What is the maximum recommended dose of isosorbide (isosorbide mononitrate)?

Maximum Recommended Dose of Isosorbide Mononitrate

The maximum recommended dose of isosorbide mononitrate is 240 mg daily, though this dose is rarely required for most patients. 1

Dosing Guidelines for Isosorbide Mononitrate

• The recommended starting dose is 30 mg or 60 mg once daily 1
• After several days, the dosage may be increased to 120 mg once daily 1
• Rarely, a maximum dose of 240 mg may be required for optimal therapeutic effect 1
• Daily doses should be taken in the morning upon arising 1
• The medication should be swallowed whole with fluid, not chewed or crushed 1

Dosing in Heart Failure Management

For patients with heart failure with reduced ejection fraction (HFrEF), isosorbide dinitrate is often used in combination with hydralazine:

• Fixed-dose combination: Starting with 20 mg isosorbide dinitrate/37.5 mg hydralazine three times daily, with a target dose of 40 mg isosorbide dinitrate/75 mg hydralazine three times daily (total daily dose: 120 mg isosorbide dinitrate) 2
• When prescribed separately: Starting with 20-30 mg isosorbide dinitrate 3-4 times daily, with a target dose of up to 120 mg total daily in divided doses 2

Clinical Evidence and Efficacy

• In heart failure treatment, the mean dose achieved in clinical trials was approximately 90 mg isosorbide dinitrate daily when used in fixed-dose combination with hydralazine 2
• The combination of hydralazine and isosorbide dinitrate has shown a 43% relative risk reduction in mortality in patients with HFrEF 2
• Number needed to treat (NNT) to prevent one death over 10 months is 25 (standardized to 7 for 36 months) 2

Dose-Response Relationship

• Studies suggest that near-maximal improvement in exercise tolerance for angina patients may occur at lower doses (15-30 mg four times daily) 3
• During sustained therapy, partial tolerance to antianginal effects may develop, potentially requiring dose adjustments 3
• Progressive dose escalation may be needed to maintain efficacy, but should not exceed the maximum recommended dose of 240 mg daily 1, 3

Important Considerations and Precautions

• Headache is a common side effect, occurring in approximately 7.6% of patients, but tends to decrease with continued use 4
• Hypotension can occur, particularly when initiating therapy or increasing doses 3
• Tolerance may develop with sustained therapy, potentially reducing efficacy over time 3
• The medication should not be abruptly discontinued; gradual dose reduction is recommended 1
• Phosphodiesterase inhibitors (e.g., sildenafil, tadalafil) should not be used concurrently due to risk of profound hypotension 2

Monitoring Parameters

• Blood pressure and heart rate should be monitored, especially during dose titration 4
• Assess for symptomatic improvement (reduction in angina frequency or heart failure symptoms) 4, 5
• Watch for signs of hypotension, particularly in elderly patients or those on multiple antihypertensive medications 2, 3

By following these dosing guidelines and monitoring parameters, isosorbide mononitrate can be safely administered up to the maximum recommended dose of 240 mg daily when clinically indicated, though most patients achieve therapeutic benefit at lower doses.