What is the recommended dose of hydralazine (direct vasodilator) for treating hypertension (high blood pressure) and heart failure?

Hydralazine Dosing for Hypertension and Heart Failure

Recommended Dosing Regimens

For heart failure with reduced ejection fraction, start hydralazine at 37.5 mg three times daily (combined with isosorbide dinitrate 20 mg three times daily) and titrate to a target of 75 mg three times daily; for resistant hypertension, start at 25 mg three times daily and titrate to a maximum of 100-200 mg daily in divided doses. 1

Heart Failure Dosing (HFrEF)

• Initial dose: 37.5 mg hydralazine + 20 mg isosorbide dinitrate three times daily 1, 2
• Target dose: 75 mg hydralazine + 40 mg isosorbide dinitrate three times daily 1, 2
• Titration schedule: Increase doses after 2-4 weeks if tolerated and no symptomatic hypotension occurs 1
• This combination is particularly beneficial in African American patients with HFrEF who remain symptomatic despite standard therapy with ACE inhibitors, beta-blockers, and aldosterone antagonists 2
• In cases of ACE-inhibitor and ARB intolerance, the hydralazine/nitrate combination can be used as an alternative 3

Hypertension Dosing

• Initial dose: 25 mg three times daily 1, 4
• Maximum dose: 100-200 mg daily in divided doses 1, 4
• Frequency: 2-3 times daily due to duration of action 4
• Hydralazine should be used as a step 5 agent for resistant hypertension, not as first-line therapy 1
• The drug has an unpredictable response and prolonged duration of action, making it unsuitable for acute blood pressure control 1, 4

Critical Monitoring Requirements

Blood Pressure Monitoring

• Check blood pressure before each dose escalation 1
• When initiating therapy, monitor at 10-30 minutes, 1 hour, and 2-4 hours after each dose 4
• Do not use in patients with blood pressure <140/90 mmHg or diastolic blood pressure <60 mmHg 1

Drug-Induced Lupus Surveillance

• Monitor for arthralgia, myalgia, joint swelling, pericarditis/pleuritis, rash, or fever 1, 2
• Check ANA if drug-induced lupus is suspected 1
• Risk increases significantly at doses >200 mg daily 1

Essential Concomitant Therapy

Hydralazine causes reflex tachycardia and sodium/water retention, requiring mandatory use with a beta-blocker and diuretic. 1, 4

• Beta-blocker prevents compensatory tachycardia 1, 4
• Diuretic counteracts fluid retention 1, 4
• Without these agents, hydralazine's efficacy is compromised and adverse effects increase 5

Dose-Response Considerations

Acetylator Status Impact

• The daily dose that elicits 50% of maximum response (D50) is 0.87 mg/kg for slow acetylators and 1.68 mg/kg for fast acetylators 6
• Slow acetylators achieve larger hypotensive effects compared to rapid acetylators 7
• Once-daily conventional hydralazine is unsatisfactory in rapid acetylators due to waning effect at 24 hours 7

Renal Function Impact

• Duration of action is significantly longer in patients with creatinine clearance <35 mL/min (14.3 hours) compared to adequate renal function (7.9 hours) 8
• Dosing intervals require adjustment based on renal function 8

Dose Titration in Severe Heart Failure

For patients with severe refractory heart failure, individualized dosing is necessary based on hemodynamic response: 8

• 50 mg produces no significant hemodynamic effects 8
• 75 mg produces modest improvements (19% decrease in systemic vascular resistance) 8
• 100 mg produces substantial improvements (31% decrease in systemic vascular resistance, +0.60 L/min/m² increase in cardiac index) 8
• Some patients require 150-200 mg for hemodynamic response 8

Pediatric Dosing

• Starting dose: 0.75 mg/kg daily in four divided doses 9
• Maximum dose: 7.5 mg/kg or 200 mg daily, whichever is lower 9
• Increase gradually over 3-4 weeks 9

Common Pitfalls to Avoid

• Never use hydralazine as a one-time dose for acute blood pressure control due to unpredictable response and prolonged duration (effects last 2-4 hours) 1, 4
• Do not use as first-line therapy for hypertension 1
• Always combine with beta-blocker and diuretic to prevent reflex tachycardia and fluid retention 1, 4
• Avoid doses >200 mg daily due to significantly increased lupus risk 1
• Do not administer more than three times daily—twice daily dosing is sufficient for most patients 7

Drug Interactions

• When combined with other potent antihypertensive drugs like diazoxide, continuous observation for several hours is required due to risk of profound hypotensive episodes 9
• Administration with food results in higher plasma levels 9