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Disopyramide Phosphate ER (Capsule, Extended Release)

Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/893

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Disopyramide Phosphate ER (Capsule, Extended Release)
dailymed-instance:dosage
The dosage of disopyramide (as the phosphate) must be individualized for each patient on the basis of response and tolerance. The usual adult dosage of disopyramide is 400 to 800 mg (calculated as the disopyramide base) per day given in divided doses. The recommended dosage for most adults is 600 mg/day given in divided doses (300 mg every 12 hours for the extended-release product). For patients whose body weight is less than 110 pounds (50 kg), the recommended dosage is 400 mg/day given in divided doses (200 mg every 12 hours for the extended-release product). In the event of increased anticholingeric side effects, plasma levels of disopyramide should be monitored and the dose of the drug adjusted accordingly. A reduction of the dose by one third, from the recommended 600 mg/day to 400 mg/day, would be reasonable, without changing the dosing interval. For patients with cardiomyopathy or possible cardiac decompensation, a loading dose should not be given, and initial dosage should be limited to 100 mg of immediate-release disopyramide phosphate every 6 to 8 hours. Subsequent dosage adjustments should be made gradually, with close monitoring for the possible development of hypotension and/or congestive heart failure . For patients with moderate renal insufficiency (creatinine clearance greater than 40 mL/min) or hepatic insufficiency, the recommended dosage is 400 mg/day given in divided doses (200 mg every 12 hours for the extended-release product). Disopyramide Phosphate Extended-release Capsules, USP are not recommended for patients with severe renal insufficiency. Disopyramide Phosphate Extended-release Capsules, USP should not be used initially if rapid establishment of disopyramide plasma levels is desired.<br/>Transferring to Disopyramide Phosphate Extended-release Capsules, USP: The following dosage schedule based on theoretical considerations rather than experimental data is suggested for transferring patients with normal renal function from either quinidine sulfate or procainamide therapy (Type 1 antiarrhythmic agents) to Disopyramide Phosphate Extended-release Capsules, USP therapy. Disopyramide Phosphate Extended-release Capsules, USP should be started using the regular maintenance schedule without a loading dose 6 to 12 hours after the last dose of quinidine sulfate or 3 to 6 hours after the test dose of procainamide. In patients in whom withdrawal of quinidine sulfate or procainamide is likely to produce life-threatening arrhythmias, the physician should consider hospitalization of the patient. When transferring a patient from immediate-release disopyramide to extended-release disopyramide, the maintenance schedule of Disopyramide Phosphate Extended-release Capsules, USP may be started 6 hours after the last dose of immediate-release disopyramide phosphate capsules.<br/>Pediatric dosage: There is no adequate data to recommend use of Disopyramide Phosphate Extended-release Capsules, USP in pediatric patients. Disopyramide Phosphate Extended-release Capsules, USP should not be used to prepare extemporaneous suspensions.
dailymed-instance:descripti...
Disopyramide phosphate is an antiarrhythmic drug available for oral administration in extended-release capsules equivalent to 150 mg of disopyramide present as the phosphate. The base content of the phosphate salt is 77.66%. The structural formula of disopyramide phosphate is: (��)-��-[2-(Diisopropylamino)ethyl]-��-phenyl-2-pyridineacetamide phosphate (1:1) Disopyramide phosphate is freely soluble in water, and the free base (pKa 10.4) has an aqueous solubility of 1 mg/mL. The chloroform water partition coefficient of the base is 3.1 at pH 7.2. Disopyramide phosphate is a racemic mixture of d-and l-isomers. This drug is not chemically related to other antiarrhythmic drugs. Disopyramide Phosphate Extended-release Capsules, USP are designed to afford a gradual and consistent release of disopyramide. Thus, for maintenance therapy, Disopyramide Phosphate Extended-release Capsules, USP provide the benefit of less frequent dosing (every 12 hours) as compared with the every-6-hour dosage schedule of immediate-release capsules. Inactive ingredients: aluminum hydrate, black iron oxide, calcium stearate, D&C Red No. 28, D&C Yellow No. 10, dibutyl sebacate, ethylcellulose, FD&C Blue No. 1, FD&C Red No. 40, gelatin, lecithin, pharmaceutical glaze, povidone, simethicone, starch, sucrose, talc and titanium dioxide. This product meets USP Drug Release Test 2.
dailymed-instance:clinicalP...
Mechanisms of Actions: Disopyramide phosphate is a Type 1 antiarrhythmic drug (i.e., similar to procainamide and quinidine). In animal studies, disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium and has no effect on alpha- or beta-adrenergic receptors.<br/>Electrophysiology: In man, disopyramide at therapeutic plasma levels shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.<br/>Hemodynamics: At recommended oral doses, disopyramide phosphate rarely produces significant alterations of blood pressure in patients without congestive heart failure . With intravenous disopyramide phosphate, either increases in systolic/diastolic or decreases in systolic blood pressure have been reported, depending on the infusion rate and the patient population. Intravenous disopyramide phosphate may cause cardiac depression with an approximate mean 10% reduction of cardiac output, which is more pronounced in patients with cardiacdysfunction.<br/>Anticholinergic Activity: The in vitro anticholinergic activity of disopyramide phosphate is approximately 0.06% that of atropine, however, the usual dose for disopyramide phosphate is 150 mg every 6 hours and for disopyramide phosphate extended-release 300 mg every 12 hours compared to 0.4 to 0.6 mg for atropine .<br/>Pharmacokinetics: The usual therapeutic plasma levels of disopyramide base are 2 to 4 mcg/mL and at these concentrations protein binding varies from 50 to 65%. Because of concentration-dependent protein binding, it is difficult to predict the concentration of the free drug when total drug is measured. The mean plasma half-life of disopyramide in healthy humans is 6.7 hours (range of 4 to 10 hours). In six patients with impaired renal function (creatinine clearance less than 40 mL/min), disopyramide half-life values were 8 to 18 hours. After the oral administration of immediate release disopyramide to 10 cardiac patients with borderline to moderate heart failure, the time to peak serum concentration was increased and the mean peak serum concentration was higher than in healthy volunteers. After intravenous administration in these same patients, the mean elimination half-life was 9.7��4.2 hours, (range in healthy volunteers of 4.4 to 7.8 hours). In a second study of the oral administration of disopyramide to 7 patients with heart disease, including left ventricular dysfunction, the mean plasma half-life was slightly prolonged to 7.8��1.9 hours (range of 5 to 9.5 hours). In healthy men, about 50% of a given dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite and 10% as the other metabolites. The plasma concentration of the major metabolite is approximately one tenth that of disopyramide. Altering the urinary pH in man does not affect the plasma half-life of disopyramide. In a single-dose crossover study in 12 healthy subjects, the mean peak serum concentration of disopyramide following a single 150 mg oral dose of KV's Disopyramide Phosphate Extended-release Capsules, USP was 2.39 (��0.89) mcg/mL, achieved at 5.58 (��1.44) hours. Following multiple doses (300 mg every 12 hours) of KV's Disopyramide Phosphate Extended-release capsules, USP steady-state plasma levels of between 2 and 4 mcg/mL were attained. Total bioavailability was shown to be similar to an immediate-release product.<br/>Drug Interactions: Effects of other drugs on disopyramide pharmacokinetics: In vitro metabolic studies indicated that disopyramide is metabolized by cytochrome P450 3A4 and that inhibitors of this enzyme may result in elevation of plasma levels of disopyramide. Although specific drug interaction studies have not been done, cases of life-threatening interactions have been reported for disopyramide when given with clarithromycin and erythromycin.
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dailymed-instance:supply
Disopyramide Phosphate Extended-release Capsules, USP 150 mg are purple and orange hard gelatin capsules imprinted���ETHEX���and���002���in black ink containing 150 mg of disopyramide (as the phosphate) in extended-release beads. NDC Number Size 58177-002-04 Bottle of 100 Recommended Storage: Store at 25��C (77��F); excursions permitted to 15��-30��C (59��- 86��F). [see USP Controlled Room Temperature.] Manufactured byKV Pharmaceutical Co. forETHEX CorporationSt. Louis, MO 63043-2413
dailymed-instance:boxedWarn...
Mortality: In the National Heart, Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long term, multi-center, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had a myocardial infarction more than 6 days but less than 2 years previously, an excessive mortality or non-fatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3%). The average duration of treatment with encainide or flecainide in this study was 10 months. The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) is uncertain. Considering the known proarrhythmic properties of disopyramide phosphate and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of disopyramide phosphate as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
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Disopyramide Phosphate
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Disopyramide Phosphate ER (Capsule, Extended Release)
dailymed-instance:adverseRe...
The adverse reactions which were reported in disopyramide phosphate clinical trials encompass observations in 1,500 patients, including 90 patients studied for at least 4 years. The most serious adverse reactions are hypotension and congestive heart failure. The most common adverse reactions which are dose dependent are associated with the anticholinergic properties of the drug. These may be transitory but may be persistent or can be severe. Urinary retention is the most serious anticholinergic effect. The following reactions were reported in 10% to 40% of patients: The following reactions were reported in 3% to 9% of patients: The following reactions were reported in 1% to 3% of patients: The following reactions were reported in less than 1%: Hypoglycemia has been reported in association with disopyramide administration . Infrequent occurrences of reversible cholestatic jaundice, fever, and respiratory difficulty have been reported in association with disopyramide administration as have rare instances of thrombocytopenia, reversible agranulocytosis and gynecomastia. Some cases of LE (lupus erythematosus) symptoms have been reported; most cases occurred in patients who had been switched to disopyramide from procainamide following the development of LE symptoms. Rarely, acute psychosis has been reported following disopyramide therapy, with prompt return to normal mental status when therapy was stopped. The physician should be aware of these possible reactions and should discontinue disopyramide phosphate therapy promptly if they occur.
dailymed-instance:indicatio...
Disopyramide Phosphate Extended-release Capsules, USP are indicated for the treatment of documented ventricular arrhythmias such as sustained ventricular tachycardia, that in the judgement of the physician, are life-threatening. Because of the proarrhythmic effects of disopyramide, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Initiation of disopyramide treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. The extended-release capsules should not be used initially if rapid establishment of disopyramide plasma levels is desired. Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.
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Disopyramide Phosphate ER