Isosorbide Dinitrate and Isosorbide Mononitrate Are NOT Dosed the Same
No, isosorbide dinitrate (ISDN) and isosorbide mononitrate (ISMN) are dosed differently and are not interchangeable. The American College of Cardiology explicitly states that isosorbide mononitrate is not recommended for heart failure management, while isosorbide dinitrate is the preferred nitrate formulation 1.
Key Dosing Differences
Isosorbide Dinitrate (ISDN)
- Starting dose: 20 mg three times daily 1
- Target dose: 40 mg three times daily 1
- Frequency: Three times daily dosing required 1
- Duration of action: Shorter half-life of approximately 36-54 minutes 2, 3
Isosorbide Mononitrate (ISMN)
- Standard dosing: 20 mg twice daily 4
- Duration of action: 12-24 hours with extended-release formulations 4
- Frequency: Once or twice daily dosing 4
- Half-life: Approximately 4-5 hours, significantly longer than ISDN 5, 6
Why They Differ: Pharmacokinetic Rationale
The dosing differences stem from fundamental pharmacokinetic distinctions between these two nitrates:
- ISDN undergoes extensive first-pass metabolism (approximately 70% metabolized during first pass through the liver), resulting in only 20-29% bioavailability 7, 3
- ISMN has 100% bioavailability with no first-pass metabolism, as it is already the active metabolite of ISDN 5, 6
- ISDN is rapidly metabolized to IS-5-MN (the active mononitrate) and IS-2-MN, with 75% converted to IS-5-MN and 25% to IS-2-MN 3
- ISMN has an 8-times longer half-life than ISDN (approximately 4-5 hours versus 36-54 minutes), allowing for less frequent dosing 6, 2
Critical Clinical Caveat
The American College of Cardiology specifically does NOT recommend isosorbide mononitrate for heart failure management 1. When prescribing nitrates for heart failure with reduced ejection fraction, particularly in African American patients or those intolerant to ACE inhibitors/ARBs, use isosorbide dinitrate (not mononitrate) in combination with hydralazine 1, 8.
Tolerance Management
Both formulations require a nitrate-free interval of at least 10-14 hours daily to prevent tolerance development 4, 9. However, the three-times-daily dosing of ISDN naturally provides this interval overnight, while ISMN dosing must be specifically timed to ensure adequate nitrate-free periods 4, 9.
Common Pitfall to Avoid
Do not assume these medications are interchangeable or that you can simply convert doses between them based on milligram equivalence. The different pharmacokinetics, bioavailability, and clinical evidence base (particularly for heart failure) make them distinct therapeutic agents requiring different dosing strategies 1, 5.