Norpace

Anti-arrhythmics, Class I-A

Oral Administration

Switching from Norpace to Norpace CR: The maintenance schedule of Norpace CR may be started 6 hours after the last dose of Norpace.

Extemporaneous Compounding-Oral

For patients unable to swallow the capsules, an oral suspension containing 1—10 mg/mL may be prepared by using the contents of the conventional capsules suspended in cherry syrup. Do not use extended-release capsules to prepare suspension. Shake well before each use. The suspension is stable for 4 weeks refrigerated in an amber glass bottle.

Severe

heart failure / Delayed / 1.0-3.0
AV block / Early / 0-1.0
agranulocytosis / Delayed / 0-1.0
torsade de pointes / Rapid / Incidence not known
ventricular tachycardia / Early / Incidence not known
arrhythmia exacerbation / Early / Incidence not known

Moderate

urinary retention / Early / 15.0-15.0
constipation / Delayed / 11.0-11.0
blurred vision / Early / 3.0-9.0
angina / Early / 1.0-3.0
edema / Delayed / 1.0-3.0
dyspnea / Early / 1.0-3.0
hypotension / Rapid / 1.0-3.0
hypokalemia / Delayed / 1.0-3.0
hypertriglyceridemia / Delayed / 1.0-3.0
hypercholesterolemia / Delayed / 1.0-3.0
impotence (erectile dysfunction) / Delayed / 1.0-3.0
dysuria / Early / 0-1.0
jaundice / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
anemia / Delayed / 0-1.0
hypoglycemia / Early / 0-1.0
depression / Delayed / 0-1.0
QT prolongation / Rapid / Incidence not known

Mild

xerostomia / Early / 32.0-32.0
urinary urgency / Early / 3.0-9.0
increased urinary frequency / Early / 3.0-9.0
xerosis / Delayed / 3.0-9.0
abdominal pain / Early / 3.0-9.0
flatulence / Early / 3.0-9.0
nausea / Early / 3.0-9.0
headache / Early / 3.0-9.0
malaise / Early / 3.0-9.0
fatigue / Early / 3.0-9.0
dizziness / Early / 3.0-9.0
weight gain / Delayed / 1.0-3.0
syncope / Early / 1.0-3.0
vomiting / Early / 1.0-3.0
diarrhea / Early / 1.0-3.0
anorexia / Delayed / 1.0-3.0
pruritus / Rapid / 1.0-3.0
rash / Early / 1.0-3.0
paresthesias / Delayed / 0-1.0
insomnia / Early / 0-1.0
musculoskeletal pain / Early / Incidence not known

Apheresis, AV block, bradycardia, bundle-branch block, celiac disease, females, fever, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, mortality, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sick sinus syndrome, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE), ventricular arrhythmias, Wolff-Parkinson-White syndrome

Disopyramide, a Class IA antiarrhythmic agent, has proarrhythmic properties which can result in exacerbation or induction of cardiac arrhythmias. In the CAST trial, a randomized double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias, an excessive rate of mortality or non-fatal cardiac arrest was seen in patients treated with encainide or flecainide (7.7%) compared to placebo (3%). The enrolled patients had a history of myocardial infarction (more than 6 days but less than 2 years); the average duration of antiarrhythmic therapy was 10 months. The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) or other antiarrhythmics is uncertain. Considering the known proarrhythmic properties of disopyramide and the lack of evidence of improved survival for antiarrhythmic drugs in patients without life-threatening arrhythmias, the use of disopyramide should be reserved for patients with life-threatening ventricular arrhythmias. Disopyramide is contraindicated in patients with congenital QT prolongation. Disopyramide is relatively contraindicated in patients with Wolff-Parkinson-White syndrome or heart block (e.g., left or right bundle-branch block, or sick sinus syndrome) because of the drug's unpredictable effects on AV conduction. Disopyramide should not be used in patients with second- or third-degree AV block in the absence of a pacemaker. Use disopyramide with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

Norpace, Norpace CR

Rx

Oral class IA antiarrhythmic; similar pharmacology to procainamide and quinidine
Used only for life-threatening ventricular arrhythmia
Significant proarrhythmic, anticholinergic, and negative inotropic properties limit its use

For the treatment of documented, life-threatening arrhythmias such as sustained ventricular tachycardia. Oral dosage (immediate-release capsules) Adults > 18 years and weighing > 50 kg

150—200 mg PO every 6 hours. If rapid control of the arrhythmia is needed, may use an initial loading dose of 300 mg PO, followed by the appropriate maintenance dose. Maximum dosage is 800 mg/day PO; however, up to 1600 mg/day PO has been used in the hospital setting to treat severe refractory ventricular tachycardia. For patients with cardiomyopathy or possible cardiac decompensation, no loading dose should be given and the initial maintenance dose should be limited to 100 mg PO every 6—8 hours; subsequent dosage adjustments should be made gradually.

Adults > 18 years and weighing < 50 kg

100 mg PO every 6 hours. If rapid control of the arrhythmia is needed, may use an initial loading dose of 200 mg PO, followed by the appropriate maintenance dose. Maximum dosage is 800 mg/day PO; however, up to 1600 mg/day PO has been used in the hospital setting to treat severe refractory ventricular tachycardia.

Geriatric

See adult dosage. Elderly patients are sensitive to anticholinergic effects of the drug and are more likely to have age-associated decreases in renal function; dosage selection should be conservative (see dosage for patients with renal impairment).

Adolescents

6—15 mg/kg/day PO, given in equally divided doses every 6 hours.

Children 5—12 years

10—15 mg/kg/day PO, given in equally divided doses every 6 hours.

Children 1-4 years

10—20 mg/kg/day PO, given in equally divided doses every 6 hours.

Infants < 1 year

10—30 mg/kg/day PO, given in equally divided doses every 6 hours.

Oral dosage (extended-release capsules) Adults weighing > 50 kg

300 mg PO every 12 hours. In patients with cardiomyopathy or possible cardiac decompensation, immediate-release capsules should be used for initial treatment (see above). Maximum dosage is 800 mg/day PO; however, up to 1600 mg/day PO has been used in the hospital setting to treat severe refractory ventricular tachycardia.

Adults weighing < 50 kg

200 mg PO every 12 hours. In patients with cardiomyopathy or possible cardiac decompensation, immediate-release capsules should be used for initial treatment (see above). Maximum dosage is 800 mg/day PO; however, up to 1600 mg/day PO has been used in the hospital setting to treat severe refractory ventricular tachycardia.

Geriatric

See adult dosage. Elderly patients are sensitive to anticholinergic effects of the drug and are more likely to have age-associated decreases in renal function; dosage selection should be conservative (see dosage for patients with renal impairment).

Children

Extended-release capsules are not recommended for use in children.

For maintenance of sinus rhythm in patients with atrial fibrillation† or atrial flutter†. Oral dosage (extended-release capsules) Adults

200 to 400 mg PO every 12 hours. Clinical practice guidelines recommend disopyramide in combination with a beta blocker or nondihydropyridine calcium channel blocker to prevent recurrent atrial fibrillation in patients with hypertrophic cardiomyopathy.

Oral dosage (immediate-release capsules) Adults

100 to 200 mg PO every 6 hours. Clinical practice guidelines recommend disopyramide in combination with a beta blocker or nondihydropyridine calcium channel blocker to prevent recurrent atrial fibrillation in patients with hypertrophic cardiomyopathy.

†Indicates off-label use

Hepatic Impairment

The recommended dosage is 400 mg/day PO given in divided doses (either 100 mg PO every 6 hours for immediate-release capsules or 200 mg PO every 12 hours for extended-release capsules).

Renal Impairment

CrCl 40—60 mL/min: 400 mg/day PO in divided doses (either 100 mg PO every 6 hours for immediate-release capsules or 200 mg PO every 12 hours for extended-release capsules).
CrCl 30—40 mL/min: reduce dose to 100 mg (immediate-release capsules) PO every 8 hours.
CrCl 15—29 mL/min: reduce dose to 100 mg (immediate-release capsules) PO every 12 hours.
CrCl < 15 mL/min: reduce dose to 100 mg (immediate-release capsules) PO every 24 hours.
 
Intermittent hemodialysis
It appears that no dosage adjustment is needed. A small amount (<= 2.4%) of the total disopyramide dose is removed from the plasma during a 2-hour dialysis session, without a significant change in drug half-life. However, hemodialysis may be used to enhance drug elimination in the setting of drug overdose.

Abarelix: (Contraindicated) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as Class IA antiarrhythmics.
Acarbose: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Acebutolol: (Major) Disopyramide and beta-blockers, like acebutolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) The anticholinergic effects of sedating H1-blockers, such as diphenhydramine, may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Acetaminophen; Chlorpheniramine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Acetaminophen; Diphenhydramine: (Moderate) The anticholinergic effects of sedating H1-blockers, such as diphenhydramine, may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Adagrasib: (Major) Avoid concomitant use of adagrasib and disopyramide due to the potential for increased disopyramide exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, monitor for disopyramide-related adverse effects and consider taking additional steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Disopyramide is a CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation.
Alfuzosin: (Major) Alfuzosin should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
Alogliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents, such as alogliptin, should be monitored for changes in glycemic control.
Alogliptin; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents, such as alogliptin, should be monitored for changes in glycemic control.
Alogliptin; Pioglitazone: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents, such as alogliptin, should be monitored for changes in glycemic control.
Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like disopyramide, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Alpha-glucosidase Inhibitors: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Amantadine: (Moderate) Amantadine may exhibit anticholinergic activity. Medications with significant anticholinergic activity, such as disopyramide, may potentiate the anticholinergic effects of amantadine, and may increase the risk of antimuscarinic-related side effects.
Amiodarone: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP) and is a substrate for CYP3A4. Life-threatening interactions have been reported with the coadministration of disopyramide with clarithromycin and erythromycin, both have a possible risk for QT prolongation and TdP and inhibit CYP3A4. The coadministration of disopyramide and CYP3A4 inhibitors may result in a potentially fatal interaction. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation andTdP and is a CYP3A4 inhibitor. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with disopyramide. Amisulpride causes dose- and concentration- dependent QT prolongation. Disopyramide administration is associated with QT prolongation and TdP.
Amoxapine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and amoxapine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent administration of clarithromycin and disopyramide has been associated with post-marketing reports of torsades de pointes (TdP) and hypoglycemia. If these drugs are administered together, closely monitor ECGs for QT prolongation, blood glucose concentrations, and consider monitoring disopyramide serum concentrations. Both clarithromycin and disopyramide have been associated with an established risk for QT prolongation and TdP.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include disopyramide.
Anticholinergics: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Apalutamide: (Moderate) Monitor disopyramide serum concentrations and for loss of efficacy when coadministration with apalutamide is necessary. Disopyramide exposure may be decreased during concurrent use. Apalutamide is a strong CYP3A4 inducer and disopyramide is a CYP3A4 substrate.
Apomorphine: (Major) Use apomorphine and disopyramide together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP).
Aprepitant, Fosaprepitant: (Moderate) Use caution if disopyramide and aprepitant, fosaprepitant are used concurrently and monitor for an increase in disopyramide-related adverse effects, including for several days after administration of a multi-day aprepitant regimen. Disopyramide is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of disopyramide. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Major) Concomitant use of disopyramide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) If possible, disopyramide should be discontinued prior to initiating arsenic trioxide therapy. If coadministered, these drugs should be used cautiously and with close monitoring. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Artemether; Lumefantrine: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if disopyramide must be used with or after artemether; lumefantrine treatment.
Articaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Asciminib: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with asciminib is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and asciminib is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Asenapine: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect, such as disopyramide.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and orphenadrine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Atazanavir: (Major) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of disopyramide and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur.
Atazanavir; Cobicistat: (Major) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of disopyramide and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur. (Major) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of disopyramide with cobicistat. Disopyramide is a substrate for CYP3A4; cobicistat is a strong inhibitor of this enzyme. Concurrent use may result in elevated disopyramide plasma concentration. Cases of life-threatening interactions have been reported for disopyramide when given with another strong CYP3A4 inhibitor.
Atenolol: (Major) Disopyramide and beta-blockers have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. Atenolol has been reported to decrease the clearance of intravenous disopyramide by about 20%, with no change in its elimination half-life; atenolol may also cause additive myocardial depressive effects when given in combination with disopyramide. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Atenolol; Chlorthalidone: (Major) Disopyramide and beta-blockers have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. Atenolol has been reported to decrease the clearance of intravenous disopyramide by about 20%, with no change in its elimination half-life; atenolol may also cause additive myocardial depressive effects when given in combination with disopyramide. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Atomoxetine: (Major) Concomitant use of disopyramide and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atropine: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Atropine; Difenoxin: (Moderate) Coadministration of disopyramide and diphenoxylate/difenoxin may cause an additive decrease in GI motility and should be used cautiously. (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Avacopan: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with avacopan is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and avacopan is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Azithromycin: (Major) Avoid coadministration of azithromycin with disopyramide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Disopyramide is associated with QT prolongation and TdP.
Barbiturates: (Moderate) Hepatic microsomal enzyme-inducing agents, such as barbiturates, have the potential to accelerate the hepatic metabolism of disopyramide, a CYP3A4 substrate. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with disopyramide. Both drugs have been reported to prolong the QT interval, and disopyramide is also associated with TdP. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
Belladonna; Opium: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Belumosudil: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with belumosudil is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and belumosudil is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Benztropine: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Berotralstat: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with berotralstat is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other moderate CYP3A4 inhibitors.
Betaxolol: (Major) Disopyramide and beta-blockers, like betaxolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Bicalutamide: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with bicalutamide is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A4 inhibitors.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bisoprolol: (Major) Disopyramide and beta-blockers, like bisoprolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Disopyramide and beta-blockers, like bisoprolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Brimonidine; Timolol: (Major) Disopyramide and beta-blockers, like timolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Brompheniramine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Brompheniramine; Phenylephrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Brompheniramine; Pseudoephedrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Bupivacaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Bupivacaine; Lidocaine: (Major) The effects of concomitant administration of disopyramide with other antiarrhythmics could potentially be synergistic or antagonistic, and adverse cardiac effects could potentially be additive. Class IA antiarrhythmic agents are associated with proarrhythmias (e.g., torsades de pointes) resulting from QTc prolongation. Coadministration of disopyramide with other Class IA antiarrhythmics should be reserved for patients with life-threatening arrhythmias who are unresponsive to single-agent antiarrhythmic therapy. Lidocaine has occasionally been used concurrently with disopyramide; however, additive electrophysiologic effects may occur. Since disopyramide and lidocaine are both sodium-channel-acting agents, it is somewhat irrational to use these drugs together; isolated cases of intraventricular conduction abnormalities have been reported with this drug combination. Patients receiving more than one antiarrhythmic drug must be carefully monitored.
Buprenorphine: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
Buprenorphine; Naloxone: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
Cabotegravir; Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Canagliflozin; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Carbamazepine: (Moderate) Hepatic microsomal enzyme-inducing agents, such as carbamazepine, have the potential to accelerate the hepatic metabolism of disopyramide, a CYP3A4 substrate. Patients should be monitored for loss of disopyramide activity if carbamazepine is added. In addition, disopyramide doses may need to be reduced if acarbamazepine is stopped and disopyramide therapy is continued.
Carbinoxamine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Carteolol: (Major) Disopyramide and beta-blockers, like carteolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Carvedilol: (Major) Disopyramide and beta-blockers, like carvedilol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Ceritinib: (Major) Avoid coadministration of ceritinib with disopyramide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Additionally, closely monitor for disopyramide-related adverse reactions. Disopyramide is a CYP3A4 substrate that has been associated with QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when administered with another strong CYP3A4 inhibitor.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorcyclizine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlordiazepoxide; Clidinium: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Chloroquine: (Major) Avoid coadministration of chloroquine with disopyramide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Disopyramide administration is associated with QT prolongation and TdP.
Chlorpheniramine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Codeine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Dextromethorphan: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Hydrocodone: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Phenylephrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpheniramine; Pseudoephedrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Chlorpromazine: (Major) Avoid use of disopyramide with chlorpromazine if possible due to an increased risk for QT prolongation. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Phenothiazines have been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Additive anticholinergic effects are also possible, as both drugs exhibit significant anticholinergic activity.
Cholinergic agonists: (Moderate) Disopyramide possesses clinically significant antimuscarinic properties and these appear to be dose-related. It is possible that disopyramide could antagonize the muscarinic actions of cholinergic agonists. Clinicians should be alert to this possibility.
Ciprofloxacin: (Major) Concomitant use of disopyramide and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Administration of Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) is associated with QT prolongation and TdP. Because of the potential for TdP, concurrent use of Class IA antiarrhythmics and cisapride is contraindicated.
Citalopram: (Major) Concomitant use of disopyramide and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Concurrent administration of clarithromycin and disopyramide has been associated with post-marketing reports of torsades de pointes (TdP) and hypoglycemia. If these drugs are administered together, closely monitor ECGs for QT prolongation, blood glucose concentrations, and consider monitoring disopyramide serum concentrations. Both clarithromycin and disopyramide have been associated with an established risk for QT prolongation and TdP.
Clemastine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and disopyramide, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
Clofazimine: (Major) Concomitant use of clofazimine and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clozapine: (Major) Clozapine should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Additive anticholinergic effects are also possible; both drugs exhibit significant anticholinergic activity.
Cobicistat: (Major) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of disopyramide with cobicistat. Disopyramide is a substrate for CYP3A4; cobicistat is a strong inhibitor of this enzyme. Concurrent use may result in elevated disopyramide plasma concentration. Cases of life-threatening interactions have been reported for disopyramide when given with another strong CYP3A4 inhibitor.
Codeine; Phenylephrine; Promethazine: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with disopyramide include promethazine. Additive anticholinergic effects may also occur, and may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Codeine; Promethazine: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with disopyramide include promethazine. Additive anticholinergic effects may also occur, and may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of antiarrhythmics if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics at least 1 hour before or at least 4 hours after colesevelam.
Conivaptan: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with conivaptan is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other moderate CYP3A inhibitors.
Crizotinib: (Major) Avoid coadministration of crizotinib with disopyramide due to the risk of QT prolongation; disopyramide exposure may also increase. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; also monitor for an increase in disopyramide-related adverse reactions. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib is a moderate CYP3A inhibitor that has been associated with concentration-dependent QT prolongation. Disopyramide is a CYP3A4 substrate that is also associated with QT prolongation and torsade de pointes (TdP). Cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate CYP3A4 inhibitors.
Cyclobenzaprine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and cyclobenzaprine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Cyproheptadine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Dalfopristin; Quinupristin: (Moderate) Caution is warranted during coadministration of disopyramide and dalfopristin; quinupristin due to the potential for elevated disopyramide plasma concentrations and associated adverse events including QT prolongation. Disopyramide is a CYP3A4 substrate; dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
Danazol: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of disopyramide. Patients receiving disoyramide should be closely monitored for toxicity if danazol is added to therapy.
Dapagliflozin; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Dapagliflozin; Saxagliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Darunavir: (Major) Darunavir can inhibit CYP3A4, an isoenzyme that is partially responsible for the metabolism of disopyramide. Although no definitive clinical data have yet confirmed this interaction, the concurrent use of disopyramide with darunavir should be approached with caution due to the potential for serious disopyramide toxicity.
Darunavir; Cobicistat: (Major) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of disopyramide with cobicistat. Disopyramide is a substrate for CYP3A4; cobicistat is a strong inhibitor of this enzyme. Concurrent use may result in elevated disopyramide plasma concentration. Cases of life-threatening interactions have been reported for disopyramide when given with another strong CYP3A4 inhibitor. (Major) Darunavir can inhibit CYP3A4, an isoenzyme that is partially responsible for the metabolism of disopyramide. Although no definitive clinical data have yet confirmed this interaction, the concurrent use of disopyramide with darunavir should be approached with caution due to the potential for serious disopyramide toxicity.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of disopyramide with cobicistat. Disopyramide is a substrate for CYP3A4; cobicistat is a strong inhibitor of this enzyme. Concurrent use may result in elevated disopyramide plasma concentration. Cases of life-threatening interactions have been reported for disopyramide when given with another strong CYP3A4 inhibitor. (Major) Darunavir can inhibit CYP3A4, an isoenzyme that is partially responsible for the metabolism of disopyramide. Although no definitive clinical data have yet confirmed this interaction, the concurrent use of disopyramide with darunavir should be approached with caution due to the potential for serious disopyramide toxicity.
Dasatinib: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and disopyramide is necessary. Disopyramide administration is associated with QT prolongation and TdP. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Degarelix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as class IA antiarrhythmics. Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Delavirdine: (Major) Delavirdine is a potent inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as disopyramide, should be expected with concurrent use. Coadministration should be approached with caution due to the potential for serious disopyramide toxicity.
Desflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
Deutetrabenazine: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and disopyramide. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Dexchlorpheniramine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The anticholinergic effects of sedating H1-blockers, such as diphenhydramine, may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Dextromethorphan; Quinidine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided.
Dicyclomine: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Diltiazem: (Major) Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction such as disopyramide. In addition, diltiazem can theoretically inhibit the CYP3A4 metabolism of disopyramide.
Dimenhydrinate: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Diphenhydramine: (Moderate) The anticholinergic effects of sedating H1-blockers, such as diphenhydramine, may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Diphenhydramine; Ibuprofen: (Moderate) The anticholinergic effects of sedating H1-blockers, such as diphenhydramine, may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Diphenhydramine; Naproxen: (Moderate) The anticholinergic effects of sedating H1-blockers, such as diphenhydramine, may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Diphenhydramine; Phenylephrine: (Moderate) The anticholinergic effects of sedating H1-blockers, such as diphenhydramine, may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Diphenoxylate; Atropine: (Moderate) Coadministration of disopyramide and diphenoxylate/difenoxin may cause an additive decrease in GI motility and should be used cautiously. (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Dofetilide: (Major) Coadministration of dofetilide and disopyramide is not recommended as concurrent use may increase the risk of QT prolongation. Class I antiarrhythmic agents, such as disopyramide, should be withheld for at least 3 half-lives prior to initiating dofetilide therapy. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Disopyramide administration is associated with QT prolongation and TdP.
Dolasetron: (Major) Dolasetron should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Dolutegravir; Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Donepezil: (Major) Concurrent use of disopyramide and donepezil should be avoided if possible. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy, and disopyramide has a possible risk for QT prolongation and TdP. In addition, disopyramide may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine.
Donepezil; Memantine: (Major) Concurrent use of disopyramide and donepezil should be avoided if possible. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy, and disopyramide has a possible risk for QT prolongation and TdP. In addition, disopyramide may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine.
Dorzolamide; Timolol: (Major) Disopyramide and beta-blockers, like timolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Doxylamine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Doxylamine; Pyridoxine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Dronedarone: (Contraindicated) Concurrent use of dronedarone and disopyramide is contraindicated. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is as

sociated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
Dulaglutide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Duvelisib: (Major) Monitor for increased toxicity of disopyramide if coadministered with duvelisib. Coadministration may increase the exposure of disopyramide. Disopyramide is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor. Cases of life-threatening interactions have been reported for disopyramide when given with other moderate CYP3A4 inhibitors.
Efavirenz: (Major) If possible, avoid coadministration of efavirenz and disopyramide, as use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Disopyramide administration is associated with QT prolongation and TdP. In addition, efavirenz can induce CYP3A4, an isoenzyme that is partially responsible for the metabolism of disopyramide. Use these drugs together with caution due to the potential for decreased disopyramide efficacy.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) If possible, avoid coadministration of efavirenz and disopyramide, as use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Disopyramide administration is associated with QT prolongation and TdP. In addition, efavirenz can induce CYP3A4, an isoenzyme that is partially responsible for the metabolism of disopyramide. Use these drugs together with caution due to the potential for decreased disopyramide efficacy.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) If possible, avoid coadministration of efavirenz and disopyramide, as use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Disopyramide administration is associated with QT prolongation and TdP. In addition, efavirenz can induce CYP3A4, an isoenzyme that is partially responsible for the metabolism of disopyramide. Use these drugs together with caution due to the potential for decreased disopyramide efficacy.
Elagolix: (Moderate) Monitor disopyramide serum concentrations and for loss of efficacy when coadministration with elagolix is necessary. Disopyramide exposure may be decreased during concurrent use. Elagolix is a weak to moderate CYP3A4 inducer and disopyramide is a CYP3A4 substrate.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor disopyramide serum concentrations and for loss of efficacy when coadministration with elagolix is necessary. Disopyramide exposure may be decreased during concurrent use. Elagolix is a weak to moderate CYP3A4 inducer and disopyramide is a CYP3A4 substrate.
Elbasvir; Grazoprevir: (Moderate) Administering disopyramide with elbasvir; grazoprevir may result in elevated disopyramide plasma concentrations. Disopyramide is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering ivacaftor and disopyramide concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as disopyramide, can increase disopyramide exposure leading to increased or prolonged therapeutic effects and adverse events.
Eliglustat: (Major) Coadministration of disopyramide and eliglustat is not recommended. If coadministration is necessary, use extreme caution and close monitoring. Disopyramide is associated with QT prolongation and torsades de pointes (TdP). Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of disopyramide with cobicistat. Disopyramide is a substrate for CYP3A4; cobicistat is a strong inhibitor of this enzyme. Concurrent use may result in elevated disopyramide plasma concentration. Cases of life-threatening interactions have been reported for disopyramide when given with another strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of disopyramide with cobicistat. Disopyramide is a substrate for CYP3A4; cobicistat is a strong inhibitor of this enzyme. Concurrent use may result in elevated disopyramide plasma concentration. Cases of life-threatening interactions have been reported for disopyramide when given with another strong CYP3A4 inhibitor.
Empagliflozin; Linagliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents, such as linagliptin, should be monitored for changes in glycemic control.
Empagliflozin; Linagliptin; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents, such as linagliptin, should be monitored for changes in glycemic control.
Empagliflozin; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Encorafenib: (Major) Avoid coadministration of encorafenib and disopyramide due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Entrectinib: (Major) Avoid coadministration of entrectinib with disopyramide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Enzalutamide: (Moderate) Monitor disopyramide serum concentrations and for loss of efficacy when coadministration with enzalutamide is necessary. Disopyramide exposure may be decreased during concurrent use. Enzalutamide is a strong CYP3A4 inducer; disopyramide is a CYP3A4 substrate.
Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Eribulin: (Major) Eribulin has been associated with QT prolongation. Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Ertugliflozin; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Ertugliflozin; Sitagliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Erythromycin: (Major) Cases of life-threatening interactions have been reported for disopyramide when given with erythromycin. In vitro studies have shown that erythromycin inhibits the metabolism of disopyramide. Avoid the coadministration of disopyramide with agents that are associated with QT interval prolongation, including erythromycin. Additionally, erythromycin may inhibit the CYP3A4 metabolism of disopyramide (CYP3A4 substrate). Disopyramide and erythromycin interact both pharmacokinetically and pharmacodynamically. In two patients, erythromycin caused disopyramide serum concentrations to rise significantly, which was associated with development of QT prolongation and tachyarrhythmias. Also, the antimuscarinic actions of disopyramide can interfere with the motility-enhancing properties of erythromycin in patients receiving erythromycin for this purpose.
Escitalopram: (Major) Concomitant use of disopyramide and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Esmolol: (Major) Disopyramide and beta-blockers, like esmolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Ethotoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, including disopyramide, leading to reduced efficacy of the concomitant medication. Patients should be monitored for loss of disopyramide activity if a hydantoin is added. In addition, disopyramide doses may need to be reduced if a hydantoin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
Etravirine: (Major) Etravirine is an inducer of CYP3A4; disopyramide concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor disopyramide concentrations when possible.
Everolimus: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with everolimus is necessary. Disopyramide is a CYP3A4 substrate and everolimus is a weak CYP3A4 inhibitor; concomitant use may increase plasma concentrations of disopyramide. Specific drug interaction studies have not been done for disopyramide; however, cases of life-threatening interactions have been reported when coadministered with moderate and strong CYP3A4 inhibitors. Coadministration of disopyramide with CYP3A4 inhibitors could result in a potentially fatal interaction.
Exenatide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Fedratinib: (Major) Monitor for increased toxicity of disopyramide if coadministered with fedratinib. Coadministration may increase the exposure of disopyramide. Disopyramide is a CYP3A substrate; fedratinib is a moderate CYP3A inhibitor. Cases of life-threatening interactions have been reported for disopyramide when given with other moderate CYP3A4 inhibitors.
Fingolimod: (Contraindicated) Concurrent use of fingolimod with class Ia antiarrhythmics such as disopyramide, quinidine, and procainamide is contraindicated. Fingolimod initiation results in decreased heart rate, and class IA antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.
Flavoxate: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Flecainide: (Major) The effects of concomitant administration of flecainide with other antiarrhythmics can be synergistic, additive, or antagonistic, and adverse cardiac effects can be additive. There has been little experience with the coadministration of flecainide with Class IA antiarrhythmics. Based on drug pharmacology, additive Class I electrophysiologic effects may be expected with potential for increased risk of proarrhythmias. Flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Rare cases of QT prolongation and torsades de pointes (TdP) have been reported during flecainide therapy. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Class IA antiarrhythmics are associated with a substantial risk for QT prolongation and torsades de pointes (TdP). In addition, flecainide should not be coadministered with disopyramide or quinidine (including dextromethorphan; quinidine) due to the potential for additive negative inotropic effects, unless the benefits of combined therapy outweigh the risks. Quinidine, a CYP2D6 inhibitor may increase the plasma concentrations of flecainide, especially in patients who are extensive metabolizers. Based on theoretical considerations, the manufacturer recommends allowing at least 2-4 plasma half-lives to elapse following flecainide discontinuation before switching to another antiarrhythmic drug. In patients for whom withdrawal of a prior antiarrhythmic drug is likely to produce life-threatening arrhythmias, the physician should consider hospitalizing the patient.
Fluconazole: (Contraindicated) The concomitant administration of fluconazole and disopyramide is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as disopyramide. Coadministration of fluconazole with disopyramide may result in elevated plasma concentrations of disopyramide, causing an increased risk for adverse events, such as QT prolongation.
Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval, including disopyramide. In addition, CYP3A4 inhibitors, such as fluoxetine may increase serum plasma concentrations of disopyramide, a CYP3A4 substrate. Monitor clinical response and serum disopyramide concentrations.
Fluphenazine: (Minor) Fluphenazine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Fluvoxamine: (Major) There may be an increased risk for QT prolongation, torsade de pointes (TdP), or elevated disopyramide concentrations during concurrent use of fluvoxamine and disopyramide. Disopyramide is associated with QT prolongation and TdP. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. In addition, CYP3A4 inhibitors such as fluvoxamine may increase plasma concentrations of disopyramide, a CYP3A4 substrate. Caution should be used when CYP3A4 inhibitors are coadministered with disopyramide; monitor clinical response and serum disopyramide concentrations.
Fosamprenavir: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if concurrent use of fosamprenavir is necessary. Concomitant use may increase the exposure of disopyramide. Disopyramide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other moderate CYP3A inhibitors.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as disopyramide. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Disopyramide administration is also associated with QT prolongation and TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosphenytoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, including disopyramide, leading to reduced efficacy of the concomitant medication. Patients should be monitored for loss of disopyramide activity if a hydantoin is added. In addition, disopyramide doses may need to be reduced if a hydantoin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
Fostemsavir: (Major) Use disopyramide and fostemsavir together with caution. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Galantamine: (Moderate) The therapeutic benefits of galantamine may be diminished when co-administered with the antimuscarinics, such as disopyramide. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy.
Gemifloxacin: (Major) According to the manufacturer, gemifloxacin should be avoided in patients receiving Class IA antiarrhythmics (such as disopyramide, quinidine and procainamide). Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and disopyramide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Disopyramide administration is associated with QT prolongation and TdP.
Gilteritinib: (Major) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and disopyramide is necessary. Gilteritinib has been associated with QT prolongation. Disopyramide has been associated with QT prolongation and torsade de pointes (TdP). Coadministration has the potential for additive QT prolongation.
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
Glasdegib: (Major) Avoid coadministration of glasdegib with disopyramide due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Glipizide; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Glyburide; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Glycopyrrolate: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Glycopyrrolate; Formoterol: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Granisetron: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Grapefruit juice: (Major) CYP3A4 inhibitors, such as grapefruit juice, may increase serum plasma concentrations of disopyramide. Caution should be used with this combination; monitor clinical response and serum disopyramide concentrations.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
Haloperidol: (Major) Haloperidol should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Homatropine; Hydrocodone: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Hydantoins: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, including disopyramide, leading to reduced efficacy of the concomitant medication. Patients should be monitored for loss of disopyramide activity if a hydantoin is added. In addition, disopyramide doses may need to be reduced if a hydantoin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Disopyramide should be used cautiously and with close monitoring with hydroxyzine. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Disopyramide administration is associated with QT prolongation and TdP. In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other medications with anticholinergic effects, such as disopyramide. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Hyoscyamine: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Ibutilide: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with disopyramide, a CYP3A substrate, as disopyramide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Major) Iloperidone should be avoided in combination with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Iloperidone has been associated with QT prolongation; however, TdP has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect.
Imatinib: (Major) Imatinib is a potent inhibitor of cytochrome P450 CYP 3A4. Disopyramide is a CYP3A4 substrate and coadministration with imatinib may increase serum plasma concentrations of disopyramide.
Incretin Mimetics: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Indacaterol; Glycopyrrolate: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Indinavir: (Major) Indinavir inhibits CYP3A4. Although specific interactions have not been studied, indinavir may interfere with the metabolism of CYP3A4 substrates such as disopyramide, and caution is warranted with coadministration.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with disopyramide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Disopyramide administration is associated with QT prolongation and TdP.
Insulin Degludec; Liraglutide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Insulin Glargine; Lixisenatide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Insulins: (Moderate) Monitor patients receiving disopyramide concomitantly with insulin for changes in glycemic control. Disopyramide may enhance the hypoglycemic effects of insulin.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with disopyramide may result in increased serum concentrations of disopyramide. Disopyramide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
Isoniazid, INH: (Moderate) Caution should be used when isoniazid is coadministered with disopyramide; monitor clinical response and serum disopyramide concentrations. CYP3A4 inhibitors, such as isoniazid, may increase serum plasma concentrations of disopyramide, a CYP3A4 substrate.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of disopyramide. Patients should be monitored for loss of disopyramide activity if rifampin is added. In addition, disopyramide doses may need to be reduced if rifampin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy. (Moderate) Caution should be used when isoniazid is coadministered with disopyramide; monitor clinical response and serum disopyramide concentrations. CYP3A4 inhibitors, such as isoniazid, may increase serum plasma concentrations of disopyramide, a CYP3A4 substrate.
Isoniazid, INH; Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of disopyramide. Patients should be monitored for loss of disopyramide activity if rifampin is added. In addition, disopyramide doses may need to be reduced if rifampin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy. (Moderate) Caution should be used when isoniazid is coadministered with disopyramide; monitor clinical response and serum disopyramide concentrations. CYP3A4 inhibitors, such as isoniazid, may increase serum plasma concentrations of disopyramide, a CYP3A4 substrate.
Itraconazole: (Contraindicated) Use of disopyramide during and for 2 weeks after discontinuation of itraconazole treatment is contraindicated due to the potential for elevated disopyramide concentrations and QT prolongation. Serious cardiovascular events including ECG changes (i.e., QT prolongation) and cardiac arrhythmias, including ventricular arrhythmias and torsade de pointes, may occur when these drugs are administered together. Itraconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation. Disopyramide is a CYP3A4 substrate that is associated with QT prolongation and torsade de pointes (TdP).
Ivacaftor: (Moderate) Use caution when administering ivacaftor and disopyramide concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as disopyramide, can increase disopyramide exposure leading to increased or prolonged therapeutic effects and adverse events.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with disopyramide due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and disopyramide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Labetalol: (Major) Disopyramide and beta-blockers, like labetalol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concurrent administration of clarithromycin and disopyramide has been associated with post-marketing reports of torsades de pointes (TdP) and hypoglycemia. If these drugs are administered together, closely monitor ECGs for QT prolongation, blood glucose concentrations, and consider monitoring disopyramide serum concentrations. Both clarithromycin and disopyramide have been associated with an established risk for QT prolongation and TdP.
Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with disopyramide is necessary; also monitor for an increase in disopyramide-related adverse reactions. Correct electrolyte abnormalities prior to treatment. Disopyramide is a CYP3A4 substrate that is associated with QT prolongation and torsade de pointes (TdP). Lapatinib is a weak CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Concomitant use may increase plasma concentrations of disopyramide. Specific drug interaction studies have not been done for disopyramide; however, cases of life-threatening interactions have been reported when coadministered with moderate and strong CYP3A4 inhibitors. Coadministration of disopyramide with CYP3A4 inhibitors could result in a potentially fatal interaction.
Larotrectinib: (Moderate) Caution is warranted during coadministration of disopyramide and larotrectinib due to the potential for elevated disopyramide plasma concentrations and associated adverse events including QT prolongation. Disopyramide is a CYP3A4 substrate; larotrectinib is a weak CYP3A4 inhibitor.
Lefamulin: (Major) Avoid coadministration of lefamulin with disopyramide as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Lenacapavir: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with lenacapavir is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other moderate CYP3A inhibitors.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with disopyramide due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of disopyramide; monitor for potential reduction in efficacy. Disopyramide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of disopyramide; monitor for potential reduction in efficacy. Disopyramide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of disopyramide may occur during concurrent administration with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. If these drugs are given together, closely monitor for disopyramide-related adverse events (e.g., QT prolongation). In vitro metabolic studies indicated that disopyramide is metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor.
Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Levofloxacin: (Major) Levofloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and disopyramide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lidocaine: (Major) The effects of concomitant administration of disopyramide with other antiarrhythmics could potentially be synergistic or antagonistic, and adverse cardiac effects could potentially be additive. Class IA antiarrhythmic agents are associated with proarrhythmias (e.g., torsades de pointes) resulting from QTc prolongation. Coadministration of disopyramide with other Class IA antiarrhythmics should be reserved for patients with life-threatening arrhythmias who are unresponsive to single-agent antiarrhythmic therapy. Lidocaine has occasionally been used concurrently with disopyramide; however, additive electrophysiologic effects may occur. Since disopyramide and lidocaine are both sodium-channel-acting agents, it is somewhat irrational to use these drugs together; isolated cases of intraventricular conduction abnormalities have been reported with this drug combination. Patients receiving more than one antiarrhythmic drug must be carefully monitored.
Lidocaine; Epinephrine: (Major) The effects of concomitant administration of disopyramide with other antiarrhythmics could potentially be synergistic or antagonistic, and adverse cardiac effects could potentially be additive. Class IA antiarrhythmic agents are associated with proarrhythmias (e.g., torsades de pointes) resulting from QTc prolongation. Coadministration of disopyramide with other Class IA antiarrhythmics should be reserved for patients with life-threatening arrhythmias who are unresponsive to single-agent antiarrhythmic therapy. Lidocaine has occasionally been used concurrently with disopyramide; however, additive electrophysiologic effects may occur. Since disopyramide and lidocaine are both sodium-channel-acting agents, it is somewhat irrational to use these drugs together; isolated cases of intraventricular conduction abnormalities have been reported with this drug combination. Patients receiving more than one antiarrhythmic drug must be carefully monitored. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Lidocaine; Prilocaine: (Major) The effects of concomitant administration of disopyramide with other antiarrhythmics could potentially be synergistic or antagonistic, and adverse cardiac effects could potentially be additive. Class IA antiarrhythmic agents are associated with proarrhythmias (e.g., torsades de pointes) resulting from QTc prolongation. Coadministration of disopyramide with other Class IA antiarrhythmics should be reserved for patients with life-threatening arrhythmias who are unresponsive to single-agent antiarrhythmic therapy. Lidocaine has occasionally been used concurrently with disopyramide; however, additive electrophysiologic effects may occur. Since disopyramide and lidocaine are both sodium-channel-acting agents, it is somewhat irrational to use these drugs together; isolated cases of intraventricular conduction abnormalities have been reported with this drug combination. Patients receiving more than one antiarrhythmic drug must be carefully monitored.
Linagliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents, such as linagliptin, should be monitored for changes in glycemic control.
Linagliptin; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents, such as linagliptin, should be monitored for changes in glycemic control.
Liraglutide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Lithium: (Major) Concomitant use of lithium and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lixisenatide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with disopyramide due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Disopyramide administration is associated with QT prolongation and TdP.
Lonafarnib: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with lonafarnib is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other strong CYP3A4 inhibitors.
Loperamide: (Major) Concomitant use of loperamide and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with disopyramide due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Disopyramide is associated with QT prolongation and torsade de pointes (TdP). (Major) Caution is warranted when ritonavir is coadministered with antiarrhythmics, including disopyramide. Ritonavir is an inhibitor of CYP3A4, and increased concentrations of disopyramide may be expected during coadministration. Therapeutic antiarrhythmic concentration monitoring is suggested when available. Monitor therapeutic response closely; dosage reduction may be needed. In some cases, the drug interaction may require more than 50% dosage reduction due to potent inhibitory effects and drug accumulation. Cardiac and neurologic events have been reported when ritonavir was concurrently administered with disopyramide.
Loxapine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and loxapine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of disopyramide by significantly decreasing its systemic exposure. If used together, monitor disopyramide plasma concentrations and adjust the dose as appropriate. Disopyramide is a CYP3A4 substrate. Lumacaftor is a strong inducer of CYP3A.
Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and disopyramide concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as disopyramide, can increase disopyramide exposure leading to increased or prolonged therapeutic effects and adverse events.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as disopyramide. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Maprotiline: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Disopyramide is associated with a possible risk for QT prolongation and TdP and should be used cautiously with maprotiline. In addition to effects on the EKG, disopyramide also has significant anticholinergic effects that are additive to those of maprotiline.
Maribavir: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with maribavir is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and maribavir is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Mavacamten: (Major) Avoid concomitant use of mavacamten and disopyramide. This medication combination may increase the risk of left ventricular systolic dysfunction and heart failure symptoms. If concomitant therapy with disopyramide is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Meclizine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Mefloquine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering disopyramide with mefloquine. Disopyramide administration is associated with QT prolongation and TdP. There is also evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Meglitinides: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Metformin; Repaglinide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Metformin; Rosiglitazone: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Metformin; Saxagliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Metformin; Sitagliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Methadone: (Major) The need to coadminister methadone with disopyramide should be done with extreme caution and a careful assessment of treatment risks versus benefits. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Methscopolamine: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Metoprolol: (Major) Disopyramide and beta-blockers, like metoprolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Disopyramide and beta-blockers, like metoprolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Metreleptin: (Moderate) Upon initiation or discontinuation of metreleptin in a patient receiving disopyramide, drug concentration and clinical monitoring should be performed and the disopyramide dosage adjusted as needed. Leptin is a cytokine and may have the potential to alter the formation of cytochrome P450 (CYP450) enzymes. The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with a narrow therapeutic index, such as disopyramide.
Metronidazole: (Major) Concomitant use of metronidazole and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) The concomitant use of midostaurin and disopyramide may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. Closely monitor patients who experience QT prolongation greater than 25% compared with baseline; consider discontinuing disopyramide if the ectopy persists. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Disopyramide is considered to have a well-established risk for QT prolongation and torsades de pointes (TdP) (or polymorphic ventricular tachycardia) and is capable of inducing QT prolongation or TdP even at low therapeutic doses.
Mifepristone: (Contraindicated) When mifepristone is used chronically for hormonal conditions, such as Cushing's disease, the concomitant use of CYP3A substrates with narrow therapeutic index, such as disopyramide, is contraindicated. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Disopyramide is a substrate for CYP3A4. Drugs with a possible risk for QT prolongation that are also CYP3A4 inhibitors include mifepristone. Life-threatening interactions have been reported with the coadministration of disopyramide with other CYP3A4 inhibitors with a potential to prolong the QT interval. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Miglitol: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patie nts receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Mirtazapine: (Major) Concomitant use of disopyramide and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mitotane: (Major) Use caution if mitotane and disopyramide are used concomitantly, and monitor serum disopyramide concentrations and adjust the dose of disopyramide if necessary. In addition, disopyramide doses may need to be reduced if mitotane is stopped and disopyramide therapy is continued. Mitotane is a strong CYP3A4 inducer and disopyramide is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of disopyramide.
Mobocertinib: (Major) Concomitant use of mobocertinib and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Moxifloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, quinidine, and procainamide). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
Nadolol: (Major) Disopyramide and beta-blockers, like nadolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Nebivolol: (Major) Disopyramide and beta-blockers, like nebivolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Nebivolol; Valsartan: (Major) Disopyramide and beta-blockers, like nebivolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Nefazodone: (Moderate) CYP3A4 inhibitors, such as nefazodone, may increase serum plasma concentrations of disopyramide, a CYP3A4 substrate. Caution should be used when CYP3A4 inhibitors are co-administered with disopyramide; monitor clinical response and serum disopyramide concentrations.
Nelfinavir: (Major) Nelfinavir is a potent inhibitor of CYP3A4 and is expected to inhibit the metabolism of disopyramide. Although no definitive clinical data have yet confirmed this interaction, the concurrent use of disopyramide with nelfinavir should be approached with caution due to the potential for serious disopyramide toxicity.
Neostigmine: (Moderate) Disopyramide possesses clinically significant antimuscarinic properties and these appear to be dose-related. It is possible that disopyramide could antagonize the muscarinic actions of parasympathomimetics, including both the direct agonists and the cholinesterase-inhibitors. Clinicians should be alert to this possibility.
Neostigmine; Glycopyrrolate: (Moderate) Disopyramide possesses clinically significant antimuscarinic properties and these appear to be dose-related. It is possible that disopyramide could antagonize the muscarinic actions of parasympathomimetics, including both the direct agonists and the cholinesterase-inhibitors. Clinicians should be alert to this possibility. (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Nevirapine: (Minor) Monitor for reduced efficacy of disopyramide if coadministration with nevirapine is necessary. Concomitant use may decrease disopyramide exposure. Disopyramide is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nicardipine: (Moderate) Because nicardipine inhibits CYP3A4, the metabolism of disopyramide may be inhibited.
Nifedipine: (Major) Nifedipine has some potential to reduce cardiac contractility. Use caution when administering concomitantly with other agents known to affect cardiac contractility and/or conduction such as disopyramide.
Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval. Disopyramide has been established to have a causal association with QT prolongation and torsade de pointes. Additionally, nilotinib is a moderate inhibitor of CYP3A4 and disopyramide is a substrate of CYP3A4; administering these drugs together may result in increased disopyramide levels. If the use of disopyramide is necessary, hold nilotinib therapy. If these drugs are used together, consider a disopyramide dose reduction and monitor patients for toxicity (e.g., QT interval prolongation).
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of ritonavir-boosted nirmatrelvir and disopyramide and consider an alternative COVID-19 therapy. Coadministration may increase disopyramide exposure resulting in increased toxicity. Disopyramide is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. (Major) Caution is warranted when ritonavir is coadministered with antiarrhythmics, including disopyramide. Ritonavir is an inhibitor of CYP3A4, and increased concentrations of disopyramide may be expected during coadministration. Therapeutic antiarrhythmic concentration monitoring is suggested when available. Monitor therapeutic response closely; dosage reduction may be needed. In some cases, the drug interaction may require more than 50% dosage reduction due to potent inhibitory effects and drug accumulation. Cardiac and neurologic events have been reported when ritonavir was concurrently administered with disopyramide.
Ofloxacin: (Major) Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) should be used cautiously and with close monitoring with ofloxacin. Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) are associated with QT prolongation and torsades de pointes (TdP). Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP).
Olanzapine: (Major) Olanzapine should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Additive anticholinergic effects are also possible; both drugs exhibit significant anticholinergic activity.
Olanzapine; Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval, including disopyramide. In addition, CYP3A4 inhibitors, such as fluoxetine may increase serum plasma concentrations of disopyramide, a CYP3A4 substrate. Monitor clinical response and serum disopyramide concentrations. (Major) Olanzapine should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Additive anticholinergic effects are also possible; both drugs exhibit significant anticholinergic activity.
Olanzapine; Samidorphan: (Major) Olanzapine should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Additive anticholinergic effects are also possible; both drugs exhibit significant anticholinergic activity.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Hepatic microsomal enzyme-inducing agents, such as rifabutin, have the potential to accelerate the hepatic metabolism of disopyramide, a CYP3A4 substrate. Patients should be monitored for loss of disopyramide activity if rifabutin is added.
Ondansetron: (Major) Concomitant use of ondansetron and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Oritavancin: (Moderate) Disopyramide is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of disopyramide may be reduced if these drugs are administered concurrently. Disopyramide doses may need to be reduced if any of these agents are stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and orphenadrine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Osilodrostat: (Major) Monitor ECGs in patients receiving osilodrostat with disopyramide. Osilodrostat is associated with dose-dependent QT prolongation. Disopyramide administration is associated with QT prolongation and torsade de pointes.
Osimertinib: (Major) Avoid coadministration of disopyramide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Disopyramide administration is associated with QT prolongation and TdP.
Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and disopyramide concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Disopyramide administration is also associated with QT prolongation and TdP.
Oxybutynin: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking disopyramide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Disopyramide administration is associated with QT prolongation and TdP.
Pacritinib: (Major) Concomitant use of disopyramide and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase disopyramide exposure and the risk for other disopyramide-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Disopyramide is a substrate of CYP3A4 and pacritinib is a weak CYP3A4 inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A4 inhibitors.
Palbociclib: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with palbociclib is necessary. Disopyramide is a CYP3A4 substrate and palbociclib is a weak time-dependent CYP3A4 inhibitor; concomitant use may increase plasma concentrations of disopyramide. Specific drug interaction studies have not been done for disopyramide; however, cases of life-threatening interactions have been reported when coadministered with moderate and strong CYP3A4 inhibitors. Coadministration of disopyramide with CYP3A4 inhibitors could result in a potentially fatal interaction.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Antiarrhythmic medicines with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include disopyramide.
Paroxetine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and paroxetine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Pasireotide: (Major) Cautious use of pasireotide and disopyramide is needed, as coadministration may have additive effects on the prolongation of the QT interval. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP).
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. Disopyramide is established to have a causal association with QT prolongation and TdP (torsade de pointe). If pazopanib and disopyramide must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and disopyramide, a CYP3A4 substrate, may cause an increase in systemic concentrations of disopyramide. Use caution when concurrent administration of disopyramide and pazopanib is necessary.
Pentamidine: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include disopyramide. Additive effects on the QT interval are possible.
Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with anticholinergic activity. Coadministration of pentazocine with disopyramide may result in additive anticholinergic effects, such as urinary retention and constipation.
Pentazocine; Naloxone: (Moderate) Use pentazocine with caution in any patient receiving medication with anticholinergic activity. Coadministration of pentazocine with disopyramide may result in additive anticholinergic effects, such as urinary retention and constipation.
Perphenazine: (Moderate) Perphenazine should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Additive anticholinergic effects are also possible.
Perphenazine; Amitriptyline: (Moderate) Perphenazine should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Additive anticholinergic effects are also possible.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Phenytoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, including disopyramide, leading to reduced efficacy of the concomitant medication. Patients should be monitored for loss of disopyramide activity if a hydantoin is added. In addition, disopyramide doses may need to be reduced if a hydantoin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP).
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of disopyramide with pimozide is contraindicated.
Pindolol: (Major) Disopyramide and beta-blockers, like pindolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Pioglitazone; Metformin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Pirtobrutinib: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with pirtobrutinib is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and pirtobrutinib is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Pitolisant: (Major) Avoid coadministration of pitolisant with disopyramide as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking disopyramide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Disopyramide administration is associated with QT prolongation and TdP.
Posaconazole: (Contraindicated) The concurrent use of posaconazole and disopyramide is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of disopyramide. These drugs used in combination may result in elevated disopyramide plasma concentrations, causing an increased risk for disopyramide-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as disopyramide.
Prilocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include disopyramide.
Procainamide: (Major) Procainamide, a Class IA antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP) and is should generally be avoided with other Class IA antiarrhythmics (disopyramide, quinidine) due to the potential for QT prolongation, other side effects, and an increased risk of torsade de pointes. Concurrent use of procainamide with other Class IA antiarrhythmic agents such as quinidine or disopyramide may produce enhanced prolongation of conduction or depression of contractility and hypotension, especially in patients with cardiac decompensation. Such use should be reserved for patients with serious arrhythmias unresponsive to a single drug and employed only with close observation. In addition, disopyramide exhibits significant anticholinergic activity that may be additive to procainamide.
Prochlorperazine: (Moderate) Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Concurrent use of drugs that are associated with a possible risk for QT prolongation and torsade de pointes (TdP) with prochlorperazine should be approached with caution. Disopyramide is associated with a possible risk for QT prolongation and TdP. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Additive anticholinergic effects may also be seen when phenothiazines such as prochlorperazine are used concomitantly with other drugs with antimuscarinic activity such as disopyramide. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Promethazine: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with disopyramide include promethazine. Additive anticholinergic effects may also occur, and may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Promethazine; Dextromethorphan: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with disopyramide include promethazine. Additive anticholinergic effects may also occur, and may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Promethazine; Phenylephrine: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with disopyramide include promethazine. Additive anticholinergic effects may also occur, and may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Propafenone: (Major) Concomitant use of propafenone and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propantheline: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Propranolol: (Major) Because the pharmacologic effects of propranolol include AV nodal conduction depression and negative inotropy, additive effects are possible when used in combination with disopyramide. Propranolol has occasionally been used with disopyramide; however, the manufacturer states that the concomitant use of disopyramide with propranolol should be reserved for patients with refractory life-threatening arrhythmias. Such use may produce serious negative inotropic effects, or may excessively prolong conduction. In healthy subjects, no significant drug interaction has been observed when propranolol is coadministered with disopyramide.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Because the pharmacologic effects of propranolol include AV nodal conduction depression and negative inotropy, additive effects are possible when used in combination with disopyramide. Propranolol has occasionally been used with disopyramide; however, the manufacturer states that the concomitant use of disopyramide with propranolol should be reserved for patients with refractory life-threatening arrhythmias. Such use may produce serious negative inotropic effects, or may excessively prolong conduction. In healthy subjects, no significant drug interaction has been observed when propranolol is coadministered with disopyramide.
Pseudoephedrine; Triprolidine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Pyridostigmine: (Moderate) Disopyramide possesses anticholinergic properties. Disopyramide should not be used in patients with myasthenia gravis because the anticholinergic properties of the drug could precipitate a myasthenic crisis. It is unclear if disopyramide can interfere with the cholinomimetic activity of pyridostigmine.
Quetiapine: (Major) Quetiapine should be used cautiously and with close monitoring with disopyramide. Disopyramide is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Additive anticholinergic effects are also possible with disopyramide, as both quetiapine and disopyramide exhibit significant anticholinergic activity.
Quinidine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided.
Quinine: (Major) Concurrent use of quinine and disopyramide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been associated with prolongation of the QT interval and rare cases of TdP. In addition, concentrations of disopyramide may be increased with concomitant use of quinine. Disopyramide is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Quizartinib: (Major) Concomitant use of quizartinib and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Disopyramide is a substrate for CYP3A4. Life-threatening interactions have been reported with the coadministration of disopyramide with clarithromycin and erythromycin, both have a possible risk for QT prolongation and TdP and inhibit CYP3A4. The coadministration of disopyramide and CYP3A4 inhibitors may result in a potentially fatal interaction. Drugs with a possible risk for QT prolongation and TdP that are also inhibitors of CYP3A4 that should be used cautiously with disopyramide include ranolazine.
Relugolix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as disopyramide. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Relugolix; Estradiol; Norethindrone acetate: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as disopyramide. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Ribociclib: (Major) Avoid coadministration of ribociclib with disopyramide due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of disopyramide may also be increased resulting in an increase in disopyramide-related adverse reactions. Disypyramide is a CYP3A4 substrate that has been associated with QT prolongation and TdP; cases of life-threatening interactions have been reported for disopyramide when given with other CYP3A4 inhibitors. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with disopyramide due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of disopyramide may also be increased resulting in an increase in disopyramide-related adverse reactions. Disypyramide is a CYP3A4 substrate that has been associated with QT prolongation and TdP; cases of life-threatening interactions have been reported for disopyramide when given with other CYP3A4 inhibitors. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner.
Rifabutin: (Moderate) Hepatic microsomal enzyme-inducing agents, such as rifabutin, have the potential to accelerate the hepatic metabolism of disopyramide, a CYP3A4 substrate. Patients should be monitored for loss of disopyramide activity if rifabutin is added.
Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of disopyramide. Patients should be monitored for loss of disopyramide activity if rifampin is added. In addition, disopyramide doses may need to be reduced if rifampin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
Rifapentine: (Moderate) Monitor disopyramide plasma concentrations and for decreased efficacy if coadministered with rifapentine as concurrent use may decrease disopyramide exposure. Disopyramide is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Risperidone: (Major) Risperidone should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Ritlecitinib: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with ritlecitinib is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other moderate CYP3A inhibitors.
Ritonavir: (Major) Caution is warranted when ritonavir is coadministered with antiarrhythmics, including disopyramide. Ritonavir is an inhibitor of CYP3A4, and increased concentrations of disopyramide may be expected during coadministration. Therapeutic antiarrhythmic concentration monitoring is suggested when available. Monitor therapeutic response closely; dosage reduction may be needed. In some cases, the drug interaction may require more than 50% dosage reduction due to potent inhibitory effects and drug accumulation. Cardiac and neurologic events have been reported when ritonavir was concurrently administered with disopyramide.
Rivastigmine: (Moderate) Concurrent use of disopyramide and rivastigmine should be avoided if possible. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Disopyramide may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. Disopyramide also prolongs the QT interval. If romidepsin and disopyramide must be continued, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
Rucaparib: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with rucaparib is necessary. Disopyramide is a CYP3A4 substrate and rucaparib is a weak CYP3A4 inhibitor; concomitant use may increase plasma concentrations of disopyramide. Specific drug interaction studies have not been done for disopyramide; however, cases of life-threatening interactions have been reported when coadministered with moderate and strong CYP3A4 inhibitors. Coadministration of disopyramide with CYP3A4 inhibitors could result in a potentially fatal interaction.
Saquinavir: (Contraindicated) The concurrent use of disopyramide and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening cardiac arrhythmias such as torsades de pointes (TdP). Saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of disopyramide. Coadministration may result in large increases in disopyramide serum concentrations, which could cause fatal cardiac arrhythmias. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; if possible, avoid use with other drugs that may prolong the QT or PR interval, such as all Class 1A antiarrhythmics.
Saxagliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Scopolamine: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation and for other disopyramide-related adverse reactions if coadministration of selpercatinib with disopyramide is necessary. Concurrent use may increase disopyramide exposure and cause additive QT prolongation. Disopyramide is a CYP3A4 substrate that is associated with QT prolongation and torsade de pointes (TdP). Selpercatinib is a weak CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner.
Semaglutide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Sertraline: (Major) Concomitant use of sertraline and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving disopyramide due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Disopyramide administration is associated with QT prolongation and torsade de pointes.
Sitagliptin: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
Sorafenib: (Major) Avoid coadministration of sorafenib with disopyramide due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Sorafenib is associated with QTc prolongation.
Sotalol: (Major) Sotalol administration is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Drugs that prolong the QT interval should be used with extreme caution in combination with sotalol. Ventricular tachycardia, including torsade de pointes and monomorphic ventricular tachycardia can occur with excessive prolongation of the QT interval. Examples of agents that may prolong the QT interval include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Before initiating sotalol, the previous Class I antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of (2-3) plasma half-lives for the discontinued drug.
Spironolactone: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with spironolactone is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with spironolactone is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
St. John's Wort, Hypericum perforatum: (Major) Hepatic microsomal enzyme-inducing agents, such as St. John's wort, have the potential to accelerate the hepatic metabolism of disopyramide (CYP3A4 substrate). Patients should be monitored for loss of disopyramide activity. In addition, disopyramide doses may need to be reduced if these agents are stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy.
Streptogramins: (Moderate) Caution is warranted during coadministration of disopyramide and dalfopristin; quinupristin due to the potential for elevated disopyramide plasma concentrations and associated adverse events including QT prolongation. Disopyramide is a CYP3A4 substrate; dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
Sulfonylureas: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of disopyramide with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Disopyramide administration is also associated with QT prolongation and TdP.
Tacrolimus: (Major) Disopyramide and tacrolimus both prolong the QT interval; also, both drugs are metabolized by CYP3A4. Although the manufacturer recommends dose adjustment and close monitoring when tacrolimus is coadminsitered with other drugs that prolong the QT interval and are subtrates or inhibitors of CYP3A4, it may be prudent to avoid coadministration as the risk of torsade de pointes may be increased.
Tamoxifen: (Major) Concomitant use of tamoxifen and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Teduglutide: (Moderate) Teduglutide may increase absorption of disopyramide because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of disopyramide is recommended.
Telavancin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with telavancin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and telavancin has been associated with QT prolongation.
Tetrabenazine: (Major) The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP).
Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and disopyramide concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as disopyramide, can increase disopyramide exposure leading to increased or prolonged therapeutic effects and adverse events.
Thiazolidinediones: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of disopyramide and thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. In addition, both thioridazine and disopyramide have significant anticholinergic effects that may be additive during coadministration.
Timolol: (Major) Disopyramide and beta-blockers, like timolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Tipranavir: (Major) Tipranavir can inhibit CYP3A4, an isoenzyme that is partially responsible for the metabolism of disopyramide. Although no definitive clinical data have yet confirmed this interaction, the concurrent use of these agents should be approached with caution due to the potential for serious disopyramide toxicity.
Tirzepatide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Tolterodine: (Major) Tolterodine should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6. In addition to its electrophysiologic effects, disopyramide exhibits clinically significant antimuscarinic anticholinergic properties. These can be additive with tolterodine. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Toremifene: (Major) Avoid coadministration of disopyramide with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Toremifene has also been shown to prolong the QTc interval in a dose- and concentration-related manner.
Trandolapril; Verapamil: (Contraindicated) Disopyramide and verapamil should not be used concomitantly due to potential for additive negative inotropic effects which could result in left ventricular impairment. Avoid disopyramide administration within 48 hours before or 24 hours after verapamil administration. In addition, verapamil can theoretically inhibit the CYP3A4 metabolism of disopyramide.
Trazodone: (Major) Concomitant use of trazodone and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Major) Concomitant use of triclabendazole and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tricyclic antidepressants: (Major) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). The need to coadminister TCAs with any of these therapies should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA. In addition to effects on the EKG, disopyramide has significant anticholinergic effects that are additive to those of the TCAs.
Trifluoperazine: (Moderate) Trifluoperazine and disopyramide should be used cautiously due to the potential for QT prolongation. Trifluoperazine, a phenothiazine, has a possible risk for QT prolongation. Disopyramide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). In addition, trifluoperazine and disopyramide have significant anticholinergic effects which may be additive during coadministration.
Trihexyphenidyl: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Triprolidine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Trofinetide: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with trofinetide is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and trofinetide is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Trospium: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like trospium are used concomitantly with other drugs with moderate to significant anticholinergic effects like disopyramide.
Tucatinib: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with tucatinib is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other strong CYP3A4 inhibitors.
Vandetanib: (Major) Avoid coadministration of vandetanib with disopyramide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Disopyramide administration is also associated with QT prolongation and TdP.
Vardenafil: (Major) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. The effect of vardenafil on the QT interval should be considered when prescribing the drug.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug, such as disopyramide, that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, disopyramide is a CYP3A4 substrate, while vemurafenib is a CYP3A4 substrate and inducer; therefore, decreased concentrations of disopyramide may occur.
Venlafaxine: (Major) Concomitant use of venlafaxine and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verapamil: (Contraindicated) Disopyramide and verapamil should not be used concomitantly due to potential for additive negative inotropic effects which could result in left ventricular impairment. Avoid disopyramide administration within 48 hours before or 24 hours after verapamil administration. In addition, verapamil can theoretically inhibit the CYP3A4 metabolism of disopyramide.
Viloxazine: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with viloxazine is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A4 substrate and viloxazine is a weak CYP3A4 inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A4 inhibitors.
Voclosporin: (Major) Use caution if disopyramide is coadministered with voclosporin due to the risk of additive QT prolongation. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with vonoprazan is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministere d with moderate and strong CYP3A inhibitors.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concurrent administration of clarithromycin and disopyramide has been associated with post-marketing reports of torsades de pointes (TdP) and hypoglycemia. If these drugs are administered together, closely monitor ECGs for QT prolongation, blood glucose concentrations, and consider monitoring disopyramide serum concentrations. Both clarithromycin and disopyramide have been associated with an established risk for QT prolongation and TdP. (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with vonoprazan is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Voriconazole: (Major) Caution is advised when administering voriconazole with disopyramide due to the potential for additive effects on the QT interval and increased exposure to disopyramide. Both drugs have been associated with QT prolongation; coadministration may increase this risk. Voriconazole has also been associated with rare cases of torsades de pointes, cardiac arrest, and sudden death. In addition, coadministration of voriconazole (a strong CYP3A4 inhibitor) with disopyramide (a CYP3A4 substrate) may result in elevated disopyramide plasma concentrations and could increase the risk for adverse events, including QT prolongation. Cases of life-threatening interactions have been reported for disopyramide when given with CYP3A4 inhibitors. If these drugs are given together, closely monitor for prolongation of the QT interval. Rigorous attempts to correct any electrolyte abnormalities (i.e., potassium, magnesium, calcium) should be made before initiating concurrent therapy.
Vorinostat: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with disopyramide.
Voxelotor: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with voxelotor is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with other moderate CYP3A inhibitors.
Warfarin: (Minor) A single case of the use of disopyramide with warfarin reported that discontinuation of disopyramide resulted in a drop in the prothrombin time; however, causality was not established and other factors may have contributed to reduction of anticoagulant effect. A direct interaction between disopyramide and warfarin has not been established.
Zafirlukast: (Moderate) Zafirlukast is a CYP3A4 inhibitor which theoretically may decrease the hepatic metabolism of disopyramide.
Ziprasidone: (Contraindicated) Concomitant use of ziprasidone and class 1A antiarrhythmics, such as disopyramide, is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Class 1A antiarrhythmics are associated with a well-established risk of QT prolongation and TdP.

Disopyramide/Disopyramide Phosphate/Norpace Oral Cap: 100mg, 150mg
Norpace CR Oral Cap ER: 100mg, 150mg

Adults

800 mg/day PO; however, up to 1600 mg/day PO has been used in the hospital setting to treat severe refractory ventricular tachycardia.

Elderly

800 mg/day PO; however, up to 1600 mg/day PO has been used in the hospital setting to treat severe refractory ventricular tachycardia.

Adolescents

15 mg/kg/day PO.

Children

5—12 years: 15 mg/kg/day PO.
1—4 years: 20 mg/kg/day PO.

Infants

30 mg/kg/day PO.

Disopyramide has properties similar to those of other class IA antiarrhythmics (quinidine and procainamide). These drugs decrease myocardial conduction velocity, excitability, and contractility by inhibiting the influx of sodium through "fast" channels of the myocardial cell membrane, thereby increasing the recovery period after repolarization. Disopyramide suppresses atrial flutter or fibrillation by increasing the effective refractory period and the action potential duration in the atria, ventricles, and His-Purkinje system. The effective refractory period is increased more than the action potential duration, so the myocardium remains refractory even after the resting membrane potential has been restored. Disopyramide decreases automaticity in the His-Purkinje system and decreases conduction velocity in the atria and ventricles. Conduction velocity through accessory pathways is also decreased. Disopyramide prolongs the QRS and QT intervals in both normal sinus rhythm and atrial arrhythmias, and measurement of these intervals can be used to monitor therapy.
 
Disopyramide also exhibits anticholinergic properties. The anticholinergic effects appear to be more pronounced for disopyramide than for quinidine and may offset some of disopyramide's other effects. The anticholinergic effects may counteract the direct depressant action of disopyramide on the SA node so that no net change in heart rate occurs. When using disopyramide to treat atrial flutter or fibrillation, ventricular rate can accelerate due to vagolytic effects on the AV node. The antimuscarinic effects of disopyramide on other tissues should not be overlooked. Urinary retention has been reported in approximately 2% of patients and disopyramide has precipitated closed-angle glaucoma.
 
At therapeutic doses, disopyramide decreases cardiac output by 10% to 15% in uncompromised patients, without decreasing resting sinus rate or affecting blood pressure. However, IV doses of 2 mg/kg administered over a period of 3 minutes can increase heart rate and total peripheral resistance. Disopyramide has no known alpha- or beta-adrenergic pharmacologic activity.

Disopyramide is administered orally. It is well distributed throughout the body; it crosses the placenta and distributes into breast milk. Disopyramide is highly protein bound to both albumin and alpha-1-acid glycoprotein (AGP) in amounts greater than 90%. Onset of action generally occurs within 30 minutes, peaks within 3 hours, and lasts 1.5—8.5 hours. It is metabolized in the liver to one active and many inactive metabolites. Disopyramide is a CYP3A4 substrate. The active, N-monodealkylated metabolite has less antiarrhythmic activity, but greater anticholinergic activity than the parent compound. Plasma half-life varies from 4—10 hours. Serum concentrations of 2—4 mcg/mL will usually suppress ventricular arrhythmias, but some patients require up to 7 mcg/mL. Plasma concentrations greater than 9 mcg/mL are considered toxic.
 
Affected cytochrome P450 isoenzymes: CYP3A4

Oral Route

Disopyramide is well absorbed following an oral dose, with a bioavailability of 87—95%. Approximately 40% of an oral dose is excreted in the urine unchanged, 10% in the feces, 15—25% as the active metabolite, with the rest excreted in the urine as metabolites.

Pregnancy

Disopyramide is classified as a FDA pregnancy risk category C drug. Although it has been shown to cause adverse effects during gestation in laboratory rats, well-controlled studies have not been performed in humans. The drug has been found in human fetal blood. Disopyramide has also been shown to stimulate contractions of the pregnant uterus. Use of disopyramide during pregnancy should be avoided unless the potential benefit justifies the risk to the fetus.

Following oral administration, disopyramide has been detected in human milk at concentrations less than or equal to those of plasma. According to the manufacturer, because of the potential for serious adverse reactions in nursing infants from disopyramide, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. If pharmacotherapy is necessary in the nursing woman, the American Academy of Pediatrics considers disopyramide, procainamide, lidocaine, and quinidine to be usually compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.