Hydralazine Dosing and Treatment Protocol for Hypertension
For acute hypertensive emergencies, hydralazine is NOT a first-line agent due to unpredictable response and prolonged duration of action; when used, administer 10-20 mg IV slowly, repeated every 4-6 hours as needed. 1
Intravenous Administration for Hypertensive Emergencies
Hydralazine should be reserved for situations where preferred agents (nicardipine, clevidipine, labetalol) are unavailable or contraindicated. 1
Dosing Protocol
- Initial dose: 10 mg via slow IV infusion (maximum initial dose 20 mg) 1, 2
- Repeat dosing: Every 4-6 hours as needed 1
- Onset of action: Blood pressure begins to decrease within 10-30 minutes 1, 2
- Duration of effect: Hypotensive effect lasts 2-4 hours 1, 2
Critical Limitations
The ACC/AHA explicitly states that the unpredictability of response and prolonged duration of action do not make hydralazine a desirable first-line agent for acute treatment in most patients. 1, 2 This unpredictability creates risk for both inadequate blood pressure control and excessive hypotension that cannot be rapidly reversed.
Oral Administration for Chronic Hypertension
For chronic hypertension management, 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. 3
Standard Titration Schedule (FDA-Approved)
- Days 1-4: 10 mg four times daily 3
- Days 5-7: 25 mg four times daily 3
- Week 2 and beyond: 50 mg four times daily 3
- Maximum dose: Up to 300 mg daily in divided doses for resistant cases 3
- Maintenance: Adjust to lowest effective dose 3
Alternative Dosing Regimens
Twice-daily dosing is adequate for blood pressure control when hydralazine is combined with beta-blockers and diuretics. 4, 5 Research demonstrates that conventional hydralazine 100 mg twice daily provides satisfactory 24-hour control in both rapid and slow acetylators when combined with atenolol and a diuretic. 4
- Twice-daily regimen: 75-150 mg per dose (150-300 mg total daily) 4, 6, 7
- Once-daily regimen: NOT recommended with conventional formulation due to waning effect at 24 hours, particularly in rapid acetylators 4
Combination Therapy Requirements
Hydralazine must be combined with a beta-blocker and/or diuretic to prevent reflex tachycardia and fluid retention. 8, 3, 9 The FDA label specifically recommends combining with thiazide and/or reserpine or beta-blocker when higher doses are needed. 3
A propranolol-hydralazine combination (80 mg propranolol/50 mg hydralazine twice daily) controlled 46% of patients with mild-to-moderate hypertension and prevented the cardiovascular adverse effects (severe tachycardia, palpitations) seen with hydralazine monotherapy. 9
Acetylator Status Considerations
Slow acetylators require lower doses than fast acetylators to achieve equivalent blood pressure reduction. 6 The dose producing 50% of maximum response (D50) is 0.87 mg/kg for slow acetylators versus 1.68 mg/kg for fast acetylators. 6 However, slow acetylators have higher risk of lupus-like syndrome at higher doses. 8, 3
Critical Safety Monitoring
High-Risk Adverse Effects
- Lupus-like syndrome: Incidence is high in patients receiving large doses, particularly slow acetylators 8, 3
- Reflex tachycardia: Requires concurrent beta-blocker 8, 9
- Fluid retention: Requires concurrent diuretic 8
- Headache: Common, dose-related 8
Monitoring Requirements
- Monitor for lupus-like symptoms (arthralgias, fever, rash) especially at doses >200 mg/day 8, 3
- Avoid abrupt discontinuation after prolonged use 8
- Individual titration is essential when combining with other antihypertensives 3
Heart Failure Context (Not Primary Hypertension)
For heart failure with reduced ejection fraction, hydralazine is used differently: always combined with isosorbide dinitrate, starting at 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily, targeting 75 mg/40 mg three times daily. 1, 2 This combination provides mortality benefit (NNT=7 over 36 months), but this is a distinct indication from hypertension management. 1, 2