What is the recommended dosage and management of angina pectoris with Isosorbide (isosorbide dinitrate or isosorbide mononitrate)?

Isosorbide Dosage and Management for Angina Pectoris

For angina pectoris management, isosorbide mononitrate (ISMN) should be started at 30-60 mg once daily (extended-release) or 20 mg twice daily (standard), while isosorbide dinitrate (ISDN) should be initiated at 5-20 mg two to three times daily, with a mandatory nitrate-free interval of at least 14 hours to prevent tolerance. 1, 2, 3

Dosage Recommendations

Isosorbide Mononitrate (ISMN)

• Starting dose: 30 mg once daily (extended-release) 3
• Titration: After several days, may increase to 60 mg once daily, then to 120 mg once daily if needed 3
• Maximum dose: 240 mg daily (rarely required) 3
• Administration: Take in the morning upon arising; tablets should not be chewed or crushed 3
• Standard formulation: 20 mg twice daily 1

Isosorbide Dinitrate (ISDN)

• Starting dose: 5-20 mg two or three times daily 2
• Maintenance dose: 10-40 mg two or three times daily 2
• Nitrate-free interval: At least 14 hours daily to minimize tolerance 2
• Administration: Distribute doses throughout waking hours, ensuring the nitrate-free interval 2

Treatment Algorithm

1. First-line therapy for angina:

   • Short-acting nitroglycerin for acute symptom relief 4
   • Beta-blockers as initial therapy (unless contraindicated) 4

2. When to use isosorbide:

   • As monotherapy if beta-blockers are not tolerated 4
   • As add-on therapy if beta-blocker monotherapy is insufficient 4
   • For vasospastic angina, often in combination with calcium channel blockers 4

3. Dose optimization:

   • Start with lowest effective dose
   • Titrate upward based on symptom control
   • ISMN is more cost-effective as it requires 1.5-2 times lower doses than ISDN for similar efficacy 5

4. Combination therapy:

   • If symptoms persist on isosorbide monotherapy, add calcium channel blocker 4, 1
   • For vasospastic angina, high-dose calcium channel blockers plus long-acting nitrates are recommended 4

Important Considerations

• Preventing nitrate tolerance:

  • Implement a daily nitrate-free interval of 14+ hours 2
  • ISMN extended-release formulation taken once daily in the morning helps maintain this interval 3
  • Continuous 24-hour plasma levels lead to refractory tolerance 2

• Contraindications:

  • Absolute contraindication: Concomitant use with phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) 1
  • Do not use nitrates within 24 hours of sildenafil or 48 hours of tadalafil 1

• Monitoring:

  • Blood pressure should be monitored, especially when initiating therapy or increasing doses 1
  • Watch for common side effects: headache, hypotension, and flushing 1
  • ISMN is generally better tolerated than ISDN 1, 6

• Special considerations for vasospastic angina:

  • Higher doses of calcium channel blockers (up to 480 mg/day verapamil, up to 260 mg/day diltiazem) combined with long-acting nitrates 4
  • Consider tapering and discontinuing treatment 6-12 months after angina has disappeared, as spontaneous remission occurs in about half of patients 4

Efficacy and Evidence

• Both ISDN and ISMN demonstrate good antiischemic effects, with ISMN requiring lower doses for similar efficacy 5
• High-dose ISDN (up to 480 mg/day) may benefit selected patients who don't respond to lower doses 7
• Partial tolerance to exercise time improvement may develop after 2 weeks of therapy, though ST-segment benefits are sustained 8
• For vasospastic angina, both nitrates and calcium channel blockers significantly decrease the number of anginal attacks 6

By following these dosing recommendations and management principles, isosorbide can effectively reduce angina frequency, increase exercise tolerance, and improve quality of life in patients with stable angina pectoris.