What is the typical dosage of hydralazine (direct vasodilator) for hypertension and heart failure?

Hydralazine Dosing for Hypertension and Heart Failure

Heart Failure with Reduced Ejection Fraction (HFrEF)

For heart failure, start hydralazine at 37.5 mg three times daily (using the fixed-dose combination with isosorbide dinitrate 20 mg), titrating to a target of 75 mg three times daily, which provides a 7% mortality reduction and 33% reduction in hospitalizations. 1

Dosing Regimens for HFrEF

• Fixed-dose combination (preferred): Begin with 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily, increasing to 75 mg hydralazine/40 mg isosorbide dinitrate three times daily 2, 1

• Separate components: If using hydralazine without the fixed combination, start with 25-50 mg three or four times daily, with a maximum of 300 mg daily in divided doses 2

• Mean effective dose in trials: Approximately 175 mg hydralazine daily (divided three times daily) achieved the mortality benefit demonstrated in clinical trials 1

Critical Pharmacokinetic Rationale

• Three times daily dosing is mandatory because hydralazine has a short duration of action (2-4 hours for peak effects), and the mortality/morbidity benefits in clinical trials specifically used this regimen 1

• Deviating from three times daily dosing compromises efficacy, as once-daily conventional hydralazine shows waning hypotensive effect at 24 hours with significant peak-trough differences 3

Required Concurrent Therapy

• Always combine with beta-blocker and diuretic to counteract reflex tachycardia and sodium/water retention—hydralazine monotherapy is explicitly not recommended for chronic hypertension 4

• This combination is particularly beneficial in African American patients with HFrEF who remain symptomatic despite ACE inhibitors, beta-blockers, and aldosterone antagonists 5

Hypertension

For hypertension, initiate hydralazine at 25 mg three times daily, titrating upward to a maximum of 100-200 mg daily in divided doses. 4

FDA-Approved Dosing Schedule

• Start with 10 mg four times daily for the first 2-4 days 6

• Increase to 25 mg four times daily for the remainder of the first week 6

• For the second and subsequent weeks, increase to 50 mg four times daily 6

• For maintenance, adjust to the lowest effective level 6

• In resistant cases, up to 300 mg daily may be required, but consider combining with thiazide and/or beta-blocker at lower hydralazine doses 6

Practical Hypertension Dosing

• The American Heart Association recommends starting at 25 mg three times daily with upward titration to 100-200 mg daily maximum 1

• Twice-daily dosing with conventional hydralazine provides satisfactory 24-hour control in both rapid and slow acetylators, eliminating the need for more frequent administration 3

• The dose that elicits 50% of maximum antihypertensive response (D50) is 0.87 mg/kg for slow acetylators and 1.68 mg/kg for fast acetylators 7

Special Population: End-Stage Renal Disease (ESRD)

• Start at 25 mg three times daily with careful upward titration to maximum 100-200 mg daily due to impaired elimination 4

• Duration of action is significantly prolonged in patients with creatinine clearance <35 mL/min (14.3 hours vs 7.9 hours in normal renal function), requiring longer dosing intervals 8

• Keep total daily doses below 150 mg to minimize drug-induced lupus risk 4

• Reserve as fifth-line agent after optimizing other antihypertensive regimens 4

Monitoring Requirements

• Blood pressure monitoring: Check at 10-30 minutes, 1 hour, and 2-4 hours after initial doses and during titration 1, 4

• Drug-induced lupus surveillance: At cumulative daily doses >200 mg/day, there is increased risk of lupus-like syndrome 1, 5

• Monitor for headache, dizziness, and gastrointestinal complaints 5

• Serial electrolyte monitoring in ESRD patients 4

Critical Pitfalls to Avoid

• Never use hydralazine as monotherapy for chronic hypertension—the reflex tachycardia and sodium retention will undermine efficacy and potentially cause harm 4

• Do not use once-daily dosing for heart failure—this deviates from the evidence-based regimen that demonstrated mortality benefit 1

• Avoid for acute blood pressure control in ESRD due to unpredictable response and prolonged duration of action 4

• Do not skip the beta-blocker when prescribing hydralazine, as beta-blockers may mask warning side-effects and are essential for counteracting reflex tachycardia 9