Dosage of Oral Isosorbide Mononitrate in Long-Term Nitrate Therapy
For immediate-release isosorbide mononitrate, administer 20 mg twice daily with doses separated by 7 hours (e.g., 7 AM and 2 PM) to prevent tolerance while maintaining daytime antianginal coverage. 1
Immediate-Release Formulation Dosing
The 20 mg twice-daily regimen with a 7-hour interval is the cornerstone of long-term oral nitrate therapy, providing 12-14 hours of antianginal efficacy while preserving a nitrate-free period overnight. 1
This eccentric dosing schedule (morning dose followed by afternoon dose 7 hours later) prevents the rapid tolerance development that occurs with continuous 24-hour nitrate exposure. 1
The asymmetric timing maintains daytime coverage when angina episodes are most likely while allowing overnight nitrate-free intervals critical for sustained efficacy. 1
Extended-Release Formulation Alternative
Extended-release isosorbide mononitrate should be initiated at 30-60 mg once daily in the morning, with potential titration to 120 mg daily after several days if needed. 2
Rarely, doses up to 240 mg once daily may be required for refractory symptoms. 2
Extended-release formulations provide antianginal activity for at least 12 hours after morning administration without developing tolerance at doses of 120-240 mg. 2
Critical Tolerance Considerations
Continuous or symmetric dosing regimens (e.g., every 8 or 12 hours) rapidly produce tolerance within 24 hours, resulting in loss of antianginal and anti-ischemic effects. 3, 4
The 7-hour interval between immediate-release doses is specifically designed to create a nitrate-free period that prevents tolerance while maintaining therapeutic coverage during waking hours. 1
Studies demonstrate that symmetric twice-daily dosing (8 AM and 8 PM) produces tolerance, whereas asymmetric dosing (7 AM and 2 PM) maintains efficacy during chronic therapy. 5
Absolute Contraindications and Safety Parameters
Isosorbide mononitrate is absolutely contraindicated within 24 hours of sildenafil use or 48 hours of tadalafil use due to risk of profound hypotension, myocardial infarction, and death. 1
Avoid administration in patients with systolic blood pressure <90 mmHg or >30 mmHg below baseline. 1
The combination of nitrates with phosphodiesterase-5 inhibitors causes markedly exaggerated and prolonged vasodilation through cyclic guanosine monophosphate accumulation. 6
Common Pitfalls to Avoid
Do not prescribe three or four times daily dosing regimens, as these produce tolerance and provide inadequate antianginal prophylaxis despite higher total daily doses. 4, 5
Recognize that intermittent daytime dosing leaves patients unprotected during nighttime and early morning hours—if nocturnal angina is problematic, add a long-acting beta-blocker or calcium channel blocker rather than extending nitrate coverage. 4
Headache is the most common adverse effect but typically improves with continued therapy and rarely necessitates discontinuation. 7
Abrupt discontinuation after long-term therapy may exacerbate anginal symptoms—taper gradually if stopping treatment. 7