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

Isosorbide Dosage and Management for Angina Pectoris

For angina pectoris management, isosorbide mononitrate (ISMN) is preferred at 30-60 mg once daily (extended-release) or 20 mg twice daily (standard), while isosorbide dinitrate (ISDN) should be dosed at 10-40 mg two to three times daily with a mandatory 14-hour nitrate-free interval to prevent tolerance. 1, 2, 3

Comparison of Isosorbide Preparations

Isosorbide Mononitrate (ISMN)

• Starting dose: 30-60 mg once daily (extended-release) 3
• Maintenance dose: Can be increased to 120 mg once daily after several days; rarely 240 mg may be required 3
• Administration: Take in the morning upon arising; extended-release tablets should not be crushed or chewed 3
• Duration of action: 12-24 hours 1
• Advantages: Better bioavailability, once-daily dosing (extended-release), fewer side effects 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
• Duration of action: Up to 8 hours 4
• Administration: Must include a daily nitrate-free interval of at least 14 hours to minimize tolerance 2

Managing Nitrate Tolerance

Nitrate tolerance is a significant concern with both ISMN and ISDN:

• Mandatory nitrate-free interval: At least 14 hours for ISDN 2 and 10-12 hours for ISMN 1
• Avoid continuous 24-hour therapy: This leads to complete tolerance and loss of efficacy 4, 1
• Dosing schedule examples:
  • ISDN: Last dose no later than 3-4 PM if first dose is taken at 8 AM
  • ISMN (extended-release): Single morning dose provides coverage with natural overnight nitrate-free interval

Clinical Efficacy and Combination Therapy

Both ISMN and ISDN effectively:

• Reduce frequency and severity of anginal attacks
• Increase exercise tolerance
• Improve quality of life in patients with stable angina 4, 5

For optimal management:

1. Start with monotherapy at the lowest effective dose
2. Optimize dosing of one drug before adding another 4
3. Consider combination therapy with:
   • Beta-blockers: First-line agents that reduce heart rate and myocardial oxygen demand 4
   • Calcium channel blockers: Particularly dihydropyridines can be safely combined with nitrates 4

Important Precautions

• Absolute contraindication: Concomitant use with phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) due to risk of profound hypotension 4
  • Avoid nitrates within 24 hours of sildenafil
  • Avoid nitrates within 48 hours of tadalafil
• Common side effects: Headache, hypotension, and flushing 1
• Monitoring: Blood pressure should be monitored, especially when initiating therapy or increasing doses

Special Considerations

• Higher doses of ISDN (up to 480 mg/day) may benefit selected patients who don't respond to standard doses 6
• ISMN may be more cost-effective than ISDN as the effective dose is typically 1.5-2 times lower 5
• Intravenous ISMN (20 mg in 250 ml normal saline twice daily) can be used for acute management with fewer adverse reactions than glyceryl trinitrate 7

Remember that nitrates should be part of a comprehensive management approach for angina that includes risk factor modification and consideration of other anti-anginal medications based on individual patient characteristics and comorbidities.