Is hydralazine (hydrochlorothiazide) appropriate for a patient already on Bumex (bumetanide)?

Hydralazine Monotherapy is NOT Appropriate for This Patient

Hydralazine should NOT be used as monotherapy in this patient already on bumetanide (Bumex), as it is contraindicated without concurrent isosorbide dinitrate in heart failure with reduced ejection fraction and causes harmful reflex tachycardia and sodium/water retention when used alone. 1, 2

Critical Contraindication

• The American Heart Association explicitly states that hydralazine without a nitrate is Class III (Harm) in heart failure with reduced ejection fraction 1
• This is not simply "not recommended"—it is associated with worse outcomes and should be avoided 1

Why Hydralazine Alone is Harmful

Reflex Tachycardia and Fluid Retention

• Hydralazine causes direct arterial vasodilation, which triggers compensatory reflex tachycardia and sodium/water retention 3, 2
• This worsens heart failure by increasing cardiac workload and fluid overload—exactly what you're trying to avoid with bumetanide 2
• The patient is already on a loop diuretic (bumetanide), suggesting volume management is a concern; adding hydralazine alone would counteract this therapy 1

Required Concurrent Medications

• Hydralazine must be combined with a beta-blocker AND a diuretic to counteract its adverse hemodynamic effects when used for hypertension 2
• In heart failure, hydralazine must be combined with isosorbide dinitrate to achieve mortality benefit 1, 4
• The combination of hydralazine-isosorbide dinitrate reduces mortality by 43% in African American patients with NYHA class III-IV heart failure, but this benefit requires BOTH drugs given three times daily 4, 2

Appropriate Use of Hydralazine

If Heart Failure with Reduced Ejection Fraction

• Use hydralazine ONLY in combination with isosorbide dinitrate (37.5 mg/20 mg initially, titrated to 75 mg/40 mg three times daily) 4, 2
• This is particularly beneficial for self-identified African American patients with NYHA class III-IV symptoms despite optimal therapy with ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists 1, 4, 2
• Can also be used as an alternative in patients intolerant of ACE inhibitors or ARBs, but again ONLY with isosorbide dinitrate 4, 2

If Resistant Hypertension (Without Heart Failure)

• Hydralazine may be considered as a fifth-line agent for resistant hypertension 2
• Must be combined with both a beta-blocker (to prevent reflex tachycardia) and a diuretic (to prevent sodium retention) 2
• Keep total daily dose below 150 mg to avoid drug-induced lupus 2

Stepwise Approach for Hypertension in Heart Failure

The European Society of Cardiology provides a clear algorithm 1:

1. Step 1: ACE inhibitor (or ARB), beta-blocker, and mineralocorticoid receptor antagonist 1
2. Step 2: Add or switch to a loop diuretic (like bumetanide, which your patient already has) 1
3. Step 3: Add amlodipine OR hydralazine-isosorbide dinitrate combination 1

Common Pitfalls to Avoid

• Do not confuse hydralazine monotherapy with the hydralazine-isosorbide dinitrate combination—they have completely different indications and safety profiles 1, 2
• Do not use hydralazine alone thinking the existing bumetanide is sufficient—you also need a beta-blocker to prevent reflex tachycardia 2
• Be aware that hydralazine can cause drug-induced lupus (especially at doses >150 mg/day), ANCA-positive vasculitis, and hepatotoxicity 2, 5, 6, 7
• In patients with renal impairment, hydralazine half-life increases significantly (up to 15.8 hours with severe renal dysfunction), requiring dose adjustment 8

Bottom Line

If you're considering hydralazine for this patient, you must add isosorbide dinitrate and ensure they're on a beta-blocker. Otherwise, choose a different antihypertensive agent such as amlodipine, which is safe and effective in heart failure 1.