What is the dose of disopyramide for symptomatic obstructive hypertrophic cardiomyopathy (HCM)?

Disopyramide Dosing for Symptomatic Obstructive Hypertrophic Cardiomyopathy

For symptomatic obstructive hypertrophic cardiomyopathy (HCM), disopyramide should be titrated to a maximum tolerated dose of 400-600 mg/day, usually in divided doses, after beta-blockers or verapamil have proven ineffective. 1, 2

Dosing Recommendations

• The FDA-approved dosage of disopyramide for most adults is 600 mg/day given in divided doses (150 mg every 6 hours) 2
• For patients weighing less than 110 pounds (50 kg), the recommended dosage is 400 mg/day given in divided doses (100 mg every 6 hours) 2
• For patients with cardiomyopathy specifically, initial dosage should be limited to 100 mg every 6 to 8 hours with subsequent gradual adjustments 2
• The European Society of Cardiology (ESC) recommends titrating disopyramide up to a maximum tolerated dose, usually 400–600 mg/day 1
• Disopyramide should be combined with a beta-blocker or verapamil for optimal management of symptoms in obstructive HCM 1, 3

Clinical Evidence and Efficacy

• Long-term studies show disopyramide effectively reduces left ventricular outflow tract (LVOT) gradients by approximately 37-57% and improves symptoms in patients with obstructive HCM 4
• In a multicenter study, two-thirds of obstructive HCM patients treated with disopyramide (mean dose 432 mg/day) were successfully managed medically with symptom improvement and about 50% reduction in subaortic gradient over ≥3 years 5
• Even at low therapeutic drug levels, disopyramide can produce a 49% reduction in outflow tract gradient 6

Monitoring and Precautions

• The QTc interval should be monitored during dose up-titration and the dose reduced if it exceeds 480 ms 1
• If anticholinergic side effects occur (dry mouth, dry eyes, urinary hesitancy, constipation), plasma levels should be monitored and dosage adjusted accordingly 2
• Disopyramide should be avoided in patients with glaucoma, prostatism, and in those taking other QT-prolonging medications such as amiodarone and sotalol 1
• Disopyramide should not be used as monotherapy in patients with atrial fibrillation, as it may enhance atrioventricular conduction and increase ventricular rate 1

Treatment Algorithm

1. First-line therapy: Start with non-vasodilating beta-blockers titrated to maximum tolerated dose 1, 3
2. Alternative first-line: If beta-blockers are ineffective or contraindicated, use verapamil titrated up to 480 mg/day 1, 3
3. Second-line therapy: Add disopyramide when symptoms persist despite optimal beta-blocker or verapamil therapy 1, 3
   • Start at 100 mg every 6-8 hours for patients with cardiomyopathy 2
   • Gradually increase to 400-600 mg/day in divided doses as tolerated 1, 2
   • Monitor QTc interval during titration 1
4. Dose adjustment: If anticholinergic side effects occur, consider reducing the dose by one-third (from 600 mg/day to 400 mg/day) without changing the dosing interval 2

Important Considerations

• Disopyramide should always be combined with beta-blockers or verapamil in obstructive HCM; monotherapy with disopyramide is potentially harmful in patients with atrial fibrillation 1
• For patients with renal insufficiency, dosage adjustment is required: for creatinine clearance 30-40 mL/min, administer every 8 hours; for 15-30 mL/min, every 12 hours; and for <15 mL/min, every 24 hours 2
• Disopyramide has been safely used for extended periods, with studies showing efficacy and safety in patients treated for at least 5 years 4

Common Pitfalls to Avoid

• Avoid using disopyramide as monotherapy without beta-blockers or verapamil in patients with atrial fibrillation 1
• Do not administer loading doses in patients with cardiomyopathy or possible cardiac decompensation 2
• Avoid concomitant use with other cardiac myosin inhibitors like mavacamten due to potential additive negative inotropic effects 7
• Monitor closely for hypotension and congestive heart failure, especially during initial titration 2