Isosorbide Dinitrate Dosing for Angina Pectoris Management
For angina pectoris management, isosorbide dinitrate should be dosed at 5-80 mg orally 2-3 times daily for regular formulation, or 40 mg 1-2 times daily for slow-release formulation, with a mandatory daily nitrate-free interval of at least 14 hours to prevent tolerance. 1, 2
Dosing Regimens by Formulation
Oral Regular Release
- Dosage: 5-80 mg
- Frequency: 2-3 times daily
- Duration of effect: Up to 8 hours
- Important note: Must include a daily nitrate-free interval of at least 14 hours to maintain efficacy 2, 3
Oral Slow Release
- Dosage: 40 mg
- Frequency: 1-2 times daily
- Duration of effect: Up to 8 hours 1
Sublingual
- Dosage: 2.5-5 mg
- Usage: 15 minutes before activity likely to cause angina or to abort an acute anginal episode (though sublingual nitroglycerin is preferred for acute episodes) 3
- Note: Sublingual isosorbide dinitrate is recommended only in patients who fail to respond to sublingual nitroglycerin 3
Administration Guidelines
For Chronic Angina Prevention
- Timing: Administer during waking hours only to maintain a nitrate-free interval
- Dosing schedule examples:
- Morning and early afternoon doses (e.g., 8 AM and 2 PM)
- Three times daily with last dose no later than early evening (e.g., 7 AM, 1 PM, and 6 PM) 2
- Initial dosing: Start with lower doses (5-20 mg) and titrate as needed based on response
For Acute Angina Episodes
- Sublingual isosorbide dinitrate (2.5-5 mg) can be used if patient fails to respond to sublingual nitroglycerin 3
- Take approximately 15 minutes before activity expected to cause angina 3
Important Clinical Considerations
Tolerance Prevention
- A daily nitrate-free interval of at least 14 hours is essential to maintain efficacy 2, 3
- Multiple studies have shown that continuous 24-hour plasma levels result in refractory tolerance 3
- No dosing regimen should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day 3
Monitoring Parameters
- Blood pressure response (avoid if systolic BP <90 mmHg)
- Headache (common side effect)
- Relief of anginal symptoms
- Exercise tolerance
Contraindications
- Concomitant use with phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil)
- Severe hypotension (systolic BP <90 mmHg)
- Right ventricular infarction
- Severe bradycardia or tachycardia 2
Special Situations
Unstable Angina/NSTEMI
- For patients with ongoing symptoms despite oral therapy, intravenous nitroglycerin is preferred over oral isosorbide dinitrate 2
- When symptoms are controlled, transition from IV to oral nitrates with appropriate nitrate-free intervals 2
Microvascular Angina
- Nitrates have limited efficacy as small arterioles are nitrate-resistant
- Consider alternative therapies such as beta-blockers or calcium channel blockers 2
While some case reports suggest that higher doses (up to 120 mg four times daily) may be effective in selected patients with refractory angina 4, these high doses should only be considered in specialized settings after standard dosing has failed, as tolerance develops rapidly with sustained therapy 5.