Disopyramide: Drug information

For additional information see "Disopyramide: Patient drug information" and "Disopyramide: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table

ALERT: US Boxed Warning

Mortality:

In the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had an MI more than 6 days but less than 2 years previously, an excessive mortality or nonfatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3%). The average duration of treatment with encainide or flecainide in this study was 10 months.

The applicability of the CAST results to other populations (eg, those without recent MI) is uncertain. Considering the known proarrhythmic properties of disopyramide and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of disopyramide as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.

Brand Names: US

Norpace;
Norpace CR

Brand Names: Canada

Rythmodan

Pharmacologic Category

Antiarrhythmic Agent, Class Ia

Dosing: Adult

Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction

Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction (off-label use): Oral: Initial: Controlled release: 200 to 250 mg twice daily. If symptoms do not improve, increase by 100 mg/day at 2-week intervals to a maximum daily dose of 600 mg administered in 2 divided doses (Ref).

Note: May consider the use of pyridostigmine to mitigate anticholinergic adverse effects (eg, urinary retention, constipation, dry mouth) associated with disopyramide (Ref).

Ventricular arrhythmias

Ventricular arrhythmias: Oral: Note: Since newer agents with less toxicity are available, the use of disopyramide for this indication has fallen out of favor. Controlled release formulation is not to be used when rapid achievement of disopyramide plasma concentrations is desired. A maximum dose up to 400 mg every 6 hours (immediate release) may be required for patients with severe refractory ventricular tachycardia. Avoid loading dose in patients with cardiomyopathy or possible cardiac decompensation.

<50 kg:

Immediate release: An initial loading dose of 200 mg may be administered if rapid onset is required. Maintenance dose: 100 mg every 6 hours.

Controlled release: Maintenance dose: 200 mg every 12 hours.

≥50 kg:

Immediate release: An initial loading dose of 300 mg may be administered if rapid onset is required. Maintenance dose: 150 mg every 6 hours. If rapid control is necessary and no response seen within 6 hours of loading dose, may increase maintenance dose to 200 mg every 6 hours.

Controlled release: Maintenance dose: 300 mg every 12 hours.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Manufacturer's labeling:

Immediate release:

CrCl >40 mL/minute: 100 mg every 6 hours

CrCl 30 to 40 mL/minute: 100 mg every 8 hours

CrCl 15 to 30 mL/minute: 100 mg every 12 hours

CrCl <15 mL/minute: 100 mg every 24 hours

Controlled release:

CrCl >40 mL/minute: 200 mg every 12 hours

CrCl ≤40 mL/minute: Not recommended for use

Alternative recommendations (Ref): Immediate release:

CrCl >50 mL/minute: 100 to 200 mg every 8 hours

CrCl 10 to 50 mL/minute: 100 to 200 mg every 12 to 24 hours

CrCl <10 mL/minute: 100 to 200 mg every 24 to 48 hours

Dialysis: Not dialyzable (0% to 5%) by hemo- or peritoneal methods; supplemental dose is not necessary.

Dosing: Hepatic Impairment: Adult

Manufacturer's labeling:

Immediate release: 100 mg every 6 hours

Controlled release: 200 mg every 12 hours

Dosing: Older Adult

Avoid use (Ref).

Dosing: Pediatric

(For additional information see "Disopyramide: Pediatric drug information")

Ventricular arrhythmias

Ventricular arrhythmias: Note: Patient should be hospitalized during the initial treatment and dose initiated at the lower end of dose range.

Immediate release: Oral:

Infants: 10 to 30 mg/kg/day in divided doses every 6 hours

Children 1 to 4 years: 10 to 20 mg/kg/day in divided doses every 6 hours

Children >4 to 12 years: 10 to 15 mg/kg/day in divided doses every 6 hours

Children >12 and Adolescents ≤18 years: 6 to 15 mg/kg/day in divided doses every 6 hours; adult maximum daily dose: 1,600 mg/day

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric specific recommendations; based on experience in adult patients, dosage adjustment suggested.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric specific recommendations; based on experience in adult patients, dosage adjustment suggested.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not always defined. The most common adverse effects are related to cholinergic blockade. The most serious adverse effects of disopyramide are hypotension and cardiac failure.

>10%:

Gastrointestinal: Xerostomia (32%), constipation (11%)

Genitourinary: Urinary hesitancy (14% to 23%)

1% to 10%:

Cardiovascular: Cardiac conduction disturbance, cardiac failure, chest pain, edema, hypotension, syncope

Central nervous system: Dizziness, fatigue, headache, malaise, myasthenia, nervousness

Dermatologic: Generalized dermatosis, pruritus, skin rash

Endocrine & metabolic: Hypokalemia, increased serum cholesterol, increased serum triglycerides, weight gain

Gastrointestinal: Abdominal distention, anorexia, bloating, diarrhea, flatulence, nausea, vomiting

Genitourinary: Impotence (1% to 3%), urinary frequency, urinary retention, urinary urgency

Neuromuscular & skeletal: Myalgia

Ophthalmic: Blurred vision, xerophthalmia

Respiratory: Dry throat, dyspnea

<1%, postmarketing, and/or case reports: Agranulocytosis, atrioventricular block, cardiac arrhythmia (new or worsened; proarrhythmic effect), cholestatic jaundice, decreased hematocrit, decreased hemoglobin, depression, dysuria, fever, gynecomastia, hepatotoxicity, hypoglycemia, increased blood urea nitrogen, increased serum creatinine, increased serum transaminases, insomnia, mydriasis, numbness, paresthesia, peripheral neuropathy, psychosis, psychotic reaction, respiratory distress, skin blister (toxic), systemic lupus erythematosus (rare; generally in patients previously receiving procainamide), thrombocytopenia, tingling sensation

Contraindications

Hypersensitivity to disopyramide or any component of the formulation; cardiogenic shock; preexisting second- or third-degree heart block (except in patients with a functioning artificial pacemaker); congenital long QT syndrome

Canadian labeling: Additional contraindications (not in US labeling): Renal failure, severe intraventricular conduction defects (ie, bundle-branch block associated with first-degree atrioventricular block, double block [left posterior or anterior hemiblock and right bundle-branch block]); severe sinus node dysfunction; decompensated or inadequately compensated heart failure; concurrent use with other antiarrhythmics or other drugs capable of provoking ventricular arrhythmias (especially torsade de pointes); glaucoma; urinary retention

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Hypotension: May occur during the initiation of therapy; monitor closely.

• Proarrhythmic effects: Monitor for proarrhythmic effects; may cause QT_c prolongation and subsequent torsade de pointes; avoid use in patients with diagnosed or suspected congenital long QT syndrome. Monitor and adjust dose to prevent QT_c prolongation. Increases in QT_c >25% over baseline should result in cessation or reduction in disopyramide dosing. Because of the risk of QT_c prolongation and arrhythmias, disopyramide should be initiated within the hospital with cardiac monitoring. In patients with preexisting cardiovascular disease, the incidence of proarrhythmic effects and mortality may be increased with Class Ia antiarrhythmic agents.

Disease-related concerns:

• Atrial fibrillation/flutter: May increase ventricular response rate in patients with atrial fibrillation or flutter; control AV conduction before initiating.

• BPH/urinary retention: Do not use in patients with BPH and/or urinary retention due to significant anticholinergic effects.

• Conduction disturbances: Use with caution in patients with bundle branch block or heart block.

• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.

• Glaucoma: Do not use in patients with glaucoma due to significant anticholinergic effects.

• Heart failure: Use with caution or avoid in patients with any degree of left ventricular dysfunction or history of heart failure; may precipitate or exacerbate condition.

• Hepatic impairment: Use with caution in patients with hepatic impairment; reduced dosage recommended.

• Myasthenia gravis: Do not use in patients with myasthenia gravis due to significant anticholinergic effects.

• Renal impairment: Use with caution in renal impairment; reduced dosage recommended. The controlled release form is not recommended for CrCl ≤40 mL/minute.

• Wolff-Parkinson-White syndrome: Use with caution in patients with Wolff-Parkinson-White syndrome.

Other warnings/precautions:

• CAST trial: [US Boxed Warning]: In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, non-life-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress the arrhythmia with flecainide or encainide. An increased mortality or nonfatal cardiac arrest rate (7.7%) was seen in the active treatment group compared with patients in the placebo group (3%). The applicability of the CAST results to other populations is unknown. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Norpace: 100 mg, 150 mg

Generic: 100 mg, 150 mg

Capsule Extended Release 12 Hour, Oral:

Norpace CR: 100 mg, 150 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Capsule, 12-hour (Norpace CR Oral)

100 mg (per each): $5.13

150 mg (per each): $6.06

Capsules (Disopyramide Phosphate Oral)

100 mg (per each): $2.86

150 mg (per each): $3.38

Capsules (Norpace Oral)

100 mg (per each): $5.66

150 mg (per each): $6.69

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Rythmodan: 100 mg [contains corn starch, fd&c blue #2 (indigotine,indigo carmine)]

Administration: Adult

Do not break or chew controlled-release capsules. Administer around-the-clock rather than 4 times/day (ie, 12-6-12-6, not 9-1-5-9) to promote less variation in peak and trough serum levels.

Bariatric surgery: Capsule, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR capsule or extemporaneously compounded oral suspension.

Administration: Pediatric

Oral: Do not crush, break, or chew controlled-release capsules; swallow whole

Use: Labeled Indications

Ventricular arrhythmias: Life-threatening ventricular arrhythmias (eg, sustained ventricular tachycardia).

Use: Off-Label: Adult

Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction

Medication Safety Issues

Sound-alike/look-alike issues:

Disopyramide may be confused with desipramine, dipyridamole

Norpace may be confused with Norpramin

Older Adult: High-Risk Medication:

Beers Criteria: Disopyramide is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its risk for inducing heart failure (potent negative inotrope) and its strong anticholinergic properties; other antiarrhythmic agents are preferred (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Agents with Clinically Relevant Anticholinergic Effects: May enhance the adverse/toxic effect of other Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Ajmaline: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase the serum concentration of Ajmaline. Risk X: Avoid combination

Amantadine: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Amiodarone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, consider dose reductions of the class IA antiarrhythmic (30% to 50%) and monitor for QTc interval prolongation and ventricular arrhythmias. Risk D: Consider therapy modification

Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Benperidol: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Benperidol. Risk C: Monitor therapy

Beta-Blockers: Disopyramide may enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Risk C: Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Bromperidol: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Bromperidol. Risk C: Monitor therapy

Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Carbetocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Ceritinib. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Chloral Betaine: May enhance the adverse/toxic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy

Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination

Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination

Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

ClomiPRAMINE: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

Crizotinib: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Crizotinib. Crizotinib may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Crizotinib may increase the serum concentration of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Disopyramide. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Disopyramide. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Disopyramide. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Disopyramide. Risk C: Monitor therapy

Dabrafenib: May enhance the QTc-prolonging effect of Disopyramide. Dabrafenib may decrease the serum concentration of Disopyramide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and reduced disopyramide efficacy. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Dimethindene (Systemic). Risk C: Monitor therapy

Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

DroPERidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of DroPERidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Encorafenib: May enhance the QTc-prolonging effect of Disopyramide. Encorafenib may decrease the serum concentration of Disopyramide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased disopyramide concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Erythromycin (Systemic): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Erythromycin (Systemic) may increase the serum concentration of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Etelcalcetide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination

Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Fluconazole: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider therapy modification

Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Gemifloxacin: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination

Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification

Glucagon: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Haloperidol: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Iboga: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Ipratropium (Nasal): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Itopride: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Itraconazole: May increase the serum concentration of Disopyramide. Risk X: Avoid combination

Ketoconazole (Systemic): May increase the serum concentration of Disopyramide. Risk X: Avoid combination

Lacosamide: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy

Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination

Levofloxacin-Containing Products (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination

Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination

Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lidocaine (Systemic): Disopyramide may enhance the arrhythmogenic effect of Lidocaine (Systemic). Disopyramide may increase the serum concentration of Lidocaine (Systemic). Specifically, the unbound/free fraction of lidocaine may be increased. Risk C: Monitor therapy

Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Lonafarnib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Mavacamten: Disopyramide may enhance the adverse/toxic effect of Mavacamten. Specifically, negative inotropic effects may be increased. Risk X: Avoid combination

Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Methadone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Mianserin: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination

Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination

Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ondansetron: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Opioid Agonists: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy

Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Oxatomide: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Oxytocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

PAZOPanib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of PAZOPanib. Risk X: Avoid combination

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination

Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination

Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination

Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination

Pramlintide: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid combination

Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination

Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination

Propofol: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of other QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination

QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for increased class IA toxicities, including QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

Quizartinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination

RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Saquinavir: May enhance the QTc-prolonging effect of Disopyramide. Saquinavir may increase the serum concentration of Disopyramide. Risk X: Avoid combination

Secretin: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination

SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Terbutaline: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Topiramate: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Umeclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Verapamil: May enhance the adverse/toxic effect of Disopyramide. Of particular concern is the potential for profound depression of myocardial contractility. Management: Concurrent use of disopyramide within 48 hours prior to or 24 hours after verapamil should be avoided. Risk X: Avoid combination

Voriconazole: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Voriconazole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pregnancy Considerations

Disopyramide levels have been reported in human fetal blood. Disopyramide may stimulate contractions in pregnant women. In a case report, disopyramide use in the third trimester resulted in painful uterine contractions after the first dose and hemorrhage after the second dose (Abbi 1999).

Breastfeeding Considerations

Disopyramide is present in breast milk. Due to the potential for serious adverse reactions in breastfed infants, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the treatment to the mother.

Monitoring Parameters

ECG, blood pressure, urinary retention, CNS anticholinergic effects (confusion, agitation, hallucinations, etc); disopyramide drug level (if available); signs and symptoms of heart failure

Reference Range

Therapeutic concentration:

Atrial arrhythmias (off-label use), hypertrophic cardiomyopathy (off-label use): 2 to 4 mcg/mL (SI: 5.9 to 11.8 micromole/L) (Niarchos 1976; Verlinden 2015)

Ventricular arrhythmias: 3.3 to 7 mcg/mL (SI: 9.7 to 20.6 micromole/L) (Niarchos 1976)

Toxic concentration: >7 mcg/mL (SI: >20.6 micromole/L)

Mechanism of Action

Class Ia antiarrhythmic: Decreases myocardial excitability and conduction velocity; reduces disparity in refractory between normal and infarcted myocardium; possesses anticholinergic, peripheral vasoconstrictive, and negative inotropic effects

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: 0.5 to 3.5 hours

Duration: Immediate release: 1.5 to 8.5 hours

Absorption: Rapid and almost complete

Distribution: V_d:

Children 5 to 12 years: 1.02 ± 0.2 L/kg (Chiba 1992)

Adults: 0.8 to 2 L/kg

Protein binding (concentration dependent): 50% to 65%

Metabolism: Hepatic; N-dealkylation to the active metabolite N-despropyldisopyramide (or mono-N-dealkylated [MND] metabolite) and other inactive metabolites

Half-life elimination:

Children 5 to 12 years: 3.15 ± 0.64 hours (Chiba 1992)

Adults: 4 to 10 hours; prolonged with heart failure and hepatic or renal impairment

Time to peak, serum: Immediate release: Within 2 hours; Controlled release: 4 to 7 hours

Excretion: Urine (~50% as unchanged drug; ~20% as MND; 10% other metabolites); feces (10% to 15%)

Clearance: Children 5 to 12 years: 3.79 ± 0.82 mL/minute/kg (Chiba 1992) (greater than adults)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Heart failure: T_max and C_max are increased.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Norpace | Rythmodan;
(AU) Australia: Norpace | Rythmodan;
(BD) Bangladesh: Norbit;
(BE) Belgium: Dirytmin | Rythmodan;
(BR) Brazil: Dicorantil;
(CH) Switzerland: Norpace;
(CO) Colombia: Dicorantyl;
(CZ) Czech Republic: Korapeis | Norpace | Rytmilen;
(DE) Germany: Norpace | Rythmodul;
(EE) Estonia: Durbis | Rythmodan;
(EG) Egypt: Norpace;
(ES) Spain: Dicorynan;
(FI) Finland: Disaloc | Disomet | Norpace | Rytmilen;
(FR) France: Isorythm | Rythmodan;
(GB) United Kingdom: Dirythmin | Dirythmin sa | Disopyramide | Disopyramide kent | Isomide | Norpace | Rythmodan;
(GR) Greece: Rythmodan;
(HK) Hong Kong: Norpace;
(HU) Hungary: Palpitin | Rythmodan;
(ID) Indonesia: Disopyramide | Norpace | Rythmodan | Rytmilen;
(IE) Ireland: Rythmodan;
(IL) Israel: Rythmical;
(IN) India: Norpace;
(IT) Italy: Ritmodan;
(JO) Jordan: Rythmodan;
(JP) Japan: Chiyoban | Disopra r nichiiko | Disopyra r | Disopyramide | Disopyramide Np | Disopyramide sw | Disopyran | Fanmil | Fanmil-r | Kafier | Lispine chemiphar | Lispine r | Mycorten r | Norpace | Postormin | Rislamid r | Rizoramid | Rizoramid choseido | Rythmodan | Rythmodan r | Sopyrat | Tailinder taiyo | Tailinder towa;
(KR) Korea, Republic of: Disopyramide | Norpace;
(KW) Kuwait: Rythmodan;
(LB) Lebanon: Rythmodan;
(LT) Lithuania: Rytmilen;
(LU) Luxembourg: Dirytmin | Rythmodan;
(LV) Latvia: Rytmilen;
(MA) Morocco: Rythmodan;
(MX) Mexico: Dimodan;
(MY) Malaysia: Norpace;
(NL) Netherlands: Dirytmin | Disopyramide gf | Disopyramide pch | Ritmoforine | Rythmodan;
(NO) Norway: Durbis | Rythmodul;
(NZ) New Zealand: Rythmodan;
(PH) Philippines: Norpace;
(PK) Pakistan: Norpace;
(PL) Poland: Disocor | Rythmodan | Rytmilen;
(PR) Puerto Rico: Disopyramide | Norpace | Norpace cr;
(PT) Portugal: Disopiramida | Ritmodan | Rythmodan;
(RU) Russian Federation: Norpace;
(SE) Sweden: Durbis;
(SG) Singapore: Norpace;
(SI) Slovenia: Norpace S;
(SK) Slovakia: Korapeis;
(TH) Thailand: Norpace;
(TN) Tunisia: Rythmodan;
(TR) Turkey: Norpace;
(TW) Taiwan: Modiparil | Norpace | Rytmilen;
(UA) Ukraine: Corapeis;
(VE) Venezuela, Bolivarian Republic of: Disopiramida;
(ZA) South Africa: Norpace | Rythmodan

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Disopyramide: Drug information