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Disopyramide: Pediatric drug information

Disopyramide: Pediatric drug information
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For additional information see "Disopyramide: Drug information" and "Disopyramide: Patient 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
Therapeutic Category
  • Antiarrhythmic Agent, Class I-A
Dosing: Pediatric
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: Liver Impairment: Pediatric

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

Dosing: Adult

(For additional information see "Disopyramide: Drug information")

Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction

Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction (off-label use):

Note: May consider as additional therapy in patients with persistent symptoms caused by left ventricular outflow tract obstruction despite treatment with a beta blocker or nondihydropyridine calcium channel blocker. Use in combination with an atrioventricular (AV) blocking agent (eg, a beta blocker or nondihydropyridine calcium channel blocker) since disopyramide can increase conduction through the AV node (Ref). May consider using pyridostigmine to mitigate anticholinergic adverse effects (eg, urinary retention, constipation, dry mouth) associated with disopyramide (Ref).

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).

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: Liver Impairment: Adult

Manufacturer's labeling:

Immediate release: 100 mg every 6 hours

Controlled release: 200 mg every 12 hours

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 QTc prolongation and subsequent torsade de pointes; avoid use in patients with diagnosed or suspected congenital long QT syndrome. Monitor and adjust dose to prevent QTc prolongation. Increases in QTc >25% over baseline should result in cessation or reduction in disopyramide dosing. Because of the risk of QTc 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): $5.18

150 mg (per each): $6.12

Capsules (Disopyramide Phosphate Oral)

100 mg (per each): $2.86

150 mg (per each): $3.38

Capsules (Norpace Oral)

100 mg (per each): $5.72

150 mg (per each): $6.76

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)]

Extemporaneous Preparations

10 mg/mL Oral Suspension

A 10 mg/mL suspension may be prepared using the 100 mg immediate-release capsules. Empty the contents of ten 100 mg capsules into a mortar. Triturate with cherry syrup and transfer mixture to graduated amber glass bottle. Rinse mortar with cherry syrup and add sufficient quantity of cherry syrup to make 100 mL. Label as “shake well” and “refrigerate.” Stable for 4 weeks in amber glass bottles stored at 5°C (41°F), 30°C (86°F), or at room temperature. Note: Do not use extended release capsules for this suspension.

Mathur LK, Lai PK, Shively CD. Stability of disopyramide phosphate in cherry syrup. Am J Hosp Pharm. 1982;39(2):309-310.7058805
Administration: Pediatric

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

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.

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Use

Treatment of life-threatening ventricular arrhythmias (ie, sustained ventricular tachycardia) (FDA approved in infants, children, adolescents, and adults)

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.

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

Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor

Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

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

Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Amiodarone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Antidiabetic Agents: May increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 decrease therapeutic effects of Benperidol. Risk C: Monitor

Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor

Beta-Blockers: Disopyramide may increase bradycardic effects of Beta-Blockers. Beta-Blockers may increase negative inotropic effects of Disopyramide. Risk C: Monitor

Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor

Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor

Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Bromperidol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bromperidol. Risk C: Monitor

Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor

Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor

Carbetocin: May increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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

Chloroquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase anticholinergic effects of Chlorprothixene. Risk C: Monitor

Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid

Citalopram: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Citalopram. Risk X: Avoid

Clarithromycin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Clarithromycin. Risk X: Avoid

Clofazimine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects 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

CloZAPine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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

Crizotinib: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of Crizotinib. Crizotinib may increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Crizotinib may increase 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

Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

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

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

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

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

Dabrafenib: May increase QTc-prolonging effects of Disopyramide. Dabrafenib may decrease 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

Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor

Dasatinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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

Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor

Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor

Domperidone: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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

DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid

DroPERidol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase constipating effects of Eluxadoline. Risk X: Avoid

Encorafenib: May increase QTc-prolonging effects of Disopyramide. Encorafenib may decrease 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 increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid

Erythromycin (Systemic): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of Erythromycin (Systemic). Erythromycin (Systemic) may increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Erythromycin (Systemic) may increase 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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

Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor

Fexinidazole: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid

Fingolimod: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid

Flecainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Flupentixol. Risk X: Avoid

FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Fusidic Acid (Systemic): May increase 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 increase QTc-prolonging effects 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 decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor

Gemifloxacin: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid

Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Gilteritinib: May increase QTc-prolonging effects 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 increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor

Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid

Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor

Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Grapefruit Juice: May increase serum concentration of Disopyramide. Risk C: Monitor

Halofantrine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor

HydrOXYzine: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk C: Monitor

Hypoglycemia-Associated Agents: May increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor

Iboga: May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor

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

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

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

Lefamulin: May increase QTc-prolonging effects 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

Levofloxacin-Containing Products (Systemic): May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid

Levoketoconazole: QT-prolonging CYP3A4 Substrates may increase QTc-prolonging effects of Levoketoconazole. Levoketoconazole may increase serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid

Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid

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

Lofexidine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor

Mavacamten: Disopyramide may increase adverse/toxic effects of Mavacamten. Specifically, negative inotropic effects may be increased. Risk X: Avoid

Meglumine Antimoniate: May increase QTc-prolonging effects 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

Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Methadone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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

Methotrimeprazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methotrimeprazine. Risk C: Monitor

Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor

Midostaurin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase adverse/toxic effects of Mirabegron. Risk C: Monitor

Monoamine Oxidase Inhibitors: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Moxifloxacin (Systemic). Risk X: Avoid

Nilotinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Nilotinib. Risk X: Avoid

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

OLANZapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase adverse/toxic effects of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor

Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Osimertinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor

Oxytocin: May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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

PAZOPanib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of PAZOPanib. Risk X: Avoid

Pegvisomant: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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

Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor

Pilsicainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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

Piperaquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid

Posaconazole: May increase 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

Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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

Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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

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

Probucol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Probucol. Risk X: Avoid

Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor

Propafenone: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid

Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor

Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Propofol: May increase QTc-prolonging effects 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 increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

QT-prolonging Agents (Indeterminate Risk - Avoid): May increase QTc-prolonging effects 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

QT-prolonging Agents (Indeterminate Risk - Caution): May increase QTc-prolonging effects 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

QT-prolonging Class IA Antiarrhythmics (Highest Risk): May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid

QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase 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 increase QTc-prolonging effects of QUEtiapine. Risk X: Avoid

Quinolones: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Quinolones may decrease therapeutic effects 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

Quizartinib: May increase QTc-prolonging effects 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 increase constipating effects of Ramosetron. Risk C: Monitor

Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid

Ribociclib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Ribociclib. Risk X: Avoid

RisperiDONE: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of RisperiDONE. QT-prolonging Agents (Highest Risk) may increase CNS depressant effects 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 decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects 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 increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Saquinavir: May increase QTc-prolonging effects of Disopyramide. Saquinavir may increase serum concentration of Disopyramide. Risk X: Avoid

Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor

Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects 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 Inhibitor: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Sertindole: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid

Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid

Sparfloxacin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Sparfloxacin. Risk X: Avoid

SUNItinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Thioridazine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid

Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor

Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor

Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid

Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor

Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor

Toremifene: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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

Tricyclic Antidepressants: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tricyclic Antidepressants. Risk C: Monitor

Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor

Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor

Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Vemurafenib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase adverse/toxic effects 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

Voriconazole: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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

Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor

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).

Monitoring Parameters

Blood pressure, ECG, urinary retention, CNS anticholinergic effects (confusion, agitation, hallucinations, etc), drug serum concentrations; serum potassium, glucose; especially important to monitor ECG in patients with hepatic or renal disease, heart disease, or others with increased risk of adverse effects

Reference Range

Therapeutic:

Ventricular arrhythmias: 2 to 5 mcg/mL (SI: 5.9 to 14.7 micromole/L) (Chiba 1992)

Toxic: >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: Vd:

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: Tmax and Cmax 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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