What is procainamide (Procanbid, generic name: procainamide)?

From the Guidelines

Procainamide is an antiarrhythmic medication that should be used with caution due to its potential side effects, and its use is generally reserved for specific acute situations where other medications are contraindicated. Procainamide works by slowing electrical conduction in the heart, helping to restore normal rhythm, and is primarily used to treat and prevent abnormal heart rhythms, particularly ventricular arrhythmias and atrial fibrillation. The typical adult dosage ranges from 250-500 mg orally every 3-4 hours, or 20-50 mg/minute intravenously for acute situations, with maintenance infusions of 1-4 mg/minute, as recommended by the 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care 1.

Some key points to consider when using procainamide include:

• Procainamide requires careful monitoring due to its potential side effects, which include hypotension, QT interval prolongation, and a lupus-like syndrome with long-term use.
• Blood level monitoring is often necessary, with therapeutic levels between 4-10 μg/mL.
• The medication should be used cautiously in patients with kidney or liver dysfunction, as dose adjustments may be needed, and it is metabolized to N-acetylprocainamide (NAPA), which also has antiarrhythmic properties but accumulates in patients with renal impairment.
• Procainamide has largely been replaced by newer antiarrhythmic drugs with better safety profiles for long-term use, though it remains valuable in specific acute situations where other medications are contraindicated, as noted in the 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.

In terms of specific dosing and administration, the recommended dosage of procainamide is 20 to 50 mg/min until arrhythmia suppressed, hypotension ensues, or QRS prolonged by 50%, or total cumulative dose of 17 mg/kg; or 100 mg every 5 minutes until arrhythmia is controlled or other conditions described above are met 1. It is essential to avoid using procainamide in patients with QT prolongation and congestive heart failure (CHF), as it can exacerbate these conditions. Overall, procainamide should be used judiciously and with careful consideration of its potential benefits and risks in each individual patient.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Procainamide (PA) increases the effective refractory period of the atria, and to a lesser extent the bundle of His-Purkinje system and ventricles of the heart It reduces impulse conduction velocity in the atria, His-Purkinje fibers, and ventricular muscle, but has variable effects on the atrioventricular (A-V) node, a direct slowing action and a weaker vagolytic effect which may speed A-V conduction slightly Myocardial excitability is reduced in the atria, Purkinje fibers, papillary muscles, and ventricles by an increase in the threshold for excitation, combined with inhibition of ectopic pacemaker activity by retardation of the slow phase of diastolic depolarization, thus decreasing automaticity especially in ectopic sites Contractility of the undamaged heart is usually not affected by therapeutic concentrations, although slight reduction of cardiac output may occur, and may be significant in the presence of myocardial damage Therapeutic levels of PA may exert vagolytic effects and produce slight acceleration of heart rate, while high or toxic concentrations may prolong A-V conduction time or induce A-V block, or even cause abnormal automaticity and spontaneous firing by unknown mechanisms The electrocardiogram may reflect these effects by showing slight sinus tachycardia (due to the anticholinergic action) and widened QRS complexes and, less regularly, prolonged Q-T and P-R intervals (due to longer systole and slower conduction), as well as some decrease in QRS and T wave amplitude These direct effects of PA on electrical activity, conduction, responsiveness, excitability and automaticity are characteristic of a Group 1A antiarrhythmic agent, the prototype for which is quinidine; PA effects are very similar. However, PA has weaker vagal blocking action than does quinidine, does not induce alpha-adrenergic blockade, and is less depressing to cardiac contractility Following intramuscular injection, procainamide is rapidly absorbed into the bloodstream, and plasma levels peak in 15 to 60 minutes, considerably faster than orally administered procainamide hydrochloride tablets or capsules which produce peak plasma levels in 90 to 120 minutes Intravenous administration of Procainamide Hydrochloride Injection can produce therapeutic procainamide levels within minutes after infusion is started. About 15 to 20 percent of PA is reversibly bound to plasma proteins, and considerable amounts are more slowly and reversibly bound to tissues of the heart, liver, lung, and kidney The apparent volume of distribution eventually reaches about 2 liters per kilogram body weight with a half-time of approximately five minutes. While PA has been shown in the dog to cross the blood-brain barrier, it did not concentrate in the brain at levels higher than in plasma. It is not known if PA crosses the placenta. Plasma esterases are far less active in hydrolysis of PA than of procaine The half-time for elimination of PA is three to four hours in patients with normal renal function, but reduced creatinine clearance and advancing age each prolong the half-time of elimination of PA Procainamide is a Group 1A antiarrhythmic agent that works by:

• Increasing the effective refractory period of the atria
• Reducing impulse conduction velocity in the atria, His-Purkinje fibers, and ventricular muscle
• Decreasing myocardial excitability
• Inhibiting ectopic pacemaker activity The key effects of procainamide include:
• Slight sinus tachycardia
• Widened QRS complexes
• Prolonged Q-T and P-R intervals
• Decrease in QRS and T wave amplitude The pharmacokinetics of procainamide are characterized by:
• Rapid absorption into the bloodstream after intramuscular injection
• Peak plasma levels in 15 to 60 minutes
• Apparent volume of distribution of about 2 liters per kilogram body weight
• Half-time for elimination of three to four hours in patients with normal renal function 2

From the Research

Overview of Procainamide

• Procainamide is a widely used antiarrhythmic agent in clinical practice 3
• It is used to prevent recurrent ventricular tachycardia or symptomatic nonsustained ventricular tachycardia, as well as for short-term treatment of ventricular tachycardia and supraventricular tachycardias such as atrial flutter and atrial fibrillation 3, 4

Efficacy and Safety

• The efficacy of procainamide against acute ventricular arrhythmias and chronic stable ventricular premature depolarizations (VPDs) is associated with plasma drug concentrations of 4 to 10 micrograms per ml 5
• Procainamide has been shown to be safe and effective in the treatment of acute atrial fibrillation or flutter in the emergency department, with a conversion rate of 52.2% for atrial fibrillation and 28.0% for atrial flutter 4
• Oral procainamide has also been shown to be effective in reducing implantable cardioverter-defibrillator (ICD) interventions and ventricular arrhythmias in patients with recurrent ventricular tachyarrhythmias 6

Side Effects and Monitoring

• Long-term procainamide therapy is limited by systemic side effects, including lupus-like syndrome, gastrointestinal disturbances, and autoimmune blood dyscrasias 3
• Procainamide levels and QRS and QT interval measurements can be useful in preventing drug toxicity, and patients starting procainamide therapy should be monitored in the hospital to ensure that their QT interval is not excessively prolonged 3
• Adverse events associated with procainamide use include hypotension, bradycardia, atrioventricular block, and ventricular tachycardia, but are generally rare 4, 6

Comparison with Other Antiarrhythmic Agents

• Procainamide has been compared with other antiarrhythmic agents, including lidocaine, bretylium, and amiodarone, and has been shown to be effective for stable ventricular tachycardia 7
• Further studies are needed to establish the role of procainamide in comparison with newer antiarrhythmic agents and other treatment strategies 3, 7