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  • CLASSES

    Anti-arrhythmics, Class I-A

    BOXED WARNING

    Alcoholism, arrhythmia exacerbation, AV block, bradycardia, bundle-branch block, cardiac arrhythmias, cardiac disease, cardiomyopathy, coronary artery disease, diabetes mellitus, digitalis toxicity, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, malnutrition, mortality, myocardial infarction, QT prolongation, thyroid disease, torsade de pointes, ventricular dysfunction

    Procainamide is contraindicated in patients with second- or third-degree AV block unless controlled by a pacemaker due to the risk of additive cardiac depression. In general, use procainamide cautiously in patients with certain types of cardiac disease. Procainamide has proarrhythmic properties and can induce or worsen cardiac arrhythmias. Procainamide should not be used in patients with preexisting heart block, such as first-degree AV block, bundle-branch block, or severe digitalis toxicity, because it can worsen the conduction defect or cause ventricular asystole or fibrillation. Antiarrhythmic agents with proarrhythmic properties (arrhythmia exacerbation), including procainamide and other Class I agents, should not be used in patients with asymptomatic non-life threatening ventricular arrhythmias, especially in patients at risk for proarrhythmic effects such as heart failure, myocardial infarction, or cardiomegaly. Procainamide has not been shown to reduce mortality in patients with non-life-threatening ventricular arrhythmias. There is, however, evidence of an increased risk of death and non-fatal cardiac arrest with the use of flecainide after myocardial infarction in patients with asymptomatic PVCs or non-sustained ventricular tachycardia. Considering the known proarrhythmic properties of procainamide and the lack of evidence of improved survival for antiarrhythmic drugs in patients without life-threatening arrhythmias, the use of procainamide should be reserved for patients with life-threatening ventricular arrhythmias. Procainamide should also be used with caution in patients with congestive heart failure, coronary artery disease, left ventricular dysfunction, myocardial infarction, acute ischemic heart disease, or cardiomyopathy, since even slight depression of myocardial contractility may further reduce the cardiac output of the damaged heart. In addition, patients with congestive heart failure can have undiagnosed heart block, and the administration of procainamide to such patients would be hazardous. The use of procainamide is contraindicated in patients with torsade de pointes as procainamide can actually aggravate this arrhythmia instead of suppressing it. Similarly, procainamide should be avoided when possible in patients with QT prolongation due to the increased risk of proarrhythmic effects. Use procainamide with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic impairment may also be at increased risk for QT prolongation.

    Positive antinuclear antibodies, systemic lupus erythematosus (SLE)

    Procainamide is contraindicated in patients with an established diagnosis of systemic lupus erythematosus (SLE), as aggravation of symptoms is likely to occur. However, in SLE patients with recurrent life-threatening arrhythmias not controlled by other agents, procainamide may be used in combination with corticosteroid suppressive therapy. The procainamide-induced SLE-like syndrome rarely results in pathologic renal changes; therefore, procainamide may not have to be terminated unless the symptoms of serositis and the possibility of further lupoid effects are a greater risk than the benefit of procainamide in controlling life-threatening arrhythmias. Per the boxed warning, the prolonged administration of procainamide often leads to the development of positive antinuclear antibodies (ANA) (more common in patients who are slow acetylators), with or without symptoms of a SLE-like syndrome. If a positive ANA titer develops, assess the benefits versus risks of continued procainamide therapy.

    Agranulocytosis, bone marrow suppression, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia

    Procainamide should be used with caution in patients with pre-existing marrow failure or cytopenia of any type, including agranulocytosis, aplastic anemia, hemolytic anemia, neutropenia, leukopenia, pancytopenia, and/or thrombocytopenia. Severe bone marrow suppression, agranulocytosis, neutropenia, hypoplastic anemia, and thrombocytopenia have been reported in patients receiving procainamide at a rate of approximately 0.5%. Most of these patients received procainamide within the recommended dosage range. Fatalities have occurred (with approximately 20—25% mortality in reported cases of agranulocytosis). Since most of these events have been noted during the first 12 weeks of therapy, complete blood counts including white cell, differential, and platelet counts should be performed weekly for the first 3 months of therapy, and periodically thereafter. Complete blood counts should be performed immediately if the patient develops any signs of infection, bruising, or bleeding. If any of these hematologic disorders are identified, procainamide hydrochloride should be discontinued. Blood counts usually return to normal within 1 month of discontinuation.

    DEA CLASS

    Rx

    DESCRIPTION

    IV class IA antiarrhythmic agent
    Used for atrial fibrillation/flutter, paroxysmal atrial tachycardia, and ventricular tachycardia
    Derivative of the local anesthetic procaine

    HOW SUPPLIED

    Procainamide/Procainamide Hydrochloride Intramuscular Inj Sol: 1mL, 100mg, 500mg
    Procainamide/Procainamide Hydrochloride Intravenous Inj Sol: 1mL, 100mg, 500mg

    DOSAGE & INDICATIONS

    For the treatment of ventricular tachycardia with pulses (stable monomorphic or wide-complex regular ventricular tachycardia) during cardiopulmonary resuscitation (CPR) in patients with preserved left ventricular function.
    NOTE: ACLS guidelines recommend the use of procainamide for patients with hemodynamically stable monomorphic ventricular tachycardia who do not have severe congestive heart failure, acute myocardial infarction, or prolonged QT.
    Intravenous dosage (loading dosage followed by continuous IV infusion)
    Adults

    ACLS recommendation is 20 to 50 mg/minute IV until either the arrhythmia is suppressed, hypotension occurs, the QRS complex is widened by 50%, or the maximum dose of 17 mg/kg is given (Class IIa, Evidence Level B recommendation). Avoid use in patients with prolonged QT and congestive heart failure. Alternatively, 100 mg IV may be administered every 5 minutes until the arrhythmia is suppressed, hypotension occurs, the QRS complex is widened by 50%, or a total of 500 mg has been administered. Then wait at least 10 minutes to allow for distribution to tissues before resuming treatment. If indicated, follow with 1 to 4 mg/minute as a continuous IV infusion. Further dosage should be adjusted according to patient response, renal function, serum procainamide concentration and, when indicated, serum NAPA concentration.

    Infants†, Children†, and Adolescents†

    15 mg/kg IV; give over 30 to 60 minutes. Monitor ECG and blood pressure continuously during administration; stop or slow the infusion if QT prolongation, heart block, or hypotension occurs or QRS widens to more than 50% of baseline. Pediatric Advanced Life Support guidelines (PALS) recommend procainamide for the treatment of SVT unresponsive to vagal maneuvers and adenosine and/or electric cardioversion and for the treatment of wide-complex tachycardia in hemodynamically stable patients. In patients with SVT, PALS states that additional doses may be administered if there is no effect and no toxicity from the initial dose; however, a maximum dose is not provided. Advanced Cardiac Life Support (ACLS) guidelines for adults recommend a maximum dose of 17 mg/kg. May give IO if no IV access.

    For the treatment of ventricular arrhythmias such as sustained ventricular tachycardia or junctional ectopic tachycardia† in situations other than cardiac arrest; or for the conversion to and/or maintenance of sinus rhythm in patients with supraventricular arrhythmias† including paroxysmal atrial tachycardia†, atrial fibrillation†, atrial flutter†, or paroxysmal supraventricular tachycardia (PSVT)†; or for paroxysmal supraventricular tachycardia (PSVT) prophylaxis† in patients with reentrant tachycardia, including patients with Wolff-Parkinson-White (WPW) syndrome†.
    NOTE: For dosing related to the emergency use of procainamide, see the CPR indication.
    Adult loading dose.
    Intravenous loading dosage
    Adults

    15 to 17 mg/kg as an IV infusion, infused at a rate of 20 to 30 mg/minute. Alternatively, 100 mg IV every 5 minutes given by slow IV push until arrhythmia disappears, or up to 1,000 mg.

    Adult maintenance dosage.
    Intravenous maintenance dosage
    Adults

    Initially, 1 to 4 mg/minute as a continuous IV infusion. The usual initial maintenance dose is about 50 mg/kg/day; lower doses should be used in patients with renal dysfunction or reduced cardiac output. Adjust dosage based on renal function, clinical goals, and serum drug level monitoring.

    Intramuscular maintenance dosage
    Adults

    The usual initial dosage is 50 mg/kg/day IM, given in divided doses every 3 to 6 hours. Adjust dosage based on renal function, clinical goals, and serum drug level monitoring.

    Pediatric dosing.
    Intravenous dosage
    Infants, Children, and Adolescents

    3.5 to 15 mg/kg IV given over 20 to 60 minutes followed by a continuous infusion of 10 to 80 mcg/kg/minute IV (Max: 2 g/day IV) has been recommended in pediatric patients with various tachyarrhythmias. In a retrospective study of patients with various tachyarrhythmias, procainamide (n=14, age 0 days to 19 years) given as a loading dose of 3.5 to 10 mg/kg IV followed by a continuous infusion of 10 to 40 mcg/kg/minute IV was effective in 50% of patients and partially effective in another 21% of patients compared to amiodarone (n = 26, age 0 days to 8 years, 1 to 10 mg/kg IV loading dose followed by 2.5 to 15 mcg/kg/minute IV), which was effective and partially effective in 15% and 19% of patients, respectively. Higher infusion rates have been used in a small study of infants and young children (n = 17, age 0.7 to 41 months) with postsurgical junctional tachycardia. A subset of patients (n = 12) received loading doses of 10 mg/kg IV given over 20 minutes followed by infusions of 20 mcg/kg/minute IV titrated up by increments of 10 mcg/kg IV every 10 to 15 minutes to a maximum rate of 120 mcg/kg/minute. The mean infusion rate required to lower the heart rate to less than 180 beats/minute was 63 mcg/kg/minute IV; 5 patients received infusion rates of 80 mcg/kg/minute or more.

    Neonates

    3.5 to 10 mg/kg IV given over 60 minutes followed by a continuous infusion of 10 to 80 mcg/kg/minute IV has been studied in patients with various tachyarrhythmias. A loading dose of 7 to 10 mg/kg IV given over 1 hour followed by a continuous infusion of 20 to 80 mcg/kg/minute IV was used in a small study of premature (n = 7, gestational age 25 to 36 weeks) and term (n = 14) neonates with various tachyarrhythmias. Five patients in the study had supratherapeutic procainamide concentrations (more than 10 mg/L) after administration of continuous infusion doses of 20 to 60 mcg/kg/minute; 4 of the 5 were premature neonates indicating lower doses may be necessary in this population. Efficacy was not reported; however, no patients experienced adverse reactions due to procainamide. In a retrospective study including 4 neonatal patients with various tachyarrhythmias, a loading dose of 3.5 to 10 mg/kg IV followed by a continuous infusion of 10 to 40 mcg/kg/minute IV was effective in 50% of patients and partially effective in another 25% of patients compared to amiodarone (n = 16, 1 to 10 mg/kg IV loading dose followed by 2.5 to 15 mcg/kg/minute IV), which was effective and partially effective in 25% and 19% of patients, respectively.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Procainamide has a narrow therapeutic index. In all populations, dosage is individualized based on patient weight, renal function, clinical goals, patient response, serum procainamide concentrations and, when needed, serum N-acetylprocainamide (NAPA) levels.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Although no specific guidelines are available, dosage reduction may be needed in individual patients with hepatic impairment and in patients who have reduced hepatic acetylation status. Adjust dosage based on serum procainamide and NAPA concentrations.

    Renal Impairment

    Reduction of dosage is required due to accumulation of procainamide and NAPA. Dosage adjustments should be made in conjunction with monitoring of procainamide and NAPA levels, in addition to other factors such as clinical response, patient age, renal status, and hepatic function and acetylator status.
     
    Adult patients: Initial dosage adjustment recommendations are as follows:
    CrCl > 60 mL/min: No initial dosage adjustment is required.
    CrCl 35 to 59 mL/min: Decrease initial maintenance dosage by approximately 30%.
    CrCl 15 to 34 mL/min: Decrease initial maintenance dosage by 40% to 60%.
    CrCl < 15 mL/min: Individualize dosage.
     
    Pediatric patients: No specific guidelines are available for pediatric patients with renal impairment; use lower initial doses and adjust as required. Dosage adjustments should be made in conjunction with monitoring of procainamide and NAPA levels, in addition to other factors such as clinical response, patient age, renal status, and hepatic function and acetylator status.
     
    Intermittent hemodialysis
    Procainamide and NAPA are removed from the circulation by hemodialysis. Adjust dose based on procainamide and NAPA concentrations.
     
    Peritoneal dialysis
    Procainamide and NAPA are not removed from the circulation by peritoneal dialysis.

    ADMINISTRATION

    Injectable Administration

    Intravenous injection or infusion is preferred over intramuscular injection.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Intravenous injection:
    Each 100 mg of procainamide must be diluted in 10 ml of sterile water for injection or D5W injection.
    Inject by slow IV push at a rate not to exceed 50 mg/minute.
     
    Intravenous infusion:
    NOTE: According to the manufacturer, procainamide injection is compatible in D5W. However, data indicate procainamide may quickly form an association complex with dextrose. The clinical implications of this complexation are unknown. Refrigeration and pH adjustment may reduce the rate of complexation. Other sources indicate procainamide also is not compatible with D5NS but is compatible with NS and 0.45% NS.
    Dilute 0.2—1 gram in 50—500 ml of D5W injection to give an infusion solution containing 2—4 mg/ml. A slight yellow color may be present but it does not alter potency. Discard any solution that has a color darker than light amber or contains a precipitate.
    Blood pressure and ECG should be monitored continuously.
    Prior to administration, the patient should be in the supine position. Using an infusion pump, the initial loading infusion should be over 30—60 minutes at a rate not to exceed 25—50 mg/minute. Dosage should be adjusted according to patient response, renal function, serum procainamide concentration and, when indicated, serum NAPA concentration.

    Intramuscular Administration

    Use IM route only if IV route is not feasible. IM injection may be painful and can increase CPK levels.
    Inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh). Aspirate prior to injection to avoid injection into a blood vessel.

    Other Injectable Administration

    Intraosseous infusion
    Procainamide is not approved by the FDA for intraosseous administration.
    During cardiopulmonary resuscitation in pediatric patients, the same dosage may be given via the intraosseous route when IV access is not available.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Procanbid:
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Pronestyl:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Pronestyl-SR:
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    In laboratory testing, supratherapeutic concentrations of lidocaine and meprobamate may inhibit fluorescence of procainamide and NAPA. In addition, propranolol shows a native fluorescence close to the procainamide/NAPA peak wavelengths, so that tests which depend on fluorescence measurement may be affected.

    Ester local anesthetic hypersensitivity

    In patients sensitive to procaine or other ester local anesthetic hypersensitivity, cross sensitivity to procainamide is unlikely. However, it should be borne in mind, and procainamide should not be used if it produces acute allergic dermatitis, asthma, or anaphylactic symptoms. Procainamide is contraindicated in patients with idiosyncratic hypersensitivity to procainamide.

    Cardiogenic shock, hemorrhagic shock, hypotension, shock

    Fast rates of intravenous administration of procainamide may be associated with hypotension; caution is advised and care should be taken to avoid overly rapid administration of procainamide, especially in patients with significant hypotension or shock states (e.g., anaphylactic shock, cardiogenic shock, hemorrhagic shock).

    Alcoholism, arrhythmia exacerbation, AV block, bradycardia, bundle-branch block, cardiac arrhythmias, cardiac disease, cardiomyopathy, coronary artery disease, diabetes mellitus, digitalis toxicity, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, malnutrition, mortality, myocardial infarction, QT prolongation, thyroid disease, torsade de pointes, ventricular dysfunction

    Procainamide is contraindicated in patients with second- or third-degree AV block unless controlled by a pacemaker due to the risk of additive cardiac depression. In general, use procainamide cautiously in patients with certain types of cardiac disease. Procainamide has proarrhythmic properties and can induce or worsen cardiac arrhythmias. Procainamide should not be used in patients with preexisting heart block, such as first-degree AV block, bundle-branch block, or severe digitalis toxicity, because it can worsen the conduction defect or cause ventricular asystole or fibrillation. Antiarrhythmic agents with proarrhythmic properties (arrhythmia exacerbation), including procainamide and other Class I agents, should not be used in patients with asymptomatic non-life threatening ventricular arrhythmias, especially in patients at risk for proarrhythmic effects such as heart failure, myocardial infarction, or cardiomegaly. Procainamide has not been shown to reduce mortality in patients with non-life-threatening ventricular arrhythmias. There is, however, evidence of an increased risk of death and non-fatal cardiac arrest with the use of flecainide after myocardial infarction in patients with asymptomatic PVCs or non-sustained ventricular tachycardia. Considering the known proarrhythmic properties of procainamide and the lack of evidence of improved survival for antiarrhythmic drugs in patients without life-threatening arrhythmias, the use of procainamide should be reserved for patients with life-threatening ventricular arrhythmias. Procainamide should also be used with caution in patients with congestive heart failure, coronary artery disease, left ventricular dysfunction, myocardial infarction, acute ischemic heart disease, or cardiomyopathy, since even slight depression of myocardial contractility may further reduce the cardiac output of the damaged heart. In addition, patients with congestive heart failure can have undiagnosed heart block, and the administration of procainamide to such patients would be hazardous. The use of procainamide is contraindicated in patients with torsade de pointes as procainamide can actually aggravate this arrhythmia instead of suppressing it. Similarly, procainamide should be avoided when possible in patients with QT prolongation due to the increased risk of proarrhythmic effects. Use procainamide with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic impairment may also be at increased risk for QT prolongation.

    Positive antinuclear antibodies, systemic lupus erythematosus (SLE)

    Procainamide is contraindicated in patients with an established diagnosis of systemic lupus erythematosus (SLE), as aggravation of symptoms is likely to occur. However, in SLE patients with recurrent life-threatening arrhythmias not controlled by other agents, procainamide may be used in combination with corticosteroid suppressive therapy. The procainamide-induced SLE-like syndrome rarely results in pathologic renal changes; therefore, procainamide may not have to be terminated unless the symptoms of serositis and the possibility of further lupoid effects are a greater risk than the benefit of procainamide in controlling life-threatening arrhythmias. Per the boxed warning, the prolonged administration of procainamide often leads to the development of positive antinuclear antibodies (ANA) (more common in patients who are slow acetylators), with or without symptoms of a SLE-like syndrome. If a positive ANA titer develops, assess the benefits versus risks of continued procainamide therapy.

    Hepatic disease, renal disease, renal failure, renal impairment, slow acetylation

    In patients with hepatic disease, lower doses or longer dosing intervals of procainamide may be needed due to reduced procainamide elimination. Procainamide is about 15 to 35% metabolized by N-acetylation, depending on genetic acetylation status. Slow acetylation status may indicate a higher risk for procainamide accumulation and toxicity (e.g., SLE symptoms, rate of development of ANA antibodies), especially in patients with renal dysfunction. Procainamide must also be used with extreme caution in patients with renal failure, renal impairment, or other renal disease. Renal insufficiency may lead to accumulation of high plasma levels from conventional doses, with effects similar to those of overdosage, unless dosage is adjusted for the individual patient. Approximately 65% of a dose is excreted as unchanged drug (procainamide). The active metabolite, NAPA, is also significantly excreted unchanged in the urine.

    Myasthenia gravis

    Procainamide should be used cautiously in patients with myasthenia gravis because it has been reported to exacerbate the muscle weakness associated with this condition. Patients with myasthenia gravis may show worsening of symptoms from procainamide due to its procaine-like effect on diminishing acetylcholine release at skeletal muscle motor nerve endings. Procainamide administration may be hazardous without optimal adjustment of anticholinesterase medications and other precautions.

    Agranulocytosis, bone marrow suppression, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia

    Procainamide should be used with caution in patients with pre-existing marrow failure or cytopenia of any type, including agranulocytosis, aplastic anemia, hemolytic anemia, neutropenia, leukopenia, pancytopenia, and/or thrombocytopenia. Severe bone marrow suppression, agranulocytosis, neutropenia, hypoplastic anemia, and thrombocytopenia have been reported in patients receiving procainamide at a rate of approximately 0.5%. Most of these patients received procainamide within the recommended dosage range. Fatalities have occurred (with approximately 20—25% mortality in reported cases of agranulocytosis). Since most of these events have been noted during the first 12 weeks of therapy, complete blood counts including white cell, differential, and platelet counts should be performed weekly for the first 3 months of therapy, and periodically thereafter. Complete blood counts should be performed immediately if the patient develops any signs of infection, bruising, or bleeding. If any of these hematologic disorders are identified, procainamide hydrochloride should be discontinued. Blood counts usually return to normal within 1 month of discontinuation.

    Pregnancy

    Procainamide is classified as FDA pregnancy risk category C. It is not known if procainamide causes fetal harm or can affect reproduction capacity, and animal reproduction studies have not been conducted. Only administer to a pregnant woman if clearly needed.

    Breast-feeding

    Procainamide and NAPA are both distributed into breast milk and absorbed by the nursing infant. According to the manufacturer, because of the potential for serious adverse reactions in nursing infants from procainamide, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. Despite this warning by the manufacturer, the American Academy of Pediatrics considers procainamide, as well as disopyramide and quinidine, to be usually compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Atrial fibrillation, atrial flutter

    It is recommended that patients with atrial flutter or atrial fibrillation be adequately digitalized or have undergone cardioversion prior to therapy with procainamide in order to avoid enhancement of AV conduction and acceleration of ventricular rate. Digitalization in these patients reduces but does not eliminate the possibility of ventricular rate increases.

    Asthma, sulfite hypersensitivity

    Use procainamide injection cautiously in patients with a sulfite hypersensitivity. Procainamide injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite hypersensitivity is seen more frequently in patients with asthma.

    Geriatric

    Anticipate that less than the usual dosage or infusion rate of procainamide may suffice in older adult patients (i.e., over 50 years of age and geriatric adult), since the urinary elimination of procainamide and its metabolite N-acetylprocainamide (NAPA) may be reduced, leading to gradual accumulation beyond normally predicted amounts. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. The OBRA guidelines caution that antiarrhythmics can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals.

    ADVERSE REACTIONS

    Severe

    agranulocytosis / Delayed / 0-1.0
    pancytopenia / Delayed / 0-1.0
    aplastic anemia / Delayed / 0-1.0
    hemolytic anemia / Delayed / 0-1.0
    hepatic failure / Delayed / 0-1.0
    arrhythmia exacerbation / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    ventricular fibrillation / Early / Incidence not known
    heart failure / Delayed / Incidence not known
    asystole / Rapid / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known

    Moderate

    thrombocytopenia / Delayed / 0-1.0
    leukopenia / Delayed / 0-1.0
    neutropenia / Delayed / 0-1.0
    depression / Delayed / Incidence not known
    hallucinations / Early / Incidence not known
    psychosis / Early / Incidence not known
    bone marrow suppression / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    PR prolongation / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known

    Mild

    dyspepsia / Early / 3.0-4.0
    vomiting / Early / 3.0-4.0
    diarrhea / Early / 3.0-4.0
    anorexia / Delayed / 3.0-4.0
    abdominal pain / Early / 3.0-4.0
    nausea / Early / 3.0-4.0
    weakness / Early / Incidence not known
    dizziness / Early / Incidence not known
    asthenia / Delayed / Incidence not known
    fever / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    chills / Rapid / Incidence not known
    myalgia / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    flushing / Rapid / Incidence not known
    rash / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    positive antinuclear antibodies / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Abacavir; Lamivudine, 3TC: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Abarelix: (Severe) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as Class IA antiarrhythmics.
    Acebutolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like acebutolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as procainamide, may decrease adefovir elimination by competing for common renal tubular transport systems, therefore increasing serum concentrations of either adefovir and/or these coadministered drugs.
    Albuterol: (Minor) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Albuterol; Ipratropium: (Minor) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Alfuzosin: (Major) Alfuzosin should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
    Aliskiren; Amlodipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Aliskiren; Valsartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Alosetron: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as procainamide, however, this interaction has not been studied.
    Ambenonium Chloride: (Moderate) Disopyramide possesses anticholinergic properties. Disopyramide should not be used in patients with myasthenia gravis because the anticholinergic properties of the drug could precipitate a myasthenic crisis. It is unclear if disopyramide can interfere with the cholinomimetic activity of ambenonium. Procainamide also has anticholinergic properties, albeit somewhat less than disopyramide. These antiarrhythmics should be used cautiously in patients with myasthenia gravis.
    Amiloride: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amiodarone: (Major) Amiodarone may increase procainamide serum concentrations, with potential for drug toxicity. Procainamide and N-acetylprocainamide or NAPA (a pharmacologically active metabolite) serum concentrations increase by approximately 55 and 33%, respectively, during the first 7 days of concomitant amiodarone therapy. The precise pharmacokinetic mechanism of this interaction has not been elucidated, although a reduction the renal clearance of both parent and metabolite, as well as a reduction in hepatic metabolism seem likely. Additive electrophysiologic activity occurs with combination therapy and prolonged QT and QRS intervals or acceleration of preexisting ventricular tachycardia may result. Careful clinical observation of the patient as well as close monitoring of the ECG and serum procainamide and NAPA concentrations is essential with adjustment of the procainamide dosing regimen performed as necessary to avoid enhanced toxicity or pharmacodynamic effects. If amiodarone is to be coadministered with procainamide, the manufacturer recommends reducing the procainamide dosage by 33%. Combination antiarrhythmic therapy is reserved for patients with refractory life-threatening arrhythmias. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amitriptyline: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Amitriptyline; Chlordiazepoxide: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Amlodipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amlodipine; Atorvastatin: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amlodipine; Benazepril: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amlodipine; Olmesartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amlodipine; Telmisartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amlodipine; Valsartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Clarithromycin should be used cautiously with procainamide. Procainamide and clarithromycin are both associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin should be used cautiously with procainamide. Procainamide and clarithromycin are both associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include procainamide.
    Angiotensin II receptor antagonists: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Angiotensin-converting enzyme inhibitors: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Anticholinergics: (Moderate) The anticholinergic effects of procainamide may be significant and may be enhanced when combined with anticholinergics. Anticholinergic agents administered concurrently with procainamide may produce additive antivagal effects on AV nodal conduction, although this is not as well documented for procainamide as for quinidine.
    Apomorphine: (Major) Apomorphine should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2-10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended.
    Arformoterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes. Aripiprazole should be used cautiously and with close monitoring with procainamide.
    Arsenic Trioxide: (Major) If possible, procainamide should be discontinued prior to initiating arsenic trioxide therapy. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
    Artemether; Lumefantrine: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if procainamide must be used with or after artemether; lumefantrine treatment.
    Asenapine: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
    Atenolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like atenolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Atenolol; Chlorthalidone: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like atenolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include procainamide.
    Atropine; Edrophonium: (Moderate) Procainamide has anticholinergic properties and may interfere with the cholinomimetic activity of edrophonium.
    Azilsartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Azilsartan; Chlorthalidone: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Azithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering procainamide with azithromycin. Procainamide is associated with a well-established risk of QT prolongation and TdP, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with procainamide. Procainamide is associated with a well-established risk of QT prolongation and TdP. Bedaquiline has also been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Bendroflumethiazide; Nadolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like nadolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Bepridil: (Severe) Bepridil is contraindicated for use with drugs that prolong the QT interval, including class 1A antiarrhythmic agents, due to the risk of torsade de pointes (TdP). Bepridil has Class I antiarrhythmic properties and is associated with a well-established risk of QT prolongation and TdP. Patients receiving other drugs which have the potential for QT prolongation, such as class 1A antiarrhythmics, have an increased risk of developing proarrhythmias during bepridil therapy.
    Betaxolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like betaxolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Bethanechol: (Moderate) Drugs that possess antimuscarinic properties, such as procainamide, are pharmacologic opposites of bethanechol. These agents should not be used with bethanechol except when the specific intent is to counteract excessive actions of one or the other.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include procainamide.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include procainamide.
    Bisoprolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like bisoprolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like bisoprolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as procainamide. The dose of the concomitant drug may need to be adjusted.
    Brimonidine; Timolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like timolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Budesonide; Formoterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Bupivacaine; Lidocaine: (Major) Concurrent use of systemic lidocaine and other antiarrhythmic drugs such as procainamide may result in additive or antagonistic cardiac effects and additive toxicity. Patients receiving more than one antiarrhythmic drug must be carefully monitored; dosage reduction may be necessary.
    Buprenorphine: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Calcium-channel blockers: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Candesartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Procainamide could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Carteolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like carteolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Carvedilol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like carvedilol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Central-acting adrenergic agents: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and procainamide; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Chloroquine: (Major) Chloroquine and procainamide are both associated with an increased risk of QT prolongation and torsades de pointes (TdP). The need to coadminister chloroquine with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits and should be avoided when possible.
    Chlorpromazine: (Major) Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Phenothiazines have been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use.
    Cimetidine: (Moderate) H2-blockers, such as cimetidine, inhibit the renal tubular secretion of procainamide. Clearance of procainamide is reduced and serum concentrations are increased by cimetidine.
    Ciprofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering procainamide with ciprofloxacin. Procainamide is associated with a well-established risk of QT prolongation and TdP, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP.
    Cisapride: (Severe) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Administration of Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) is associated with QT prolongation and TdP. Because of the potential for TdP, concurrent use of Class IA antiarrhythmics and cisapride is contraindicated.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Clarithromycin: (Major) Clarithromycin should be used cautiously with procainamide. Procainamide and clarithromycin are both associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Clevidipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with procainamide. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Clomipramine: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Clozapine: (Major) Clozapine should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include procainamide.
    Codeine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include procainamide.
    Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of antiarrhythmics if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics at least 1 hour before or at least 4 hours after colesevelam.
    Crizotinib: (Major) Avoid coadministration of crizotinib with procainamide due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Procainamide is also associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Dasatinib: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking procainamide.
    Degarelix: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP). Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking class IA antiarrhythmics.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Desipramine: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Deutetrabenazine: (Major) For patients taking a deutetrabenazine dosage more than 24 mg/day with procainamide, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Dextromethorphan; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include procainamide.
    Dextromethorphan; Quinidine: (Major) According to the manufacturer of procainamide, use with other Class 1A agents, such as quinidine, is contraindicated; however, the manufacturer also states such use may be reserved for patients with serious arrhythmias unresponsive to a single drug if under close observation. Quinidine should only be used with extreme caution with procainamide, due to the potential for QT prolongation and similar effects on the cardiac action potential. Coadministration of quinidine may increase serum concentrations of procainamide, possibly by competing for pathways of renal clearance.
    Diltiazem: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Disopyramide: (Major) Procainamide, a Class IA antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP) and is should generally be avoided with other Class IA antiarrhythmics (disopyramide, quinidine) due to the potential for QT prolongation, other side effects, and an increased risk of torsade de pointes. Concurrent use of procainamide with other Class IA antiarrhythmic agents such as quinidine or disopyramide may produce enhanced prolongation of conduction or depression of contractility and hypotension, especially in patients with cardiac decompensation. Such use should be reserved for patients with serious arrhythmias unresponsive to a single drug and employed only with close observation. In addition, disopyramide exhibits significant anticholinergic activity that may be additive to procainamide.
    Dofetilide: (Severe) The concurrent use of dofetilide and procainamide is contraindicated. Before switching from procainamide to dofetilide therapy, procainamide generally should be withheld for at least three half-lives prior to initiating dofetilide. Concurrent use of procainamide should be avoided with other Class III antiarrhythmics (amiodarone, ibutilide, sotalol) due to the potential for QT prolongation, other side effects, and an increased risk of torsade de pointes.
    Dolasetron: (Major) Dolasetron should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
    Dolutegravir; Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include procainamide.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include procainamide. (Major) Cationic drugs that are eliminated by renal tubular secretion such as procainamide, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or procainamide is recommended to assess for needed dosage adjustments. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Dorzolamide; Timolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like timolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Doxazosin: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Doxepin: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Dronabinol: (Major) Use caution if coadministration of dronabinol with procainamide is necessary, and monitor for an increase in procainamide-related adverse effects. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
    Dronedarone: (Severe) Concurrent use of procainamide and dronedarone is contraindicated. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
    Dupilumab: (Moderate) Coadministration of dupilumab may result in altered exposure to procainamide. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP450 enzymes could be normalized during dupilumab administration. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as procainamide. Monitor procainamide concentrations if dupilumab is initiated or discontinued in a patient taking procainamide; procainamide dose adjustments may be needed.
    Edrophonium: (Moderate) Procainamide has anticholinergic properties and may interfere with the cholinomimetic activity of edrophonium.
    Efavirenz: (Major) Coadministration of efavirenz and procainamide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and procainamide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and procainamide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Procainamide is associated with a well-established risk of QT prolongation and TdP. (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Eliglustat: (Major) Coadministration of procainamide and eliglustat is not recommended. If coadministration is necessary, use extreme caution and close monitoring. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias).
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Enalapril; Felodipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Encorafenib: (Major) Avoid coadministration of encorafenib and procainamide due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Enflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Entecavir: (Major) Both entecavir and procainamide are secreted by active tubular secretion. In theory, coadministration of entecavir with procainamide may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Eplerenone: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Epoprostenol: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Eprosartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Eribulin: (Major) Eribulin has been associated with QT prolongation. Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with procainamide. Concurrent use of erythromycin with procainamide should be avoided.
    Erythromycin; Sulfisoxazole: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with procainamide. Concurrent use of erythromycin with procainamide should be avoided.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as procainamide, should be done with caution and close monitoring.
    Esmolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like esmolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Ethanol: (Moderate) Alcohol consumption tends to decrease the half-life of procainamide in the blood through induction of its acetylation to NAPA.
    Ezogabine: (Major) Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with ezogabine include class IA antiarrhythmics (disopyramide, procainamide, quinidine).
    Felodipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Fingolimod: (Severe) Concurrent use of fingolimod with class Ia antiarrhythmics such as disopyramide, quinidine, and procainamide is contraindicated. Fingolimod initiation results in decreased heart rate, and class IA antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.
    Flecainide: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Class IC antiarrhythmic agents, such as flecainide, moricizine and propafenone, have proarrhythmic properties, and may have additive electrophysiologic effects with procainamide; use concomitantly with caution. The manufacturer of propafenone recommends against the use of propafenone with Class 1A agents such as procainamide.
    Fluconazole: (Major) Procainamide should be used cautiously with fluconazole. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Fluconazole has been associated with QT prolongation and rare cases of TdP.
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include procainamide.
    Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include procainamide. (Major) Olanzapine should be used cautiously and with close monitoring with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP).
    Fluphenazine: (Minor) Fluphenazine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Fluticasone; Salmeterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Vilanterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and procainamide. Procainamide is associated with a well-established risk of QT prolongation and TdP. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Formoterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Formoterol; Mometasone: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as procainamide. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Procainamide is associated with a well-established risk of QT prolongation and TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Gemifloxacin: (Major) According to the manufacturer, gemifloxacin should be avoided in patients receiving Class IA antiarrhythmics (such as disopyramide, quinidine and procainamide). Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and procainamide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Glasdegib: (Major) Avoid coadministration of glasdegib with procainamide due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Glycopyrrolate; Formoterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Goserelin: (Major) Procainamide should be used cautiously and with close monitoring with goserelin. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Granisetron: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
    Halofantrine: (Severe) Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes. Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation; these drugs include class IA antiarrhythmics.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Haloperidol: (Major) Haloperidol should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
    Halothane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Hawthorn, Crataegus laevigata: (Major) It would be prudent to avoid use of Hawthorn, Crataegus laevigata (also known as C. oxycantha) during therapy with antiarrhythmic agents whenever possible, due to the possibility of additive effects on cardiac conduction and the known effects of antiarrhythmic drugs on the heart. Following hawthorn administration to guinea pigs, the cardiac action potential duration was increased and the refractory period was prolonged. Hawthorn may also lower peripheral vascular resistance. Hawthorn could potentially interact with antiarrhythmics that have similar actions to hawthorn on cardiac electrophysiology. Use extreme caution with class IA antiarrhythmics, due to the potential for QT prolongation. However, no human clinical data are available. Patients should be advised to only use hawthorn with these antiarrhythmic agents after discussion with their prescriber. If co-use is advised, patients should receive periodic blood pressure and heart rate monitoring.
    Histrelin: (Major) Consider periodic monitoring of EGCs for QT prolongation and monitor electrolytes if coadministration of histrelin and procainamide is necessary; correct any electrolyte abnormalities. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (e.g., histrelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like metoprolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension. Procainamide's elimination half-life was not significantly changed when administered concomitantly with metoprolol.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Hydrochlorothiazide, HCTZ; Propranolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like propranolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension. Procainamide's elimination half-life was not significantly changed when administered concomitantly with propranolol.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and procainamide. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include procainamide.
    Ibutilide: (Severe) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
    Iloperidone: (Major) Iloperidone should be avoided in combination with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Iloperidone has been associated with QT prolongation; however, TdP has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect.
    Imipramine: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Indacaterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Indacaterol; Glycopyrrolate: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with procainamide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Irbesartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Isoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Isradipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include procainamide.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with procainamide due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include procainamide.
    Labetalol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like labetalol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
    Lamivudine, 3TC: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with procainamide is necessary; correct electrolyte abnormalities prior to treatment. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Lapatinib has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with procainamide due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Leuprolide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include procainamide.
    Leuprolide; Norethindrone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include procainamide.
    Levalbuterol: (Minor) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Levofloxacin: (Major) Levofloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
    Levomethadyl: (Severe) Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval, such as Class IA antiarrhythmics.
    Lidocaine: (Major) Concurrent use of systemic lidocaine and other antiarrhythmic drugs such as procainamide may result in additive or antagonistic cardiac effects and additive toxicity. Patients receiving more than one antiarrhythmic drug must be carefully monitored; dosage reduction may be necessary.
    Lithium: (Major) Lithium should be used cautiously and with close monitoring with procainamide. Lithium has been associated with QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with procainamide due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Lomefloxacin: (Severe) Lomefloxacin has been associated with QT prolongation and infrequent cases of arrhythmia. Lomefloxacin should be avoided in patients receiving Class IA Antiarrhythmics.
    Long-acting beta-agonists: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Loop diuretics: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like procainamide, should be used cautiously and with close monitoring with loperamide.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like procainamide, should be used cautiously and with close monitoring with loperamide.
    Lopinavir; Ritonavir: (Major) Lopinavir; ritonavir should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes. Lopinavir; ritonavir is associated with QT prolongation. Coadministration may result in additive QT prolongation.
    Losartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as procainamide. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Maprotiline: (Major) Maprotiline should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Mefloquine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering procainamide with mefloquine. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Memantine: (Major) Cationic drugs that are eliminated by renal tubular secretion such as procainamide, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or procainamide is recommended to assess for needed dosage adjustments. In selected individuals, procainamide serum concentration monitoring may be appropriate.
    Meperidine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include procainamide.
    Mesoridazine: (Severe) Mesoridazine has been associated with orthostatic hypotension and a risk of QT prolongation and/or torsades de pointes, particularly at higher doses and is generally contraindicated in combination with other agents that prolong the QT interval including class IA antiarrhythmics.
    Metaproterenol: (Minor) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Methadone: (Major) The need to coadminister methadone with procainamide should be done with extreme caution and a careful assessment of treatment risks versus benefits. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
    Metoprolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like metoprolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension. Procainamide's elimination half-life was not significantly changed when administered concomitantly with metoprolol.
    Metronidazole: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include procainamide.
    Midodrine: (Minor) Although the exact mechanism is uncertain, midodrine may be excreted by the same base-secreting pathway of the kidneys responsible for secretion of other basic drugs like procainamide. By this pathway, midodrine may potentially interact with procainamide; however, no drug interactions of this kind have been reported.
    Midostaurin: (Major) The concomitant use of midostaurin and procainamide may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram (ECG) monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes.
    Mifepristone: (Major) Mifepristone should be used cautiously and with close monitoring with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effect dose should always be used.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and procainamide. Procainamide is associated with a well-established risk of QT prolongation and TdP. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Moricizine: (Severe) The effects of concomitant administration of Class IC antiarrhythmic agents with other antiarrhythmics can be synergistic, additive, or antagonistic, and adverse cardiac effects can be additive. Based on Class IC drug pharmacology, moricizine may have additive sodium channel blockade effects with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Additive Class I electrophysiologic effects can increase the risk for proarrhythmias. Although moricizine primarily is associated with Class IB and IC actions, it also is associated with quinidine-like (i.e, Class IA) features.
    Moxifloxacin: (Major) Moxifloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, quinidine, and procainamide). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
    Nadolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like nadolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Nebivolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like nebivolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Nebivolol; Valsartan: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like nebivolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension. (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Neostigmine: (Moderate) Procainamide may antagonize the effects of cholinesterase inhibitors such as neostigmine in the treatment of myasthenia gravis. Isolated case reports describe worsening symptoms shortly after procainamide is added however, this interaction may be due more to procainamide's local anesthetic properties than its anticholinergic properties.
    Neuromuscular blockers: (Moderate) Patients taking procainamide who require depolarizing neuromuscular blocking agents may require less than usual doses, due to procainamide effects of reducing acetylcholine release. In addition, procainamide appears to potentiate or prolong the effects of nondepolarizing neuromuscular blockers. Patients receiving procainamide following surgery should be monitored for potential prolongation of neuromuscular blockade.
    Nicardipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Nifedipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and procainamide; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes.
    Nimodipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Nisoldipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as procainamide.
    Norfloxacin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with norfloxacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, torsade de pointes has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Nortriptyline: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Octreotide: (Major) Administer octreotide cautiously in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) should be used cautiously and with close monitoring with ofloxacin. Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) are associated with QT prolongation and torsades de pointes (TdP). Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP).
    Olanzapine: (Major) Olanzapine should be used cautiously and with close monitoring with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP).
    Olmesartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Olodaterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Ondansetron: (Major) Ondansetron should be used cautiously and with close monitoring with procainamide. If ondansetron and procainamide must be coadministered, ECG monitoring is recommended. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). Among 42 patients receiving a 4 mg bolus dose of intravenous ondansetron for the treatment of postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after antiemetic administration (p < 0.0001).
    Osimertinib: (Major) Avoid coadministration of procainamide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of procainamide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Procainamide is associated with a well-established risk of QT prolongation and TdP. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    Panobinostat: (Major) The co-administration of panobinostat with procainamide is not recommended; QT prolongation has been reported with both of these agents. If concomitant use cannot be avoided, closely monitor patients for signs and symptoms of procainamide toxicity, including QT prolongation and cardiac arrhythmias. Panobinostat is a CYP2D6 inhibitor and procainamide is a CYP2D6 substrate. When a single-dose of a CYP2D6-sensitive substrate was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
    Pasireotide: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and pasireotide is needed, as coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include procainamide.
    Penbutolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like penbutolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Pentamidine: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include procainamide. Additive effects on the QT interval are possible.
    Perindopril; Amlodipine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Perphenazine: (Minor) Perphenazine should be used cautiously and with close monitoring with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Perphenazine; Amitriptyline: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA. (Minor) Perphenazine should be used cautiously and with close monitoring with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Phenoxybenzamine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Phentolamine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include procainamide.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of procainamide with pimozide is contraindicated.
    Pindolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like pindolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Pirbuterol: (Minor) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Polymyxins: (Moderate) Procainamide can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
    Posaconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering posaconazole with procainamide. Procainamide is associated with a well-established risk of QT prolongation and TdP. Posaconazole also has been associated with QT prolongation and in rare cases, TdP.
    Potassium-sparing diuretics: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Prazosin: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include procainamide.
    Prochlorperazine: (Minor) Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with prochlorperazine include procainamide.
    Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include procainamide.
    Propafenone: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Class IC antiarrhythmic agents, such as propafenone, have proarrhythmic properties, and may have additive electrophysiologic effects with procainamide; use concomitantly with caution. The manufacturer of propafenone recommends against the use of propafenone with Class 1A agents such as procainamide.
    Propranolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like propranolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension. Procainamide's elimination half-life was not significantly changed when administered concomitantly with propranolol.
    Protriptyline: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Pyridostigmine: (Major) Procainamide may antagonize the effects of cholinesterase inhibitors such as pyridostigmine in the treatment of myasthenia gravis. Isolated case reports describe worsening symptoms shortly after procainamide is added however, this interaction may be due more to procainamide's local anesthetic properties than its anticholinergic properties.
    Quetiapine: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with quetiapine. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Quinidine: (Major) According to the manufacturer of procainamide, use with other Class 1A agents, such as quinidine, is contraindicated; however, the manufacturer also states such use may be reserved for patients with serious arrhythmias unresponsive to a single drug if under close observation. Quinidine should only be used with extreme caution with procainamide, due to the potential for QT prolongation and similar effects on the cardiac action potential. Coadministration of quinidine may increase serum concentrations of procainamide, possibly by competing for pathways of renal clearance.
    Quinine: (Major) Concurrent use of quinine and procainamide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Procainamide is also associated with a well-established risk of QT prolongation and TdP.
    Ranitidine: (Moderate) When ranitidine is used in doses more than 300 mg/day, such as those used in the treatment of Zollinger-Ellison syndrome, the renal tubular secretion of procainamide is inhibited; procainamide clearance is reduced leading to elevated procainamide and N-acetyl-procainamide plasma concentrations. It may be prudent to monitor patients for procainamide toxicity if procainamide and high doses of ranitidine are coadministered.
    Ranolazine: (Major) Ranolazine should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Reserpine: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Ribociclib: (Major) Avoid coadministration of ribociclib with procainamide due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Procainamide is also associated with a well-established risk of QT prolongation and TdP. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with procainamide due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Procainamide is also associated with a well-established risk of QT prolongation and TdP. Concomitant use may increase the risk for QT prolongation.
    Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Risperidone: (Major) Risperidone should be used cautiously and with close monitoring with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
    Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. Procainamide also prolongs the QT interval. If romidepsin and procainamide must be continued, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Sacubitril; Valsartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Salmeterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Saquinavir: (Major) Concurrent use of procainamide and saquinavir should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. Procainamide is also associated with a well-established risk of QT prolongation and TdP.
    Sertraline: (Major) There have been postmarketing reports of QT prolongation and torsade de pointes (TdP) during treatment with sertraline and the manufacturer of sertraline recommends avoiding concurrent use with drugs known to prolong the QTc interval. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Sevelamer: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of procainamide from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because procainamide has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
    Sevoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Short-acting beta-agonists: (Minor) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Solifenacin: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval.Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
    Sorafenib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with procainamide is necessary; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib has been associated with QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Sotalol: (Major) Sotalol administration is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Drugs that prolong the QT interval should be used with extreme caution in combination with sotalol. Ventricular tachycardia, including torsade de pointes and monomorphic ventricular tachycardia can occur with excessive prolongation of the QT interval. Examples of agents that may prolong the QT interval include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Before initiating sotalol, the previous Class I antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of (2-3) plasma half-lives for the discontinued drug.
    Sparfloxacin: (Severe) Sparfloxacin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Increases in QTc interval have been observed in healthy volunteers treated with sparfloxacin, and torsade de pointes has been reported in patients receiving sparfloxacin with disopyramide and amiodarone. Therefore, sparfloxacin is contraindicated in patients receiving these drugs. The use of sparfloxacin in conjunction with other drugs known to prolong the QT interval has not been studied and is not recommended due to the potential risk for torsade de pointes. Drugs which have been established to have a causal association with QT prolongation and TdP include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine).
    Spironolactone: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Trimethoprim and procainamide both undergo tubular secretion, and as a result, each drug can interfere with the renal clearance of the other. Although it is not necessary to avoid concomitant use of these two drugs, lower doses of procainamide may be necessary during trimethoprim administration.
    Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of procainamide with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Tacrolimus: (Major) Tacrolimus should be used cautiously and with close clinical monitoring with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP) and tacrolimus causes QT prolongation.
    Tamoxifen: (Major) Caution is advised with the concomitant use of tamoxifen and procainamide due to an increased risk of QT prolongation and torsade de pointes (TdP). Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Teduglutide: (Moderate) Teduglutide may increase absorption of procainamide because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of procainamide is recommended.
    Telavancin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with telavancin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and telavancin has been associated with QT prolongation.
    Telithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with procainamide. Both telithromycin and procainamide are associated with QT prolongation and TdP.
    Telmisartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Terazosin: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Terbutaline: (Minor) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Terfenadine: (Severe) Use together is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Terfenadine has a well-established risk for QT prolongation and torsade de pointes (TdP). Other drugs that have also been independently associated with prolonged QT syndrome and/or TdP, such as procainamide (a class 1A antiarrhythmic agent), should not be used concomitantly with terfenadine.
    Tetrabenazine: (Major) The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Thiazide diuretics: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Thioridazine: (Severe) Because of the potential for torsades de pointes (TdP), use of a Class IA antiarrhythmic (disopyramide, procainamide, and quinidine) with thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Timolol: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like timolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
    Tiotropium; Olodaterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Tolterodine: (Major) Tolterodine should be used cautiously and with close monitoring with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. This should be taken into consideration when prescribing tolterodine to patients taking other drugs that are associated with QT prolongation. In addition, the anticholinergic effects of procainamide may be significant and may be enhanced when combined with tolterodine. Anticholinergic agents administered concurrently with procainamide may produce additive antivagal effects on AV nodal conduction, although this is not as well documented for procainamide as for quinidine.
    Toremifene: (Major) Avoid coadministration of procainamide with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Trandolapril; Verapamil: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Trazodone: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP) and should be avoided in combination with trazodone. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of TdP. Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
    Treprostinil: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Triamterene: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Tricyclic antidepressants: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Trifluoperazine: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with Class IA antiarrhythmics.
    Trimethoprim: (Major) Trimethoprim and procainamide both undergo tubular secretion, and as a result, each drug can interfere with the renal clearance of the other. Although it is not necessary to avoid concomitant use of these two drugs, lower doses of procainamide may be necessary during trimethoprim administration.
    Trimipramine: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA.
    Triptorelin: (Major) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with triptorelin include procainamide.
    Trospium: (Major) Both trospium and procainamide are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or procainamide due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or procainamide is recommended.
    Umeclidinium; Vilanterol: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Valsartan: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Vandetanib: (Major) Avoid coadministration of vandetanib with procainamide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Vardenafil: (Major) The manufacturer recommends that vardenafil be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction) The effect of vardenafil on the QT interval should be considered when prescribing the drug.
    Vasodilators: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with vemurafenib include procainamide
    Venlafaxine: (Major) Venlafaxine should be used cautiously and with close clinical monitoring with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Venlafaxine administration is associated with a possible risk of QT prolongation; TdP has reported with post-marketing use.
    Verapamil: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Voriconazole: (Major) Voriconazole should be used cautiously and with close clinical monitoring with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Voriconazole has been associated with QT prolongation and rare cases of torsades de pointes.
    Vorinostat: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with procainamide.
    Ziprasidone: (Severe) Concomitant use of ziprasidone and class 1A antiarrhythmics, such as procainamide, is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Class 1A antiarrhythmics are associated with a well-established risk of QT prolongation and TdP.

    PREGNANCY AND LACTATION

    Pregnancy

    Procainamide is classified as FDA pregnancy risk category C. It is not known if procainamide causes fetal harm or can affect reproduction capacity, and animal reproduction studies have not been conducted. Only administer to a pregnant woman if clearly needed.

    Procainamide and NAPA are both distributed into breast milk and absorbed by the nursing infant. According to the manufacturer, because of the potential for serious adverse reactions in nursing infants from procainamide, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. Despite this warning by the manufacturer, the American Academy of Pediatrics considers procainamide, as well as disopyramide and quinidine, to be usually compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Like procaine, procainamide inhibits the influx of sodium through membrane pores. Procainamide exerts its effects on 'fast' channels of the myocardial cell membrane, prolonging the recovery period after repolarization. The effective refractory period and the action potential duration in the atria, ventricles, and His-Purkinje system are prolonged. The effective refractory period is increased more than the action potential duration; therefore, the myocardium remains refractory even after the resting membrane potential has been restored. The drug decreases myocardial automaticity, excitability, conduction velocity, and possibly contractility. Procainamide also exhibits anticholinergic properties that may modify its myocardial effects, however these actions are less pronounced than for either quinidine or disopyramide.The net effect of procainamide is to suppress ectopy in atrial and ventricular tissue. Because nodal tissue is more dependent on calcium influx, procainamide has little use in arrhythmias of nodal origin. Clinically, procainamide is used mainly in the treatment of atrial fibrillation and/or flutter, for which it is generally considered a second-line agent after quinidine. Procainamide is an alternative antiarrhythmic for the treatment of stable ventricular tachycardia in patients with preserved left ventricular function.

    PHARMACOKINETICS

    Procainamide is administered orally and parenterally. The extent of metabolism is dependent on the activity of acetyl transferase. Metabolic rate is greater in patients who are rapid acetylators. Significant amounts of both unchanged procainamide and N-acetylprocainamide (NAPA) are eliminated renally by glomerular filtration and active tubular secretion. Once absorbed, procainamide distributes widely throughout the body and is approximately 15% bound to plasma proteins. The extent of metabolism is dependent on the activity of acetyl transferase. Metabolic rate is greater in patients who are rapid acetylators.

    Oral Route

    Approximately 80—90% of an oral dose of procainamide is absorbed, with peak plasma levels occurring within 1 hour for regular-release capsules, between 2—3 hours for sustained-release tablets, and between 4—6 hours with the Procanbid T-kote delivery system. The extent of absorption of procainamide from Procanbid extended-release tablets is increased by about 20% when administered with a high-fat meal. Similar peak, trough, average plasma procainamide concentrations are achieved with either Procanbid administered twice daily or Procan SR (branded product no longer commercially available) sustained-release tablets given 4 times daily. Once absorbed, procainamide distributes widely throughout the body and is approximately 15% bound to plasma proteins.
     
    Between 10—34% of an oral dose of the drug undergoes acetylation in the liver to N-acetylprocainamide (NAPA), which also possesses electrophysiologic activity. In patients with normal renal function, the half-life of procainamide from regular-release capsules is roughly 2.5 hours in rapid acetylators and 5.2 hours in slow acetylators. This necessitates dosing as frequently as every 3—4 hours with regular-release capsules in order to maintain therapeutic plasma concentrations. Generic sustained-release tablets can be dosed every 6—8 hours in patients with normal renal function. Procanbid extended-release tablets can be dosed every 12 hours.

    MONITORING

    NOTE: Serum procainamide concentrations should be monitored in all patients receiving procainamide. Doses should also be adjusted according to age, body weight and organ function.