Isosorbide Mononitrate Dosing for Angina Pectoris
For angina prophylaxis, isosorbide mononitrate should be dosed as 20 mg twice daily (immediate-release) or 60-240 mg once daily (extended-release), with mandatory nitrate-free intervals to prevent tolerance. 1
Dosing Regimens
Immediate-Release Formulation
- Standard dose: 20 mg twice daily with 12-24 hour duration of action 1
- Administer doses 7 hours apart (e.g., 8 AM and 3 PM) to ensure a nitrate-free interval overnight 1
- This asymmetric dosing prevents tolerance while providing daytime symptom coverage 2
Extended-Release Formulation
- Initial dose: 30-60 mg once daily in the morning 3, 4
- Target dose: 60-120 mg once daily for most patients 1, 4
- Maximum dose: 240 mg once daily for refractory symptoms 1
- Single morning dosing provides 12-hour protection with a built-in nitrate-free interval overnight 2, 4
Critical Dosing Strategy to Prevent Tolerance
A nitrate-free interval of at least 10-14 hours daily is mandatory to maintain efficacy. 1, 2
- Tolerance develops after 24 hours of continuous nitrate exposure 1
- Once-daily dosing in the morning naturally provides this interval 2, 4
- Twice-daily dosing requires asymmetric timing (not every 12 hours) 1
- Without a nitrate-free interval, complete loss of anti-ischemic effects occurs 2
Minimizing Headache (Common Pitfall)
Start with 30 mg once daily for one week, then increase to 60 mg to reduce headache frequency by 21%. 5
- Headache occurs in 70% of patients but is usually mild-to-moderate 4, 5
- Starting low reduces headache from 64% to 51% of patients (p<0.02) 5
- Headache severity decreases significantly in the second week regardless of dose 5
- Aspirin or acetaminophen effectively treats nitrate headaches without reducing efficacy 1, 3
- Headache is a marker of drug activity—patients should not alter dosing schedules to avoid it 3
Absolute Contraindications
Never combine with phosphodiesterase-5 inhibitors: 1
- Sildenafil: 24-hour washout required
- Tadalafil: 48-hour washout required
- Vardenafil: 24-hour washout recommended
- Combination causes profound hypotension, MI, and death 1
Avoid in: 1
- Systolic BP <90 mmHg or >30 mmHg below baseline
- Hypertrophic cardiomyopathy (may worsen angina) 1, 3
- Severe volume depletion 3
Integration with Other Antianginal Therapy
First-Line Approach
- Beta-blockers remain first-line for angina 1
- Add isosorbide mononitrate if beta-blocker monotherapy insufficient 1
- Alternatively, add dihydropyridine calcium channel blocker to beta-blocker 1
When to Use Isosorbide Mononitrate as Initial Therapy
- Beta-blocker intolerance or contraindication 1
- Vasospastic angina (combine with high-dose calcium channel blocker) 1
- As add-on when symptoms persist on beta-blocker alone 1, 6
Combination Cautions
- Do not combine with nicorandil (no additional efficacy) 6
- Additive hypotension with other vasodilators, especially alcohol 1, 3
- Calcium channel blockers may require dose adjustment when combined 1
Acute vs. Chronic Use
Isosorbide mononitrate is NOT for acute angina relief. 3
- Onset too slow for aborting acute episodes 3
- All patients require short-acting sublingual nitroglycerin (0.3-0.6 mg) for acute symptoms 1
- If angina unrelieved by 3 sublingual doses 5 minutes apart, suspect MI 1
Long-Term Efficacy
Antianginal efficacy is maintained for at least 3 years without tolerance when dosed once daily. 7
- ST-segment depression reduced by 78% at 3 years (vs. 58% at 1 year) 7
- 57% of patients become symptom-free by 3 years 7
- Nitroglycerin consumption decreases by 98% 7
- Abrupt discontinuation may cause rebound angina—taper if stopping 4