What are the recommended doses of Hydralazine and Isosorbide dinitrate (Isordil) for treating hypertension when Angiotensin-Converting Enzyme (ACE) inhibitors are contraindicated?

From the Guidelines

For treating hypertension when ACE inhibitors are contraindicated, the recommended dosage of the fixed-dose combination of hydralazine and isosorbide dinitrate is typically 37.5 mg hydralazine/20 mg isosorbide dinitrate taken three times daily, with a target dose of 225 mg hydralazine/120 mg isosorbide dinitrate daily, as indicated by the most recent guidelines 1. The treatment should be initiated at the lower dose and gradually titrated upward as tolerated, monitoring for side effects such as headache, dizziness, and reflex tachycardia. Some key points to consider when using this combination include:

• The fixed-dose combination should be taken three times daily, with the option to increase to 2 tablets three times daily for a total daily dose of 225 mg hydralazine hydrochloride and 120 mg isosorbide dinitrate 1.
• When the 2 drugs are used separately, both pills should be administered at least 3 times daily, with initial low doses progressively increased to a goal similar to that achieved in the fixed-dose combination trial 1.
• Blood pressure should be monitored regularly, especially during dose adjustments, and patients should be advised that headaches often diminish with continued use.
• This combination may be particularly beneficial in certain patient populations, although the provided evidence does not specify which ones 1. The dual action of hydralazine and isosorbide dinitrate effectively reduces both afterload and preload, making it a useful alternative for patients with hypertension who cannot tolerate ACE inhibitors.

From the FDA Drug Label

Initiate therapy in gradually increasing dosages; adjust according to individual response. Start with 10 mg four times daily for the first 2 to 4 days, increase to 25 mg four times daily for the balance of the first week. For the second and subsequent weeks, increase dosage to 50 mg four times daily. The usual starting dose of isosorbide dinitrate is 5 mg to 20 mg, two or three times daily. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended.

The recommended doses are:

• Hydralazine: 10 mg four times daily initially, increasing to 25 mg four times daily, and then to 50 mg four times daily for maintenance 2
• Isosorbide dinitrate: 5 mg to 20 mg, two or three times daily initially, and 10 mg to 40 mg, two or three times daily for maintenance 3

From the Research

Recommended Doses of Hydralazine and Isosorbide Dinitrate

The recommended doses of Hydralazine and Isosorbide dinitrate for treating hypertension when ACE inhibitors are contraindicated are as follows:

• The fixed-dose combination of isosorbide dinitrate/hydralazine (I/H) was used in the African-American Heart Failure Trial (A-HeFT) 4
• The study found that treatment with the fixed-dose combination of I/H reduced mortality and morbidity and improved patient-reported functional status compared with standard therapy alone 4
• The doses used in the A-HeFT trial were not specified, but the study found that the combination of I/H was effective with or without ACE inhibitors or beta-blockers 4

Key Findings

Key findings related to the use of Hydralazine and Isosorbide dinitrate include:

• The combination of I/H was found to be effective in reducing mortality and morbidity in patients with heart failure 4
• The use of beta-blockers, but not ACE inhibitors, provided additional significant benefit for survival, event-free survival, and the composite score of death, HF hospitalization, and change in quality of life in patients treated with I/H 4
• The study suggests that the combination of I/H can be used as an alternative to ACE inhibitors in patients with hypertension who are contraindicated for ACE inhibitors 4

Limitations

Limitations of the available evidence include:

• The doses of Hydralazine and Isosorbide dinitrate used in the A-HeFT trial were not specified 4
• The study was conducted in patients with heart failure, and the results may not be generalizable to patients with hypertension only 4
• Further studies are needed to determine the optimal doses of Hydralazine and Isosorbide dinitrate for treating hypertension when ACE inhibitors are contraindicated 4