risk
Pregnancy and lactation: Crosses placenta and present in breast milk; reserve for situations where maternal benefit clearly outweighs fetal/neonatal risk; involve specialists
Long-term oral therapy: Risk of drug-induced lupus-like syndrome, agranulocytosis/pancytopenia, and chronic QT prolongation demands regular CBC, ANA, and ECG monitoring

QT Prolongation Warning: Avoid combining procainamide with other QT-prolonging agents unless under electrophysiology guidance. The combination markedly increases risk of torsades de pointes and other malignant ventricular arrhythmias.

Adverse Effects

Common (acute IV use):

Hypotension, especially when infused rapidly (20–50 mg/min) or in patients with marginal hemodynamics
Dizziness, lightheadedness, or feelings of warmth during infusion
Nausea, metallic taste, or mild GI upset
Mild bradycardia or first-degree AV block
QRS and QT interval prolongation on ECG

Serious (acute and chronic):

Torsades de pointes and other malignant ventricular arrhythmias due to QT prolongation, especially with electrolyte abnormalities or overlapping QT-prolonging drugs
Symptomatic hypotension or cardiogenic shock requiring vasopressors, especially in LV dysfunction
High-grade AV block or severe intraventricular conduction delay with broad QRS and hemodynamic compromise
Drug-induced lupus-like syndrome with chronic use: arthralgias, arthritis, fever, pleuritis, positive ANA, often reversible after discontinuation
Hematologic toxicity: agranulocytosis, pancytopenia, or other blood dyscrasias, which may present with fever, infections, or bleeding
Rare severe hypersensitivity reactions, including rash, hepatitis, or vasculitis

Drug-Induced Lupus Warning: With chronic oral therapy, risk of drug-induced lupus-like syndrome, agranulocytosis/pancytopenia, and chronic QT prolongation demands regular CBC, ANA, and ECG monitoring. Any new joint pain, fever, chest pain, or infection symptoms should prompt immediate evaluation.

Special Populations

Pregnancy: Crosses placenta; reserve for situations where maternal benefit clearly outweighs fetal risk. Should be used only under specialist guidance for life-threatening maternal arrhythmias
Lactation: Present in breast milk; consider risk-benefit ratio and monitor infant if maternal use is necessary
Renal impairment: Both procainamide and NAPA accumulate significantly. Reduce loading dose (e.g., to 12 mg/kg) and decrease maintenance infusion rate (e.g., to 1–2 mg/min). Consider therapeutic drug monitoring where available. In severe CKD or dialysis, consult nephrology/cardiology for dosing
Hepatic impairment: Reduced metabolism can increase exposure and prolong effect; use lower initial doses, titrate carefully, and monitor QRS/QT intervals and blood pressure closely
Elderly: Increased sensitivity to hypotensive and proarrhythmic effects; often have reduced renal function requiring dose adjustment. Start with lower doses and monitor closely
Slow acetylator phenotype: Genetically determined slower conversion to NAPA leads to higher parent drug levels and potentially different side effect profile; careful ECG and clinical monitoring essential

Monitoring

Clinical Monitoring (especially in ED/ICU):

Continuous ECG monitoring during loading and infusion; watch for QRS widening, QT prolongation, new AV block, and ventricular arrhythmias
Frequent blood pressure monitoring (q1–5 minutes during active loading and early infusion; arterial line in unstable patients)
Assessment of clinical response: rhythm conversion, ventricular rate control, symptoms (palpitations, chest pain, dyspnea), and markers of perfusion

Laboratory Monitoring:

Serum electrolytes (K⁺, Mg²⁺, Ca²⁺) and renal function at baseline and periodically during infusion, especially in longer courses or in CKD
In longer courses or oral therapy, consider serum procainamide and NAPA levels where available; maintain combined concentrations in target therapeutic range (roughly 10–30 mcg/mL) and adjust dose if levels rise or ECG changes appear
For chronic oral use: Periodic CBC, ANA, liver function tests, and interval ECGs to screen for lupus-like syndrome, blood dyscrasias, and chronic QT prolongation

ECG Critical Parameters: Stop infusion if QRS widens ≥50% from baseline, QTc becomes markedly prolonged (>500 ms), or new high-grade AV block develops. This bedside rule is at least as important as tracking cumulative dose.

Clinical Pearls

PROCAMIO Study Findings: Modern data suggest procainamide may terminate stable monomorphic VT more effectively and with fewer adverse events than IV amiodarone in selected patients with structural heart disease. Consider procainamide when lidocaine or amiodarone fails in stable VT.

For Stable Arrhythmias Only: Because loading requires time, procainamide is positioned as a drug for stable tachyarrhythmias, not for crashing patients. When in doubt, electricity (synchronized cardioversion) is faster and often safer.

WPW and Wide-Complex Tachycardia: In AF with WPW or wide-complex tachycardia of uncertain origin, procainamide (or direct current cardioversion) is preferred over AV nodal blockers. Avoiding isolated AV node blockade prevents unopposed conduction down the accessory pathway.

QRS Widening Rule: Stop the infusion if QRS widens ≥50% from baseline or significant hypotension develops. This bedside rule is at least as important as tracking the cumulative milligram dose.

Renal Function Matters: Always factor in kidney function. Accumulation of procainamide and NAPA is a common reason for delayed hypotension and proarrhythmia during what seems like standard dosing. Reduce dose and infusion rate in renal impairment.

Prehospital/Transport Simplification: In prehospital/transport environment, simple bolus regimens (e.g., 100 mg q5 min up to weight-based cap) may be easier and safer than running manually titrated mg/min infusion. Follow your specific protocol.

Not for Cardiac Arrest: Procainamide is NOT for VF/pulseless VT. For cardiac arrest, focus on defibrillation, high-quality CPR, and agents like amiodarone or lidocaine per current ACLS guidance.

Younger Patients and Long-Term Toxicity: Consider procainamide when cardiology wants to avoid more amiodarone in younger patients due to amiodarone's long-term toxicity (thyroid, pulmonary, hepatic issues). Procainamide may be preferable for short-term management.

References

1. Pritchard, B., & Thompson, H. (2023). Procainamide. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK557788/
2. King, G. S., & colleagues. (2024). Antiarrhythmic medications. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK482322/
3. Ortiz, M., Martín, A., Arribas, F., et al. (2017). Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: The PROCAMIO study. European Heart Journal, 38(17), 1329–1335. https://doi.org/10.1093/eurheartj/ehw230
4. American Heart Association. (2025). Adult tachycardia with a pulse algorithm. In 2025 AHA guidelines for CPR and ECC. https://cpr.heart.org
5. Foth, C., & colleagues. (2023). Ventricular tachycardia. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK532954/