What is the recommended dose of hydralazine (direct vasodilator) for treating hypertension?

Hydralazine Dosing for Hypertension

For hypertension treatment, hydralazine should be initiated at 10 mg four times daily for the first 2-4 days, then increased to 25 mg four times daily for the remainder of the first week, followed by 50 mg four times daily for maintenance therapy, with a maximum daily dose of 300 mg. 1

Initial Dosing and Titration Schedule

The FDA-approved oral dosing for hydralazine in hypertension follows a specific titration schedule:

• First 2-4 days: 10 mg four times daily
• Remainder of first week: 25 mg four times daily
• Second week onward: 50 mg four times daily
• Maintenance: Adjust to lowest effective dose
• Maximum dose: Up to 300 mg daily in resistant cases 1

Dosing Considerations

Combination Therapy

• When using hydralazine at higher doses (>100 mg daily), consider combining with:
  • A thiazide diuretic
  • Beta-blocker (to counteract reflex tachycardia)
  • Reserpine 1, 2

Monitoring and Titration

• Blood pressure should be monitored after each dose increase
• Watch for symptomatic hypotension, dizziness, and lightheadedness
• Titration should occur gradually every 2-4 weeks 2

Special Considerations

Side Effects to Monitor

• Headache, dizziness, flushing
• Reflex tachycardia (common with monotherapy)
• Sodium and water retention
• Gastrointestinal complaints
• Drug-induced lupus-like syndrome (with long-term use at doses >100 mg daily) 2

Alternative Dosing Approaches

While the standard approach is four times daily dosing, some evidence suggests that twice-daily dosing may be effective:

• Slow-release formulations at 200 mg once daily have shown satisfactory 24-hour control in both rapid and slow acetylators 3
• Conventional formulations are most effective when given twice daily rather than once daily 3

Pharmacokinetic Considerations

• Acetylator status affects dosing requirements:
  • Slow acetylators may require lower doses
  • Fast acetylators typically need higher doses 4
• The dose that elicits 50% of maximum response (D50) is:
  • 0.87 mg/kg for slow acetylators
  • 1.68 mg/kg for fast acetylators 4

Common Pitfalls to Avoid

1. Monotherapy without addressing reflex tachycardia: Always consider combination with beta-blockers to prevent this common side effect 2, 5

2. Inadequate fluid management: Monitor for sodium and water retention; consider concurrent diuretic therapy 2

3. Inappropriate PRN (as-needed) use: Hydralazine is frequently prescribed as PRN medication in hospital settings, often at thresholds lower than those defining acute severe hypertension, which may not be optimal practice 6, 7

4. Failure to adjust home regimens: When using hydralazine in hospitalized patients, ensure home antihypertensive medications are continued and appropriately adjusted at discharge 6

5. Overlooking lupus-like syndrome risk: Long-term use at higher doses (>100 mg daily) increases risk of drug-induced lupus-like syndrome 2