From the Guidelines
Hydralazine carries several important risks that patients and healthcare providers should be aware of, including drug-induced lupus erythematosus, hypotension, reflex tachycardia, headaches, and fluid retention, as noted in the most recent guidelines 1. The most concerning risk is drug-induced lupus erythematosus, which occurs in approximately 5-10% of patients, particularly with higher doses (>100 mg daily) and longer treatment durations. This risk is higher in slow acetylators, women, and those with HLA-DR4 phenotype. Other significant risks include:
- Hypotension
- Reflex tachycardia
- Headaches
- Fluid retention Hydralazine can cause peripheral neuropathy, particularly with long-term use. Blood dyscrasias such as neutropenia and thrombocytopenia may occur rarely. Patients may experience gastrointestinal symptoms including nausea, vomiting, and diarrhea. Hydralazine is contraindicated in patients with coronary artery disease as it can worsen angina due to reflex tachycardia. It should be used cautiously in patients with cerebrovascular disease, as rapid blood pressure reduction may reduce cerebral perfusion. Regular monitoring is essential, including complete blood counts, antinuclear antibody testing, and renal function tests, especially during long-term therapy. Patients should report symptoms like joint pain, fever, rash, or chest pain promptly as these may indicate drug-induced lupus, as recommended in the guidelines 1. The combination of hydralazine and isosorbide dinitrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III-IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated 1. In addition, hydralazine can be used in the treatment of hypertensive emergencies, with an initial dose of 10 mg via slow IV infusion and repeat doses every 4-6 hours as needed 1. Overall, hydralazine is a valuable medication for the treatment of hypertension and heart failure, but its use requires careful consideration of the potential risks and benefits, as well as regular monitoring and follow-up, as noted in the guidelines 1.
From the FDA Drug Label
PRECAUTIONS General Myocardial stimulation produced by hydrALAZINE can cause anginal attacks and ECG changes of myocardial ischemia. The drug has been implicated in the production of myocardial infarction. It must, therefore, be used with caution in patients with suspected coronary artery disease The “hyperdynamic” circulation caused by hydrALAZINE may accentuate specific cardiovascular inadequacies. For example, hydrALAZINE may increase pulmonary artery pressure in patients with mitral valvular disease. Peripheral neuritis, evidenced by paresthesia, numbness, and tingling, has been observed. Blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura, have been reported. WARNINGS In a few patients hydrALAZINE may produce a clinical picture simulating systemic lupus erythematosus including glomerulonephritis.
The risks associated with hydralazine include:
- Cardiovascular risks: anginal attacks, myocardial infarction, increased pulmonary artery pressure in patients with mitral valvular disease
- Neurological risks: peripheral neuritis, paresthesia, numbness, tingling
- Hematological risks: blood dyscrasias, reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, purpura
- Immune system risks: clinical picture simulating systemic lupus erythematosus, including glomerulonephritis 2 2
From the Research
Risks Associated with Hydralazine
The following are some of the risks associated with hydralazine:
- Reflex tachycardia, which can be prevented by the concomitant use of a β-blocker 3
- Fluid retention, which can be prevented by the concomitant use of a diuretic agent 3
- Headache, caused by the vasodilation, especially in the early days of therapy 3
- Lupus-like syndrome, which is a low risk associated with high doses and long-term use of hydralazine 3, 4
- Hemolytic anemia, vasculitis, and glomerulonephritis, which have been reported in the literature as adverse effects of hydralazine 4
- Sodium retention, which can manifest as hemodynamic deterioration in patients with heart failure 5
- Tachycardia and ventricular ectopy, which can develop in patients with chronic coronary heart disease with congestive failure refractory to digitalis, diuretics, and nitrates 5
Patient-Specific Risks
Certain patient populations may be at higher risk for adverse effects from hydralazine, including:
- Patients with heart failure, who may experience hemodynamic deterioration, tachycardia, and ventricular ectopy 5
- Patients with low systolic blood pressure, who may have a greater risk of adverse outcomes, but may still benefit from treatment with hydralazine 6
- Patients who are slow acetylators, who may be at higher risk for adverse effects due to the extensive and complex metabolism of hydralazine 7