Pill Identifier App

Disopyramide Phosphate

Class: Class Ia Antiarrhythmics
VA Class: CV300
CAS Number: 22059-60-5
Brands: Norpace, Norpace CR

Warning(s)

  • Mortality
  • Excessive mortality or nonfatal cardiac arrest rate (7.7%) in encainide- or flecainide-treated patients with asymptomatic non-life-threatening ventricular arrhythmias (with MI history >6 days but <2 years) in NHLBI’s long-term CAST study relative to placebo.a (See Mortality under Cautions.)

  • Applicability of CAST findings to other populations (e.g., those without recent MI) uncertain.a

  • Because of disopyramide’s proarrhythmic properties and lack of evidence of improved survival for any antiarrhythmic drug, reserve disopyramide for life-threatening ventricular arrhythmias.a

Introduction

Antiarrhythmic agent (class IA).b

Uses for Disopyramide Phosphate

Precise role in antiarrhythmic therapy has not been established.b Some experts recommend that disopyramide should be reserved for use as an alternative drug when lidocaine, quinidine, or procainamide is ineffective or adverse effects of these drugs are intolerable.b

Limited information is available on combination therapy with other antiarrhythmic drugs such as lidocaine, quinidine, or procainamide to treat or prevent serious, refractory arrhythmias.b

Ventricular Arrhythmias

Suppression and prevention of recurrent life-threatening ventricular arrhythmias (e.g., sustained VT).112 (See Boxed Warning.)

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Because of the disopyramide’s arrhythmogenic potential and lack of evidence for improved survival for class I antiarrhythmic agents,a use for less severe arrhythmias is not recommended.a

Avoid treatment of asymptomatic VPCs.a

Atrial Arrhythmias

IV disopyramide (not commercially available in the US) has been used to convert atrial fibrillation, atrial flutter, and paroxysmal atrial tachycardia to normal sinus rhythm when electrical cardioversion is not indicated or is ineffective.b 127 Also used to prevent recurrence after conversion by other methods.b

Other antiarrhythmic drugs (e.g., amiodarone, dofetilide, flecainide, ibutilide, propafenone) are preferred128 129 in patients with no left ventricular dysfunction.127

Adequate anticoagulation may be necessary before administration of disopyramide for conversion of atrial fibrillation to normal sinus rhythm, (atrial fibrillation is≥48 hours).127 128

Disopyramide Phosphate Dosage and Administration

General

  • Adjust dosage carefully according to individual requirements and response and the general condition and cardiovascular status of the patient.b

  • Initiate disopyramide therapy only in a hospital setting.112

  • ECG monitoring of cardiac function and determination of plasma concentrations are recommended, especially when given to patients with an increased risk of adverse reactions (e.g., those with severe heart disease, hypertension, hepatic or renal disease).a b

Administration

Administer orally.b

Oral Administration

Conventional capsules: Administer orally every 6 hours or at intervals according to individual requirements.b

Extended-release capsules: Administer orally every 12 hours.a

For rapid control of ventricular arrhythmias, conventional capsules should be used; do not use extended-release capsules.b

Dosage

Available as disopyramide phosphate; dosage expressed in terms of disopyramide.b

Reduce dosage in patients with moderate or severe renal insufficiency, hepatic insufficiency, cardiomyopathy, possible cardiac decompensation, AMI, and in patients weighing <50 kg.b

Pediatric Patients

Ventricular Arrhythmias
Oral

Optimum pediatric dosage has not been established; however, dosage recommendations have been made based on clinical experience.b

Initiate dose titration at the lower end of the recommended ranges; monitor plasma drug concentrations and therapeutic response carefully.b

For children unable to swallow the capsules, a suspension may be extemporaneously prepared by mixing the contents of disopyramide phosphate conventional capsules in cherry syrup to produce suspensions that contain 1–10 mg of disopyramide per mL.b The extended-release capsules should not be used for the preparation of an extemporaneous suspension.b

Give total daily dose in equally divided doses every 6 hours or at intervals according to individual requirements.b

Total Daily Pediatric Dosage Based on Age and Weight

Age

Total Daily Pediatric Dosage

<1 year of age

10–30 mg/kg

1–4 years of age

10–20 mg/kg

4–12 years of age

10–15 mg/kg

12–18 years of age

6–15 mg/kg

Adults

Ventricular Arrhythmias
Oral (Conventional Capsules)

Usual dosage: 400–800 mg daily, given in divided doses.112

Adults weighing ≥50 kg: Usually 150 mg every 6 hours.a b

Adults weighing <50 kg: Usually 100 mg every 6 hours.a b

Oral (Extended-release Capsules)

Usual dosage: 400–800 mg daily, given in divided doses.112

Adults weighing ≥50 kg: Usually 300 mg every 12 hours.a b

Adults weighing <50 kg: Usually 200 mg every 12 hours.a b

Rapid Control
Oral (Conventional Capsules)

Adults weighing ≥50 kg: Initially, 300 mg followed by 150 mg every 6 hours.b

Adults weighing <50 kg: Initially, 200 mg followed by 150 mg every 6 hours.b

If there is no therapeutic response and if no toxic effects occur within 6 hours after the initial 300-mg dose, 200-mg doses may be given every 6 hours.b If there is no response to this dosage in 48 hours, discontinue disopyramide and initiate alternative therapy.b

Alternatively, the patient may be hospitalized, closely evaluated, and continuously monitored while the dosage is increased to 250 or 300 mg every 6 hours.b

Severe Refractory VT
Oral (Conventional Capsules)

Up to 400 mg every 6 hours may be required (resulting in plasma disopyramide concentrations up to 9 mcg/mL).a

Patients should be hospitalized, closely evaluated, and continuously monitored.a

Rapid Control In Patients with Cardiomyopathy or Possible Cardiac Decompensation
Oral (Conventional Capsules)

Do not administer an initial loading dose.b

Do not exceed an initial dosage of 100 mg every 6 hours.b

Carefully adjust dosage in these patients while closely monitoring for hypotension and/or CHF.b (See CHF and Hypotension under Cautions.)

Switching from Another Class I Antiarrhythmic Agent
Oral (Conventional Capsules or Extended-release Capsules)

Administer the usual dosage of disopyramide (without an initial loading dose) 6–12 hours after the last dose of quinidine sulfate or 3–6 hours after the last dose of procainamide.b

If withdrawal of quinidine or procainamide is likely to produce life-threatening arrhythmias, hospitalize and closely monitor patient.b

Switching from Conventional to Extended-release Capsules
Oral (Extended-release)

Initiate usual maintenance schedule (e.g., 300 mg every 12 hours) of extended-release capsules 6 hours after the last dose of the conventional capsules.b

Dosage Modification for Toxicity

If increased anticholinergic adverse effects occur, monitor plasma concentrations of disopyramide and adjust dosage accordingly.a Dosage may be reduced by one-third and the same dosing interval maintained (e.g., 600 mg daily reduced to 400 mg daily).a

Prescribing Limits

Adults

Ventricular Arrhythmias
Patients with Cardiomyopathy or Possible Cardiac Decompensation
Oral (Conventional Capsules)

Maximum initial dosage: 100 mg every 6 hours.b

Special Populations

Hepatic Impairment

Oral

Usual dosage: 100 mg every 6 hours as conventional capsules or 200 mg every 12 hours as extended-release capsules.b

Renal Impairment

Oral

Do not use extended-release capsules in patients with a Clcr ≤40 mL/minute.b

Patients with moderately impaired renal function (Clcr >40 mL/minute): Usually, 100 mg every 6 hours as conventional capsules or 200 mg every 12 hours as extended-release capsules.b

In patients with severely impaired renal function (Clcr ≤40 mL/minute), the usual dosage of conventional capsules is 100 mg (with or without an initial 150-mg dose) given at the following approximate intervals depending on the patient’s Clcr:b

Clcr (mL/minute)

Dosage Interval

30–40

every 8 h

15–30

every 12 h

<15

every 24 h

Geriatric Patients

Select dosage with caution (generally starting at the low end of the dosing range) because of age-related decreases in hepatic, renal, and/or cardiac function, and concomitant disease and drug therapy.a

If adverse anticholinergic effects occur, monitor plasma disopyramide concentrations and adjust dosage as needed.a (See Dosage Modification for Toxicity under Dosage and Administration.)

Cautions for Disopyramide Phosphate

Contraindications

  • Preexisting 2nd or 3rd degree AV block (if an artificial pacemaker has not been inserted).b

  • Cardiogenic shock.b

  • Known hypersensitivity to disopyramide.b

Warnings/Precautions

Warnings

Mortality

In CAST study, excessive rate of mortality and nonfatal cardiac arrest reported in patients with asymptomatic, non-life-threatening ventricular arrhythmias and recent MI (>6 days but <2 years previously) who were receiving encainide or flecainide compared with placebo.a

Because of disopyramide’s arrhythmogenic potential and the lack of evidence for improved survival for class I antiarrhythmic agents,112 116 117 118 use disopyramide only for life-threatening arrhythmias.112 Use in less severe arrhythmias currently is not recommended, and treatment of asymptomatic VPCs should be avoided.112

Initiate therapy only in a hospital setting.112

CHF and Hypotension

May cause or worsen CHF or produce severe hypotension.a Hypotension occurs more commonly in patients with primary cardiomyopathy or inadequately compensated CHF.a

Do not use in patients with uncompensated or marginally compensated CHF or hypotension unless the CHF or hypotension is secondary to cardiac arrhythmia.a In patients with a history of heart failure, cardiac function must be carefully maintained, including optimal digitalization.a

If hypotension occurs or CHF worsens, discontinue disopyramide and, if necessary, resume therapy at a lower dosage only after establishing adequate cardiac compensation.a

Increased risk of severe hypotension in patients with myocarditis or other cardiomyopathy.b Do not administer a loading dose to such patients; select initial dosage and make subsequent dosage adjustments under close supervision.b (See Patients with Cardiomyopathy or Possible Cardiac Decompensation under Dosage and Administration.)

Arrhythmogenic Effects

Possible worsening of existing arrhythmias or occurrence of new arrhythmias, including VT and VF associated with prolonged QT interval.a b Increased risk of such effects if used concomitantly with other drugs (i.e., quinidine) that prolong the QT interval.a b

Atypical VT (torsades de pointes) and cardiac arrest have occurred rarely.128 a b

If a QT prolongation >25% occurs and if ectopy continues, monitor patient closely.a Consider discontinuance of disopyramide.a

Rarely, clinically important widening (>25%) of the QRS complex has occurred;a in such cases discontinue disopyramide.128 a

Hypoglycemia

Hypoglycemia reported rarely.a b

Monitor blood glucose concentrations closely in patients with compromised glucoregulatory mechanisms in the absence of food (e.g., patients with CHF, chronic malnutrition, hepatic or renal disease, those using alcohol or receiving certain drugs [e.g., β-adrenergic blockers]).b

Concurrent Use with Other Antiarrhythmics

Reserve combined use for serious arrhythmias unresponsive to monotherapy; monitor closely.a

Heart Block

Reduce dosage if first-degree AV heart block occurs.b If the block persists, weigh the benefit of therapy against the potential risk of higher degrees of AV block.b

If second- or third-degree AV block or unifascicular, bifascicular, or trifascicular block occurs, discontinue disopyramide therapy, unless the ventricular rate is adequately controlled by an artificial pacemaker.b

Anticholinergic Effects

Possible anticholinergic effects; do not use in patients with glaucoma, myasthenia gravis, or urinary retention without instituting adequate overriding measures (e.g., pilocarpine ophthalmic drops for glaucoma, catheter drainage or operative relief for urinary retention).a

Possible increased risk of urinary retention in males with benign prostatic hypertrophy.a

Measure intraocular pressure before initiating therapy in patients with a family history of glaucoma.a

May precipitate myasthenic crisis; use with caution in patients with myasthenia gravis.a

Use with caution in geriatric patients. (See Geriatric Use under Cautions.)a

General Precautions

Atrial Tachyarrhythmias

Possible enhanced AV conduction; patients with atrial flutter or fibrillation should be digitalized prior to administration.b

Conduction Abnormalities

Use with caution in patients with sick sinus syndrome (including bradycardia-tachycardia syndrome), Wolff-Parkinson-White syndrome, or bundle-branch block, since effects of the drug in these conditions are unpredictable.b

Potassium Imbalance

Correct abnormalities in serum potassium concentration before initiating therapy.a

May be ineffective in patients with hypokalemia and toxic effects may be enhanced in patients with hyperkalemia.a

Specific Populations

Pregnancy

Category C.a

Lactation

Distributed into milk.112 Discontinue nursing or the drug.112

Pediatric Use

Safety and efficacy not established.a However, disopyramide has been used in children.a b (See Pediatric Patients under Dosage and Administration.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.a

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.a (See Geriatric Patients under Dosage and Administration.)

Substantially eliminated by kidneys; assess renal function periodically and adjust dosage accordingly.a (See Renal Impairment under Dosage and Administration.)

Possible anticholinergic effects; not generally recommended for use in patients with glaucoma, urinary retention, or benign prostatic hypertrophy unless adequate overriding measures are taken.a (See Anticholinergic Effects under Warnings.)

Hepatic Impairment

Increased plasma half-life; dosage adjustment recommended.a (See Hepatic Impairment under Dosage and Administration.)

Patients with cardiac dysfunction are more likely to have comorbid hepatic impairment.a

Carefully monitor ECG for prolongation of PR interval, evidence of QRS widening, or other signs of toxicity.a

Renal Impairment

Increased plasma half-life; dosage adjustments necessary based on degree of renal impairment.a (See Renal Impairment under Dosage and Administration.)

Carefully monitor ECG for prolongation of PR interval, evidence of QRS widening, or other signs of toxicity.a

Not recommended for use in patients with severe renal insufficiency (Clcr ≤40 mL/min).a

Common Adverse Effects

Anticholinergic effects (e.g., dry mouth, urinary hesitancy, constipation, blurred vision, dry nose/eyes/throat), urinary frequency/urgency, urinary retention, nausea, pain/bloating/gas, dizziness, general fatigue/muscle weakness, headache, malaise, aches/pains.a b

Interactions for Disopyramide Phosphate

Appears to be metabolized principally by CYP3A4.a

Drugs Affecting Hepatic Microsomal Enzymes

Inducers of hepatic microsomal enzymes: Potential pharmacokinetic interaction (decreased plasma disopyramide concentrations).a b When used concomitantly, closely monitor serum disopyramide concentrations to avoid subtherapeutic concentrations.b

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma disopyramide concentrations).a

Specific Drugs

Drug

Interaction

Comments

Antiarrhythmic agents (e.g., quinidine, procainamide, lidocaine, encainide, flecainide, propafenone, propranolol)

Possible additive or antagonistic cardiac effects; toxic effects may be additiveb

Potential for severe negative inotropic effects or enhanced conduction prolongation, especially in cardiac decompensationa

Concomitant use with quinidine may result in slight increases in plasma disopyramide concentrations and slight decreases in plasma quinidine concentrations112

Reserve concomitant use for the management of life-threatening arrhythmias unresponsive to monotherapy; monitor closelyb a

Anticholinergic agents

Possible additive effectsb

Diazepam

No interaction noted in healthy individualsa

Digoxin

Concomitant use does not appear to increase serum digoxin concentrations112

Macrolide antibiotics (e.g., erythromycin, clarithromycin)

Increased plasma disopyramide concentrations and increased risk of serious toxicity (e.g., prolongation of the QT-interval, widening of the QRS complex, polymorphic ventricular tachycardia, ventricular fibrillation)112 115 126 a b

Close monitoring recommended112 a

Phenytoin

Potential for increased metabolism of disopyramideb

Monitor serum disopyramide concentrations closely to avoid subtherapeutic concentrationsb

Verapamil

Potential for additive negative inotropic effectsb

Concomitant use not recommended b

Discontinue disopyramide 48 hours prior to initiating verapamil therapy; do not reinstitute disopyramide until 24 hours after verapamil has been discontinuedb

Disopyramide Phosphate Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed (60–83%) after oral administration.b

Bioavailability of disopyramide from the extended-release and conventional capsules appears similar.a

Peak plasma concentrations attained in 2–2.5 or 4.9 hours after oral administration of conventional or extended-release capsules, respectively.a b

Onset

Onset of action usually is within 0.5–3 hours after oral administration of a single 300-mg dose (conventional capsules).a

Duration

Antiarrhythmic effect persists 1.5–8.5 hours after oral administration of conventional capsules.b

Plasma Concentrations

Plasma disopyramide concentrations of approximately 2–4 mcg/mL generally required to suppress ventricular arrhythmias; concentrations up to 9 mcg/mL have been required in a limited number of patients with severe refractory VT.a b

Plasma concentrations >9 mcg/mL associated with toxic effects.b

Distribution

Extent

Distributed throughout the extracellular body water; not extensively bound to tissues.b

Equally distributed between plasma and erythrocytes.b

Disopyramide crosses the placenta and is distributed into milk.a b

Plasma Protein Binding

Approximately 50–65%; decreases as the concentration of disopyramide and its metabolites increase.b

Special Populations

In patients with renal insufficiency, the volume of distribution is slightly decreased.b

Patients with AMI (without CHF) may have lower peak plasma concentrations and smaller volumes of distribution compared with healthy individuals.b

Elimination

Metabolism

Metabolized in the liver to an N-monodealkylated metabolite and other unidentified metabolites.b

Plasma concentration of the N-monodealkylated metabolite is approximately 10% of the concentration of disopyramide.b

The N-monodealkylated metabolite has less antiarrhythmic activity but greater anticholinergic activity than does disopyramide.b

CYP3A4 involved in metabolism.a

Elimination Route

After oral administration, 50% of an oral dose excreted in urine as unchanged drug, 20% as the N-monodealkylated metabolite, and about 10% as unidentified metabolites; about 10% is excreted in feces as unchanged drug and metabolites.a b

Urinary pH apparently does not affect the rate of renal excretion.b

Half-life

Conventional capsules: Elimination half-life 4–10 hours.a

Extended-release capsules: Elimination half-life 6.9–16.4 hours.a

Special Populations

Plasma half-life prolonged in patients with hepatic or renal insufficiency.b

In patients with Clcr <40 mL/minute, plasma half-life ranged from 8–18 hours.b

Disopyramide is removed by hemodialysis.b

In patients with heart disease, including left ventricular dysfunction, the mean plasma half-life was slightly prolonged to 7.8 hours (range: 5–9.5 hours).a

Stability

Storage

Oral

Capsules (Conventional and Extended-release)

25°C (may be exposed to 15–30°C).a

Suspension

Oral suspensions of disopyramide phosphate prepared extemporaneously from conventional capsules of the drug and cherry syrup at concentrations ranging from 1–10 mg/mL reportedly are stable for 1 month when stored at 2–8°C.b

Dispense in amber glass bottles.b

Actions

  • A class I (membrane-stabilizing) antiarrhythmic agent with actions similar to those of procainamide and quinidine.b

  • Regarded as a myocardial depressant because it decreases myocardial excitability and conduction velocity, and may depress myocardial contractility.b

  • Possesses anticholinergic properties, which may modify the direct myocardial effects of the drug.b

  • Exact mechanism of antiarrhythmic action has not been established; is believed to combine with fast sodium channels in their inactive state and thereby inhibit recovery after repolarization in a time- and voltage-dependent manner that is associated with subsequent dissociation of the drug from the sodium channels.b

  • Exhibits electrophysiologic effects characteristic of class IA antiarrhythmic agents (i.e., exhibits intermediate rates of attachment and dissociation transmembrane sodium channels).b

  • Suppresses automaticity in the His-Purkinje system.b

  • Decreases the automaticity of ectopic atrial and ventricular pacemakers, shortens or does not change the sinus node recovery time, and decreases conduction velocity in the atria and ventricles.b

  • Has little effect on conduction velocity through the AV node or the His-Purkinje system, but accessory pathway conduction velocity is decreased.b

  • Generally prolongs the effective refractory period (ERP) of the atria and the ventricles.b

  • Usually has little effect on the ERP of the AV node or the His-Purkinje system; however, the effect on the AV node is unpredictable in patients with preexisting conduction disturbances.b

  • Generally causes little or no prolongation of the PR interval or the QRS complex, but the QT interval or QT interval corrected for rate (QTc) may be prolonged.b

  • Generally has little effect on resting sinus rate and has a direct negative inotropic effect on the heart.b

  • Usually decreases cardiac output 10–15% in patients without compromised myocardial function.b

  • It has not been established whether disopyramide has local anesthetic properties.b

Advice to Patients

  • Potential for toxicity (e.g., cardiovascular, anticholinergic).a

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.a

  • Importance of informing patients of other important precautionary information.a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Disopyramide Phosphate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

100 mg (of disopyramide)*

Disopyramide Phosphate Capsules

Sandoz, Teva, Watson

Norpace

Searle

150 mg (of disopyramide)*

Disopyramide Phosphate Capsules

Sandoz, Teva, Watson

Norpace

Searle

Capsules, extended-release

100 mg (of disopyramide)*

Disopyramide Phosphate Extended-Release Capsules

Ethex

Norpace CR

Searle

150 mg (of disopyramide)*

Disopyramide Phosphate Extended-release Capsules

Ethex

Norpace CR

Searle

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Disopyramide Phosphate 100MG Capsules (WATSON LABS): 90/$46.99 or 270/$119.98

Disopyramide Phosphate 150MG Capsules (WATSON LABS): 30/$28.79 or 90/$60.42

Norpace 100MG Capsules (PFIZER U.S.): 90/$163.48 or 270/$469.75

Norpace 150MG Capsules (PFIZER U.S.): 30/$65.39 or 90/$170.01

Norpace CR 100MG 12-hr Capsules (PFIZER U.S.): 60/$129.99 or 180/$363.97

Norpace CR 150MG 12-hr Capsules (PFIZER U.S.): 60/$153.67 or 180/$439.23

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

51. Meinertz T, Langer KH, Kasper W et al. Disopyramide-induced intrahepatic cholestasis. Lancet. 1977; 2:828-9. [IDIS 76520] [PubMed 71640]

52. Riccioni N, Bozzi L, Susini N et al. Disopyramide-induced intrahepatic cholestasis. Lancet. 1977; 2:1362-3. [IDIS 77286] [PubMed 74773]

100. Haworth E, Burroughs AK. Disopyramide and warfarin interaction. Br Med J. 1977; 2:866-7. [PubMed 922330]

101. Ryll C, Davis LJ. Warfarin-disopyramide interaction? Drug Intell Clin Pharm. 1979; 13:260.

102. Sylven C, Anderson P. Evidence that disopyramide does not interact with warfarin. BMJ. 1983; 286:1181. [IDIS 169731] [PubMed 6404381]

103. Mangini RJ, ed. Drug interaction facts. St. Louis: JB Lippincott Co; 1984(Jul):41.

104. Moore AR. Disopyramide and warfarin. Br Med J. 1977; 29:1158.

105. Edmonds ME, Hayler AM, Holt DW. Untitled. (A case of intra-hepatic cholestasis after disopyramide therapy.) Eur J Clin Pharmacol. 1980; 18:285-6. Letter. (IDIS 124932)

106. Bakris GL, Cross PD, Hammarsten JE. Disopyramide-associated liver dysfunction. Mayo Clin Proc. 1983; 58:265-7. [IDIS 169726] [PubMed 6834895]

107. Craxi A, Gatto G, Maringhini A et al. Disopyramide and cholestasis. Ann Intern Med. 1980; 93(1 Part 1):150-1. [IDIS 122061] [PubMed 7396302]

108. Doody PT. Disopyramide hepatotoxicity and disseminated intravascular coagulation. South Med J. 1982; 75:496-7. [IDIS 150092] [PubMed 7071649]

109. Scheinman SJ, Poll DS, Wolfson S. Acute cardiac failure and hepatic ischemia induced by disopyramide phosphate. Yale J Biol Med. 1980; 53:361-6. [PubMed 7222741]

110. Antonelli D, Koltun B, Barzilay J. Acute hepatotoxic effect of disopyramide. Chest. 1984; 86:274. [IDIS 188645] [PubMed 6744970]

111. Tonkin AM, Joel SE, Reynolds JL. Unusual hepatocellular and cardiovascular complications of disopyramide. Chest. 1980; 77:125. [IDIS 109081] [PubMed 7351137]

112. Searle. Norpace and Norpace CR (disopyramide phosphate) prescribing information. Chicago, IL; 1997 Apr 4.

113. Epstein A, Barland P. The diagnostic value of antihistone antibodies in drug-induced lupus erythematosus. Arthritis Rheum. 1985; 28:158-62. [IDIS 196264] [PubMed 3882094]

114. Wanner WR, Irvin WS. Disopyramide and antinuclear antibodies. Am Heart J. 1981; 101:687-9. [IDIS 131129] [PubMed 6971570]

115. Ragosta M, Weihl AC, Rosenfeld LE. Potentially fatal interaction between erythromycin and disopyramide. Am J Med. 1989; 86:465-6. [IDIS 253377] [PubMed 2467560]

116. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction: an overview of results from randomized controlled trials. JAMA. 1993; 270:1589-95. [IDIS 320343] [PubMed 8371471]

117. Pratt CM, Moye L. The Cardiac Arrhythmia Suppression Trial: implications for antiarrhythmic drug development. J Clin Pharmacol. 1990; 30:967-74. [IDIS 274583] [PubMed 2122983]

118. Hine LK, Laird NM, Hewitt P et al. Meta-analysis of empirical long-term antiarrhythmic therapy after myocardial infarction. JAMA. 1989; 262:3037-40. [IDIS 260965] [PubMed 2509746]

119. The Cardiac Arrhythmia Suppression Trial (CAST) investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989; 321:406-12. [IDIS 257848] [PubMed 2473403]

120. Ruskin JN. The Cardiac Arrhythmia Suppression Trial (CAST). N Engl J Med. 1989; 321:386-8. [IDIS 257833] [PubMed 2501683]

121. Vlay SC. Lessons from the past and reflections on the Cardiac Arrhythmia Suppression Trial. Am J Cardiol. 1990; 65:112-3. [PubMed 1688480]

122. Pratt CM, Brater DC, Harrell FE Jr et al. Clinical and regulatory implications of the Cardiac Arrhythmia Suppression Trial. Am J Cardiol. 1990; 65:103-5. [PubMed 1688479]

123. Morganroth J, Bigger JT Jr, Anderson JL. Treatment of ventricular arrhythmias by United States cardiologists: a survey before the Cardiac Arrhythmia Suppression Trial results were available. Am J Cardiol. 1990; 65:40-8. [PubMed 1688481]

124. Pratt C, Ward DE, Camm AJ. Lessons from the cardiac arrhythmia suppression trial. BMJ. 1989; 299:805-6. [IDIS 259519] [PubMed 2510839]

125. Coyle JD, Schaal SF. An interim perspective on the removal of encainide and flecainide from the Cardiac Arrhythmia Suppression Trial. DICP. 1989; 23:478-9. [IDIS 254807] [PubMed 2500783]

126. Paar D, Terjung B, Sauerbruch T. Life-threatening interaction between clarithromycin and disopyramide. Lancet. 1997; 349:326-7. [IDIS 380134] [PubMed 9024381]

127. American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: advanced cardiovascular life support. Circulation. 2000; 102(Suppl I):I86-171.

128. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I):IV1-211.

129. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Circulation. 2006; 114:e257-354. [PubMed 16908781]

a. Searle. Norpace and Norpace CR (disopyramide phosphate) prescribing information. Chicago, IL; 2001 Sept.

b. AHFS drug information 2007. McEvoy GK, ed. Disopyramide Phosphate. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1584-7.

Hide
(web1)