Isosorbide Mononitrate Dosing for Angina Pectoris
For immediate-release isosorbide mononitrate, the recommended dose is 20 mg twice daily, administered at 8 AM and 3 PM (7 hours apart), which provides effective antianginal coverage throughout most of the day without causing tolerance or rebound angina. 1
Immediate-Release Formulation
Standard Dosing Regimen
- Administer 20 mg twice daily with doses separated by 7 hours (typically 8 AM and 3 PM) to maintain a nitrate-free interval and prevent tolerance development 1, 2
- This eccentric dosing schedule provides antianginal efficacy for approximately 12-14 hours daily while allowing a nitrate-free period overnight 1
- The twice-daily regimen at this interval has been demonstrated to improve exercise duration by 24-29% without development of pharmacologic tolerance over 2-3 weeks of therapy 2, 3
Alternative Dosing (Less Preferred)
- Some guidelines mention 20 mg three times daily, but this increases the risk of tolerance development with continuous nitrate exposure 1, 4
- Higher doses (50 mg three times daily) lead to rapid tolerance development and are not recommended 4
Extended-Release Formulation
FDA-Approved Dosing
- Starting dose: 30-60 mg once daily in the morning 5
- May increase to 120 mg once daily after several days if needed 5
- Rarely, 240 mg daily may be required 5
- Must be swallowed whole (not chewed or crushed) with fluid 5
Important Caveat About Extended-Release
- Research evidence suggests that once-daily extended-release formulations (50-100 mg) may develop tolerance within 20-24 hours, with no documented improvement in exercise tolerance at 4,20, or 24 hours after one week of therapy 4
- The immediate-release twice-daily regimen appears more effective than extended-release once-daily dosing based on available evidence 4
Key Clinical Considerations
Tolerance Prevention
- The 7-hour dosing interval (rather than 12 hours) is critical - it provides a nitrate-free period of approximately 14 hours overnight, which minimizes tolerance while maintaining daytime coverage when angina is most likely 1, 2
- Continuous 24-hour nitrate exposure leads to rapid tolerance development 1, 4
Contraindications
- Absolute contraindication: Recent phosphodiesterase-5 inhibitor use - sildenafil within 24 hours or tadalafil within 48 hours due to risk of profound hypotension, MI, and death 1, 6
- Avoid in systolic blood pressure <90 mmHg or >30 mmHg below baseline 1, 6
- Use extreme caution in right ventricular infarction, as these patients depend on adequate RV preload 7, 6
Efficacy Monitoring
- Exercise duration typically improves maximally at 2 hours post-dose, remains significant at 5-7 hours, and is still present (though attenuated) before the next dose 2, 3
- Reduction in anginal attack frequency of 94-98% and decreased sublingual nitroglycerin consumption have been documented with the 20 mg twice-daily regimen over 1-3 years 8
- No rebound increase in nocturnal or early-morning anginal attacks occurs with the eccentric twice-daily dosing schedule 2, 3
Common Pitfall
The most common error is prescribing extended-release formulations once daily or using symmetric dosing intervals (every 12 hours), both of which promote tolerance development and reduce long-term efficacy 1, 4.