Isosorbide Mononitrate vs Isosorbide Dinitrate for Angina Pectoris
Isosorbide mononitrate is superior to isosorbide dinitrate for managing angina pectoris due to its longer duration of action, once-daily dosing capability, better bioavailability, and improved side effect profile.
Pharmacological Differences
- Bioavailability: Isosorbide mononitrate (ISMN) has nearly 100% bioavailability after oral administration, while isosorbide dinitrate (ISDN) undergoes first-pass metabolism 1
- Metabolism: ISDN is a prodrug that must be converted to its active metabolite (ISMN) in the liver, making ISMN more directly bioavailable 1
- Duration of action:
- ISMN: 12-24 hours (standard formulation: 12 hours; slow-release: up to 24 hours)
- ISDN: Up to 8 hours
- This difference is clearly documented in the ACC/AHA guidelines 2
Dosing Advantages
Dosing frequency:
- ISMN: Once daily (slow-release) or twice daily (standard)
- ISDN: 2-3 times daily 2
Typical dosages:
- ISMN: 20 mg twice daily (standard) or 60-240 mg once daily (slow-release)
- ISDN: 5-80 mg 2-3 times daily or 40 mg 1-2 times daily (slow-release) 2
Effective dose comparison: The effective dose of ISMN is 1.5-2 times less than that of ISDN, making it more cost-effective 3
Clinical Efficacy
Both medications effectively reduce the frequency and severity of anginal attacks and may increase exercise tolerance 2
Comparative studies show that ISMN appears at least as effective as the same dosage of ISDN in reducing anginal attacks and improving exercise tolerance 4, 3
ISMN in controlled-release formulation given once daily has demonstrated significantly better antianginal effect than placebo without inducing tolerance development 4
Tolerance Management
Nitrate tolerance: Both medications can develop tolerance with continuous use, requiring a nitrate-free interval 2
Prevention strategies:
- ISMN: Easier to maintain nitrate-free interval with once-daily dosing of slow-release formulation
- ISDN: Requires more complex dosing schedule to prevent tolerance 2
The European Society of Cardiology recommends that patients treated with long-acting nitrates should have a "nitrate-free" interval each day to preserve therapeutic effects 2
Side Effect Profile
Both medications can cause headache, hypotension, and flushing 2
ISMN tends to be better tolerated with fewer headaches by the end of treatment compared to ISDN 5
Number of headache attacks increases during the first week of treatment with both drugs but becomes higher by the end of ISDN treatment and decreases by the end of ISMN treatment 5
Practical Considerations
Nitroglycerin requirement: Diminishes during the first week of use of both drugs but remains lower with ISMN and substantially rises by the end of treatment with ISDN 5
Convenience: Once-daily dosing with ISMN slow-release formulations improves patient adherence
Cost-effectiveness: ISMN is more cost-effective due to lower effective dosing requirements 3
Common Pitfalls to Avoid
Continuous administration: Avoid continuous 24-hour nitrate therapy as it leads to tolerance. Ensure a daily nitrate-free interval of 10-12 hours 2
Concomitant medications: Never use nitrates within 24-48 hours of phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) due to risk of profound hypotension 2
Underdosing: Failure to achieve adequate symptom control due to insufficient dosing is common. Titrate to effective dose while monitoring for side effects 6
Overlooking tolerance: If effectiveness diminishes over time, consider implementing or adjusting the nitrate-free interval rather than simply increasing the dose 2
In conclusion, while both medications are effective for managing angina pectoris, isosorbide mononitrate offers distinct advantages in terms of dosing convenience, duration of action, bioavailability, and side effect profile, making it generally preferable for most patients with stable angina.