Hydralazine Dosing Frequency for Heart Failure

Heart Failure Dosing

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend hydralazine 37.5 mg three times daily as the initial dose when using the fixed-dose combination with isosorbide dinitrate, titrating up to 75 mg three times daily, for patients with heart failure with reduced ejection fraction (HFrEF) 1, 2
The mean dose achieved in clinical trials that demonstrated mortality benefit was approximately 175 mg hydralazine daily (divided three times daily), which produced a 7% relative risk reduction in mortality and 33% reduction in hospitalizations, for patients with HFrEF 1
When hydralazine is used without the fixed-dose combination, the ACC/AHA recommends 25-50 mg three or four times daily, with a maximum of 300 mg daily in divided doses, for patients with HFrEF 1, 2

The American Heart Association recommends starting hydralazine at 25 mg three times daily, with upward titration to a maximum of 100-200 mg daily, for patients with resistant hypertension 3

Hydralazine has a relatively short duration of action (2-4 hours for peak effects), making three times daily dosing necessary to maintain consistent vasodilation throughout the day, for patients with HFrEF 3
The mortality and morbidity benefits demonstrated in clinical trials used three times daily dosing; deviating from this regimen may compromise efficacy, for patients with HFrEF 1
Hydralazine causes reflex tachycardia and sodium/water retention, requiring concomitant use of a beta-blocker and diuretic, which is particularly important with the three times daily dosing schedule, for patients with HFrEF 3
At higher cumulative daily doses (>200 mg/day), there is increased risk of drug-induced lupus-like syndrome, for patients taking hydralazine 3, 4
Blood pressure should be monitored after initiation and during dose titration, particularly at 10-30 minutes, 1 hour, and 2-4 hours after each dose, for patients taking hydralazine 3