Isosorbide mononitrate is a long-acting organic nitrate used for prophylaxis of angina pectoris. It is the active metabolite of isosorbide dinitrate with 100% oral bioavailability. The extended-release formulation (Imdur) is given once daily in the morning, with the built-in asymmetric dosing providing a nitrate-free interval to prevent tolerance.
Headache (most common, often diminishes over time)
Dizziness
Hypotension
Concurrent PDE-5 inhibitor use (sildenafil, tadalafil, vardenafil)
Concurrent riociguat
The bottom line
Evidence rating strong. Most-documented uses: effective prophylaxis of angina pectoris, 100% oral bioavailability (no first-pass metabolism), extended-release formulation allows once-daily dosing. 10 sources indexed (2009–2025), with 3 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Converted to nitric oxide (NO) in vascular smooth muscle. NO activates guanylyl cyclase, increasing cGMP levels and causing smooth muscle relaxation. Preferentially dilates venous capacitance vessels, reducing preload and left ventricular end-diastolic pressure. Also dilates coronary arteries and reduces afterload, decreasing myocardial oxygen demand.
Class
Organic Nitrate
Dosing
Dosing & protocol.
Common range
IR: 20 mg twice daily (7 hours apart); ER: 30–240 mg once daily in the morning (as prescribed by your physician)
Recommended form
Extended-release tablet (Imdur) preferred for once-daily dosing
Can be taken with or without food; 100% bioavailability; take in the morning; immediate-release doses should be taken 7 hours apart to allow nitrate-free interval
Safety
Full safety detail.
Side effects
Headache (most common, often diminishes over time)
Dizziness
Hypotension
Flushing
Nausea
Tolerance (mitigated by nitrate-free interval)
Contraindications
Concurrent PDE-5 inhibitor use (sildenafil, tadalafil, vardenafil)
Isosorbide mononitrate and L-arginine both increase nitric-oxide-mediated vasodilation. In a human crossover study, L-arginine enhanced the blood pressure and pulse-wave effects of isosorbide mononitrate in some older hypertensive patients. This can be useful in supervised care but can also cause excessive dizziness, headache, or fainting when added without monitoring.
Recommendation: Do not add high-dose L-arginine to isosorbide mononitrate unless your prescriber is aware. If combined, check sitting and standing blood pressure during the first week, rise slowly, and stop the supplement if you develop faintness or unusually low readings.
L-citrulline increases L-arginine availability and can lower blood pressure through nitric oxide pathways. Isosorbide mononitrate is an organic nitrate with sustained vasodilator effects. Combining them may add to blood pressure lowering, increasing dizziness, headache, flushing, or fainting risk.
Recommendation: Avoid starting high-dose L-citrulline without telling the prescriber who manages your nitrate therapy. If the combination is approved, monitor sitting and standing blood pressure during the first week and stop the supplement if lightheadedness or low readings develop.
NAC may potentiate organic nitrate effects, increasing the chance of dizziness, severe headache, flushing, or symptomatic hypotension. Evidence is strongest for nitroglycerin and isosorbide dinitrate, so this is a class-based caution for isosorbide mononitrate.
Recommendation: Do not add NAC to isosorbide mononitrate therapy without prescriber approval. If both are intentionally used, monitor blood pressure and report severe headache, lightheadedness, fainting, or chest-pain changes.
Makvandi S, Karimi L, Safyari M et al.. Efficacy and safety of isosorbide mononitrate plus misoprostol compared to misoprostol alone in the management of the first and second trimester abortion: a systematic review and meta-analysis. BMC pregnancy and childbirth. 2024
Wang R, Hu J, Li Y et al.. Compound Danshen Dripping Pills combined with isosorbide mononitrate for angina pectoris: A systematic review and a Meta-analysis. Chinese herbal medicines. 2024
Ding SH, Liu J, Wang JP. Efficacy of beta-adrenergic blocker plus 5-isosorbide mononitrate and endoscopic band ligation for prophylaxis of esophageal variceal rebleeding: a meta-analysis. World journal of gastroenterology. 2009
Zhu Y, Zhang W, Qin K et al.. Effects of Nicorandil, Isosorbide Mononitrate, or Diltiazem on Radial Artery Grafts After CABG: The Randomized ASRAB-Pilot Trial. Circulation. Cardiovascular interventions. 2025
Kang MG, Ahn JH, Hwang JY et al.. Long-acting cilostazol versus isosorbide mononitrate for patients with vasospastic angina: a randomized controlled trial. Coronary artery disease. 2024
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