Can Isordil (Isosorbide Dinitrate) Be Substituted?
No, isosorbide mononitrate (Isordil Mononitrate) cannot be substituted for isosorbide dinitrate in heart failure management—the ACC/AHA explicitly states that isosorbide mononitrate is not recommended for heart failure treatment. 1, 2
Critical Distinction Between Nitrate Formulations
Only isosorbide dinitrate (not mononitrate) is guideline-recommended for heart failure with reduced ejection fraction (HFrEF). 1, 2 The evidence base supporting mortality and morbidity reduction specifically used isosorbide dinitrate in combination with hydralazine, and this cannot be extrapolated to other nitrate formulations. 1, 3
When Isosorbide Dinitrate Is Indicated
Primary Indication (Class I Recommendation)
- Self-identified Black or African American patients with NYHA class III-IV HFrEF who remain symptomatic despite optimal therapy with ACE inhibitors/ARBs/ARNIs and beta-blockers should receive the hydralazine/isosorbide dinitrate combination. 1, 3
- This combination demonstrated a 43% reduction in mortality risk and 33% reduction in heart failure hospitalizations (NNT = 7 for mortality reduction at 36 months). 3
Alternative Indication (Class IIa Recommendation)
- Patients with HFrEF who cannot tolerate ACE inhibitors or ARBs due to hypotension, renal insufficiency, or drug intolerance may be considered for this combination therapy. 1, 3
- However, this should not be used as first-line therapy in patients who have never tried standard neurohumoral antagonist therapy. 1, 3
Proper Dosing of Isosorbide Dinitrate
Starting dose: 20 mg three times daily (or 1 tablet of fixed-dose combination containing 20 mg isosorbide dinitrate/37.5 mg hydralazine three times daily). 1, 3
Target dose: 40 mg three times daily (or 2 tablets of fixed-dose combination three times daily for total daily dose of 120 mg isosorbide dinitrate/225 mg hydralazine). 1, 3
The three-times-daily dosing naturally provides a nitrate-free interval of at least 10-12 hours overnight, which is essential to prevent complete tolerance development. 4, 2
Key Contraindications and Precautions
Absolute contraindications:
- Concurrent use of phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil) due to risk of severe hypotension. 4, 5
- Concurrent use of riociguat (soluble guanylate cyclase stimulator). 5
- Hypertrophic cardiomyopathy with outflow obstruction. 4
Common pitfall: Patient adherence can be challenging due to multiple daily dosing requirements and side effects (primarily headache and gastrointestinal complaints). 1 Consider slower titration if side effects are problematic to enhance tolerance. 3
Why Formulation Matters
The pharmacokinetic profile and evidence base differ fundamentally between isosorbide dinitrate and mononitrate. While isosorbide mononitrate has a longer duration of action (12-24 hours with extended-release formulations), it lacks the mortality and morbidity data in heart failure that isosorbide dinitrate possesses. 2 Performance measures for heart failure quality explicitly exclude other nitrate formulations from meeting numerator requirements. 1