Converting Imdur ER to Immediate Release Isosorbide Mononitrate
When converting from Imdur (isosorbide mononitrate extended-release) to immediate-release formulation, use 20 mg IR twice daily with doses separated by 7 hours, regardless of the Imdur ER dose, to maintain antianginal efficacy while preventing nitrate tolerance.
Recommended IR Dosing Strategy
The standard conversion is to 20 mg IR twice daily with a 7-hour interval between doses (typically 8 AM and 3 PM), which provides 12-14 hours of antianginal coverage while maintaining a critical nitrate-free interval overnight 1.
Key Dosing Principles
The 7-hour dosing interval is essential to minimize tolerance development while maintaining daytime coverage when angina episodes are most likely to occur 1.
This eccentric dosing schedule (rather than every 12 hours) creates a nitrate-free period of approximately 10-12 hours overnight, which is necessary to prevent the rapid tolerance that develops with continuous 24-hour nitrate exposure 2, 1.
The American College of Cardiology emphasizes that tolerance to nitrates is dose and duration dependent, typically becoming clinically important after 24 hours of continuous therapy, making the nitrate-free interval strategy mandatory 2.
Why Not Dose-Equivalent Conversion?
Do not attempt to match the total daily dose of Imdur ER when converting to IR formulation. The 20 mg twice-daily IR regimen is the evidence-based standard regardless of whether the patient was on Imdur 30 mg, 60 mg, 120 mg, or 240 mg daily 1.
Imdur ER formulations are designed to provide sustained release over 24 hours, but this continuous exposure promotes tolerance 3, 4.
The IR formulation with proper spacing allows plasma nitrate levels to be high enough for daytime antianginal protection but low enough during the latter part of the dosing interval to avoid tolerance development 4.
Managing Breakthrough Symptoms
Provide sublingual nitroglycerin (0.3-0.6 mg) for breakthrough angina, particularly during the overnight nitrate-free interval 2.
If the patient experiences frequent breakthrough symptoms during the nitrate-free period, this indicates inadequate baseline antianginal therapy and warrants optimization of beta-blockers or addition of calcium channel blockers rather than eliminating the nitrate-free interval 5.
Critical Safety Considerations
Absolute contraindications must be verified before any nitrate therapy:
Phosphodiesterase-5 inhibitor use within 24 hours (sildenafil, vardenafil) or 48 hours (tadalafil) due to risk of profound hypotension, MI, and death 1.
Systolic blood pressure <90 mmHg or >30 mmHg below baseline 1.
Common Pitfall to Avoid
Do not use continuous dosing (every 12 hours) with IR isosorbide mononitrate, as this eliminates the nitrate-free interval and leads to rapid tolerance development, with loss of antianginal efficacy typically within 24-48 hours of continuous exposure 2, 1. The asymmetric 7-hour interval is not arbitrary—it is the evidence-based approach to maintain long-term nitrate responsiveness.