Hydralazine Dosing Guidelines for Hypertension and Heart Failure
For hypertension management, hydralazine should be initiated at 10-25mg three times daily and titrated to a target dose of 75mg three times daily (100-200mg daily in divided doses), while for heart failure, the recommended starting dose is 37.5mg hydralazine with 20mg isosorbide dinitrate three times daily, titrated to a target of 75mg hydralazine with 40mg isosorbide dinitrate three times daily. 1
Dosing for Hypertension
Initial Dosing and Titration
- Starting dose: 10-25mg orally three times daily 1
- Gradual titration: Increase by 10mg increments every 2-4 weeks 1
- Target dose: 100-200mg daily in 2-3 divided doses 1
- Maximum dose: Up to 75mg three times daily for resistant hypertension 1
Administration Considerations
- Taking with food results in higher plasma levels 2
- For once-daily dosing, slow-release formulations are preferred over conventional tablets, as conventional tablets show waning effect at 24 hours 3
- Twice-daily dosing with conventional tablets provides satisfactory 24-hour control 3
Dosing for Heart Failure
Fixed-Dose Combination with Isosorbide Dinitrate
- Initial dose: 37.5mg hydralazine/20mg isosorbide dinitrate three times daily 4, 1
- Target dose: 75mg hydralazine/40mg isosorbide dinitrate three times daily 4, 1
- Consider dose up-titration after 2-4 weeks if tolerated 4
Patient Selection
- Particularly beneficial in self-identified Black patients with HFrEF who remain symptomatic despite standard therapy 4, 1
- Alternative for patients who cannot tolerate ACE inhibitors or ARBs 4
- Should not replace ACE inhibitors/ARBs in patients who tolerate these medications 4
Intravenous Dosing for Hypertensive Emergencies
- Initial dose: 10mg via slow IV infusion (maximum initial dose 20mg) 1
- Frequency: Repeat every 4-6 hours as needed 1
- Conversion ratio: 2:1 (oral:IV) when transitioning between routes 1
- Continuous blood pressure monitoring required during IV administration 1
Monitoring and Dose Adjustments
Blood Pressure Monitoring
- Monitor BP after each dose increase 1
- For IV administration, continuous monitoring is essential 1
- Goal for hypertensive emergencies: Reduce SBP by no more than 25% within first hour, then to 160/100 mmHg within 2-6 hours, and normalize over 24-48 hours 1
Special Populations
- Elderly patients may require lower IV doses due to increased sensitivity 1
- Pediatric dosing (though not established in controlled trials): Starting dose 0.75mg/kg daily in four divided doses, gradually increasing to maximum 7.5mg/kg or 200mg daily 2
- Patients with renal impairment (CCr <35ml/min) may require less frequent dosing due to prolonged duration of action (14.3 hours vs 7.9 hours in normal renal function) 5
- Acetylator status affects dosing requirements: fast acetylators may require higher doses (D50 of 1.68mg/kg vs 0.87mg/kg for slow acetylators) 6
Common Side Effects and Management
Side Effects to Monitor
- Reflex tachycardia and fluid retention (consider combination with beta-blockers and diuretics) 1
- Headache, dizziness, flushing, and gastrointestinal complaints 4, 1
- Drug-induced lupus-like syndrome with higher doses (>100mg daily) or long-term use 1
- Symptomatic hypotension (dizziness, lightheadedness) 4, 1
Combination Therapy
- Combining with beta-blockers helps counteract reflex tachycardia 1, 7
- Combining with diuretics helps manage fluid retention 1
- For heart failure, combination with isosorbide dinitrate has shown mortality benefit (43% relative risk reduction) 4
Practical Considerations
- Poor adherence may occur due to multiple daily doses and side effects 4
- Consider slower titration to enhance tolerance if side effects occur 4
- For patients with inadequate response to 100mg, doses of 150-200mg may be effective 5
- Hydralazine with isosorbide dinitrate has shown significant reduction in heart failure hospitalizations (33% relative risk reduction) 4