What is the administration protocol for hydralazine (direct vasodilator)?

Hydralazine Administration Protocol

For intravenous administration in hypertensive emergencies, give 10-20 mg as a slow IV bolus, repeated every 4-6 hours as needed; for oral administration in heart failure, start with 25-50 mg three times daily combined with isosorbide dinitrate, titrating to a target of 75 mg three times daily. 1, 2, 3

Intravenous Administration (Hypertensive Emergencies)

Initial dosing:

• Start with 10 mg via slow IV infusion (maximum initial dose 20 mg) 1
• The FDA label specifies 20-40 mg as the usual dose range, with lower doses required for patients with marked renal damage 3
• Repeat every 4-6 hours as needed to maintain blood pressure control 1

Timing and monitoring:

• Blood pressure begins to decrease within 10-30 minutes after administration 1
• The hypotensive effect lasts 2-4 hours 1
• Check blood pressure frequently; maximal decrease typically occurs within 10-80 minutes 3
• The unpredictability of response and prolonged duration make hydralazine undesirable as a first-line agent for acute hypertension in most patients 1

Critical administration details:

• Use immediately after opening the vial 3
• Do not add to infusion solutions 3
• Discard discolored solutions (hydralazine may discolor upon contact with metal) 3
• Transition to oral therapy within 24-48 hours in most patients 3

Oral Administration (Heart Failure with Reduced Ejection Fraction)

Initial dosing regimen:

• Start with 25-50 mg orally three to four times daily 2, 4
• Always combine with isosorbide dinitrate for mortality benefit in HFrEF 2
• The fixed-dose combination starts at 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily 1, 2

Titration strategy:

• Target dose: 75 mg hydralazine/40 mg isosorbide dinitrate three times daily (fixed-dose combination) 1, 2
• Maximum daily dose: 300 mg hydralazine in divided doses 2, 4
• Mean dose achieved in clinical trials: approximately 175 mg total daily (roughly 58 mg three times daily) 1, 2

Dosing frequency considerations:

• Twice-daily dosing is adequate for blood pressure control when combined with beta-blockers and diuretics 5
• Three to four times daily dosing is standard for heart failure management 1, 2
• Once-daily dosing with conventional formulations is unsatisfactory, particularly in rapid acetylators, as the hypotensive effect wanes at 24 hours 5

Acetylator Status Impact

Dose-response differences:

• The dose that elicits 50% of maximum response (D50) is 0.87 mg/kg for slow acetylators versus 1.68 mg/kg for fast acetylators 6
• Slow acetylators achieve greater hypotensive effects at equivalent doses 5, 6
• Fast acetylators may require higher doses to achieve similar blood pressure control 6

Common Pitfalls to Avoid

Do not use hydralazine as monotherapy in acute settings:

• Hydralazine causes unpredictable blood pressure responses 1
• In cases of increased intracranial pressure, lowering blood pressure may increase cerebral ischemia 3

Do not use hydralazine alone in heart failure:

• Hydralazine must be combined with isosorbide dinitrate for mortality benefit (43% relative risk reduction, NNT=25 over 10 months) 1, 2
• When used appropriately in combination, this regimen provides an NNT of 7 for preventing all-cause mortality over 36 months 1

Avoid oral substitution in true emergencies:

• While 25-50 mg oral hydralazine can substitute when IV is not feasible, onset is delayed compared to IV administration 4
• Oral administration should be reserved for situations where IV access is genuinely unavailable 4