Is it okay to continue Imdur (isosorbide mononitrate) in a patient with a history of angina and coronary artery disease without stopping it?

Continuation of Imdur (Isosorbide Mononitrate) in Stable Coronary Artery Disease

Yes, it is appropriate to continue Imdur (isosorbide mononitrate) without stopping in patients with a history of angina and coronary artery disease, as long-acting nitrates provide sustained antianginal prophylaxis and should be maintained for chronic symptom control. 1

Rationale for Continued Use

Imdur is specifically indicated for the prevention of angina pectoris due to coronary artery disease and is designed for chronic, continuous use. 1 The sustained-release formulation provides effective antianginal prophylaxis for up to 12 hours when administered once daily, typically in the morning. 2

• Once-daily dosing (60-120 mg) maintains therapeutic efficacy throughout the day without evidence of classical tolerance development. 2, 3
• The controlled-release formulation creates a plasma nitrate profile that is high enough during daytime hours to provide antianginal protection, but low enough during the latter part of the dosage interval to avoid tolerance development. 3
• Long-term studies demonstrate that improvements from baseline are maintained during repeated administration for up to 6 months. 2, 4

Critical Warnings Against Abrupt Discontinuation

Abrupt withdrawal of isosorbide mononitrate after long-term treatment can cause severe exacerbation of anginal symptoms and may precipitate acute coronary events. 1, 5

• In a study of patients on long-term Imdur therapy (≥1 year), three patients required hospitalization for severe anginal symptoms when the medication was abruptly withdrawn. 5
• During placebo periods following withdrawal, patients experienced more frequent anginal attacks, more severe symptoms, and increased use of sublingual nitroglycerin compared to active treatment periods. 5
• Industrial workers with long-term nitrate exposure have experienced chest pain, acute myocardial infarction, and even sudden death during temporary withdrawal, demonstrating true physical dependence. 1

Monitoring and Management Considerations

Continue the current dosing regimen while monitoring for hypotension, particularly in volume-depleted patients or those with baseline low blood pressure. 1

• Severe hypotension, particularly with upright posture, may occur even with small doses and should be monitored, especially in patients who may be volume depleted. 1
• Hypotension induced by isosorbide mononitrate may be accompanied by paradoxical bradycardia and increased angina pectoris. 1
• Nitrate therapy is contraindicated when systolic blood pressure is <90 mmHg or in patients who have used phosphodiesterase inhibitors within 24 hours (sildenafil/vardenafil) or 48 hours (tadalafil). 6, 1

Headache Management Without Discontinuation

Headaches are a marker of drug activity and should not prompt discontinuation; they typically resolve with continued therapy. 1, 2

• Daily headaches sometimes accompany treatment but are usually mild to moderate and improve with long-term therapy. 1
• Aspirin or acetaminophen successfully relieves isosorbide mononitrate-induced headaches with no deleterious effect on antianginal efficacy. 1
• Patients should resist altering their treatment schedule to avoid headaches, as loss of headache may be associated with simultaneous loss of antianginal efficacy. 1
• The incidence of headache decreases from 7.7% during the first week to 0.9% after 24 weeks of treatment. 4

Special Clinical Scenarios Requiring Caution

Exercise caution but do not discontinue in patients with hypertrophic cardiomyopathy, as nitrate therapy may aggravate angina in this condition. 1

• The benefits of isosorbide mononitrate in patients with acute myocardial infarction or congestive heart failure have not been established. 1
• If used in acute MI or CHF settings, careful clinical or hemodynamic monitoring must be employed to avoid hazards of hypotension and tachycardia. 1
• Nitrates are contraindicated in right ventricular infarction, where profound hypotension may occur. 6

Long-Term Efficacy Data

Clinical evidence supports sustained efficacy without tolerance development during chronic administration. 2, 3

• In a 6-month open study of 106 patients, controlled-release isosorbide mononitrate 60 mg once daily produced progressive reduction in both glyceryl trinitrate use and frequency of anginal attacks. 7
• After 6 months of treatment with isosorbide 5-mononitrate, 53.6% of patients were completely free of angina attacks compared to only 4.5% during previous treatment with isosorbide dinitrate. 4
• There is no evidence of rebound worsening of ischemia 24 hours after administration, supporting the safety of the once-daily dosing regimen. 2