What is the dosage and management of Isosorbide Mononitrate (IMN) ER for angina pectoris?

Isosorbide Mononitrate ER Dosage and Management for Angina Pectoris

The recommended starting dose of Isosorbide Mononitrate Extended-Release (IMN ER) for angina pectoris is 30-60 mg once daily in the morning, which may be increased to 120 mg once daily after several days if needed, with a maximum dose of 240 mg rarely required. 1

Initial Dosing and Titration

• Start with 30 mg (given as a single 30 mg tablet or half of a 60 mg tablet) or 60 mg (given as a single tablet) once daily 1
• After several days, the dosage may be increased to 120 mg once daily if needed for symptom control 1
• Maximum dose of 240 mg may rarely be required 1
• The daily dose should be taken in the morning upon arising 1
• Tablets should not be chewed or crushed and should be swallowed with half a glass of fluid 1

Pharmacokinetics and Administration Considerations

• IMN ER provides antianginal activity for at least 12 hours after dosing 1
• Food intake may decrease the rate but not the extent of absorption 1
• The mean plasma elimination half-life is approximately 5 hours 1
• For elderly patients (≥65 years), no initial dosage adjustment is required, though they may show slightly lower clearance at higher doses (120 mg) 1

Efficacy and Duration of Action

• IMN ER demonstrates significant antianginal activity at 4 and 12 hours after administration 1, 2
• At 120 mg and 240 mg doses, significant improvement in exercise tolerance persists even after 42 days of therapy 1, 2
• Lower doses (30 mg and 60 mg) may lose effectiveness after several weeks of continuous therapy 1
• No significant activity is detected at 24 hours after administration (immediately before next dose) 2

Nitrate Tolerance Management

• A daily nitrate-free interval is essential to prevent tolerance 3, 4
• IMN ER's once-daily morning dosing regimen inherently provides this nitrate-free interval 4, 1
• There is no evidence of rebound angina (zero-hour effect) at the end of the dosing interval with IMN ER 2

Combination Therapy

• Beta-blockers work synergistically with nitrates by preventing reflex tachycardia 4
• According to the European Society of Cardiology guidelines, anti-anginal drug treatment should be tailored to individual needs 3
• Dosing of one drug should be optimized before adding another, and it's advisable to switch drug combinations before attempting a three-drug regimen 3

Side Effects and Precautions

• Headache is the most common side effect, particularly during initial therapy 2
• Hypotension may occur, especially with higher doses 3, 4
• Use with caution in patients with low systolic blood pressure (<90 mmHg) or severe bradycardia (<50 bpm) 4

Clinical Pearls

• IMN ER once daily is as effective as conventional isosorbide dinitrate three times daily, with better compliance due to once-daily dosing 5
• Higher doses (100 mg vs 50 mg) have been shown to provide better symptom control without significantly increasing adverse effects 6
• For acute angina episodes, short-acting nitrates like sublingual nitroglycerin should be used rather than IMN ER 3, 4
• An angina attack that does not respond to short-acting nitroglycerin should be considered a possible myocardial infarction 3, 4

By following these dosing and management guidelines for IMN ER, clinicians can effectively control angina symptoms while minimizing the development of nitrate tolerance and adverse effects.