What is the recommended use and dosage of Hydralazine (hydralazine) for treating hypertension?

Hydralazine for Hypertension Management

Hydralazine should be used as a third-line agent for hypertension at an initial oral dose of 10 mg four times daily, gradually increasing to 25-50 mg four times daily, with a maximum of 200 mg daily, and should always be administered with a beta-blocker and diuretic to prevent reflex tachycardia and fluid retention. 1

Dosage and Administration

Initial Dosing

• Start with 10 mg four times daily for the first 2-4 days
• Increase to 25 mg four times daily for the remainder of the first week
• For the second week and beyond, increase to 50 mg four times daily
• Maximum daily dose: 200-300 mg (though doses above 200 mg should be used cautiously) 1

Maintenance Dosing

• Adjust to the lowest effective dose to minimize side effects
• For resistant hypertension, doses up to 300 mg daily may be required, though this increases risk of adverse effects 1
• Once-daily dosing with conventional hydralazine is not recommended as the hypotensive effect wanes at 24 hours 2

Combination Therapy Requirements

Hydralazine must be administered with:

1. A beta-blocker (e.g., propranolol, atenolol) to prevent reflex tachycardia
2. A diuretic to prevent sodium and water retention 3, 1

This combination is essential because:

• Hydralazine causes direct arterial vasodilation, triggering reflex sympathetic activation
• The resulting tachycardia and fluid retention can counteract blood pressure-lowering effects
• Studies show the propranolol-hydralazine combination is more effective than either component alone 4

Place in Therapy

Hydralazine is not a first-line agent for hypertension due to:

• Need for multiple daily dosing
• Significant side effect profile
• Requirement for combination therapy 3

Appropriate Uses:

• Resistant hypertension (when BP remains uncontrolled on 3+ medications)
• Hypertensive emergencies (IV formulation)
• Hypertension in pregnancy/preeclampsia
• Hypertension in heart failure patients (particularly African Americans) 3

Hypertensive Emergencies

For hypertensive emergencies, IV hydralazine can be used:

• Initial dose: 10 mg via slow IV infusion (maximum initial dose 20 mg)
• Repeat every 4-6 hours as needed
• Note: BP begins to decrease within 10-30 minutes, and effects last 2-4 hours
• Caution: Unpredictability of response and prolonged duration make hydralazine less desirable as a first-line agent for acute treatment 5

Side Effects and Monitoring

Common side effects include:

• Reflex tachycardia (prevented by beta-blocker use)
• Fluid retention (managed with diuretics)
• Headache, dizziness, flushing
• Lupus-like syndrome at higher doses (>200 mg/day) 5

Monitoring:

• Blood pressure response
• Heart rate (watch for tachycardia)
• Signs of fluid retention
• For long-term use: monitor for symptoms of drug-induced lupus 5

Special Considerations

Heart Failure

• Hydralazine is recommended for hypertension in heart failure patients when BP persists despite treatment with ACE inhibitor/ARB, beta-blocker, MRA, and diuretic 5
• Particularly beneficial when combined with isosorbide dinitrate in African American patients with heart failure 3

Inappropriate Use

• Studies show hydralazine is commonly prescribed for non-urgent hypertension in hospitalized patients, which is often unjustified 6, 7, 8
• Many patients receive PRN hydralazine instead of continuing their home antihypertensive regimens 8

Treatment Algorithm for Hypertension

1. First-line: ACE inhibitor/ARB, calcium channel blocker, or thiazide diuretic
2. Second-line: Add a second agent from a different class
3. Third-line: Triple therapy with ACE inhibitor/ARB + CCB + thiazide diuretic
4. Fourth-line: Add spironolactone, beta-blocker, or hydralazine (with beta-blocker and diuretic) 3

Pitfalls to Avoid

1. Using hydralazine without a beta-blocker and diuretic
2. Prescribing as first-line therapy when better-tolerated options exist
3. Using IV hydralazine for non-urgent hypertension in hospitalized patients
4. Failing to titrate dose gradually, which can lead to excessive hypotension
5. Not monitoring for lupus-like syndrome with long-term, high-dose use

Hydralazine remains a valuable option for specific hypertensive populations but should be used judiciously with appropriate combination therapy and monitoring.