VA Class:CV300
Disopyramide phosphate, an antiarrhythmic agent with cardiac effects that appear to be similar to those of quinidine and procainamide, is considered a class I antiarrhythmic agent.
Disopyramide is used to suppress and prevent the recurrence of ventricular arrhythmias (e.g., sustained ventricular tachycardia) that in the judgment of the physician are life-threatening.112 The manufacturer and many clinicians state that because of the drug's arrhythmogenic potential and the lack of evidence for improved survival for class I antiarrhythmic agents,112, 116, 117, 118 use of disopyramide for less severe arrhythmias is not recommended.112 Findings from the National Heart, Lung, and Blood Institute (NHLBI)'s Cardiac Arrhythmia Suppression Trial (CAST) study after an average of 10 months of follow-up have indicated that the rate of total mortality and nonfatal cardiac arrest in patients with recent myocardial infarction, mild-to-moderate left ventricular dysfunction, and asymptomatic or mildly symptomatic ventricular arrhythmias (principally frequent ventricular premature complexes [VPCs]) who received encainide or flecainide increased substantially compared with placebo.112, 119, 120 (See Cautions in Flecainide 24:04.04.12.) Therefore, FDA states that therapy with selected antiarrhythmic agents (e.g., disopyramide) should be reserved for the suppression and prevention of documented life-threatening ventricular arrhythmias and treatment of patients with asymptomatic ventricular premature contractions should be avoided.112 The manufacturer states that disopyramide therapy should be initiated only in a hospital setting.112
Disopyramide has been used to suppress and prevent the recurrence of unifocal and multifocal ventricular premature complexes, coupled ventricular premature complexes, and/or paroxysmal ventricular tachycardia in patients with primary arrhythmias or arrhythmias secondary to coronary artery disease; however, the arrhythmogenic potential of the drug and findings of the CAST study with other class I antiarrhythmic agents have called into question the safety of using such agents in arrhythmias that were not life-threatening.112, 119, 120, 121, 122, 123, 124, 125 Persistent ventricular tachycardia is usually treated with direct-current cardioversion. In several trials, disopyramide was more effective than placebo in suppression of ventricular arrhythmias including ventricular premature complexes, multiple ventricular premature complexes, and paroxysmal ventricular tachycardia in patients without myocardial infarction. In one unpublished study, 150 mg of disopyramide orally every 6 hours was as effective as 325 mg of quinidine sulfate orally every 6 hours in suppressing ventricular premature complexes in ambulatory patients.
Disopyramide also has been used to convert atrial fibrillation, atrial flutter, and paroxysmal atrial tachycardia† to normal sinus rhythm and to prevent the recurrence of these arrhythmias after conversion by other methods. However, other antiarrhythmic drugs (e.g., dofetilide, flecainide, ibutilide, propafenone, amiodarone) are preferred.300, 301
The precise role of disopyramide phosphate in antiarrhythmic therapy has not been established. Some experts believe 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. Limited information is available on the use of disopyramide in conjunction with other antiarrhythmic drugs such as lidocaine, quinidine, or procainamide to treat or prevent serious, refractory arrhythmias.
Disopyramide phosphate is administered orally. ECG monitoring is recommended during disopyramide therapy, especially when the drug is given to patients with increased risk of adverse effects to the drug such as those with severe heart disease, hypertension, or hepatic or renal disease.
Dosage of disopyramide phosphate is expressed in terms of disopyramide. Dosage must be carefully adjusted according to individual requirements and response and the general condition and cardiovascular status of the patient. Dosage should be reduced in patients with moderate or severe renal insufficiency, hepatic insufficiency, cardiomyopathy, possible cardiac decompensation, acute myocardial infarction, and in patients weighing less than 50 kg.
The usual adult dosage of disopyramide is 400-800 mg daily, given in divided doses.112 The usual dosage of disopyramide in adults weighing more than 50 kg is 150 mg every 6 hours as conventional capsules or 300 mg every 12 hours as extended-release capsules. The usual adult dosage of disopyramide in adults weighing less than 50 kg is 100 mg every 6 hours as conventional capsules or 200 mg every 12 hours as extended-release capsules. When rapid control of ventricular arrhythmias is required, 300 mg of disopyramide (200 mg for patients weighing less than 50 kg) may be given initially and followed by 150 mg every 6 hours (as conventional capsules); the extended-release capsules should not be used initially when rapid control of ventricular arrhythmias is necessary. Therapeutic effects are usually attained 0.5-3 hours after administration of a 300-mg loading dose.112 If there is no therapeutic response and if no toxic effects occur within 6 hours after the initial 300-mg dose, 200-mg doses of the conventional capsules may be given every 6 hours. If there is no response to this dosage in 48 hours, the drug should be discontinued and alternative therapy initiated or the patient should be hospitalized, closely evaluated, and continuously monitored while the dosage of disopyramide is increased to 250 or 300 mg every 6 hours. In a few patients with severe refractory ventricular tachycardia, up to 400 mg every 6 hours has been required. In patients with cardiomyopathy or possible cardiac decompensation, the manufacturers state that an initial loading dose should not be given and an initial dosage of 100 mg every 6 hours should not be exceeded. Dosage should be carefully adjusted while the patient is closely monitored for hypotension and/or congestive heart failure.(See Cautions: Precautions and Contraindications.)
Based on theoretical considerations, the manufacturers suggest that when patients with normal renal function who have been receiving quinidine sulfate or procainamide are changed to disopyramide, the usual dosage of disopyramide (without an initial loading dose) should be initiated 6-12 hours after the last dose of quinidine sulfate or 3-6 hours after the last dose of procainamide. If withdrawal of quinidine or procainamide is likely to produce life-threatening arrhythmias, the patient should be hospitalized and closely monitored. When transferring a patient from conventional disopyramide capsules to the extended-release capsules, the maintenance schedule of the extended-release capsules may be started 6 hours after the last dose of the conventional capsules.
Optimum pediatric dosage of disopyramide has not been established; however, dosage recommendations have been made based on clinical experience. The total daily dose should be given in equally divided doses every 6 hours or at intervals according to individual requirements. Pediatric patients should be hospitalized during the initial treatment period, and dose titration should begin at the lower end of the recommended ranges; plasma drug concentrations and therapeutic response must be carefully monitored. For children unable to swallow the capsules, a suspension may be prepared extemporaneously from the conventional capsules. (See Chemistry and Stability: Stability.) The suggested pediatric dosage of disopyramide is 10-30 mg/kg daily for children younger than 1 year of age, 10-20 mg/kg daily for children 1-4 years of age, 10-15 mg/kg daily for children 4-12 years of age, and 6-15 mg/kg daily for children 12-18 years of age.
Disopyramide has been given IV† in an initial dose of 1-2 mg/kg over a period of 1-5 minutes followed by a maintenance infusion of 20-40 mg/hour.
Dosage in Renal and Hepatic Impairment
In patients with moderately impaired renal function (creatinine clearance greater than 40 mL/minute) or hepatic insufficiency, the usual dosage of disopyramide is 100 mg every 6 hours as conventional capsules or 200 mg every 12 hours as extended-release capsules. For rapid control of a ventricular arrhythmia in these patients, an initial 200-mg dose may be given (as conventional capsules).
In patients with severely impaired renal function (creatinine clearance of 40 mL/minute or less), the usual dosage of disopyramide (as conventional capsules) is 100 mg (with or without an initial 150-mg dose) given at the following approximate intervals depending on the patient's creatinine clearance:
The extended-release capsules are not recommended for use in patients with a creatinine clearance of 40 mL/minute or less.
The most common adverse effects of disopyramide are anticholinergic and may be transient, require reduction in dosage, or necessitate cessation of therapy. Dry mouth occurs frequently and, in some patients, seems to decrease with continued administration of the drug. Constipation; paralytic ileus; dry nose, eyes, and throat; and blurred vision are other less common adverse anticholinergic effects. Urinary hesitancy occurs frequently; the most serious anticholinergic effect, urinary retention, is reported by the manufacturers to be infrequent but has occurred frequently in some studies and may necessitate discontinuance of the drug. Patients with prostatic hypertrophy are at particular risk of developing urinary retention with administration of the drug. In addition to anticholinergic effects on the urogenital system, the drug commonly causes urinary frequency and urgency.
Adverse cardiovascular effects of disopyramide include edema, weight gain, chest pain, dyspnea, syncope, and hypotension. Severe hypotension has occurred rarely, mainly in patients with myocarditis or other cardiomyopathy or uncompensated heart failure and in patients who have recently received other myocardial depressant drugs. In patients with marginally compensated heart failure, disopyramide has precipitated congestive heart failure. (See Cautions: Precautions and Contraindications.)
Adverse GI effects including nausea, vomiting, diarrhea, pain, bloating, gas, and anorexia occur rarely in patients receiving disopyramide. Hypoglycemia also has been reported rarely.
Intrahepatic cholestasis with jaundice has occurred occasionally during disopyramide therapy,51, 52, 105, 106, 107 and was evidenced by liver function test abnormalities (e.g., increased serum concentrations of bilirubin, alkaline phosphatase, ALT [SGPT], AST [SGOT], γ-glutamyltransferase [γ-glutamyl transpeptidase, GGT, GGTP]),51, 52, 105, 106, 107 dark urine,52, 106 pale stools,51, 52 malaise/fatigue,106 and/or nausea/vomiting.51 Cholestasis usually was evident 1-2 weeks after initiating disopyramide,51, 52, 105, 106, 107 and manifestations of jaundice usually resolved within several weeks following discontinuance of the drug;51, 52, 105, 106 however, abnormal liver function test results persisted for several months51, 52, 106 and, in 2 patients in whom the drug was continued for several weeks despite cholestasis, manifestations resolved much more slowly after discontinuance.107 Rarely, evidence of hepatocellular toxicity, without cholestasis, has occurred in patients receiving the drug; unlike patients with cholestatic injury, serum aminotransferase concentrations were increased while alkaline phosphatase remained within the usual range or was only slightly increased.106, 108, 109, 110, 111
Other adverse effects including generalized rash and dermatoses, itching, nervousness, confusion, acute psychosis, dizziness, general fatigue, respiratory difficulty, muscle weakness, headache, malaise, aches and/or pains, gynecomastia, paresthesia, numbness, elevated BUN and serum creatinine, decreased hemoglobin and hematocrit, elevated serum cholesterol and triglycerides, hypokalemia, thrombocytopenia, and agranulocytosis have been reported rarely. Although a causal relationship to disopyramide has not been established, mental depression, insomnia, dysuria, sexual impotence, and sensorimotor neuropathy have occurred rarely during treatment with the drug. A syndrome resembling systemic lupus erythematosus (SLE) has occurred in some patients;112, 113 most of these patients had been switched to disopyramide therapy after developing procainamide-induced SLE.112 In a limited number of patients in whom antinuclear antibody (ANA) titers were determined periodically for an average of 1 year, only one patient receiving disopyramide developed a positive ANA titer during therapy with the drug, but subsequent determinations were negative.114
Precautions and Contraindications
Findings from the postmarketing Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had myocardial infarctions more than 6 days but less than 2 years previously, indicate that the rate of total mortality and nonfatal cardiac arrest was increased in patients treated with encainide or flecainide compared with that seen in patients who received placebo.112 The applicability of these results to other populations (e.g., those without recent myocardial infarction) is uncertain.112 The manufacturer states that use of disopyramide in patients with ventricular arrhythmias should be limited to those with life-threatening arrhythmias.112 Use in less severe arrhythmias currently is not recommended and treatment of asymptomatic VPCs should be avoided.112
Because of its anticholinergic effects, disopyramide should not be used in patients with preexisting urinary retention unless palliative or corrective measures are taken. Disopyramide should be administered with caution to patients with a family history of angle-closure glaucoma and should not be administered to patients with angle-closure glaucoma unless cholinergic therapy (e.g., pilocarpine ophthalmic drops) is used to counteract the ocular anticholinergic effects of the drug. Disopyramide should be used with particular caution in patients with myasthenia gravis because the drug could precipitate a myasthenic crisis in these patients.
If hypotension occurs in patients receiving disopyramide and is not caused by an arrhythmia, disopyramide should be discontinued and, if necessary, restarted at a lower dosage only after adequate cardiac compensation has been established. Hypokalemia should be corrected before administration of disopyramide because the drug may be ineffective in hypokalemic patients.
Disopyramide should not be administered to patients with poorly compensated or uncompensated congestive heart failure unless heart failure persists after optimum therapy (including digitalization) and is caused or exacerbated by an arrhythmia amenable to disopyramide therapy; the patient must be carefully monitored. If progressive congestive heart failure occurs in patients receiving disopyramide, the drug should be discontinued and, if necessary, restarted at a lower dosage only after adequate cardiac compensation has been established.
If first-degree AV block develops in patients receiving disopyramide, dosage should be decreased. If first-degree AV block persists, the benefit of antiarrhythmic therapy with the drug must be weighed against the potential risk of higher degrees of AV block. If second- or third-degree AV block or unifascicular, bifascicular, or trifascicular block occurs, the drug should be discontinued unless the ventricular rate is adequately controlled by an artificial pacemaker. When excessive widening of the QRS complex or prolongation of the QT interval appears, the patient should be closely monitored and the drug should be discontinued if 25-50% widening of the QRS complex or prolongation of the QT interval occurs. Patients who experienced quinidine-induced prolongation of the QT interval, may be at particular risk of developing QT prolongation and worsened arrhythmias during disopyramide therapy. Patients with atrial flutter or fibrillation should be digitalized prior to disopyramide administration to ensure that enhanced AV conduction does not lead to ventricular tachycardia. Disopyramide should be administered with caution to 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.
The possibility that blood glucose may be lowered in patients with conditions (e.g., congestive heart failure, chronic malnutrition, hepatic or renal disease) or who are receiving drugs (e.g., β-adrenergic blockers, alcohol) that could compromise preservation of the usual glucose regulatory mechanisms in the absence of food should be considered when disopyramide is administered; in such patients, blood glucose should be carefully monitored.
Disopyramide should be administered with caution and in reduced dosage in patients with renal or hepatic insufficiency. The ECG should be carefully monitored in these patients.
Disopyramide is contraindicated in patients with preexisting second- or third-degree AV block (if an artificial pacemaker has not been inserted), cardiogenic shock, or known hypersensitivity to the drug.
The safety and efficacy of disopyramide in children have not been fully established; however, there is some clinical experience with the drug in this age group.
Mutagenicity and Carcinogenicity
Disopyramide was not mutagenic in an in vitro microbial test (Ames test).112 No evidence of carcinogenic potential was seen in an 18-month study in rats receiving oral disopyramide dosages up to 400 mg/kg daily (approximately 30 times the usual daily human dosage).112
Pregnancy, Fertility, and Lactation
In studies in rats, disopyramide dosages of 250 mg/kg daily (20 times the usual daily human dosage) have been associated with decreased numbers of implantation sites and decreased growth and survival of pups; this dosage also was associated with reduced weight gain and food consumption in the dams.112 In rabbits, disopyramide dosages of 60 mg/kg daily (5 or more times the usual daily human dosage) was associated with increased resorption rates; effects on implantation, pup growth, and survival were not evaluated.112 There are no adequate and controlled studies to date using disopyramide phosphate in pregnant women,112 and experience with the drug during pregnancy is limited. The possibility of fetal harm cannot be excluded. Disopyramide has been reported to stimulate contractions of the pregnant uterus.112 There has been one reported case of premature initiation of uterine contractions during the eighth month of pregnancy beginning 1 hour after administration of 300 mg of disopyramide and continuing for 24 hours until disopyramide was discontinued. Disopyramide phosphate should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.112 It is not known whether use of the drug during labor or delivery could have any immediate or delayed adverse effects on the mother or fetus, affect the duration of labor, or increase the likelihood of forceps delivery or other obstetric intervention.
In reproduction studies in rats, disopyramide dosages up to 250 mg/kg daily did not affect fertility.112
Disopyramide is distributed into milk.112 Because of the potential for serious adverse effects in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.112
Potentiation of the hypoprothrombinemic effect of warfarin has been reported in several patients receiving disopyramide and warfarin.100, 101, 103, 104 However, in a study in several patients receiving disopyramide and warfarin concomitantly, the hypoprothrombinemic effect of warfarin was not increased and, in 2 patients, actually was decreased slightly.102 Further study is needed to determine whether a potential interaction exists.101, 103
When disopyramide is administered with other antiarrhythmic drugs such as quinidine, procainamide, lidocaine, encainide, flecainide, propafenone, propranolol, or phenytoin, cardiac effects may be additive or antagonistic and toxicity may be additive; concomitant administration of disopyramide and these antiarrhythmic agents should be reserved for the management of life-threatening arrhythmias unresponsive to monotherapy. Concomitant administration of quinidine and disopyramide has resulted in slight increases in plasma disopyramide concentrations and slight decreases in plasma quinidine concentrations.112 Concomitant use of disopyramide and digoxin does not appear to increase serum digoxin concentrations.112
Disopyramide should not be administered concomitantly with IV or oral verapamil because of the possibility of additive effects and impairment of left ventricular function. Pending further accumulation of data on the safety of combined therapy, disopyramide should be discontinued 48 hours prior to initiating verapamil therapy and should not be reinstituted until 24 hours after verapamil has been discontinued.
The anticholinergic effect of disopyramide may be additive with anticholinergic drugs.
Drugs Affecting Hepatic Microsomal Enzymes
Drugs (e.g., phenytoin) that induce hepatic microsomal enzymes may accelerate the metabolism of disopyramide. When microsomal enzyme inducers are used concomitantly with disopyramide, serum concentrations of disopyramide should be closely monitored to avoid subtherapeutic concentrations.
Erythromycin and clarithromycin may alter the metabolism of disopyramide.112, 115, 126 Concomitant administration of erythromycin or clarithromycin with disopyramide may produce increased plasma concentrations of disopyramide resulting in prolongation of the QT interval and widening of the QRS complex.112, 115, 126 Initiation of erythromycin therapy in several patients receiving disopyramide reportedly has been associated with elevated serum disopyramide concentrations, QT-interval prolongation, and polymorphic ventricular tachycardia.115 Ventricular fibrillation, prolongation of the QT interval, and a marked increase in disopyramide elimination half-life (40 hours) were reported in a patient maintained on disopyramide (200 mg twice daily) who received clarithromycin (250 mg twice daily), omeprazole (20 mg twice daily), and metronidazole (400 mg twice daily) for the treatment of H. pylori -associated chronic duodenal ulceration.126 QT prolongation, which had not been documented previously during a 7-year period of disopyramide therapy, resolved with a decline in plasma disopyramide concentrations.126 Patients receiving disopyramide concomitantly with drugs that affect hepatic microsomal enzymes should be closely monitored.112
Overdosage of disopyramide has been fatal.112
The approximate oral LD50 of disopyramide phosphate in rats and mice is 580 and 700 mg/kg, respectively.112
Overdosage of disopyramide requires prompt and vigorous treatment, even in the absence of symptoms.112 There is no specific antidote for disopyramide intoxication.112 Hemodialysis or, preferably, charcoal hemoperfusion may be beneficial.112
Disopyramide is an antiarrhythmic agent whose cardiac actions appear to be similar to those of quinidine and procainamide. Disopyramide is regarded as a myocardial depressant because it decreases myocardial excitability and conduction velocity, and may depress myocardial contractility. Disopyramide, like quinidine and procainamide, also possesses anticholinergic properties which may modify the direct myocardial effects of the drug.
The exact mechanism of antiarrhythmic action of disopyramide has not been established, but the drug is considered a class I (membrane-stabilizing) antiarrhythmic agent. Like other class I antiarrhythmic agents, disopyramide 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 which is associated with subsequent dissociation of the drug from the sodium channels. Disopyramide exhibits electrophysiologic effects characteristic of class IA antiarrhythmic agents. The electrophysiologic characteristics of the subgroups of class I antiarrhythmic agents may be related to quantitative differences in their rates of attachment to and dissociation from transmembrane sodium channels, with class IA agents exhibiting intermediate rates of attachment and dissociation.
Like quinidine, procainamide, and lidocaine, disopyramide suppresses automaticity in the His-Purkinje system. In usual doses, disopyramide 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. In usual doses, the drug has little effect on conduction velocity through the atrioventricular (AV) node or the His-Purkinje system, but accessory pathway conduction velocity is decreased. Disopyramide generally prolongs the effective refractory period (ERP) of the atria and the ventricles. The drug 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. In usual doses, disopyramide 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.
In therapeutic doses, disopyramide has little effect on resting sinus rate and has a direct negative inotropic effect on the heart. In patients without compromised myocardial function, cardiac output usually decreases 10-15%. With usual oral doses, disopyramide generally does not affect blood pressure. Rarely, hypotension occurs; systolic blood pressure decreases more than diastolic pressure. However, when disopyramide was administered IV in a dose of 2 mg/kg over a period of 3 minutes, transient and moderate increases in heart rate and total peripheral resistance occurred. Disopyramide apparently has no α- or β-adrenergic effects. The drug has anticholinergic effects on the GI and urogenital systems. In vitro, the anticholinergic activity of disopyramide is about 0.06% that of atropine. It has not been established whether disopyramide has local anesthetic properties.
Disopyramide phosphate is rapidly absorbed from the GI tract and 60-83% of a dose reaches the systemic circulation unchanged. In one crossover study in healthy individuals, the bioavailability of disopyramide from the extended-release capsules was similar to that from the conventional capsules.
Plasma disopyramide concentrations necessary to produce a therapeutic response vary depending on the type of cardiac arrhythmia, the severity and duration of the arrhythmia, and the sensitivity of the patient to the drug. Plasma disopyramide concentrations of approximately 2-4 mcg/mL are generally required to suppress ventricular arrhythmias; some patients require up to 7 mcg/mL to suppress and prevent the recurrence of refractory ventricular tachycardia. Toxicity is generally associated with plasma disopyramide concentrations greater than 9 mcg/mL. In one study in healthy fasting adults, mean peak plasma concentrations of 2.0-2.8 mcg/mL were attained 2 hours after administration of a single 100-mg oral dose of disopyramide as the phosphate. Following administration of a single 300-mg oral dose (as two 150-mg capsules) to healthy individuals in another study, mean peak plasma concentrations of 3.2 mcg/mL occurred after an average of 2.5 hours with conventional capsules and mean peak plasma concentrations of 2.2 mcg/mL occurred after an average of 4.9 hours with extended-release capsules. After a single 200- to 300-mg oral dose, the onset of action usually occurs within 30 minutes to 3.5 hours and persists 1.5-8.5 hours.
Disopyramide is distributed throughout the extracellular body water but is not extensively bound to tissues. Animal studies indicate that myocardial concentrations of disopyramide are approximately twice the plasma concentration. With therapeutic plasma concentrations, disopyramide in the blood is approximately equally distributed between plasma and erythrocytes. In one study, patients with an acute myocardial infarction (without congestive heart failure) given a single 100-mg oral dose of disopyramide as the phosphate had lower peak plasma concentrations and smaller volumes of distribution than did healthy individuals given the same dose. In patients with renal insufficiency, the volume of distribution is slightly decreased. Disopyramide crosses the placenta. In rats, disopyramide and its metabolites are found in milk in concentrations 1-3 times those in plasma. In humans, disopyramide has been detected in milk at a concentration not exceeding that in plasma.
The plasma protein binding of disopyramide is variable and decreases as the concentration of the drug and its metabolites increases; with therapeutic plasma concentrations, disopyramide is approximately 50-65% protein bound.
In one study, disopyramide had a mean plasma half-life of 6.7 hours in healthy individuals, but the half-life varied from 4-10 hours. The plasma half-life of disopyramide is prolonged in patients with hepatic or renal insufficiency. In 6 patients with creatinine clearances less than 40 mL/minute, plasma half-life ranged from 8-18 hours.
Disopyramide is metabolized in the liver. In healthy individuals, the plasma concentration of the N -monodealkylated metabolite of disopyramide is about 10% of the concentration of disopyramide. The N -monodealkylated metabolite has less antiarrhythmic activity but greater anticholinergic activity than does disopyramide. In one study in healthy individuals, approximately 40-60% of an oral dose of disopyramide was excreted in urine as unchanged drug, 15-25% as the N -monodealkylated metabolite, and about 10% as unidentified metabolites; about 10% is excreted in feces as unchanged drug and metabolites. Urinary pH apparently does not affect the rate of renal excretion of disopyramide. The drug is removed by hemodialysis.
Disopyramide phosphate is a synthetic antiarrhythmic agent that differs structurally from other commercially available antiarrhythmic drugs. Disopyramide phosphate occurs as a white or practically white, crystalline powder and is freely soluble in water and slightly soluble in alcohol. Disopyramide has a pKa of 10.4. The commercially available drug is a racemic mixture of 2 optical isomers.
Disopyramide phosphate capsules and extended-release capsules should be stored in well-closed containers at 30°C or lower.112 An extemporaneous preparation of the contents of disopyramide phosphate conventional capsules in cherry syrup containing 1-10 mg of disopyramide per mL is stable for 1 month when stored at 2-8°C. The extemporaneously prepared suspension should be dispensed in amber glass bottles. The extended-release capsules should not be used for the preparation of an extemporaneous suspension.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 100 mg (of disopyramide)* | Disopyramide Phosphate Capsules | |
150 mg (of disopyramide)* | Disopyramide Phosphate Capsules | |||
Norpace® | Pfizer | |||
Capsules, extended-release | 100 mg (of disopyramide)* | Disopyramide Phosphate Extended-Release Capsules | ||
Norpace® CR | Pfizer | |||
150 mg (of disopyramide)* | Disopyramide Phosphate Extended-release Capsules | |||
Norpace® CR | Pfizer |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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