What is the recommended treatment and dosage for hypertension using Hydralazine (Apresoline)?

Hydralazine for Hypertension: Treatment and Dosing

Primary Recommendation for Hypertension

Hydralazine should NOT be used as monotherapy for chronic hypertension and must be combined with a beta-blocker and diuretic to counteract reflex tachycardia and sodium/water retention. 1, 2

FDA-Approved Dosing for Hypertension

For chronic hypertension management, the FDA label specifies the following titration schedule 3:

• Initial dose: 10 mg four times daily for 2-4 days
• Week 1: Increase to 25 mg four times daily for remainder of first week
• Week 2 and beyond: Increase to 50 mg four times daily
• Maintenance: Adjust to lowest effective dose
• Maximum dose: Up to 300 mg daily in resistant cases (though this increases risk of lupus-like syndrome)

Important caveat: The FDA label recommends four times daily dosing, but clinical evidence demonstrates that twice-daily dosing is sufficient for blood pressure control when combined with other agents. 4

Practical Clinical Dosing for Hypertension

The American Heart Association recommends a more practical approach 5:

• Starting dose: 25 mg three times daily
• Target dose: Titrate upward to maximum of 100-200 mg daily
• Position in therapy: Fifth-line agent for resistant hypertension only

Essential Combination Therapy Requirements

Hydralazine causes predictable compensatory responses that require concurrent therapy 1, 5:

• Beta-blocker: Mandatory to prevent reflex tachycardia
• Diuretic: Mandatory to prevent sodium/water retention
• Never use hydralazine alone for chronic hypertension management

Heart Failure Context (Different Indication)

If the patient has heart failure with reduced ejection fraction (HFrEF), particularly self-identified African American patients with NYHA class III-IV symptoms, the dosing differs significantly 6, 5:

• Initial dose: 37.5 mg hydralazine + 20 mg isosorbide dinitrate three times daily
• Target dose: 75 mg hydralazine + 40 mg isosorbide dinitrate three times daily
• Evidence: This combination reduces mortality by 43% and hospitalizations by 33% in this population 2
• Mean dose in trials: Approximately 175 mg hydralazine daily (divided three times daily) 5

Critical Safety Monitoring

Drug-Induced Lupus Risk

• Keep total daily dose <150 mg to minimize lupus-like syndrome risk 2
• Higher risk: Slow acetylators receiving >200 mg/day 1, 5
• Monitor for: Arthralgias, fever, rash, positive ANA

Common Side Effects to Monitor 1

• Headache (very common, especially initially)
• Tachycardia (prevented by beta-blocker)
• Fluid retention (prevented by diuretic)
• Dizziness

Discontinuation

• Avoid abrupt discontinuation after prolonged use 1

Dosing Frequency Considerations

Research demonstrates that 4, 7:

• Twice-daily dosing is adequate for blood pressure control when combined with beta-blocker and diuretic
• Three times daily dosing is NOT necessary for hypertension (unlike heart failure indication)
• Once-daily dosing with conventional formulation is inadequate due to waning effect at 24 hours

Contraindications

Absolute contraindication: Advanced aortic stenosis (unpredictable blood pressure effects) 2

Position in Hypertension Treatment Algorithm

Hydralazine is a fifth-line agent for resistant hypertension only 5. It should only be considered after optimizing:

1. ACE inhibitor or ARB
2. Calcium channel blocker
3. Thiazide diuretic
4. Mineralocorticoid receptor antagonist

Key Clinical Pitfall

The most common error is using hydralazine without concurrent beta-blocker and diuretic therapy, which leads to treatment failure due to compensatory tachycardia and fluid retention. 1, 2, 8