Hydralazine Dosing Regimens for Hypertension and Heart Failure
For hypertension, start hydralazine at 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 dosage adjustments to the lowest effective level. 1
Dosing for Hypertension
- Initial therapy should begin with 10 mg four times daily for the first 2-4 days, then increase to 25 mg four times daily for the remainder of the first week 1
- For the second week and beyond, increase dosage to 50 mg four times daily 1
- Maintenance dosage should be adjusted to the lowest effective level to minimize adverse effects 1
- For resistant hypertension, doses up to 300 mg daily may be required, though this increases risk of adverse effects including drug-induced lupus-like syndrome 1
- When higher doses are needed, consider combining hydralazine with a thiazide diuretic, reserpine, or a beta-blocker to allow for lower hydralazine doses 1, 2
Dosing for Heart Failure
- For heart failure with reduced ejection fraction (HFrEF), hydralazine is typically used in combination with isosorbide dinitrate 3
- The initial dose in the fixed-dose combination is 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily 3
- This can be increased to 75 mg hydralazine/40 mg isosorbide dinitrate three times daily as needed and tolerated 3
- This combination is particularly beneficial in African American patients with HFrEF who remain symptomatic despite standard therapy 3
- In severe refractory heart failure, doses of 75-100 mg have shown hemodynamic improvements, with 100 mg producing substantial increases in cardiac index and decreases in systemic vascular resistance 4
Special Considerations
- Acetylator status affects dosing requirements - fast acetylators may require approximately twice the dose compared to slow acetylators 5
- In patients with impaired renal function (creatinine clearance <35 ml/min), the duration of action is significantly prolonged (14.3 hours vs 7.9 hours), requiring dose adjustment and extended intervals 4
- Blood pressure should be closely monitored after initiation and during dose titration 3
- Hydralazine is not recommended as a first-line agent for hypertension but rather as a secondary agent 6
Adverse Effects and Monitoring
- Common adverse effects include headache, dizziness, and gastrointestinal complaints 3
- Hydralazine can cause sodium and water retention, reflex tachycardia, and at higher doses may induce a lupus-like syndrome 6, 1
- When using hydralazine without beta-blockers, significant increases in heart rate may occur (up to 12.4 beats/min) 2
- Combination with beta-blockers (like propranolol) can mitigate the reflex tachycardia associated with hydralazine therapy 2
Administration Timing
- For hypertension, conventional hydralazine is typically administered 2-4 times daily 1, 7
- Slow-release formulations may allow for once-daily dosing in some patients 7
- Standard formulations given once daily may provide inadequate 24-hour coverage, particularly in rapid acetylators 7
Remember that hydralazine dosing often requires individualization based on clinical response and monitoring of blood pressure, particularly in heart failure patients where hemodynamic effects can vary significantly between individuals 4.