Disopyramide (disopyramide phosphate)

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. 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. 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.

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:

Table 1.

Creatinine Clearance (mL/minute) Dosage Interval 30-40 every 8 h 15-30 every 12 h <15 every 24 h

The extended-release capsules are not recommended for use in patients with a creatinine clearance of 40 mL/minute or less.

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.

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There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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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. 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. There are no adequate and controlled studies to date using disopyramide phosphate in pregnant women, 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. 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. 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.

Disopyramide is distributed into milk. 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.

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