Yes

Antiarrhythmic Agent, Class I-A

Suppression and prevention of unifocal and multifocal atrial and premature, ventricular premature complexes, coupled ventricular tachycardia; effective in the conversion of atrial fibrillation, atrial flutter, and paroxysmal atrial tachycardia to normal sinus rhythm and prevention of the recurrence of these arrhythmias after conversion by other methods

C

Hypersensitivity to disopyramide or any component; cardiogenic shock; pre-existing second- or third-degree heart block (except in patients with a functioning artificial pacemaker); congenital QT syndrome; sick sinus syndrome

Monitor and adjust dose to prevent QTc prolongation. Watch for proarrhythmic effects. May precipitate or exacerbate CHF. Due to significant anticholinergic effects, do not use in patients with urinary retention, BPH, glaucoma, or myasthenia gravis. Reduce dosage in renal or hepatic impairment. The extended release form is not recommended for Cl_cr <40 mL/minute. In patients with atrial fibrillation or flutter, block the AV node before initiating. Use caution in Wolff-Parkinson-White syndrome or bundle branch block. Correct hypokalemia before initiating therapy. Hypokalemia may worsen toxicity. Monitor closely for hypotension during the initiation of therapy. Avoid concurrent use with other medications will prolong Qt interval or decrease myocardial contractility.

The most common adverse effects are related to cholinergic blockade. The most serious adverse effects of disopyramide are hypotension and congestive heart failure.

Gastrointestinal: Xerostomia (32%), constipation (11%)

Genitourinary: Urinary hesitancy (14% to 23%)

1% to 10%:

Cardiovascular: Congestive heart failure, hypotension, cardiac conduction disturbance, edema, syncope, chest pain

Central nervous system: Fatigue, headache, malaise, dizziness, nervousness

Dermatologic: Rash, generalized dermatoses, pruritus

Endocrine & metabolic: Weight gain, hypokalemia, elevated cholesterol, elevated triglycerides

Gastrointestinal: Dry throat, nausea, abdominal distension, flatulence, abdominal bloating, anorexia, diarrhea, vomiting

Genitourinary: Urinary retention, urinary frequency, urinary urgency, impotence (1% to 3%)

Neuromuscular & skeletal: Muscle weakness, muscular pain

Ocular: Blurred vision, dry eyes

Respiratory: Dyspnea

<1% (Limited to important or life-threatening symptoms): New or worsened arrhythmias (proarrhythmic effect), hypoglycemia, cholestatic jaundice, fever, respiratory distress, thrombocytopenia, agranulocytosis, gynecomastia, psychotic reaction, depression, insomnia, dysuria, numbness, tingling, paresthesia, elevated transaminases, AV block, increased serum creatinine, increased BUN, elevated creatinine, decreased hemoglobin, decreased hematocrit, hepatotoxicity. Rare cases of lupus have been reported (generally in patients previously receiving procainamide).

Case reports: Peripheral neuropathy, psychosis, pupillary dilation, toxic cutaneous blisters

Has a low toxic therapeutic ratio and may easily produce fatal intoxication (acute toxic dose: 1 g in adults); symptoms of overdose include sinus bradycardia, sinus node arrest or asystole, P-R, QRS or Q-T interval prolongation, torsade de pointes (polymorphous ventricular tachycardia) and depressed myocardial contractility, which along with alpha-adrenergic or ganglionic blockade, may result in hypotension and pulmonary edema; other effects are anticholinergic (dry mouth, dilated pupils, and delirium) as well as seizures, coma and respiratory arrest.

Treatment is primarily symptomatic and effects usually respond to conventional therapies (fluids, positioning, vasopressors, anticonvulsants, antiarrhythmics). Note: Do not use other type Ia or Ic antiarrhythmic agents to treat ventricular tachycardia; sodium bicarbonate may treat wide QRS intervals or hypotension; markedly impaired conduction or high degree A-V block, unresponsive to bicarbonate, indicates consideration of a pacemaker.

CYP3A3/4 enzyme substrate

Beta-blockers may cause additive/excessive negative inotropic activity.

Enzyme inducers (phenobarbital, phenytoin, rifampin) decrease disopyramide blood levels.

Erythromycin and clarithromycin increase disopyramide blood levels; may cause QRS widening and/or QT interval prolongation.

Procainamide, quinidine, propafenone, or flecainide can cause increased/excessive negative inotropic effects or prolonged conduction.

Drugs which may prolong the QT interval - amiodarone, amitriptyline, astemizole, bepridil, cisapride, disopyramide, erythromycin, haloperidol, imipramine, pimozide, quinidine, sotalol, and thioridazine may be additive with disopyramide; use with caution.

Sparfloxacin, gatifloxacin, and moxifloxacin may result in additional prolongation of the QT interval; concurrent use is contraindicated.

Extemporaneously prepared suspension is stable for 4 weeks refrigerated

Class IA antiarrhythmic: Decreases myocardial excitability and conduction velocity; reduces disparity in refractory between normal and infarcted myocardium; possesses anticholinergic, peripheral vasoconstrictive, and negative inotropic effects

Onset of action: 0.5-3.5 hours

Duration of effect: 1.5-8.5 hours

Absorption: 60% to 83%

Protein binding: Concentration dependent, ranges from 20% to 60%

Metabolism: In the liver to inactive metabolites

Half-life: Adults: 4-10 hours, increased half-life with hepatic or renal disease

Elimination: 40% to 60% excreted unchanged in urine and 10% to 15% in feces

Oral:

<1 year: 10-30 mg/kg/24 hours in 4 divided doses

1-4 years: 10-20 mg/kg/24 hours in 4 divided doses

4-12 years: 10-15 mg/kg/24 hours in 4 divided doses

12-18 years: 6-15 mg/kg/24 hours in 4 divided doses

Adults:

<50 kg: 100 mg every 6 hours or 200 mg every 12 hours (controlled release)

>50 kg: 150 mg every 6 hours or 300 mg every 12 hours (controlled release); if no response, increase to 200 mg every 6 hours. Maximum dose required for patients with severe refractory ventricular tachycardia is 400 mg every 6 hours.

Dosing adjustment in renal impairment: 100 mg (nonsustained release) given at the following intervals, based on creatinine clearance (mL/minute):

Cl_cr 30-40 mL/minute: Administer every 8 hours

Cl_cr 15-30 mL/minute: Administer every 12 hours

Cl_cr <15 mL/minute: Administer every 24 hours

or alter the dose as follows:

Cl_cr 30-<40 mL/minute: Reduce dose 50%

Cl_cr 15-30 mL/minute: Reduce dose 75%

Dialysis: Not dialyzable (0% to 5%) by hemo- or peritoneal methods; supplemental dose is not necessary.

Dosing interval in hepatic impairment: 100 mg every 6 hours or 200 mg every 12 hours (controlled release)

Should be administered on an empty stomach

EKG, blood pressure, disopyramide drug level, urinary retention, CNS anticholinergic effects (confusion, agitation, hallucinations, etc)

Therapeutic concentration:

Atrial arrhythmias: 2.8-3.2 mg/mL

Ventricular arrhythmias 3.3-7.5 mg/mL

Toxic concentration: >7 mg/mL

Disopyramide has limited antiarrhythmic effects and has a very narrow therapeutic index. Close monitoring of EKG, particularly of the QT interval, should be conducted when initiating therapy. Increases in QT >25% over baseline should result in cessation or reduction in disopyramide dosing. In patients with pre-existing cardiovascular disease, the incidence of proarrhythmic effects and mortality may be increased with Class Ia antiarrhythmic agents.

May cause drowsiness or nervousness; rare reports of depression and psychosis

Use cautiously with TCAs; may cause AV block or Q-T prolongation; phenobarbital and carbamazepine may decrease the effects of disopyramide via enzyme induction

No information available to require special precautions

No effects or complications reported

Take as directed, at regular intervals around-the-clock. Do not alter dosage or discontinue therapy without consulting prescriber. Do not crush or chew extended release form. Avoid (or limit) alcohol and caffeine. You may experience dizziness or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or dry mouth (frequent mouth care or sucking on lozenges may help). Report any change in urinary pattern or difficulty urinating; chest pain, palpitations, irregular heartbeat; unusual cough, difficulty breathing, swelling of extremities; muscle tremors or weakness; confusion or acute lethargy; or skin rash. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

Do not crush controlled release capsules

Capsule, as phosphate: 100 mg, 150 mg

Capsule, sustained action, as phosphate: 100 mg, 150 mg

Extemporaneous suspensions in cherry syrup (1 mg/mL and 10 mg/mL) are stable for 4 weeks in amber glass bottles stored at 5°C, 30°C, or at room temperature; shake well before use; do not use extended release capsules for this suspension

Accornero F, Pellanda A, Ruffini C, et al, "Prolonged Cardiopulmonary Resuscitation During Acute Disopyramide Poisoning," Vet Hum Toxicol, 1993, 35(3):231-2.

Chiba K, Koike K, Nakamoto M, et al, "Steady-State Pharmacokinetics and Bioavailability of Total and Unbound Disopyramide in Children With Cardiac Arrhythmias," Ther Drug Monit, 1992, 14(2):112-8.

Echizen H, Takahashi H, Nakamura H, et al, "Stereoselective Disposition and Metabolism of Disopyramide in Pediatric Patients," J Pharmacol Exp Ther, 1991, 259(3):953-60.

Hayler AM, Holt DW, and Volans GN, "Fatal Overdosage With Disopyramide," Lancet, 1978, 1(8071):468-9.

Morady F, Scheinman MM, and Desai J, "Disopyramide," Ann Intern Med, 1982, 96(3):337-43.

Sathyavagiswaran L, "Fatal Disopyramide Intoxication From Suicidal/Accidental Overdose," J Forensic Sci, 1987, 32(6):1813-8.

Wayne K, Manolas E, and Sloman G, "Fatal Overdose With Disopyramide," Med J Aust, 1980, 1(5):231-2.