Long-acting organic nitrate
ATC code: C01DA14 (Isosorbide mononitrate)
Denitrated in endothelial and vascular smooth muscle cells by mitochondrial aldehyde dehydrogenase to nitric oxide (NO). NO activates soluble guanylate cyclase, raises cGMP, and relaxes vascular smooth muscle. Predominantly dilates veins – lowering cardiac preload; at higher doses also dilates arteries – lowering afterload. No first-pass hepatic metabolism unlike isosorbide dinitrate – bioavailability 100%, half-life 5 hours. Extended-release form dosed once daily.
First line
First-line for long-term prevention of stable angina attacks per 2024 alongside β-blockers and calcium channel blockers. Dose 40–60 mg once daily in the morning in extended-release form. Reduces preload and improves coronary flow. Does not affect mortality or cardiovascular outcomes – a symptomatic agent. For acute attacks, sublingual is used.
Second line
Used with hydralazine in heart failure with reduced ejection fraction in African American patients (A-HeFT) or with ACEi/ARB intolerance. 2023 does not list it as first-line in the general population – base therapy is ARNI (sacubitril-valsartan), β-blockers, aldosterone antagonists, SGLT2 inhibitors.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Isosorbide mononitrate is a long-acting organic nitrate. It is prescribed for angina prophylaxis ( 2024). In sports circles, isosorbide mononitrate is occasionally promoted to improve blood flow to muscles. In healthy athletes without ischemic heart disease, no clinical studies of prophylactic use exist. The drug has specific risks: headache (common, marked), hypotension with syncope, tolerance with regular use, and dangerous blood pressure drop combined with PDE5 inhibitors (strictly contraindicated). If isosorbide mononitrate was prescribed to an athlete, consider seeking a second opinion.
4 pairs found. Sorted from critical to minor.
Mechanism
Riociguat activates sGC independently of NO. Nitrate adds NO – synergistic systemic hypotension. Adempas Section 4.3.
Symptoms
Severe hypotension.
Management
Combination contraindicated.
Mechanism
Sildenafil inhibits PDE-5; isosorbide mononitrate releases nitric oxide. Both pathways converge on cGMP accumulation in vascular smooth muscle, causing severe systemic vasodilation. Blood pressure drops to shock levels with risk of myocardial infarction and stroke. contraindicates PDE-5 inhibitors with any nitrate.
Symptoms
Sudden hypotension within an hour: dizziness, syncope, tachycardia, pallor, loss of consciousness. Cardiac arrest possible.
Management
Combination contraindicated. Allow at least 24 hours between the last sildenafil dose and any nitrate (48 hours for tadalafil). A patient with angina who has taken sildenafil should not receive nitrates – use morphine, oxygen and urgent angiography.
Sources
Mechanism
Both activate cGMP pathway. Synergistic systemic vasodilation – fatal hypotension with MI. Tadalafil's long T1/2 requires 48-hour washout.
Symptoms
Sudden hypotension, MI.
Management
Combination contraindicated. 48 hours between tadalafil and nitrate.
Mechanism
Same pharmacodynamics – synergistic hypotension.
Symptoms
Fatal hypotension.
Management
Combination contraindicated. 24-hour washout.
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Limited pregnancy data. Use in pregnancy only when clearly indicated.
Limited data. Use with caution during lactation.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Isosorbide mononitrate is evaluated for the following indications with varying evidence strength: Stable angina (evidence tier A), Heart failure (evidence tier B), Athletic endurance (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Isosorbide mononitrate (≥ 1 in 100): Headache (especially in early days), Dizziness, Hypotension and orthostatic reactions, Reflex tachycardia, Facial flushing. See the Safety section for uncommon and serious reactions.
FDA category C. Limited pregnancy data. Use in pregnancy only when clearly indicated.
Limited data. Use with caution during lactation.
Isosorbide mononitrate is contraindicated in: Nitrate hypersensitivity; Hypotension and cardiogenic shock; Hypovolemia; Hypertrophic obstructive cardiomyopathy; Severe aortic stenosis. Full list in the Safety section.