Isosorbide Mononitrate

• Angina Prevention
• Coronary Artery Disease
• Chronic Stable Angina
• Nitrate Therapy

Isosorbide mononitrate is an organic nitrate vasodilator used for the prevention of angina pectoris. As the active metabolite of isosorbide dinitrate, it offers more predictable pharmacokinetics and is available in extended-release formulations for once-daily dosing.

Mechanism of Action

Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate. It undergoes biotransformation to release nitric oxide (NO), which activates soluble guanylate cyclase in vascular smooth muscle, increasing cyclic guanosine monophosphate (cGMP) and causing vascular smooth muscle relaxation. The primary effect is venodilation, which reduces preload by decreasing venous return to the heart. This reduces left ventricular end-diastolic pressure and volume, decreasing myocardial wall tension and oxygen demand. Some arterial dilation also occurs, reducing afterload. These effects relieve and prevent angina by improving the myocardial oxygen supply-demand balance.

Available Formulations

Isosorbide mononitrate is available as immediate-release tablets (10 mg, 20 mg) and extended-release tablets (30 mg, 60 mg, 120 mg). The extended-release tablets allow once-daily dosing. The tablets should be swallowed whole; extended-release tablets should not be crushed or chewed. Generic formulations are widely available.

Medical Uses

Isosorbide mononitrate is FDA-approved for the prevention of angina pectoris due to coronary artery disease. The extended-release formulation allows for once-daily dosing while maintaining a nitrate-free interval to prevent tolerance. Unlike sublingual nitroglycerin, isosorbide mononitrate is not indicated for the acute relief of angina episodes. It is used as maintenance therapy for chronic stable angina.

Dosing Guidelines

For immediate-release tablets, initial dose is 20 mg twice daily, with doses 7 hours apart (e.g., 8 AM and 3 PM) to provide a nitrate-free interval. For extended-release tablets, initial dose is 30-60 mg once daily in the morning; may increase to 120 mg once daily if needed. The extended-release tablets should not be taken at bedtime, as a nitrate-free interval during sleep helps prevent tolerance. Do not crush extended-release tablets.

Important Safety Information

Nitrate tolerance develops with continuous exposure; dosing schedules must include a nitrate-free interval (typically overnight). Severe hypotension can occur, especially with concurrent PDE-5 inhibitors. Isosorbide mononitrate is contraindicated with PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) and riociguat. Headache is common, particularly at treatment initiation, and usually diminishes with continued therapy. Do not discontinue abruptly in patients with angina due to rebound potential.

Drug Interactions

PDE-5 inhibitors are absolutely contraindicated due to severe hypotension risk. Riociguat is contraindicated. Other antihypertensives, alcohol, and vasodilators may enhance hypotensive effects. Aspirin may enhance the vasodilatory and anti-platelet effects. Ergot alkaloids may have their vasoconstrictive effects antagonized. No significant CYP450 interactions occur.

Special Populations

There are no adequate studies in pregnant women. Use during pregnancy only if clearly needed. It is unknown whether isosorbide mononitrate is excreted in breast milk. Safety and efficacy have not been established in pediatric patients. Elderly patients may be more sensitive to hypotensive effects; start with lower doses. No specific dose adjustment is established for renal impairment, but use with caution in severe impairment. No specific dose adjustment for hepatic impairment, but bioavailability may be increased; start with lower doses.