What is the maximum recommended dose of hydralazine (antihypertensive medication) for treating hypertension?

Maximum Dosing of Hydralazine

The maximum recommended dose of hydralazine for treating hypertension is 300 mg daily in divided doses. 1

Dosing Guidelines

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 1

Maintenance and Maximum Dosing

• Adjust to the lowest effective dose for maintenance therapy
• Maximum daily dose: 300 mg 2, 1
• Most patients respond to doses below the maximum
• In resistant hypertension, hydralazine is typically added as a fifth-line agent at an initial dose of 25 mg three times daily, then titrated upward to maximum dose 3

Administration Schedule

• Typically administered in divided doses (3-4 times daily) due to its short duration of action 1
• Slow-release formulations may allow twice-daily dosing with adequate 24-hour blood pressure control 4

Special Considerations

Acetylator Status

• Acetylator status significantly affects dosing requirements:
  • Slow acetylators achieve therapeutic effect at lower doses (D50 of 0.87 mg/kg)
  • Fast acetylators may require higher doses (D50 of 1.68 mg/kg) 5
  • Slow acetylators have a greater hypotensive response 4

Combination Therapy

• When used for heart failure with isosorbide dinitrate:
  • Fixed-dose combination target: 75 mg hydralazine/40 mg isosorbide dinitrate three times daily
  • Maximum daily dose in this combination: 225 mg hydralazine 3, 2
• Often combined with beta-blockers to counteract reflex tachycardia 6
• Lower doses may be effective when combined with thiazide diuretics and/or beta-blockers 1

Safety Considerations

Risk of Lupus-Like Syndrome

• The incidence of hydralazine-induced lupus syndrome is dose-dependent:
  • No cases at 50 mg daily
  • 5.4% incidence at 100 mg daily
  • 10.4% incidence at 200 mg daily
  • Higher risk in women (11.6%) than men (2.8%) 7

Monitoring

• Individual titration is essential to determine the lowest effective dose
• Monitor for signs of lupus-like syndrome, particularly in patients on higher doses
• Regular blood pressure monitoring to assess efficacy and adjust dosing as needed

Pediatric Dosing

• For children: maximum dose is 7.5 mg/kg/day up to 200 mg/day 3
• Usually administered in four divided doses daily

The maximum dose of 300 mg daily should be reserved for resistant cases, with careful monitoring for adverse effects, particularly the lupus-like syndrome which occurs more frequently at higher doses.