Hydralazine Dosing and Treatment Protocol 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
Oral Dosing for Chronic Hypertension
Initial Titration Schedule
- Days 1-4: Start at 10 mg four times daily 1
- Days 5-7: Increase to 25 mg four times daily 1
- Week 2 and beyond: Increase to 50 mg four times daily for maintenance 1
- Maximum dose: Up to 300 mg daily may be required in resistant cases, though this increases risk of lupus-like syndrome 1
Alternative Dosing Regimens
- Twice-daily dosing: Conventional hydralazine 100 mg twice daily provides satisfactory 24-hour control in both rapid and slow acetylators 2
- Once-daily dosing: Slow-release formulations at 200 mg once daily maintain adequate blood pressure control, whereas conventional hydralazine once daily shows waning effect at 24 hours in rapid acetylators 2
- There is no need to administer hydralazine more than twice daily when using appropriate formulations 2
Combination Therapy Requirements
Hydralazine should be combined with a diuretic and/or beta-blocker to counteract reflex tachycardia and sodium/water retention. 3, 1
Recommended Combinations
- With beta-blocker and diuretic: Propranolol-hydralazine combination produces significantly better blood pressure control than either agent alone, with mean reductions of 16.8/17.6 mmHg 4
- Concomitant beta-blocker therapy induces an additional 6.6 mmHg drop in blood pressure beyond hydralazine and diuretic effects 5
- For heart failure with reduced ejection fraction (HFrEF): Combine with isosorbide dinitrate—start at 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily, titrate to 75 mg hydralazine/40 mg isosorbide dinitrate three times daily 6
Acetylator Status Considerations
Slow acetylators require lower doses than fast acetylators to achieve equivalent blood pressure reduction. 5
- D50 (dose for 50% maximum response): 0.87 mg/kg daily for slow acetylators vs. 1.68 mg/kg daily for fast acetylators 5
- Maximum antihypertensive response (Emax): 9.4 mmHg reduction in diastolic blood pressure 5
- Slow acetylators show larger hypotensive effects at equivalent doses 2
Intravenous Use for Hypertensive Emergencies
Hydralazine is NOT a desirable first-line agent for acute hypertensive emergencies due to unpredictability of response and prolonged duration of action. 6
IV Dosing When Used
- Initial dose: 10 mg via slow IV infusion (maximum initial dose 20 mg) 6
- Repeat dosing: Every 4-6 hours as needed 6
- Onset: Blood pressure begins to decrease within 10-30 minutes 6
- Duration: Effect lasts 2-4 hours 6
Preferred Alternatives for Hypertensive Emergencies
The 2017 ACC/AHA guidelines recommend nicardipine, clevidipine, or labetalol as preferred agents due to their titratable nature and predictable responses 6
Resistant Hypertension Protocol
In resistant hypertension, add hydralazine at Step 5 after optimizing thiazide-like diuretic, mineralocorticoid receptor antagonist, and beta-blocker therapy. 6
- Start at 25 mg three times daily and titrate upward to maximum dose 6
- If blood pressure remains uncontrolled, substitute minoxidil for hydralazine 6
Critical Monitoring and Side Effects
Common Side Effects to Monitor
- Headache (most common) 3
- Tachycardia and palpitations (reflex sympathetic activation) 3, 4
- Fluid retention (requires diuretic co-administration) 3
- Mean heart rate increase of 12.4 beats/min when used as monotherapy 4
Serious Adverse Effects
- Drug-induced lupus-like syndrome: High incidence with doses >200 mg daily, particularly in slow acetylators 3, 1
- Monitor for arthralgias, fever, rash, and positive ANA 3
- Avoid abrupt discontinuation after prolonged use 3
Laboratory Monitoring
- Statistically significant (but not clinically significant) decreases in hemoglobin, hematocrit, and red blood cell count may occur 7
- Monitor electrolytes when combined with diuretics 6
Clinical Pitfalls to Avoid
Do not use hydralazine as monotherapy—reflex tachycardia and fluid retention will limit efficacy and cause intolerable side effects 3, 1, 4
Do not use once-daily conventional hydralazine—the hypotensive effect wanes at 24 hours, especially in rapid acetylators 2
Do not exceed 200 mg daily without compelling indication—lupus-like syndrome risk increases substantially 1
Do not use as first-line IV agent for hypertensive emergencies—unpredictable response makes titratable agents (nicardipine, labetalol) safer choices 6
Do not combine with other vasodilators without beta-blockade—excessive tachycardia will result 4