Hydralazine Dosing Parameters
Oral Dosing for Hypertension
For chronic hypertension management, initiate hydralazine at 10 mg four times daily for 2-4 days, then increase to 25 mg four times daily for the remainder of the first week, followed by 50 mg four times daily for maintenance, with a maximum of 300 mg daily in divided doses. 1
Standard Titration Protocol
- Initial dose: 10 mg four times daily for 2-4 days 1
- Week 1: Increase to 25 mg four times daily after initial period 1
- Week 2 and beyond: Increase to 50 mg four times daily for maintenance 1
- Maximum dose: 300 mg daily in divided doses for resistant cases, though this increases risk of lupus-like syndrome 1, 2
Alternative Dosing Schedules
- Three times daily dosing: 25-50 mg three times daily is acceptable and supported by guidelines, particularly for heart failure applications 2
- Twice daily dosing: Conventional hydralazine 100 mg twice daily provides adequate 24-hour control when combined with beta-blockers and diuretics 3, 4
- Once daily dosing: Slow-release formulations at 200 mg once daily are effective, but conventional hydralazine once daily is inadequate due to waning effect at 24 hours, especially in rapid acetylators 3, 4
Pediatric Dosing
- Initial dose: 0.75 mg/kg/day 5
- Maximum dose: 7.5 mg/kg/day up to 200 mg/day 5
- Frequency: Four times daily 5
Intravenous Dosing for Acute Hypertension
For hypertensive emergencies, administer hydralazine 10-20 mg as a slow IV bolus, repeated every 4-6 hours as needed, though this is NOT a first-line agent due to unpredictable response and prolonged duration of action. 5, 6
IV Administration Protocol
- Initial dose: 10 mg slow IV infusion (maximum initial dose 20 mg) 5
- Repeat dosing: Every 4-6 hours as needed based on blood pressure response 5, 6
- Onset of action: 10-30 minutes 5
- Duration of effect: 2-4 hours, making response timing unpredictable 5, 6
Critical Limitations of IV Hydralazine
- Unpredictability: The response is highly variable and cannot be titrated like continuous infusions 5, 7
- Hypotension risk: In hospitalized patients, 11.7% experienced hypotension as an adverse event, with BP changes highly variable despite being related to baseline values 7
- Not first-line: ACC/AHA guidelines explicitly state hydralazine is not a desirable first-line agent for acute treatment in most patients 5, 6
Preferred Alternatives for Acute Control
- Nicardipine: 5-15 mg/h IV infusion, titrated every 5 minutes, provides more predictable control 5, 6
- Labetalol: 0.3-1.0 mg/kg (maximum 20 mg) slow IV injection every 10 minutes or 0.4-1.0 mg/kg/h infusion 5
- Clevidipine: 1-2 mg/h IV infusion, doubled every 90 seconds until BP approaches target 5
Special Population: Preeclampsia
- Dose: 5 mg IV bolus, repeated every 15 minutes to reduce mean arterial pressure to <125 mmHg 8
- Efficacy: Mean arterial pressure falls by 12 mmHg after first bolus, 9 mmHg after second bolus, 5 mmHg after third bolus 8
- Safety: This regimen controlled BP in 89% of cases when protocol was followed strictly 8
Heart Failure Dosing (with Isosorbide Dinitrate)
For heart failure with reduced ejection fraction, initiate hydralazine 37.5 mg three times daily (in fixed-dose combination with isosorbide dinitrate), titrating to target dose of 75 mg three times daily for mortality benefit. 2
Dosing Schedule
- Initial dose: 37.5 mg three times daily 2
- Target dose: 75 mg three times daily 2
- Mean effective dose in trials: Approximately 175 mg daily (divided three times daily) 2
- Mortality benefit: 7% relative risk reduction in mortality and 33% reduction in hospitalizations at target dose 2
Pharmacokinetic Rationale
- Short duration: Peak effects last only 2-4 hours, necessitating three times daily dosing for consistent 24-hour vasodilation 2
- Trial-proven regimen: Mortality benefits were demonstrated specifically with three times daily dosing; deviating may compromise efficacy 2
Dose-Response Relationships
The maximum antihypertensive response (Emax) to hydralazine is 9.4 mmHg, with the D50 (dose achieving 50% of maximum response) being 0.87 mg/kg/day for slow acetylators and 1.68 mg/kg/day for fast acetylators. 9
Acetylator Status Impact
- Slow acetylators: Require lower doses (D50 = 0.87 mg/kg/day) to achieve therapeutic effect 9
- Fast acetylators: Require higher doses (D50 = 1.68 mg/kg/day) and show more pronounced waning of effect with once-daily dosing 3, 9
Critical Monitoring Parameters
Blood Pressure Monitoring
- Timing: Monitor at 10-30 minutes, 1 hour, and 2-4 hours after each dose, particularly during initiation and titration 2
- IV administration: Continuous monitoring recommended to prevent "overshoot" hypotension 5
Adverse Effect Monitoring
- Lupus-like syndrome: Risk increases significantly at cumulative daily doses >200 mg/day 2, 1
- Reflex tachycardia: Requires concomitant beta-blocker therapy 2
- Fluid retention: Requires concomitant diuretic therapy 2
Common Pitfalls to Avoid
- Never use IV hydralazine as first-line for hypertensive emergencies unless other agents are contraindicated 6
- Do not use once-daily conventional hydralazine (non-slow-release formulation) as it provides inadequate 24-hour control, especially in rapid acetylators 3
- Do not exceed 300 mg daily without compelling indication due to increased lupus risk 1, 2
- Always combine with beta-blocker and diuretic to counteract reflex tachycardia and fluid retention 2, 1
- Do not deviate from three times daily dosing in heart failure as this was the trial-proven regimen for mortality benefit 2