What is the recommended dosage of isosorbide mononitrate for a patient with cardiovascular disease, specifically hypertension or heart failure?

Isosorbide Mononitrate Dosing for Cardiovascular Disease

For heart failure with reduced ejection fraction (HFrEF), isosorbide mononitrate is NOT used as monotherapy—instead, use the fixed-dose combination of isosorbide dinitrate 20-40 mg with hydralazine 37.5-75 mg three times daily, starting at the lower dose and titrating to the target dose. 1

Heart Failure Indications and Dosing

Primary Indication: HFrEF in African American Patients

• The combination of isosorbide dinitrate/hydralazine is specifically recommended for African American patients with symptomatic HFrEF who remain symptomatic despite optimal guideline-directed medical therapy. 1, 2
• This combination provides a 43% relative risk reduction in mortality with a number needed to treat of only 7 patients over 36 months. 1, 2
• Start with 20 mg isosorbide dinitrate/37.5 mg hydralazine three times daily. 1
• Target dose: 40 mg isosorbide dinitrate/75 mg hydralazine three times daily. 1
• Maximum daily dose: 120 mg isosorbide dinitrate/225 mg hydralazine total. 1, 2

Alternative Indication: ACE Inhibitor/ARB Intolerance

• Use isosorbide dinitrate/hydralazine combination in patients with symptomatic HFrEF who cannot tolerate ACE inhibitors or ARBs due to hypotension, renal insufficiency, or drug intolerance. 2
• Do NOT substitute this combination for ACE inhibitors/ARBs in patients tolerating those medications well. 2

Acute Heart Failure

• In acute heart failure with systolic blood pressure >110 mmHg, intravenous nitrates (including isosorbide mononitrate) can be used. 1
• Initial IV nitroglycerin dose: 10-20 mcg/min, increased by 5-10 mcg/min every 3-5 minutes as needed. 1
• Avoid all vasodilators including nitrates when systolic blood pressure <90 mmHg as this may reduce central organ perfusion. 1

Hypertension Considerations

Isosorbide mononitrate is NOT a first-line or recommended agent for hypertension management. 1

• For resistant hypertension, the treatment algorithm prioritizes renin-angiotensin system blockers, calcium channel blockers, and diuretics before considering other agents. 1
• Hydralazine (used with isosorbide dinitrate in HF) appears only at Step 5 of resistant hypertension management, and specifically requires concomitant beta-blocker and diuretic use. 1
• In resistant hypertension with congestive heart failure with reduced ejection fraction, hydralazine should be administered with isosorbide mononitrate 30 mg daily (maximum 90 mg daily). 1

Monotherapy Dosing (When Appropriate)

If isosorbide mononitrate extended-release is used as monotherapy (primarily for angina, not heart failure):

• Starting dose: 30 mg once daily in the morning. 3
• May increase to 60 mg once daily after several days. 3
• Maximum dose: 120 mg once daily (rarely 240 mg may be required). 3
• Take in the morning on arising; do not chew or crush tablets. 3

Tolerance Prevention Strategy

• A daily nitrate-free interval of at least 14 hours is essential to prevent tolerance development. 4
• Tolerance becomes clinically relevant after 24 hours of continuous therapy. 4
• Once-daily dosing in the morning naturally provides this nitrate-free interval overnight. 5
• For conventional (non-extended release) formulations: 20 mg twice daily with doses separated to allow a nitrate-free interval. 4, 6

Critical Safety Considerations

Absolute Contraindications

• Never use isosorbide mononitrate or isosorbide dinitrate with phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil) due to risk of profound hypotension. 2, 7

Blood Pressure Monitoring

• Monitor blood pressure and heart rate closely, especially during dose titration. 2, 7
• Use particular caution in elderly patients or those on multiple antihypertensive medications. 7
• Patients with aortic stenosis may demonstrate marked hypotension following nitrate initiation. 1

Common Adverse Effects

• Headache is the most frequent side effect (7.7% in first week, decreasing to 0.9% after 24 weeks). 8
• Hypotension may occur, particularly with IV formulations or when combined with other vasodilators. 1
• Tachyphylaxis is common after 24-48 hours with continuous dosing, necessitating dose-free intervals. 1

Clinical Pitfalls to Avoid

1. Do not use isosorbide mononitrate alone for heart failure—the evidence supports only the combination with hydralazine, specifically using isosorbide dinitrate (not mononitrate). 1

2. Do not dose nitrates three or more times daily without a nitrate-free interval—this rapidly induces tolerance and loss of efficacy. 5, 6

3. Do not use calcium antagonists in acute heart failure management—they are not recommended. 1

4. Do not continue nitrates if systolic blood pressure drops below 90 mmHg—this compromises organ perfusion. 1