Hydralazine Starting Dose
For oral hydralazine in hypertension, start with 10 mg four times daily for 2-4 days, then increase to 25 mg four times daily for the remainder of the first week, as recommended by the FDA label. 1
Oral Dosing for Hypertension
The FDA-approved dosing regimen follows a gradual titration approach to minimize adverse effects: 1
- Days 1-4: 10 mg four times daily (40 mg total daily)
- Days 5-7: 25 mg four times daily (100 mg total daily)
- Week 2 and beyond: 50 mg four times daily (200 mg total daily)
- Maximum dose: Up to 300 mg daily in divided doses for resistant cases 1
This conservative starting approach differs from some clinical practice patterns but represents the official FDA guidance. The gradual titration helps reduce the high incidence of adverse reactions (headache, dizziness, gastrointestinal complaints) that occur with hydralazine, particularly at higher doses. 2
Oral Dosing for Heart Failure with Reduced Ejection Fraction
When using hydralazine for HFrEF, always combine it with isosorbide dinitrate—hydralazine alone provides no mortality benefit. 2, 3, 4
Fixed-Dose Combination (Preferred)
- Starting dose: 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily 2, 3, 4
- Target dose: 75 mg hydralazine/40 mg isosorbide dinitrate three times daily (225 mg hydralazine/120 mg isosorbide dinitrate total daily) 2, 3
Separate Components
- Starting dose: 25-50 mg hydralazine three to four times daily, combined with isosorbide dinitrate 3, 4
- Titration: Increase gradually to goal doses similar to the fixed-dose combination trial 2
- Maximum: 300 mg hydralazine daily in divided doses 3, 4
The combination provides substantial mortality benefit with a 43% relative risk reduction and NNT of 7 for preventing all-cause mortality over 36 months. 2, 3 However, adherence is challenging due to the large pill burden, frequent dosing (three times daily minimum), and high adverse effect rate. 2
Intravenous Dosing for Hypertensive Emergencies
- Initial dose: 10-20 mg as slow IV bolus 3
- Repeat: Every 4-6 hours as needed 3
- Onset: 10-30 minutes, with effects lasting 2-4 hours 3
The unpredictable response and prolonged duration make IV hydralazine undesirable as first-line therapy for acute hypertension. 3
Critical Dosing Considerations
Acetylator status significantly affects dosing requirements. Fast acetylators require nearly twice the dose of slow acetylators to achieve the same blood pressure reduction (D50: 1.68 mg/kg vs 0.87 mg/kg). 5 However, routine acetylator phenotyping is not performed in clinical practice, so empiric dose titration based on response is necessary.
Renal function dramatically affects duration of action. In patients with creatinine clearance <35 mL/min, hydralazine's duration of action extends to 14.3 hours compared to 7.9 hours in those with normal renal function. 6 This may allow for less frequent dosing in renal impairment, though the FDA label does not provide specific renal dosing adjustments.
Dosing frequency matters less than total daily dose for blood pressure control. Studies demonstrate that twice-daily dosing provides adequate 24-hour blood pressure control when combined with beta-blockers and diuretics, despite the FDA label recommending four times daily dosing. 7, 8 However, for HFrEF mortality benefit, maintain three times daily dosing as used in clinical trials. 2
Common Pitfalls
- Never use hydralazine monotherapy for HFrEF—it must be combined with isosorbide dinitrate for mortality benefit 2, 3, 4
- Do not substitute hydralazine/isosorbide dinitrate for ACE inhibitors or ARBs in patients tolerating those medications without difficulty 2
- Avoid rapid titration—the high incidence of adverse effects (particularly lupus-like syndrome at doses >200 mg daily) necessitates slow dose escalation 2, 1
- Monitor for blood dyscrasias—discontinue immediately if hemoglobin reduction, leukopenia, agranulocytosis, or purpura develop 1