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

Oral Hydralazine Dosing for Hypertension and Heart Failure

For heart failure with reduced ejection fraction, start hydralazine at 37.5 mg three times daily (in combination with isosorbide dinitrate 20 mg three times daily), titrating to a target of 75 mg three times daily. 1 For hypertension alone, start at 25 mg three times daily, titrating to a maximum of 100-200 mg daily in divided doses. 2

Heart Failure Dosing (Primary Indication)

Hydralazine is guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF), particularly in African American patients who remain symptomatic despite ACE inhibitors, beta-blockers, and aldosterone antagonists. 1, 3

Starting and Target Doses

• Initial dose: 37.5 mg hydralazine + 20 mg isosorbide dinitrate three times daily (fixed-dose combination preferred) 1
• Target dose: 75 mg hydralazine + 40 mg isosorbide dinitrate three times daily 1
• Titration schedule: Consider dose increases after 2-4 weeks if tolerated and no symptomatic hypotension 1

Critical Monitoring Points

• Check blood pressure before each dose escalation 3
• Monitor for symptomatic hypotension (dizziness, lightheadedness)—this often improves with time 1
• Asymptomatic hypotension does not require intervention 1
• Watch for drug-induced lupus syndrome (arthralgia, muscle aches, joint swelling, pericarditis, pleuritis, rash, fever)—check ANA and discontinue if suspected 1

Hypertension Dosing (Alternative Indication)

Hydralazine should NOT be used as first-line therapy for hypertension or as a one-time "PRN" dose for acute blood pressure control due to unpredictable response and prolonged duration of action (2-4 hours). 2, 4

When Hydralazine is Appropriate for Hypertension

Hydralazine is reserved as a step 5 agent for resistant hypertension only after completing the following stepwise approach: 2

1. Optimize 3-drug regimen (ACE inhibitor/ARB + calcium channel blocker + thiazide-like diuretic)
2. Add mineralocorticoid receptor antagonist (spironolactone)
3. Add beta-blocker
4. Then consider hydralazine at 25 mg three times daily, titrating to maximum 100-200 mg daily 2

Dosing Schedule for Hypertension

• Starting dose: 25 mg three times daily 2, 5
• Maximum dose: 100-200 mg daily in divided doses 2, 5
• Frequency: Must be given 2-3 times daily (not once daily with conventional formulation) due to duration of action 6
• Titration: Increase gradually over 3-4 weeks 5

Critical Pitfalls to Avoid

Do NOT Use Hydralazine as PRN/One-Time Dosing

The ACC/AHA explicitly state that hydralazine is not a desirable first-line agent for acute blood pressure treatment. 2 A 2018 retrospective study found that 36% of PRN hydralazine doses were inappropriately given for blood pressures <180/110 mmHg (below the threshold for acute severe hypertension). 7

Contraindications to Acute Use

• Blood pressure <140/90 mmHg (not hypertensive) 4
• Diastolic blood pressure <60 mmHg (risk of excessive hypotension) 4
• Unpredictable response makes it unsuitable for non-urgent situations 2, 4

Required Concomitant Medications

Hydralazine causes reflex tachycardia and sodium/water retention—always use with a beta-blocker and diuretic. 2, 3 This is non-negotiable for safety and efficacy.

Dosing Differences by Acetylator Status

• Slow acetylators: D50 = 0.87 mg/kg daily (lower dose needed for effect) 8
• Fast acetylators: D50 = 1.68 mg/kg daily (higher dose needed for effect) 8
• Maximum antihypertensive response (Emax) is 9.4 mmHg regardless of acetylator status 8

Special Populations

Pediatric Dosing (Off-Label)

• Starting dose: 0.75 mg/kg daily in four divided doses 5
• Maximum dose: 7.5 mg/kg or 200 mg daily (whichever is lower) 5
• Increase gradually over 3-4 weeks 5

Pregnancy

• Hydralazine is Pregnancy Category C (teratogenic in mice at 20-30× human dose) 5
• Use only if benefit justifies potential risk 5
• Excreted in breast milk 5

Administration Considerations

• Take with food for higher plasma levels and better absorption 5
• Effects begin within 10-30 minutes, peak at 1 hour, last 2-4 hours 2, 4
• Monitor blood pressure at 10-30 minutes, 1 hour, and 2-4 hours after initial doses 2

Drug-Induced Lupus Risk

Risk increases significantly at doses >200 mg daily. 2, 3 Monitor for:

• Arthralgia, myalgia
• Joint swelling
• Pericarditis/pleuritis
• Rash or fever
• Check ANA if suspected and discontinue immediately 1

When to Avoid Hydralazine Entirely

• Symptomatic bradycardia or heart rate <60 bpm (reflex tachycardia may be needed) 2
• Severe renal impairment (drug accumulation risk) 5
• Coronary artery disease without beta-blocker coverage (reflex tachycardia increases myocardial oxygen demand) 2
• History of drug-induced lupus 1