What is the recommended dosing regimen for hydralazine (direct vasodilator) in patients with hypertension or heart failure?

Hydralazine Dosing Regimens for Hypertension and Heart Failure

For hypertension, start with 10 mg four times daily for the first 2-4 days, increase to 25 mg four times daily for the remainder of the first week, then increase to 50 mg four times daily for maintenance, with a maximum dose of 200 mg daily divided in 2-3 doses. 1

Dosing for Hypertension

Hydralazine is classified as a direct vasodilator and is considered a secondary agent for hypertension management according to current guidelines 2.

Initial Dosing and Titration:

• Start with 10 mg four times daily for first 2-4 days
• Increase to 25 mg four times daily for remainder of first week
• For second week and beyond, increase to 50 mg four times daily
• Maintenance dose: 100-200 mg daily divided in 2-3 doses 2, 1

Maximum Dose:

• Up to 200 mg daily for most patients
• In resistant cases, up to 300 mg daily may be required, but consider combination therapy instead 1

Important Considerations:

• Always use with a diuretic and beta-blocker to counteract sodium/water retention and reflex tachycardia 2
• Hydralazine is associated with drug-induced lupus-like syndrome at higher doses 2
• In resistant hypertension, hydralazine is recommended as a step 5 agent after optimizing diuretics, RAS blockers, calcium channel blockers, beta-blockers, and mineralocorticoid receptor antagonists 2

Dosing for Heart Failure

For heart failure, hydralazine is typically used in combination with isosorbide dinitrate, particularly in African American patients.

Fixed-Dose Combination:

• Starting dose: 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily 2
• Target dose: 75 mg hydralazine/40 mg isosorbide dinitrate three times daily 2
• Consider dose up-titration after 2-4 weeks if tolerated 2

When Used Separately:

• Initial dose: 25-50 mg hydralazine three or four times daily 2
• Target dose: Up to 75 mg hydralazine three times daily (225 mg total daily) 2
• Both medications should be administered at least three times daily 2

Special Populations

Renal Impairment:

• Patients with reduced renal function (CrCl <35 ml/min) may require longer dosing intervals due to extended duration of action (14.3 ± 1.4 hours vs 7.9 ± 0.5 hours in normal renal function) 3

Acetylator Status:

• Fast acetylators may require higher doses (approximately twice the dose) compared to slow acetylators to achieve the same blood pressure reduction 4
• The dose that elicits 50% of maximum response is 0.87 mg/kg for slow acetylators vs 1.68 mg/kg for fast acetylators 4

Monitoring and Adverse Effects

• Monitor for symptomatic hypotension, especially when initiating therapy
• Watch for signs of drug-induced lupus syndrome (arthralgia, muscle aches, joint pain, rash, fever)
• Regular monitoring of renal function and electrolytes is recommended
• Be aware that hydralazine begins to decrease blood pressure within 10-30 minutes, and the effect lasts 2-4 hours 2

Important Cautions

• Avoid in patients with coronary artery disease without adequate beta-blockade
• Unpredictability of response and prolonged duration of action make hydralazine less desirable as a first-line agent for acute treatment 2
• Adherence can be challenging due to multiple daily dosing requirements 2

For resistant hypertension, hydralazine is typically added at step 5 of therapy after optimizing other antihypertensive medications, with a starting dose of 25 mg three times daily and titrating upward to maximum dose 2.