What are the guidelines for using Disopyramide (antiarrhythmic medication)?

Guidelines for Using Disopyramide in Cardiac Management

Disopyramide is primarily indicated as a second-line therapy for symptomatic obstructive hypertrophic cardiomyopathy (HCM) when first-line treatments are ineffective, and should be combined with beta-blockers or verapamil for optimal management. 1

Primary Indications for Disopyramide

• Disopyramide is recommended for patients with obstructive HCM who remain symptomatic despite maximum tolerated doses of first-line beta-blocker therapy 1
• It can effectively reduce left ventricular outflow tract obstruction (LVOTO) and improve exercise tolerance when titrated to a maximum tolerated dose of 400-600 mg/day 1
• Disopyramide should be used in combination with beta-blockers or verapamil, not as monotherapy, especially in patients with or at risk for atrial fibrillation 1, 2
• It may also be used for treatment of ventricular and atrial arrhythmias, though this is less common in modern practice 3

Dosing Recommendations

• For most adults with HCM, the recommended dosage is 600 mg/day given in divided doses (150 mg every 6 hours) 4
• For patients weighing less than 50 kg (110 pounds), the recommended dosage is 400 mg/day (100 mg every 6 hours) 4
• In patients with cardiomyopathy or possible cardiac decompensation, initial dosage should be limited to 100 mg every 6-8 hours 4
• For patients with moderate renal or hepatic insufficiency, the recommended dosage is 400 mg/day (100 mg every 6 hours) 4
• Patients with severe renal insufficiency require adjusted dosing intervals based on creatinine clearance 4

Monitoring and Precautions

• The QTc interval should be monitored during dose up-titration and the dose reduced if it exceeds 480 ms 1, 5
• Disopyramide typically prolongs QTc by approximately 19±23 ms at a dose of 300 mg/day 5
• Disopyramide should be avoided in patients with: 1
  • Glaucoma
  • Urinary retention or prostatism
  • Patients taking other QT-prolonging medications
  • Severe heart failure due to negative inotropic effects

Potential Side Effects

• Anticholinergic effects are the most common side effects, including dry mouth, urinary hesitancy/retention, and constipation 1, 3
• Cardiovascular side effects may include QT prolongation, hypotension, and worsening of heart failure 3, 6
• Approximately 23% of patients develop side effects, with 11% discontinuing the drug due to these effects 5
• The negative inotropic properties of disopyramide require careful monitoring in patients with compromised cardiac function 3

Drug Interactions

• Disopyramide should be used cautiously in patients with atrial fibrillation as it may enhance AV conduction and increase ventricular rate 1, 2
• It is metabolized by CYP3A4, so caution is needed with inhibitors (e.g., verapamil, diltiazem, ketoconazole, macrolide antibiotics) 1
• Unlike quinidine, disopyramide appears to have fewer drug-drug interactions with digoxin 6

Special Populations

• In patients with HCM who have atrial fibrillation, disopyramide should always be combined with an AV nodal blocking agent (beta-blocker, verapamil, or diltiazem) 1
• For pediatric patients, dosing should be weight-based and carefully monitored, though controlled clinical studies in pediatric patients are limited 4
• Outpatient initiation of disopyramide at 300 mg daily has been shown to be safe in HCM patients with appropriate monitoring 5

Treatment Algorithm for Obstructive HCM

1. First-line: Non-vasodilating beta-blockers titrated to maximum tolerated dose 1
2. Alternative first-line (if beta-blockers contraindicated): Verapamil or diltiazem 1
3. Second-line: Add disopyramide (when symptoms persist despite optimal beta-blocker or calcium channel blocker therapy) 1, 2
4. Third-line: Consider septal reduction therapy (surgical myectomy or alcohol septal ablation) for severely symptomatic patients despite optimal medical therapy 1

Medications to Avoid in Combination with Disopyramide

• Dihydropyridine calcium channel blockers (e.g., nifedipine) 1, 2
• Other QT-prolonging medications (e.g., amiodarone, sotalol) when possible 1
• Vasodilators, nitrates, and phosphodiesterase inhibitors in patients with LVOTO 1
• Digoxin in patients with LVOTO 1

Disopyramide remains an important second-line option for managing symptomatic obstructive HCM, but requires careful patient selection, appropriate combination therapy, and monitoring for side effects and QT prolongation.