Procanbid

Generic Name: Procainamide Hydrochloride
Class: Class Ia Antiarrhythmics
VA Class: CV300
CAS Number: 614-39-1

Introduction

Antiarrhythmic agent (class 1A).^{b 154}

Uses for Procanbid

Comparably effective to quinidine for atrial† or ventricular arrhythmias; choice based on pharmacokinetics and adverse effect profile.^b

Ventricular Arrhythmias (General)

Treatment of ventricular arrhythmias (e.g., sustained VT) that in the judgment of the clinician are life-threatening, but the drug usually is not the antiarrhythmic of first choice.^{b 135 147 148}

Because of procainamide's arrhythmogenic potential, lack of evidence for improved survival for class I antiarrhythmic agents,^{135 136 137 138} and risk of serious, potentially fatal adverse hematologic effects (see Boxed Warning), particularly leukopenia or agranulocytosis, use for less severe arrhythmias is not recommmended.¹³⁵

Reserve for suppression and prevention of documented life-threatening ventricular arrhythmias in carefully selected patients in whom the benefits of procainamide therapy outweigh the possible risks.^{135 147}

Avoid treatment of asymptomatic VPCs.¹³⁵

Initiate procainamide therapy only in a hospital setting.¹³⁵

Efficacy in the treatment of ventricular arrhythmias (e.g., spontaneously occurring VT) is at least comparable to that of lidocaine.^{148 153}

VF and Pulseless VT

Has been used for the treatment of VF.^b

Antiarrhythmic agents can be considered for treatment of cardiac arrest secondary to VF or pulseless VT resistant to CPR, cardioversion (e.g., after 2 to 3 shocks), and a vasopressor (e.g., epinephrine, vasopressin); however, other agents are preferred for this use (i.e., amiodarone [consider lidocaine if amiodarone not available]).^{147 148 153}

Use of procainamide in emergency situations (e.g., cardiac arrest) is limited by required slow infusion rate and uncertain efficacy.^{148 153}

VT

Has been used for the treatment of VT.^b

Alternative antiarrhythmic agent (to amiodarone) in the treatment of sustained, stable monomorphic VT not associated with angina, pulmonary edema, or hypotension (BP <90 mm Hg) in patients with preserved ventricular function.^{147 153 159 160}

Slideshow: Top Prevention Tips: Springtime Allergies

Drug regimens including procainamide or amiodarone may be used initially for episodes of sustained VT that are somewhat better tolerated hemodynamically.^{147 148 159 160}

If IV antiarrhythmic therapy is used for VT, it probably should be discontinued (at least temporarily) after 6–24 hours so that the patient’s ongoing need for antiarrhythmic drugs can be reassessed.^{147 159}

Although rare, episodes of sustained polymorphic VT (“electrical storm”) associated with AMI usually are treated with an IV β-adrenergic blocking agent, IV amiodarone, IV magnesium, left stellate ganglion blockade, intra-aortic balloon counterpulsation, or emergency revascularization.^{147 159}

However, other experts recommend revascularization and β-blockade followed by IV antiarrhythmic drugs, such as procainamide or amiodarone, for patients with recurrent or incessant polymorphic VT due to acute myocardial ischemia.¹⁶⁰

VPCs

Decreases the frequency of VPCs associated with AMI, but IV or IM lidocaine is considered the drug of choice because normal doses of lidocaine do not decrease cardiac contractility or peripheral resistance or slow AV conduction to the degree produced by procainamide.^b

Like other antiarrhythmic drugs, not shown to decrease mortality rate in VPCs associated with AMI.^b

Avoid treatment of asymptomatic VPCs.^{b 135}

Used orally to prevent recurrence of VPCs when lidocaine infusion is discontinued.^b

Generally not used to treat cardiac glycoside-induced ventricular arrhythmias.^b (See Contraindications under Cautions.)

Combination Therapy of Atrial or Ventricular Arrhythmias

Although antiarrhythmic drugs such as procainamide, lidocaine, phenytoin, propranolol, and quinidine have been used concomitantly to treat or prevent serious, refractory arrhythmias, sequential or combined use of calcium-channel blockers, β-adrenergic blockers, and antiarrhythmic drugs is discouraged because of potentially additive hypotensive, bradycardic, and proarrhythmic effects.^b (See Cardiovascular Drugs under Interactions.)

Electrical cardioversion currently is preferred therapy in most patients who fail to respond to an appropriate dosage of a single antiarrhythmic drug.¹⁴⁸

Supraventricular Tachyarrhythmias (SVT)

May be considered in patients with preserved ventricular function to control heart rate in atrial fibrillation or flutter† or to control heart rhythm in atrial fibrillation or flutter with known preexcitation Wolff-Parkinson-White syndrome† or in AV reentrant, narrow-complex tachycardias (e.g., reentry SVT)† uncontrolled by adenosine and vagal maneuvers.^{148 153}

Although procainamide has been used for the treatment of atrial premature complexes†, these arrhythmias usually are treated with digoxin.^b

Atrial Fibrillation and Flutter

Management of atrial fibrillation or flutter depends on the clinical situation and the patient’s condition and ventricular rate.¹⁴⁸

For conversion of atrial fibrillation or flutter to normal sinus rhythm, electrical cardioversion usually is the treatment of choice.¹⁴⁸

Generally, do not use prophylactically for atrial fibrillation if the ventricular rate is adequately controlled by digoxin and the patient is asymptomatic.^b

Use for prevention of recurrence of atrial fibrillation† or flutter† is controversial.^b

May maintain normal sinus rhythm for long periods in recent onset of atrial fibrillation without CHF, atrial enlargement, or left ventricular hypertrophy, but long-standing atrial fibrillation is likely to recur even with procainamide maintenance therapy.^b

If used for conversion of atrial fibrillation†, control abnormal ventricular rate and CHF first with digoxin.^b (See Cardiovascular Effects under Cautions.)

When atrial fibrillation has been present for >48 hours, conversion to normal sinus rhythm may be associated with embolism unless patients are adequately anticoagulated.^{148 153}

Do not attempt electric or pharmacologic cardioversion therapy (i.e., conversion to normal sinus rhythm) in patients whose arrhythmia is >48 hours’ duration unless the patient is unstable or absence of a left atrial thrombus is documented by transesophageal echocardiography.^{148 153}

In marginal patients, in addition to adequate anticoagulation (e.g., heparin therapy), consultation with a cardiologist and diagnostic procedures to exclude atrial thrombi are recommended to assess the risks and benefits of therapeutic strategies.¹⁴⁸

Paroxysmal Supraventricular Tachycardia

IV procainamide may be considered in patients with preserved left-ventricular function for the treatment of paroxysmal supraventricular tachycardias† (PSVTs) such as paroxysmal atrial tachycardia† or paroxysmal AV junctional rhythm†.^b

If treatment of paroxysmal atrial tachycardia† (stable, reentry SVT†) is necessary, measures to increase vagal tone (e.g., carotid sinus massage, Valsalva maneuver) or administration of IV adenosine are the treatments of choice.^{148 153}

Rarely treat paroxysmal AV junctional rhythm† unless there is an extremely rapid ventricular rate; if treatment is necessary, use measures to increase vagal tone, IV adenosine, IV amiodarone, calcium-channel blocking agents (e.g., diltiazem, verapamil), β-adrenergic blocking agents, or electrical cardioversion.^b

Because of potentially additive hypotensive, bradycardic, and proarrhythmic effects, sequential or combined use of calcium-channel blocking agents, β-adrenergic blocking agents, and/or antiarrhythmic drugs is discouraged.^b

Wide-complex Tachycardia of Uncertain Mechanism

Has been used for the treatment of wide-complex tachycardias of uncertain mechanism†, but procainamide usually is not the antiarrhythmic of first choice.^{147 153}

Wide-complex tachycardias of uncertain mechanism† usually are treated with synchronized electrical cardioversion or amiodarone.^{148 153}

Arrhythmias during Surgery and Anesthesia

Used parenterally (preferably IM) in the treatment of arrhythmias that occur during surgery and anesthesia.^b

Malignant Hyperthermia

IV procainamide has been used effectively in the treatment of malignant hyperthermia†.^b

Procanbid Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response, age, renal function, and the general condition and cardiovascular status of the patient.^{152 b 153}

• Initiate therapy for life-threatening ventricular arrhythmias in a hospital.^{135 c}

• Monitor BP, cardiac function (via ECG), also renal function (i.e., Cl_cr), especially when given IV or when given orally for prolonged periods and in patients with an increased risk of adverse reactions (e.g., patients >50 years of age, those with severe heart disease, hypotension, hepatic or renal disease).^{121 135 151 152 153}

• Use with caution, if at all, in combination with other drugs that prolong the QT interval (e.g., amiodarone); consider expert consultation.^{153 158} (See Drugs Affecting QT Interval under Interactions.)

Administration

Usually administer orally.^b

When oral therapy is not feasible or when rapid therapeutic effect is necessary, may administer IV or IM.^{153 b}

Oral therapy should replace IV or IM therapy as soon as possible.^{b c}

For ACLS in pediatric patients, may be administered by intraosseous injection†;¹⁵³ onset of action and systemic concentrations are comparable to those achieved with central venous administration.¹⁵³

Oral Administration

Use conventional tablets or capsules for initial oral therapy; extended-release tablets should be used only for maintenance dosage.^b

Swallow extended-release tablets whole; do not chew or crush.^{b 135}

Allow at least 3–4 hours to elapse between the last IV dose of procainamide and the first oral dose of the drug.¹²¹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer slowly by direct IV injection or IV infusion.^{b 153}

Risk of toxic systemic concentrations and significant hypotension with rapid IV (i.e., bolus) administration.¹⁵³

Dilution

To facilitate control of rate of administration, dilute the commercially available injections prior to IV administration.¹²¹

Usually diluted with a suitable IV infusion fluid to a concentration of 2 or 4 mg/mL.^{b HID 121}

Rate of Administration

Usually administer with the patient in a supine position at a rate not exceeding 50 mg/minute,¹²¹ or 20 mg/minute as an IV loading dose in pediatric patients.¹⁵⁷

Infuse slowly. Continuously monitor BP for hypotension and ECG for prolongation of QT interval and heart block; adjust the rate of administration accordingly.^{152 b 153}

IM Administration

Administer by IM injection when oral administration is not feasible in patients with less threatening arrhythmias (e.g., in those with nausea or vomiting, preoperatively, in those with malabsorptive problems).^c

Dosage

Available as procainamide hydrochloride; dosage expressed in terms of the salt.^{b 135}

Reduce dosage in renal insufficiency and/or CHF and in critically ill patients; determine plasma concentrations of procainamide and its major metabolite (N-acetyl procainamide) and adjust dosage to maintain desired concentrations.^{151 152 153}

Pediatric Patients

Ventricular and Supraventricular Arrhythmias

Oral (Conventional Tablets or Capsules)

15–50 mg/kg daily(not to exceed 4 g in 24 hours), given in divided doses (every 3–6 hours).^{152 154 157}

IV

Loading dose: 2–6 mg/kg ^{152 154 157} (not to exceed 100 mg)^{152 154} over 5 minutes,^{152 154 157} repeat as necessary at intervals of 5–10 minutes^{152 154} (not to exceed a total loading dose of 15 mg/kg or 500 mg in a 30-minute period). ^{152 154 157}

Maintenance dose: 0.02–0.08 mg (20–80 mcg)/kg per minute as an IV infusion,^{152 154 157} up to a total maintenance infusion dose of 2 g in 24 hours.^{152 154}

IM

20–30 mg/kg (not to exceed 4 g) daily,^{152 154} given in divided doses (every 4–6 hours).¹⁵²

ACLS

IV or Intraosseous†

15 mg/kg given over 30–60 minutes.^{148 152 153 158} Discontinue infusion if widening of the QRS complex (>50%) from baseline occurs or hypotension develops.¹⁵³

Adults

Ventricular Arrhythmias

Oral (Conventional Tablets or Capsules)

Usual dosage: Initially, up to 50 mg/kg daily (to achieve therapeutic plasma procainamide concentrations), given in divided doses every 3 hours.^{120 152}

6.25 mg/kg has been administered every 3 hours for VPCs.^b

Oral (Extended-release Tablets Designed for Administration Every 6 Hours)

Usual dosage: Up to 50 mg/kg daily given in equally divided doses at 6-hour intervals.^{152 b}

Maintenance: One-fourth of the total required daily dose may be given every 6 hours.^{152 b}

Oral (Extended-release Tablets Designed for Administration Every 12 Hours [Procanbid])

Usual dosage: Up to 50 mg/kg (2–5 g, depending on weight) daily, given in equally divided doses at 12-hour intervals.¹³⁵

Maintenance: One-half of the total required daily dose may be given every 12 hours.¹³⁵

Patients receiving other formulations of procainamide may be switched to Procanbid extended-release tablets at the nearest equivalent total daily dosage; however, retitration with Procanbid is recommended.¹³⁵

IV

Initially, 100 mg every 5 minutes until the arrhythmia is controlled, adverse effects occur, or a total of 500 mg is administered, after which it may be advisable to wait ≥10 minutes to allow for distribution of the drug before giving additional doses.¹²¹

Alternatively, a loading-dose IV infusion of 500–600 mg administered at a constant rate over a period of 25–30 minutes.¹²¹

Although it is unusual to require >600 mg to initially control an arrhythmia, the maximum recommended total dose given by either method of IV administration is 1 g.¹²¹

Maintainence of therapeutic plasma concentrations: Subsequently, continuous IV infusion of 2–6 mg/minute.¹²¹ Alternatively, continuous IV infusion of 0.02–0.08 mg (20–80 mcg)/kg per minute.^b

IM

Initially, 50 mg/kg daily given in divided doses every 3–6 hours.^{152 c}

Urgent cases: May give initial loading dose IM, followed in 3 hours by oral maintenance dose.^b

ACLS

IV

Loading-dose infusion: 20 mg/minute until the arrhythmia is suppressed, a fall in BP of >15 mm Hg occurs (i.e., hypotension ensues), excessive widening of the QRS complex (≥50%) from baseline or prolongation of the PR interval occurs, severe adverse effects appear, or a total dose of 17 mg/kg (1.2 g for a 70-kg patient) is given.^{b 153}

Follow loading dose with a continuous IV infusion at a rate of 1–4 mg/minute; infusion rates should be lower in patients with renal insufficiency since accumulation of the drug can occur and the risk of torsades de pointes may be increased.^{147 148 153}

Atrial Fibrillation† and Paroxysmal Atrial Tachycardia†

Conversion to Normal Sinus Rhythm

Oral (Conventional Tablets or Capsules)

Initially, 1.25 g; if no change in ECG, give 750 mg 1 hour later.^b

Give additional doses of 0.5–1 g every 2 hours until normal sinus rhythm is restored or until toxic effects appear.^b

Maintenance Therapy

Oral (Extended-Release Tablets Designed for Administration Every 6 Hours)

One-fourth of the total required daily dose given every 6 hours; usual dosage is 1 g every 6 hours.^b

Atrial Flutter†

Conversion to Normal Sinus Rhythm

Oral (Conventional Tablets or Capsules)

Individualize dosage according to the therapeutic response.^b

Maintainance Therapy

Oral (Conventional Tablets or Capsules)

Usual dosage: 0.5–1 g every 4–6 hours.^b

Supraventricular Arrhythmias

IV

Initially, 100 mg every 5 minutes until the arrhythmia is controlled, adverse effects occur, or until a total of 500 mg is administered, after which it may be advisable to wait ≥10 minutes to allow for distribution of the drug before giving additional doses.¹²¹

Alternatively, a loading-dose IV infusion of 500–600 mg administered at a constant rate over a period of 25–30 minutes.¹²¹

Although it is unusual to require >600 mg to initially control an arrhythmia, the maximum recommended total dose given by either method of IV administration is 1 g.¹²¹

Maintainence of therapeutic plasma concentrations: Subsequently, continuous IV infusion of 2–6 mg/minute.¹²¹ Alternatively, continuous IV infusion of 0.02–0.08 mg (20–80 mcg)/kg per minute.^b

IM

Initially, 50 mg/kg daily given in divided doses every 3–6 hours.¹²¹

Urgent cases: May give initial loading dose IM, followed in 3 hours by oral maintenance dose.^b

ACLS

IV

Loading-dose infusion: 20 mg/minute until the arrhythmia is suppressed, a fall in BP of >15 mm Hg occurs (i.e., hypotension ensues), excessive widening of the QRS complex (≥50%) from baseline or prolongation of the PR interval occurs, severe adverse effects appear, or a total dose of 17 mg/kg (1.2 g for a 70-kg patient) is given.^{b 153}

Follow loading dose with a continuous IV infusion at a rate of 1–4 mg/minute; infusion rates should be lower in patients with renal insufficiency since accumulation of the drug can occur and the risk of torsades de pointes may be increased.^{147 148 153}

Arrhythmias Occurring during Surgery and Anesthesia

IM

100–500 mg.^{121 c}

Malignant Hyperthermia†

Various dosages have been given.^b

IV

200–900 mg, generally followed by a maintenance infusion.^b

Prescribing Limits

Pediatric Patients

Ventricular and Supraventricular Arrhythmias

Oral (Conventional Tablets or Capsules)

Maximum daily dosage is 4 g.^{152 154 157}

IV

Loading dose: Maximum 100 mg as a single dose, up to a total loading dose of 15 mg/kg or 500 mg in a 30-minute period. ^{152 b 154 157}

Maintenance dose: Maximum daily dosage is 2 g.^{154 152}

IM

Maximum daily dosage is 4 g.^{152 154}

Adults

Ventricular Arrhythmias

Oral

Usual dosage: Initially, maximum 50 mg/kg daily.^{120 152 b}

IV

Unusual to require >600 mg to initially control an arrhythmia; maximum recommended total dose is 1 g for initial control.¹²¹

ACLS

IV

Maximum total dose of 17 mg/kg.¹⁵³

Supraventricular Arrhythmias

IV

Unusual to require >600 mg to initially control an arrhythmia; maximum recommended total dose is 1 g for initial control.¹²¹

ACLS

IV

Maximum total dose of 17 mg/kg.¹⁵³

Special Populations

Hepatic Impairment

No specific dosage recommendations.^{b 155}

Renal Impairment

Adjust dosage because of risk of drug accumulation and toxicity secondary to decreased clearance and increased elimination half-life.^{135 155}

Use slower IV infusion rates in renal insufficiency because of risk of accumulation and resultant adverse effects (e.g., torsades de pointes).^{147 148 153}

Geriatric Patients

Monitor ECG and renal function and dose cautiously, especially IV or prolonged therapy.^{121 135 151} Maintenance dosage generally lower than that in younger adults; base dosage on response, tolerance, and serum concentrations.¹⁵⁵

Cautions for Procanbid

Contraindications

• Patients with complete AV heart block and in patients with second- or third-degree AV nodal block unless an electrical pacemaker is operative.^b

• Atypical VT (torsades de pointes), since class IA antiarrhythmic agents may aggravate this ventricular arrhythmia.^{b 152}

• Established diagnosis of SLE since symptomatic aggravation is likely.^{135 152}

• Known hypersensitivity to procainamide or any ingredient in the respective formulation.^b

• May be contraindicated in patients with myasthenia gravis, since procainamide has been reported to increase muscle weakness in these patients. ^b (See Anticholinesterase and Anticholinergic Agents under Interactions.)

Warnings/Precautions

Warnings

Use Limited to Life-threatening Arrhythmias

Because of procainamide’s arrhythmogenic potential, the lack of evidence for improved survival for class I antiarrhythmic agents,^{135 136 137 138} and the risk of serious, potentially fatal adverse hematologic effects (see Boxed Warning), limit use of procainamide in patients with ventricular arrhythmias to life-threatening arrhythmias in carefully selected patients in whom benefits of procainamide therapy outweigh the possible risks, taking into account possible alternative antiarrhythmic therapy.¹³⁵

Use in less severe arrhythmias currently is not recommended; treatment of asymptomatic VPCs should be avoided.¹³⁵

ECG and Clinical Monitoring

Associated with the development or exacerbation of arrhythmias in some patients; clinical and ECG evaluations are essential prior to and during procainamide therapy to monitor for the appearance of arrhythmias and to determine the need for continued therapy.^{118 119 120 121 152 153}

Laboratory Test Monitoring

Monitor CBCs, including differential leukocyte counts and platelet counts.^{118 119 120 121} (See Boxed Warning.)

If a serious adverse hematologic effect is identified, discontinue the drug.^{118 119 120 121 124}

Perform laboratory tests for detection of procainamide-induced SLE (e.g., ANA titer determinations) before and periodically during maintenance or prolonged procainamide therapy, even in asymptomatic patients.^b

AV Conduction Disturbances

Use with extreme caution, if at all, in patients with marked disturbances of AV conduction (e.g., second- or third-degree heart block, bundle-branch block, or severe cardiac glycoside intoxication) because procainamide may cause additional depression of conduction resulting in ventricular asystole or fibrillation.^{b 152}

Reduce dosage in patients who exhibit or develop first-degree heart block with procainamide.¹³⁵

Cardioversion or Digitalization in Atrial Flutter or Fibrillation

Cardiovert or digitalize prior to procainamide in atrial flutter or fibrillation to avoid enhanced AV conduction.¹³⁵

Heart Disease

Exercise caution (especially parenterally) in the treatment of ventricular arrhythmias in patients with severe organic heart disease since these patients may have undiagnosed complete heart block.^b If the ventricular rate is slowed by procainamide and normal AV conduction does not occur, the drug should be discontinued and the patient reevaluated, since asystole may result.^b

Concurrent Use with Class IA Antiarrhythmics

Concurrent use with class IA antiarrhythmics (e.g., disopyramide, quinidine) can enhance conduction prolongation, contractility depression, and hypotension, especially in cardiac decompensation.¹³⁵

Reserve combined use for serious arrhythmias unresponsive to monotherapy; monitor closely.¹³⁵

Coronary Occlusion

Use with extreme caution in the treatment of VT occurring during coronary occlusion.^b

Hypokalemia, Hypoxia, and Disorders of Acid-Base Balance

Hypokalemia, hypoxia, and disorders of acid-base balance must be eliminated as potentiating factors in patients who require large doses of antiarrhythmic agents to control ventricular arrhythmias.^b

CHF, Ischemic Heart Disease, or Cardiomyopathy

Exercise caution since even slight depression of myocardial contractility may further decrease cardiac output.^{135 152}

Drug accumulation and associated toxicity may occur in CHF.^b

Bone Marrow Depression

Use with caution in patients with preexisting bone marrow depression or cytopenia of any type.^{118 119 120} (See Blood Dyscrasias in Boxed Warning.)

Sensitivity Reactions

Should not be used if it causes acute allergic dermatitis, asthma, or anaphylactic symptoms.^b

Cross-sensitivity

The possibility of cross-sensitivity to procaine and chemically related drugs (e.g., ester-type local anesthetics) must be considered; however, cross-sensitivity is unlikely.¹³⁵

Sulfite Reactions

Some formulations contain sulfites, which may cause allergic-type reactions¹⁵⁵ (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.^b

Antinuclear Antibodies

Antinuclear antibodies (ANA) are found in at least 50% of patients receiving long-term procainamide therapy (usually within 2–18 months after starting therapy); induction of ANA appears to be independent of the dosage.^b

Patients with procainamide-induced increases in ANA titers may develop a syndrome resembling SLE,^{135 152} characterized by polyarthralgia, arthritis, pleurisy, pleural effusion, dyspnea, fever, chills, myalgia, skin lesions (including urticaria, erythema multiforme, and morbilliform eruptions), headache, fatigue, weakness, abdominal pain, nausea, vomiting, pericarditis, pericardial effusion, pericardial tamponade, acute hepatomegaly, splenomegaly, lymphadenopathy, acute pancreatitis, and the presence of LE cells in the blood.^b

Patients with procainamide-induced SLE may have a positive direct antiglobulin (Coombs’) test.^{b 152 157} Thrombocytopenia,^{152 b 157} Coombs’ positive hemolytic anemia,^{152 b 157} increased serum concentrations of AST, ALT, and amylase rarely have been associated with procainamide-induced SLE.^{b 152}

Discontinue procainamide in patients who develop symptoms of SLE and/or who have rising ANA titers, unless the benefit of antiarrhythmic therapy with the drug outweighs the potential risk.^b

If procainamide-induced SLE develops in a patient with a life-threatening arrhythmia uncontrolled by other antiarrhythmic drugs, corticosteroid therapy may be used concomitantly with procainamide.^b

Signs and symptoms of SLE usually regress when procainamide is discontinued, but long-term treatment with corticosteroids may be necessary if symptoms do not regress.^b

If arthralgia, fever, rash, malaise, or other unexplained symptoms occur, perform appropriate laboratory studies (e.g., LE cell preparations, ANA titer determinations).^b

General Precautions

Has numerous adverse effects that may necessitate cessation of therapy in many patients.^b

Patients should be instructed to promptly report to their clinician any sign of infection (e.g., sore mouth, throat, or gums; unexplained fever; chills), unusual bleeding or bruising, rash, arthralgia, myalgia, dark urine or icterus, wheezing, muscular weakness, chest or abdominal pain, palpitation, nausea, vomiting, anorexia, diarrhea, hallucinations, dizziness, or mental depression associated with procainamide therapy.^b

Cardiovascular Effects

The arrhythmogenic effect of procainamide may result in atypical VT (torsades de pointes).^{147 157 153}

Procainamide cardiotoxicity is evidenced by conduction defects (50% widening of the QRS complex), VT, frequent VPCs, and complete AV block; when these ECG signs appear, discontinue procainamide and closely monitor the patient.^b

Less frequently, ECG signs of toxicity may include prolongation of the PR and QT intervals and decreases in voltage of the QRS complexes and T waves.^{b 157}

Use with caution in patients with preexisting QT interval prolongation.¹⁵³

Adverse cardiac effects occur most commonly with IV administration.^b

The hazard of VF increases with increasing dosage and may be accompanied by ECG signs of toxicity; large IV doses may cause heart block and asystole, and death has occurred rarely.^b

Severe hypotension may occur following rapid IV administration or oral overdosage.^{b 153}

Phenylephrine or norepinephrine should be available to treat severe hypotension caused by IV procainamide.^b

Specific Populations

Pregnancy

Category C.^{135 156}

Lactation

Both procainamide and N-acetylprocainamide (NAPA) distribute into milk.^{135 156} Discontinue nursing or the drug.¹³⁵

Pediatric Use

Safety and efficacy have not been established.^{b 135 150 153} However, drug is used (e.g., SVT unresponsive to adenosine or vagal maneuvers, recurrent or refractory wide-complex VT with pulses and poor perfusion).^{b 154 152 153 157 158} Consider consulting an expert in pediatric arrhythmias prior to treating tachycardia in pediatric patients who are hemodynamically stable.¹⁵³ (See Use Limited to Life-threatening Arrhythmias under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.^{151 135}

In general, carefully titrate the dosage, usually initiating therapy at the low end of the dosage range.^{151 135} (See Geriatric Patients under Dosage and Administration.)

Consider the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in the elderly.^{151 135}

Renal Impairment

Use with caution in patients with renal disease.^{152 b 135} Because the drug is known to be substantially excreted by the kidney, patients with renal impairment may be at increased risk of procainamide-induced toxicity.^{151 135 155}

Common Adverse Effects

Hypotension,^{154 157} maculopapular rash,^b urticaria,^b pruritus,^b flushing,^b angioedema,^b fever,^{154 157} lupus-like syndrome.¹⁵²

Interactions for Procanbid

Drugs Affecting QT Interval

Possibility that potentially serious cardiac arrhythmias, including torsades de pointes, could occur if procainamide were used concomitantly with other drugs that prolong the QT_c interval.^{146 149} Use with caution, if at all, in combination with other drugs that prolong the QT interval; consider expert consultation.^{153 158}

Class IA Antiarrhythmic Agents

Concurrent use with class IA antiarrhythmics (e.g., disopyramide, quinidine) can enhance conduction prolongation, contractility depression, and hypotension, especially in cardiac decompensation.¹³⁵ Reserve combined use for serious arrhythmias unresponsive to monotherapy; monitor closely.¹³⁵

Specific Drugs

Drug	Interaction	Comments
Alcohol	Enhances acetylation of procainamide to NAPA; alcohol consumption may reduce half-life135
Amiodarone	Possible increased plasma procainamide and NAPA concentrations and subsequent toxicity114 115 116 152 157	Reduce procainamide dosage by 20–33% when amiodarone therapy is initiated in patients currently receiving procainamide, or discontinue procainamide114 116 117
Anticholinesterase and anticholinergic agents (e.g., neostigmine, pyridostigmine)	Theoretically, the anticholinergic effect of procainamide may be additive with anticholinergic drugsb or procainamide may enhance effects of anticholinergic agents152	Use with caution, if at all, in patients with myasthenia gravis; may need to increase the dose of anticholinesterase drugsb
β-adrenergic blocking agents	Possible increased plasma procainamide concentrations 152
Cardiovascular drugs	Possible additive hypotensive effects in patients receiving hypotensive drugs and procainamide parenterally or in high oral dosesb	Observe such patients closelyb
Cimetidine	Possible increased plasma procainamide and NAPA concentrations and subsequent toxicity101 102 107 108 111 152 157	May be more marked in geriatric patients and patients with renal impairment since such patients eliminate procainamide, NAPA, and cimetidine more slowly101 108 111
Famotidine	Does not substantially interact with procainamide109 112
Lidocaine	Cardiac effects may be additive or antagonistic and toxic effects may be additiveb
Neuromuscular blocking agents (pancuronium bromide, succinylcholine chloride, tubocurarine chloride)	Procainamide may potentiate the effects of both nondepolarizing and depolarizing skeletal muscle relaxantsb	Clinical importance not established; use concomitantly with cautionb
Ofloxacin	Possible decreased clearance of procainamide155
Quinidine	Cardiac effects may be additive or antagonistic and toxic effects may be additiveb
Phenytoin	Cardiac effects may be additive or antagonistic and toxic effects may be additiveb
Propranolol	Cardiac effects may be additive or antagonistic and toxic effects may be additiveb
Ranitidine	Possible increased plasma procainamide and NAPA concentrations101 103 104 152	Use concomitantly with caution, particularly in geriatric patients and patients with renal impairment;101 102 103 104 107 108 111 closely monitor the patient and plasma procainamide concentrations and adjust procainamide dosage accordingly101 102 103 104 108 111
Skeletal muscle relaxants	Procainamide may enhance effects of skeletal muscle relaxants 152
Trimethoprim	Possible increased plasma procainamide and NAPA concentrations135 152

Procanbid Pharmacokinetics

Absorption

Bioavailability

Oral: About 83–85% (range: 75–95%) absorbed from the intestine, but a few patients may absorb less than 50% of an oral dose.^{b 135 155}

IM administration: Rapid and complete (100%); appears in plasma in 2 minutes.^{b 155}

Onset

IM administration: Within 10–30 minutes.^b

Food

Oral absorption slowed by delayed gastric emptying, decreased intestinal motility, presence of food in the GI tract, decreases in intestinal pH, or decreased splanchnic blood flow.^b

Plasma Concentrations

Peak, oral (conventional preparations): Within 0.75–2.5 hours in normal fasting adults.^{b 155}

Peak, oral (extended-release 6-hour): Within 3–4 hours.¹⁵⁵

Peak, IM: Averages 30% higher than after oral administration, and attained in 15–60 minutes.^b

Therapeutic range, procainamide: 4–10 mcg/mL.¹⁵⁵ Concentrations up to 15–20 mcg/mL may be appropriate in selected patients with careful monitoring.¹⁵⁵

Therapeutic range, procainamide + NAPA: 5–30 mcg/mL.^{155 152 154}

Distribution

Extent

Rapidly distributed into the CSF, liver, spleen, kidneys, lungs, muscles, brain, and heart.^b

Procainamide and NAPA cross the placenta.^{100 156}

Procainamide and NAPA distribute into breast milk.^{b 135 156}

Plasma Protein Binding

14–23%.^{b 155}

Elimination

Metabolism

Acetylated, presumably in the liver, to form N-acetylprocainamide (NAPA), an active metabolite.^{b 154}

Rate of acetylation is genetically determined by acetylator phenotype (fast versus slow) and varies among individuals; however, it is constant for each person.^{b 155}

Elimination Route

Procainamide and its metabolites are mainly excreted in urine.^b

Half-life

Procainamide: Approximately 3 hours (range: 2.5–4.7 hours).^{b 155}

NAPA: 6–7 hours.^{b 155}

Special Populations

Elimination half-life of procainamide may be prolonged in patients with renal impairment and in geriatric patients, and shorter in children 1–12 years of age.^{b 155}

Stability

Storage

Oral

Capsules and Tablets

Well-closed¹³⁵ or tight containers; 20–25°C¹³⁵ (avoid exposure to temperatures >40°C).^{118 119 120}

Suspensions (extemporaneous)

Oral suspensions prepared extemporaneously from oral procainamide hydrochloride capsules and cherry syrup reportedly are stable for at least 6 months when refrigerated at 4–6°C at concentrations of 5–100 mg/mL and at a pH adjusted to 6 with hydrochloric acid.¹³⁴

Consider the need for addition of a preservative to the extemporaneous oral suspension to prevent possible microbial contamination of such suspensions; a shorter storage period may be prudent in the absence of specific sterility data for such extemporaneous preparations.¹²⁷

While the specific duration of stability was not determined, such suspensions are stable for <1 week at 24–25°C.¹³⁴

Parenteral

Injection

10–27°C; refrigeration retards oxidation and associated development of color.^b

When diluted with 0.9% sodium chloride injection or sterile water for injection, solutions containing 2–4 mg/mL are stable for 24 hours at room temperature or for 7 days at 2–8°C.^b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

pH adjusted to approximately 7.5 with sodium bicarbonate 8.4%.

Compatible
Dextrose 5% in water (neutralized)
Sodium chloride 0.45 or 0.9%
Incompatible
Dextrose 5% in water
Variable
Dextrose 5% in sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Amiodarone HCl
Atracurium besylate
Dobutamine HCl
Flumazenil
Lidocaine HCl
Verapamil HCl
Incompatible
Esmolol HCl
Ethacrynate sodium
Milrinone lactate
Variable
Bretylium tosylate

Y-site CompatibilityHID

Compatible
Alcohol 10% in dextrose 5%
Amiodarone HCl
Bivalirudin
Dexmedetomidine HCl
Diltiazem HCl
Famotidine
Fenoldopam mesylate
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hydrocortisone sodium succinate
Potassium chloride
Ranitidine HCl
Remifentanil HCl
Sodium nitroprusside
Vasopressin
Vitamin B complex with C
Incompatible
Lansoprazole
Milrinone lactate
Variable
Inamrinone lactate

Actions

• Regarded as a myocardial depressant because it decreases myocardial excitability and conduction velocity, and may depress myocardial contractility.^b

• Possesses anticholinergic properties, which may modify the direct myocardial effects.^b

• Exact mechanism of antiarrhythmic action has not been established, but is a class I (membrane-stabilizing) antiarrhythmic agent.^{b 154}

• Believed to combine with fast sodium channels in their inactive state and thereby inhibit recovery after repolarization in a time- and voltage-dependent manner which is associated with subsequent dissociation of the drug from the sodium channels.^b

• Electrophysiologic characteristics of the subgroups of class I antiarrhythmic agents may be related to quantitative differences in their rates of attachment to and dissociation from transmembrane sodium channels, with class IA agents exhibiting intermediate rates of attachment and dissociation.^b

• NAPA, a metabolite of procainamide, exhibits class III antiarrhythmic activity.¹⁴⁷

• Suppresses automaticity in the His-Purkinje system.^b

• Extremely high concentrations may increase myocardial automaticity.^b

• Decreases conduction velocity in the atria, ventricles, and His-Purkinje system, and may decrease or cause no change in conduction velocity through the AV node.^b

• Shortens the ERP of the AV node, and the anticholinergic action of the drug may also increase the conductivity of the AV node.^b

• Causes prolongation of the PR and QT intervals, but the QRS complex is usually not prolonged beyond the normal range.^b

• Effect on heart rate is unpredictable, but generally causes no change or slightly increases heart rate.^b

• May have a direct negative inotropic effect, but therapeutic plasma concentrations do not usually depress contractility in the normal heart.^b

• Cardiac output is not usually decreased, except in the presence of myocardial damage.^b

• May reduce peripheral resistance and BP as a result of peripheral vasodilation.^b

• Decreased BP is most likely to occur with high plasma concentrations.^b

• IV procainamide may decrease pulmonary arterial pressure.^b

• At high plasma concentrations, procainamide may produce sinus tachycardia because of reflex sympathetic response to its hypotensive effect.^b

• Has local anesthetic properties equal to but more sustained than those of procaine; procainamide produces less CNS stimulation than does procaine.^b

Advice to Patients

• Importance of promptly reporting any sign of infection (e.g., sore mouth, throat, or gums; unexplained fever; chills), unusual bleeding or bruising, lupus-like manifestations (e.g., rash, arthralgia, myalgia), dark urine or icterus, wheezing, muscular weakness, chest or abdominal pain, palpitation, nausea, vomiting, anorexia, diarrhea, hallucinations, dizziness, or mental depression associated with procainamide therapy.^b

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.^b

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^b

• Importance of informing patients of other important precautionary information.^b (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Procainamide Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	250 mg*	Procainamide Hydrochloride Capsules
		500 mg*	Procainamide Hydrochloride Capsules
	Tablets, extended-release, film-coated	250 mg*	Procainamide Hydrochloride Tablets Extended-Release (scored)
		500 mg*	Procainamide Hydrochloride Tablets Extended-Release (scored)
			Procanbid (12 hours)	Monarch
		1 g*	Procainamide Hydrochloride Tablets Extended-Release (scored)
			Procanbid (12 hours)	Monarch
Parenteral	Injection	100 mg/mL*	Procainamide Hydrochloride Injection
		500 mg/mL*	Procainamide Hydrochloride Injection