Disopyramide

Associated with severe bradycardia, asystole, and heart failure when administered with beta-blockers.

Associated with severe bradycardia, asystole, and heart failure when combined with beta-blockers due to potent negative inotropic and chronotropic effects.

amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine digoxin ↑ ranolazine ↑ ivabradine ↑ dronedarone ↑ antiarrhythmics ↑ digoxin Co-administration is contraindicated due to potential for serious and/or life-threatening reactions.

amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine digoxin ↑ ranolazine ↑ ivabradine ↑ dronedarone ↑ antiarrhythmics ↑ digoxin Co-administration is contraindicated due to potential for serious and/or life-threatening reactions.

dronedarone ↑ dronedarone Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias Other antiarrhythmics e.g., amiodarone, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine ↑ antiarrhythmics Clinical monitoring is recommended upon co-administration with antiarrhythmics.

Little experience with coadministration. Should not be administered concurrently unless benefits outweigh risks due to negative inotropic properties.

Antiarrhythmics Disopyramide Dofetilide Dronedarone Quinidine a Contraindicated during and 2 weeks after itraconazole treatment.

(See PRECAUTIONS: DRUG INTERACTIONS .) Additionally, the following other drugs are contraindicated with ketoconazole tablets: methadone, disopyramide, dronedarone, ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine, methylergometrine, irinotecan, lurasidone, oral midazolam, alprazolam, triazolam, felodipine, nisoldipine, ranolazine, tolvaptan, eplerenone, lovastatin, simvastatin and colchicine.

Concomitant use is contraindicated due to increased risk of QT prolongation and torsades de pointes.

Telaprevir Decrease AUC by 92% Systemic Hormonal Contraceptives Prevention or Management Advise patients to change to non-hormonal methods of birth control during rifampin therapy Estrogens Decrease exposure Progestins Anticonvulsants Phenytoin § Decrease exposure § Antiarrhythmics Disopyramide Decrease exposure Mexiletine Decrease exposure Quinidine Decrease exposure Propafenone Decrease AUC by 50% to 67% Tocainide Decrease exposure Antiestrogens Tamoxifen Decrease AUC by 86% Toremifene Decrease steady state concentrations of toremifene in serum Antithrombotic Agents Clopidogrel Prevention or Management Concomitant use of clopidogrel and rifampin should be discouraged Increase active metabolite exposure and risk of bleeding Ticagrelor Prevention or Management Avoid use Decrease exposure Antipsychotics Haloperidol Decrease plasma concentrations by 70% Lurasidone Prevention or Management: Concomitant use is contraindicated (See CONTRADICTIONS ) Decrease exposure Oral Anticoagulants Prevention or Management Perform prothrombin time daily or as frequently as necessary to establish and maintain the required dose of anticoagulant Warfarin Decrease exposure Antifungals Fluconazole Decrease AUC by 23% Itraconazole Prevention or Management Not recommended 2 weeks before and during itraconazole treatment Decrease exposure Ketoconazole Decrease exposure Beta-blockers Metoprolol Decrease exposure Propranolol Decrease exposure Benzodiazepines Diazepam *,¶ Decrease exposure Benzodiazepine-Related Drugs Zopiclone Decrease AUC by 82% Zolpidem Decrease AUC by 73% Calcium Channel Blockers ¶ Diltiazem Decrease exposure Nifedipine # Decrease exposure Verapamil Decrease exposure Corticosteroids Þ Prednisolone Decrease exposure Cardiac Glycosides Digoxin Prevention or Management Measure serum digoxin concentrations before initiating rifampin.

Class Ia antiarrhythmic; potential to prolong refractoriness. Discontinue for at least three half-lives prior to sotalol dosing.

( 7.3 ) 7.1 Drugs that Prolong QT Avoid use of anagrelide in patients taking medications that may prolong QT interval (including, but not limited to, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, amiodarone, disopyramide, procainamide, and pimozide) [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ] .

( 7.3 ) 7.1 Drugs that Prolong QT Avoid use of AGRYLIN in patients taking medications that may prolong QT interval (including, but not limited to, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, amiodarone, disopyramide, procainamide, and pimozide) [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ] .

Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects. Disopyramide has been associated with severe bradycardia, asystole and heart failure when administered with beta blockers.

Antiarrhythmic agent that depresses myocardium and inhibits AV conduction; use with care when combined with bisoprolol fumarate.

Postmarketing reports of torsades de pointes with concurrent use. CYP3A-based interaction may increase disopyramide concentrations. Hypoglycemia reported with concomitant administration.

Drug Interactions If phenytoin or other hepatic enzyme inducers are taken concurrently with disopyramide phosphate, lower plasma levels of disopyramide may occur. Monitoring of disopyramide plasma levels is recommended in such concurrent use to avoid ineffective therapy. Other antiarrhythmic drugs (e.g., quinidine, procainamide, lidocaine, propranolol) have occasionally been used concurrently with disopyramide phosphate.

May increase the risk of hypoglycemia. Dose adjustment and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased glucose monitoring may be required.

May increase the risk of hypoglycemia; dose adjustment and increased glucose monitoring required.

Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited [see Warnings and Precautions (5.1) ] .

Antiarrhythmic agent; nebivolol can exacerbate its effects on myocardial depression and AV conduction.

Antiarrhythmic agent can exacerbate effects of myocardial depression and AV conduction inhibition.

Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects and has been associated with severe bradycardia, asystole and heart failure when administered with propranolol.

Class IA antiarrhythmic that prolongs QT interval; should be avoided with toremifene citrate or requires close monitoring.

In rare instances, including when patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction were given intravenous beta-adrenergic blocking agents or disopyramide concomitantly with intravenous verapamil, serious adverse effects have occurred.

There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with disopyramide and quinidine. There have been postmarketing reports of hypoglycemia with the concomitant administration of clarithromycin and disopyramide. Prevention or Management Disopyramide Avoid concomitant use with VOQUEZNA TRIPLE PAK.

Bisoprolol fumarate and hydrochlorothiazide tablets should be used with caution when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.

disopyramide flecainide systemic lidocaine mexiletine propafenone quinidine ↑ antiarrhythmics ↑ digoxin Caution is warranted and therapeutic concentration monitoring, if available, is recommended for antiarrhythmics when coadministered with GENVOYA.

Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir Calcium channel blockers Nifedipine, nimodipine, nisoldipine, verapamil Other Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine 7.3 Hyperammonemia with Concomitant Use of Valproate Concomitant administration of phenytoin and valproate has been associated with an increased risk of valproate-associated hyperammonemia.

May potentiate hypoglycemic action of glyburide. Patient should be observed closely for hypoglycemia when administered and for loss of control when withdrawn.

May increase glucose-lowering effect of glimepiride, increasing susceptibility to and/or intensity of hypoglycemia.

May increase glucose-lowering effect of glipizide and susceptibility to hypoglycemia; monitor closely.

Class 1A antiarrhythmic known to prolong QTc interval; caution advised when used with haloperidol decanoate due to risk of QT prolongation.

Class 1A antiarrhythmic that prolongs QTc interval; caution advised when used with haloperidol due to risk of QT prolongation.

May increase risk of hypoglycemia. Dose adjustment and increased glucose monitoring may be required.

May increase risk of hypoglycemia; dosage reductions and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased glucose monitoring may be required.

May increase the risk of hypoglycemia. Dose reductions and increased frequency of glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased frequency of glucose monitoring may be required.

May increase risk of hypoglycemia. Dose adjustment and increased glucose monitoring may be required.

May increase risk of hypoglycemia; dose adjustment and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dose reductions and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dose reductions and increased glucose monitoring may be required.

Antiarrhythmics lidocaine (systemic), disopyramide ↑ antiarrhythmic Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available.

Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir Calcium channel blockers Nifedipine, nimodipine, nisoldipine, verapamil Other Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine 7.3 Hyperammonemia with Concomitant Use of Valproate Concomitant administration of phenytoin and valproate has been associated with an increased risk of valproate-associated hyperammonemia.

Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir Calcium channel blockers Nifedipine, nimodipine, nisoldipine, verapamil Other Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine 7.3 Hyperammonemia with Concomitant Use of Valproate Concomitant administration of phenytoin and valproate has been associated with an increased risk of valproate-associated hyperammonemia.

May increase susceptibility to hypoglycemia when coadministered with SYMLIN. Use with caution.

May increase risk of hypoglycemia. Repaglinide dose reductions and increased glucose monitoring may be required.

Rifapentine may increase metabolism and decrease activity. Dosage adjustment may be necessary.

Antiarrhythmics: disopyramide, lidocaine, mexiletine ↑ antiarrhythmics Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics when co-administered with ritonavir, if available.

Antiarrhythmics: disopyramide, lidocaine, mexiletine ↑ antiarrhythmics Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics when co-administered with ritonavir, if available.

Antiarrhythmics: Other antiarrhythmic drugs, such as quinidine, procainamide, disopyramide, and phenytoin, have been used concurrently with amiodarone. Disopyramide causes QT prolongation which could induce arrhythmia.

amiodarone, quinidine lidocaine (systemic), disopyramide, flecainide mexiletine, propafenone digoxin ↑ other antiarrhythmics ↑ digoxin Clinical monitoring is recommended upon coadministration with antiarrhythmics.

Other antiarrhythmics: e.g., amiodarone disopyramide flecainide mexiletine propafenone quinidine ↑ antiarrhythmics Clinical monitoring is recommended upon coadministration with antiarrhythmics.

amiodarone, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine ↑ antiarrhythmics Clinical monitoring is recommended upon co-administration with antiarrhythmics.

disopyramide flecainide systemic lidocaine mexiletine propafenone quinidine ↑ antiarrhythmics ↑ digoxin Therapeutic concentration monitoring, if available, is recommended for antiarrhythmics when coadministered with STRIBILD.

There have been spontaneous or published reports of CYP3A based interactions of erythromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methyl-prednisolone, cilostazol, vinblastine and bromocriptine.

(See Viagra package insert.) There have been spontaneous or published reports of CYP3A based interactions of erythromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, vinblastine, and bromocriptine.

There have been reports of interactions of erythromycin with carbamazepine, cyclosporine, hexobarbital, phenytoin, alfentanil, disopyramide, bromocriptine, valproate, terfenadine, and astemizole.

Other agents Antiarrhythmics : digoxin amiodarone bepridil disopyramide flecainide lidocaine (systemic) mexiletine propafenone quinidine ↔ etravirine ↑ digoxin ↓ antiarrhythmics For patients who are initiating a combination of etravirine tablets and digoxin, the lowest dose of digoxin should initially be prescribed. Other agents Antiarrhythmics : digoxin amiodarone bepridil disopyramide flecainide lidocaine (systemic) mexiletine propafenone quinidine ↔ etravirine ↑ digoxin ↓ antiarrhythmics For patients who are initiating a combination of etravirine tablets and digoxin, the lowest dose of digoxin should initially be prescribed.

Antiarrhythmics: Amiodarone, disopyramide, lidocaine (systemic), and quinidine Flecainide, propafenone ↑ Antiarrhythmics ↑Antiarrhythmics Therapeutic concentration monitoring, if available, is recommended for antiarrhythmics.

Clinically Significant Drug Interactions with Clarithromycin Tablets Drugs That Are Affected By Clarithromycin tablets Drug(s) with Pharmacokinetics Affected by Clarithromycin tablets Recommendation Comments Antiarrhythmics: Disopyramide Quinidine Dofetilide Amiodarone Sotalol Procainamide Not Recommended Disopyramide, Quinidine : There have been postmarketing reports of torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with disopyramide and quinidine. There have been postmarketing reports of hypoglycemia with the concomitant administration of clarithromycin and disopyramide.

Antiarrhythmics: Amiodarone, disopyramide, lidocaine Plasma concentrations may be decreased.

The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including glimepiride, a component of pioglitazone and glimepiride tablets, increasing the susceptibility to and/or intensity of hypoglycemia: oral anti-diabetic medications, pramlintide acetate, insulin, angiotensin converting enzyme (ACE) inhibitors, H2 receptor antagonists, fibrates, propoxyphene, pentoxifylline, somatostatin analogs, anabolic steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors.

Antiarrhythmic Agents Verapamil Component Disopyramide Phosphate Data on possible interactions between verapamil and disopyramide phosphate are not available. Therefore, disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration.

Examples: Class 1A antiarrhythmics: quinidine, procainamide, disopyramide; Class 3 antiarrhythmics: amiodarone, sotalol; Antipsychotics: ziprasidone, chlorpromazine, thioridazine; Antibiotics: gatifloxacin

7 DRUG INTERACTIONS The table below presents clinically significant drug interactions with KIRSTY Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. • Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics ( 7 ).