procainamide

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procainamide

Classes

Anti-arrhythmics, Class I-A

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.

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

Boxed Warning
Apheresis, arrhythmia exacerbation, AV block, bradycardia, bundle-branch block, cardiomyopathy, celiac disease, digitalis toxicity, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, mortality, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, 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 conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) 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. Additionally, SLE may increase the risk of prolonging the QT interval when using procainamide.

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 to 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

Parenteral, class IA antiarrhythmic agent
Used for the treatment of life-threatening ventricular arrhythmias
Associated with serious and sometimes fatal hematologic adverse events, particularly agranulocytosis or leukopenia

Dosage And Indications
For the treatment of ventricular tachycardia. For the treatment of hemodynamically stable monomorphic ventricular tachycardia. Intravenous dosage Adults

20 to 50 mg/minute IV continuous infusion or 100 mg IV every 5 minutes until arrhythmia suppressed, hypotension, QRS prolonged by 50%, or a total cumulative dose of 17 mg/kg, then 1 to 4 mg/minute continuous IV infusion.

For the treatment of wide-complex ventricular tachycardia†. Intravenous or Intraosseous dosage Infants, Children, and Adolescents

15 mg/kg/dose (Max: 100 mg/dose) IV or IO as a single dose. Consider procainamide for the treatment of wide-complex tachycardia in hemodynamically stable patients.

For the treatment of junctional ectopic tachycardia† or pre-excitatory atrial fibrillation† in persons with Wolff-Parkinson-White (WPW) syndrome†. Intravenous dosage Adults

20 to 50 mg/minute IV continuous infusion or 100 mg IV every 5 minutes until arrhythmia suppressed, hypotension, QRS prolonged by 50%, or a total cumulative dose of 17 mg/kg, then 1 to 4 mg/minute continuous IV infusion.

For the treatment of supraventricular tachycardia (SVT)†. For the treatment of SVT† excluding during cardiopulmonary resuscitation. Intravenous dosage Infants, Children, and Adolescents

3.5 to 15 mg/kg/dose (Max: 100 mg/dose) IV as a single dose, then 10 to 80 mcg/kg/minute continuous IV infusion. Max: 2 g/day.

Neonates

3.5 to 10 mg/kg/dose IV as a single dose, then 10 to 80 mcg/kg/minute continuous IV infusion has been studied for various tachyarrhythmias.

For the treatment of SVT† during cardiopulmonary resuscitation. Intravenous or Intraosseus dosage Infants, Children, and Adolescents

15 mg/kg/dose (Max: 100 mg/dose) IV or IO as a single dose. Additional doses may be administered if there is no effect and no toxicity from the initial dose; however, a maximum dose is not provided. Adult guidelines recommend a maximum dose of 17 mg/kg. Consider procainamide for SVT unresponsive to vagal maneuvers and adenosine and/or electric cardioversion.

†Indicates off-label use

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.

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: (Contraindicated) 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.
Adagrasib: (Major) Concomitant use of adagrasib and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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.
Alosetron: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as procainamide, however, this interaction has not been studied.
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.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with procainamide. Amisulpride causes dose- and concentration- dependent QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and TdP.
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; Celecoxib: (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; 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; Valsartan; 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.
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) Use apomorphine and procainamide together with caution due to the risk of additive QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) Concomitant use of procainamide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Articaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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) Concomitant use of procainamide and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Concomitant use of procainamide and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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) Concomitant use of metronidazole and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Bupivacaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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.
Cabotegravir; 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.
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) Avoid coadministration of ceritinib with procainamide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; 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) Avoid coadministration of chloroquine with procainamide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Procainamide is associated with a well-established risk of QT prolongation and TdP.
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) Concomitant use of procainamide and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) 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) Concomitant use of procainamide and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Concomitant use of clofazimine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Concomitant use of promethazine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of promethazine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Colistin: (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.
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) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as class IA antiarrhythmics. Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
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).
Deutetrabenazine: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and procainamide. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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: (Contraindicated) Coadministration of dofetilide and procainamide is contraindicated as concurrent use may increase the risk of QT prolongation and torsade de pointes (TdP). Class I antiarrhythmic agents, such as procainamide, should be withheld for at least 3 half-lives prior to initiating dofetilide therapy. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Procainamide is also associated with a well-established risk of QT prolongation and TdP.
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; 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.
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.
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: (Contraindicated) 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.
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 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.
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.
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).
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.
Entrectinib: (Major) Avoid coadministration of entrectinib with procainamide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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.
Escitalopram: (Major) Concomitant use of procainamide and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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: (Major) Advise patients to avoid alcohol consumption while taking procainamide. Alcohol consumption has been observed to decrease procainamide overall exposure by approximately 20% in healthy volunteers. (Moderate) Alcohol consumption tends to decrease the half-life of procainamide in the blood through induction of its acetylation to NAPA.
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: (Contraindicated) 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) Concomitant use of procainamide and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Major) Concomitant use of procainamide and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluoxetine: (Major) Concomitant use of procainamide and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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.
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.
Fostemsavir: (Major) Avoid coadministration of procainamide with fostemsavir as concomitant use may increase the risk of QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
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.
Gilteritinib: (Major) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and procainamide is necessary. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Gilteritinib has also been associated with QT prolongation.
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).
Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc 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.
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.
Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Hydroxychloroquine: (Major) Concomitant use of procainamide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of procainamide and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibutilide: (Contraindicated) 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.
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.
Irbesartan; 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.
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: (Contraindicated) Avoid concomitant use of ketoconazole and procainamide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
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.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lansoprazole; Amoxicillin; 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).
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 c

oncentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
Lefamulin: (Major) Avoid coadministration of lefamulin with procainamide as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
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) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Levamlodipine: (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.
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.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and procainamide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
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.
Lidocaine; Epinephrine: (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. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Lidocaine; Prilocaine: (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) Concomitant use of procainamide and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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) Concomitant use of loperamide and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with procainamide due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
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.
Losartan; 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.
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.
Mavacamten: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and procainamide. If concomitant therapy with procainamide is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Mecamylamine: (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.
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.
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.
Metoprolol; 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 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) Concomitant use of metronidazole and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Concomitant use of procainamide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirtazapine: (Major) Concomitant use of procainamide and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mobocertinib: (Major) Concomitant use of mobocertinib and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Neostigmine; Glycopyrrolate: (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) A lower neuromuscular blocker dose may be required to achieve neuromuscular block with concomitant procainamide use due to procainamide effects on reducing acetylcholine release. Concomitant use of neuromuscular blockers and procainamide may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
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.
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).
Olanzapine; Fluoxetine: (Major) Concomitant use of procainamide and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (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).
Olanzapine; Samidorphan: (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.
Olmesartan; 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.
Olmesartan; 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.
Ondansetron: (Major) Concomitant use of procainamide and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Major) Monitor ECGs in patients receiving osilodrostat with procainamide. Osilodrostat is associated with dose-dependent QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes.
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.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking procainamide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Procainamide is associated with a well-established risk of QT prolongation and TdP.
Pacritinib: (Major) Concomitant use of pacritinib and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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: (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.
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: (Contraindicated) 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.
Pitolisant: (Major) Avoid coadministration of pitolisant with procainamide as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking procainamide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Procainamide is associated with a well-established risk of QT prolongation and TdP.
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.
Prilocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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) Concomitant use of promethazine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of propafenone and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Propranolol; 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 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.
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) Concomitant use of quetiapine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Quizartinib: (Major) Concomitant use of quizartinib and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Relugolix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
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.
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.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with procainamide is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Sertraline: (Major) Concomitant use of sertraline and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
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).
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving procainamide due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Avoid coadministration of sorafenib with procainamide due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Sorafenib is associated with QTc prolongation.
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.
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.
Spironolactone; 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.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor procainamide plasma concentrations, if available, and for clinical and ECG signs of procainamide toxicity with concomitant trimethoprim use. Trimethoprim increases the plasma concentrations of procainamide and its active N-acetyl metabolite (NAPA). The increased procainamide and NAPA plasma concentrations are associated with further prolongation of the QTc interval.
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) Concomitant use of tamoxifen and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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.
Telmisartan; 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.
Telmisartan; 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.
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.
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: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of procainamide and thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use with agents that 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.
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) Concomitant use of trazodone and procaonamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Triamterene; 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.
Triclabendazole: (Major) Concomitant use of triclabendazole and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) Trifluoperazine and procainamide should be used cautiously due to the potential for QT prolongation. Trifluoperazine, a phenothiazine, has a possible risk for QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Trimethoprim: (Moderate) Monitor procainamide plasma concentrations, if available, and for clinical and ECG signs of procainamide toxicity with concomitant trimethoprim use. Trimethoprim increases the plasma concentrations of procainamide and its active N-acetyl metabolite (NAPA). The increased procainamide and NAPA plasma concentrations are associated with further prolongation of the QTc interval.
Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
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.
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.
Valsartan; 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.
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) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. 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) Concomitant use of venlafaxine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Voclosporin: (Major) Use caution if procainamide is coadministered with voclosporin due to the risk of additive QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; 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).
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: (Contraindicated) 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.

How Supplied

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

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.

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.

Pregnancy And Lactation
Pregnancy

Use procainamide during pregnancy only if clearly needed. It is not known whether procainamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Animal reproduction studies have not been conducted with procainamide.

According to the manufacturer, due to the potential for serious adverse reactions in the nursing infant, discontinue breast-feeding or discontinue procainamide, taking into account the importance of the drug to the mother. Procainamide and NAPA are both distributed into breast milk and absorbed by the nursing infant. However, previous American Academy of Pediatrics (AAP) recommendations considered procainamide, as well as disopyramide and quinidine, to be usually compatible with breast-feeding.