Starting Hydralazine for Severe Hypertension on Losartan/HCTZ
For severe hypertension inadequately controlled on losartan 100 mg daily and hydrochlorothiazide 25 mg twice daily, start hydralazine at 25 mg three times daily, with plans to titrate upward to 50 mg three times daily based on blood pressure response. 1, 2
Initial Dosing Strategy
Begin with hydralazine 25 mg three times daily (total 75 mg/day), which represents the standard starting dose for hypertension management 1, 2
The three-times-daily frequency is essential because hydralazine has a short duration of action (2-4 hours for peak effects), making less frequent dosing inadequate for 24-hour blood pressure control 2, 3
Target dose is 50 mg three times daily (total 150 mg/day) for most patients with hypertension, though some may require up to 100-200 mg daily in divided doses 1, 2
Critical Monitoring and Titration
Monitor blood pressure at 10-30 minutes, 1 hour, and 2-4 hours after the first dose to assess response and detect excessive hypotension 2, 3
Titrate upward every 2-4 weeks based on blood pressure response, but do not exceed 200 mg total daily dose due to significantly increased risk of drug-induced lupus-like syndrome at higher cumulative doses 2, 4, 3
Continue monitoring blood pressure during each dose escalation with the same timing intervals 2
Mandatory Concurrent Therapy Adjustments
You must add a beta-blocker if not already prescribed because hydralazine causes reflex tachycardia that can be severe and counterproductive 1, 2, 4
The patient is already on adequate diuretic therapy (HCTZ 50 mg/day total), which addresses the sodium and water retention caused by hydralazine 1, 2, 4
Without a beta-blocker, hydralazine-induced reflex tachycardia will limit efficacy and potentially worsen cardiovascular outcomes 2, 4
Important Caveats and Pitfalls
Never use once-daily dosing with conventional hydralazine—this provides inadequate 24-hour control, especially in rapid acetylators who metabolize the drug quickly 2
Hydralazine is appropriately positioned as a fourth-line or fifth-line agent for resistant hypertension after maximizing ACE inhibitors/ARBs, calcium channel blockers, and diuretics 1, 4
The patient's current regimen (losartan 100 mg + HCTZ 50 mg total daily) is already at maximum recommended doses for the combination 5, 6, making addition of a third agent appropriate for severe hypertension
Common adverse effects include headache, dizziness, and gastrointestinal complaints, which may limit adherence 4
If blood pressure remains uncontrolled after reaching hydralazine 50 mg three times daily plus beta-blocker, consider adding a calcium channel blocker (such as amlodipine or felodipine extended-release) before further increasing hydralazine dose 5
Alternative Consideration
If this patient has heart failure with reduced ejection fraction (not specified in the question), the dosing strategy would differ: start with hydralazine 37.5 mg three times daily combined with isosorbide dinitrate 20 mg three times daily, targeting 75 mg/40 mg three times daily for mortality benefit 1, 2, 4, 3