What is the maximum daily dose of hydralazine (direct vasodilator)?

Maximum Daily Dose of Hydralazine

The maximum daily dose of hydralazine is 300 mg in divided doses, as established by the American Heart Association guidelines. 1

Dosing Guidelines for Hydralazine

Standard Oral Dosing

• Initial dosing: 25-50 mg 3-4 times daily 1
• Target dosing: Titrate up to maximum of 300 mg daily in divided doses 1
• Optimal administration: Divided into 3-4 doses per day for hypertension management 1

Combination Therapy with Isosorbide Dinitrate

• Fixed-dose combination:
  • Initial: 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily 1
  • Target: 75 mg hydralazine/40 mg isosorbide dinitrate three times daily 1
  • Maximum daily dose: 225 mg hydralazine when used in this combination 2

Heart Failure-Specific Dosing

• When used specifically for heart failure:
  • Fixed combination: Target dose of 75 mg hydralazine three times daily (225 mg total) 2
  • Individual components: Up to 300 mg hydralazine total daily in divided doses 2

Clinical Considerations

Acetylator Status Impact

• Acetylator status significantly affects dosing requirements:
  • Slow acetylators: Achieve therapeutic effect at lower doses (D50 of 0.87 mg/kg) 3
  • Fast acetylators: May require higher doses (D50 of 1.68 mg/kg) 3
  • Consider acetylator status when titrating dose to avoid toxicity in slow acetylators

Dosing Frequency

• While traditionally given in 3-4 divided doses, some evidence suggests twice-daily dosing may be effective:
  • Studies have shown no significant difference in blood pressure control between twice-daily and more frequent dosing regimens 4
  • Once-daily conventional formulation is not recommended as the hypotensive effect wanes at 24 hours 5

Monitoring Requirements

• Complete blood counts and antinuclear antibody titers should be monitored before and periodically during prolonged therapy 6
• Blood pressure monitoring is essential during dose titration to assess efficacy and prevent excessive hypotension

Cautions and Contraindications

• Drug interactions: Use caution when combining with:
  • MAO inhibitors 6
  • Other potent antihypertensives (especially diazoxide) 6
• Side effects increase with higher doses, particularly:
  • Tachycardia and palpitations
  • Headache
  • Fluid retention

Clinical Efficacy

• In heart failure, hydralazine combined with nitrates has shown a 43% relative risk reduction in all-cause mortality 2
• The number needed to treat (NNT) to prevent one death over 10 months is 25, making it one of the more effective heart failure therapies 2

Remember that while 300 mg is the established maximum daily dose, the actual effective dose should be determined based on clinical response and tolerability, with particular attention to acetylator status which can significantly affect the dose-response relationship.