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Disopyramide Phosphate

Pronunciation: DIE-so-PIR-uh-mide
Class: Antiarrhythmic agent

Trade Names

Norpace
- Capsules 100 mg
- Capsules 250 mg as phosphate

Norpace CR
- Capsules, extended-release 100 mg
- Capsules, extended-release 150 mg as phosphate

Rythmodan (Canada)
Rythmodan-LA (Canada)

Pharmacology

Decreases rate of diastolic depolarizations rate; decreases upstroke velocity; increases action potential duration; prolongs refractory period.

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Pharmacokinetics

Absorption

Immediate release (IR)

Rapidly and almost completely absorbed. T max is 2 h.

Extended release (ER) (300 mg dose)

C max approximately 3.23 mcg/mL. T max is approximately 2.5 h.

Distribution

50% to 65% protein bound (concentration dependent). Excreted in human milk.

Elimination

The t ½ is approximately 6.7 h (IR) and approximately 11.65 h (ER). Approximately 50% excreted unchanged in the urine and approximately 30% as metabolites.

Special Populations

Renal Function Impairment

Because more than 50% excreted in the urine, dosage reduction recommended.

Hepatic Function Impairment

The t ½ increased. Dosage reduction recommended.

Heart failure

T max and C max are increased. The t ½ is also prolonged.

Heart disease

The t ½ slightly prolonged to approximately 7.8 h.

Indications and Usage

Suppression and documented prevention of ventricular arrhythmias considered to be life threatening.

Unlabeled Uses

Treatment of paroxysmal supraventricular tachycardia.

Contraindications

Cardiogenic shock; preexisting second- or third-degree AV block (if no pacemaker present); congenital QT prolongation; sick sinus syndrome; known hypersensitivity to the drug.

Dosage and Administration

Adults

PO 400 to 800 mg/day. Divide total daily dose and administer every 6 h in IR form or every 12 h in ER form. If patient weighs less than 50 kg, give 400 mg/day in divided doses; administer every 6 h for IR or every 12 h for ER.

Children (12 to 18 yr of age)

PO 6 to 15 mg/kg/day in divided doses.

Children (4 to 12 yr of age)

PO 10 to 15 mg/kg/day in divided doses.

Children (1 to 4 yr of age)

PO 10 to 20 mg/kg/day in divided doses.

Children (younger than 1 yr of age)

PO 10 to 30 mg/kg/day in divided doses.

Rapid Control Of Ventricular Arrhythmia

PO Initial loading dose 300 mg IR (200 mg for less than 50 kg), followed by appropriate maintenance dose.

Severe Refractory Ventricular Tachycardia

PO May give up to 400 mg every 6 h.

With Cardiomyopathy or Cardiac Decompensation

PO Limit initial dose 100 mg every 6 to 8 h.

Renal/Hepatic Function Impairment
Adults

PO For moderate renal insufficiency (Ccr greater than 40 mL/min) or hepatic insufficiency, give 400 mg in divided doses as 100 mg every 6 h for IR, or 200 mg every 12 h for ER. In severe renal insufficiency, administer the immediate-release form as follows with or without an initial loading dose of 150 mg. Ccr 30 to 40 mL/min: give 100 mg every 8 h. Ccr 15 to 30 mL/min: give 100 mg every 12 h. Ccr less than 15 mL/min: give 100 mg every 24 h.

General Advice

  • May be used alone or in combination with other antiarrhythmic medications.
  • Initiate therapy for life-threatening arrhythmias in hospital with close monitoring of cardiac rhythm.
  • Do not use ER capsules for rapid control of ventricular arrhythmia or in patient with Ccr less than 40 mL/min.
  • Have patient swallow ER capsules whole. Do not crush, chew, or open capsules.
  • When converting from IR to ER disopyramide, start maintenance schedule of ER capsules 6 h after last dose of IR.
  • An extemporaneous suspension can be made for administration to children. Contents of IR (not ER) capsule can be mixed with cherry syrup. Shake suspension well before measuring dose. Measure and administer prescribed dose using dosing syringe, spoon, or cup.

Storage/Stability

Store capsules at controlled room temperature (59° to 86°F). Store extemporaneous suspension in refrigerator (36° to 46°F). Discard any unused suspension after 30 days.

Drug Interactions

Antiarrhythmic agents

May cause widened QRS and prolonged QT.

Beta-blockers (eg, metoprolol, propranolol)

Both agents may depress cardiac output, increasing the risk of side effects (eg, sinus bradycardia).

Cisapride, quinolone antibiotics (eg, sparfloxacin), thioridazine, ziprasidone

Possible additive prolongation of the QT interval, increasing the risk of life-threatening cardiac arrhythmias, including torsades de pointes.

CYP3A4 inhibitors (eg, azole antifungal agents [ketoconazole], macrolide antibiotics [eg, clarithromycin, erythromycin])

Disopyramide plasma levels may be elevated. Arrhythmias, increased QTc intervals, and hypoglycemia have been reported with coadministration of erythromycin or clarithromycin and disopyramide.

Hydantoins

May decrease disopyramide serum levels, t ½ , and bioavailability.

Quinidine

Disopyramide levels may be elevated, increasing the risk of toxicity, while quinidine levels may be reduced, decreasing the therapeutic response to quinidine.

Rifamycins (eg, rifampin)

Disopyramide plasma levels may be decreased while levels of the active metabolite may be increased. The clinical importance of this interaction has not been determined.

Verapamil

Do not administer disopyramide within 48 h before or 24 h after verapamil.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Cardiac conduction disturbances, increased CHF, hypotension, syncope (1% to 3%).

CNS

Dizziness, fatigue, headache, malaise (3% to 9%); nervousness (1% to 3%).

Dermatologic

Generalized rash/dermatoses, itching (1% to 3%).

EENT

Blurred vision, dry nose, dry eyes, and dry throat (3% to 9%).

GI

Dry mouth (32%); constipation (11%); nausea, pain/bloating/gas (3% to 9%); anorexia, diarrhea, vomiting (1% to 3%).

Genitourinary

Urinary hesitancy (14%); urinary frequency, urgency, urinary retention (3% to 9%); impotence (1% to 3%).

Lab Tests

Elevated cholesterol/triglycerides, hypokalemia (1% to 3%).

Metabolic-Nutritional

Edema, weight gain (1% to 3%); hypoglycemia.

Musculoskeletal

Muscle weakness (3% to 9%).

Respiratory

Shortness of breath (1% to 3%).

Miscellaneous

Aches, pain (3% to 9%); chest pain (1% to 3%).

Precautions

Warnings

Because of the known proarrhythmic properties of disopyramide and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, reserve the use of disopyramide for patients with life-threatening ventricular arrhythmias.


Monitor

Ensure that IOP is measured in patient with family history of glaucoma before therapy is initiated. Ensure that patient with atrial flutter or fibrillation is adequately digitalized before initiating therapy with disopyramide to prevent accelerated ventricular rates.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established. See Route/Dosage.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Reduce dosage.

Hepatic Function

Reduce dosage.

Special Risk Patients

Because disopyramide has anticholinergic activity, do not use disopyramide in patients with glaucoma, urinary retention, or benign prostatic hypertrophy.

Anticholinergic activity

Use with extreme caution in patients with urinary retention, glaucoma, or myasthenia gravis.

Cardiomyopathy

Patients with myocarditis or other cardiomyopathy may develop significant hypotension.

Conduction abnormalities

Use with caution in patients with bundle branch block, sick sinus syndrome, or Wolff-Parkinson-White syndrome.

Heart block

Reduce dose if first-degree block occurs; drug may need to be discontinued if heart block continues.

Heart failure/hypotension

May cause or aggravate CHF or produce severe hypotension, especially in patients with depressed systolic function.

Hypoglycemia

In rare cases may produce significant lowering of blood glucose.

Potassium imbalance

Disopyramide may be ineffective in hypokalemia and have enhanced toxicity in hyperkalemia.

QRS widening

Widening of the QRS complex more than 25% may occur.

QT prolongation

Prolongation of the QT interval and worsening of arrhythmia may occur.

Overdosage

Symptoms

Loss of consciousness, cardiac arrhythmias, loss of spontaneous respiration, death.

Patient Information

  • Advise patient that dose of medication may be changed periodically to obtain max benefit and minimize side effects.
  • Caution patient to take prescribed dose of IR disopyramide every 6 h exactly as ordered. Advise patient that serious heart disturbances can result from missing doses or taking more often than prescribed.
  • Caution patient to take prescribed dose of ER disopyramide every 12 h exactly as ordered. Advise patient to swallow capsule whole and not to chew, crush, or open capsule.
  • Advise patient or caregiver using extemporaneous suspension to shake suspension well before measuring dose, then measure and administer prescribed dose using dosing syringe, spoon, or cup.
  • Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
  • Caution patient not to change the dose or stop taking unless advised by health care provider. Advise patient that serious side effects can result from increasing or decreasing the dose without medical supervision.
  • Inform patient that drug controls, but does not cure, abnormal heart rhythm and to continue taking as prescribed once the heart rhythm has been controlled.
  • Instruct patient to continue taking other heart medications as prescribed by health care provider.
  • Instruct patient in BP and pulse measurement skills.
  • Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
  • Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
  • Advise patient to notify health care provider if any of the following occur: frequent episodes of dizziness or lightheadedness; intolerable dry mouth; difficulty with urination; constipation; breathing difficulty; blurred vision; or any other unusual or unexplained symptom or sign.
  • Instruct patient to immediately report fainting, pounding in chest, or change in pulse or heart rhythm to health care provider.
  • Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Inform patient that medication may cause pupils to dilate resulting in intolerance to bright lights or sunlight. Advise patient to wear dark glasses to make bright lights or sunlight tolerable.
  • Caution patient that drug may cause dizziness, lightheadedness, or blurred vision and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
  • Advise patient to carry medical identification (eg, card, bracelet) describing cardiac condition and medication regimen.
  • Offer family instruction in basic life support.

Copyright © 2009 Wolters Kluwer Health.

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