Oral Hydralazine Starting Dose
Yes, oral hydralazine typically starts at 25 mg, but the initial dosing is 25-50 mg given three to four times daily, not as a single daily dose. 1
Standard Initial Dosing Regimen
The American Heart Association guidelines for resistant hypertension specifically recommend starting hydralazine at 25 mg three times daily and titrating upward to maximum dose. 2 This is the established approach when adding hydralazine as a fifth-line agent after optimizing other antihypertensive medications.
For heart failure with reduced ejection fraction (HFrEF), the ACC/AHA guidelines provide a slightly broader range:
- Initial dose: 25-50 mg orally three to four times daily 2, 1
- Maximum dose: 300 mg daily in divided doses (typically 100 mg three times daily or 75 mg four times daily) 2, 1
Fixed-Dose Combination Option
When using the fixed-dose combination with isosorbide dinitrate (which is preferred for HFrEF):
- Start: 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily 2, 1
- Maximum: 75 mg hydralazine/40 mg isosorbide dinitrate three times daily 2, 1
Critical Dosing Considerations
Multiple daily doses are essential - hydralazine is NOT dosed once daily at 25 mg. 2 The drug requires:
- Minimum frequency: Three times daily 2
- Research confirms that once-daily conventional hydralazine is unsatisfactory as its hypotensive effect wanes at 24 hours 3
Always combine with other medications:
- In HFrEF: Must be combined with isosorbide dinitrate for mortality benefit 2, 1
- In resistant hypertension: Should be used with a diuretic to prevent sodium/water retention and reflex tachycardia 4
- Concomitant beta-blocker therapy is often necessary to control reflex tachycardia 4, 5
Common Pitfalls to Avoid
Do not start at 25 mg once daily - this is inadequate dosing frequency. The medication must be given at least three times daily for sustained blood pressure control. 2, 3
Monitor for side effects from the start:
- Headache, tachycardia, and fluid retention are common 4
- Drug-induced lupus-like syndrome risk, especially in slow acetylators on higher doses 4
- Avoid abrupt discontinuation after prolonged use 4
Titration matters - the mean dose achieved in clinical trials was approximately 175 mg total daily (roughly 58 mg three times daily), indicating most patients require upward titration from the starting dose. 2, 1
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