What are the contraindications and precautions for using hydralazine (direct vasodilator) in patients?

Contraindications and Precautions for Hydralazine Use

Hydralazine should be avoided in patients with coronary artery disease, mitral valvular disease, and as monotherapy for chronic hypertension, and is not a first-line agent for most acute hypertensive emergencies due to unpredictable blood pressure response and prolonged duration of action. 1, 2

Absolute Contraindications

• Coronary artery disease or suspected ischemic heart disease – Hydralazine causes myocardial stimulation that can precipitate anginal attacks, ECG changes of myocardial ischemia, and has been implicated in myocardial infarction production 2

• Concurrent use without beta-blocker and diuretic in chronic hypertension – The drug causes reflex tachycardia and sodium/water retention, making monotherapy harmful and requiring concurrent beta-blocker and diuretic therapy 3

• Heart failure without concurrent nitrate therapy – Using hydralazine without isosorbide dinitrate in heart failure with reduced ejection fraction is associated with harm (Class III recommendation) 3

Major Precautions and Relative Contraindications

Cardiovascular Considerations

• Mitral valvular disease – The "hyperdynamic" circulation caused by hydralazine may increase pulmonary artery pressure in these patients 2

• Advanced aortic stenosis – Hydralazine is contraindicated in this population 1

• Cerebrovascular disease – Use with caution in patients with cerebral vascular accidents due to unpredictable blood pressure effects 2

Acute Hypertensive Management Limitations

• Not first-line for most hypertensive emergencies – Blood pressure begins to decrease within 10-30 minutes with effects lasting 2-4 hours, but the unpredictability of response and prolonged duration of action make it undesirable as a first-line agent 1, 4, 5

• Bradycardia – Hydralazine can cause reflex tachycardia, which is problematic in patients with pre-existing bradycardia 4, 5

Renal and Metabolic Concerns

• Advanced renal damage – Should be used with caution, though hydralazine may actually improve renal blood flow and glomerular filtration rate in some patients 2

• Drug-induced lupus risk – Total daily doses should be less than 150 mg to avoid drug-induced systemic lupus erythematosus 3

• Acetylator status matters – Peripheral neuritis (paresthesia, numbness, tingling) has been observed, suggesting an antipyridoxine effect; pyridoxine should be added if symptoms develop 2

Monitoring Requirements

• Complete blood counts and antinuclear antibody titers are indicated before and periodically during prolonged therapy, even if the patient is asymptomatic 2

• Blood dyscrasias including reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura have been reported; therapy should be discontinued if these develop 2

• Careful observation for arthralgia, fever, chest pain, continued malaise, or other unexplained signs or symptoms requires repeat laboratory testing 2

Drug Interactions

• MAO inhibitors should be used with caution in patients receiving hydralazine 2

• Diazoxide – Profound hypotensive episodes may occur when diazoxide injection and hydralazine are used concomitantly; patients should be continuously observed for several hours 2

• Epinephrine – Hydralazine may reduce the pressor responses to epinephrine 2

Special Clinical Contexts

When Hydralazine IS Appropriate

• Eclampsia/preeclampsia – Hydralazine is specifically indicated for hypertensive emergencies in eclampsia, with demonstrated safety in obstetrical patients 4, 6

• African American patients with HFrEF – The combination of hydralazine and isosorbide dinitrate is recommended for self-identified African American patients with NYHA class III-IV heart failure who remain symptomatic despite optimal therapy 1, 3

• ACE inhibitor/ARB/ARNI intolerance in HFrEF – Hydralazine-isosorbide dinitrate combination serves as an alternative, though evidence is weaker 3

Common Pitfalls to Avoid

• Using hydralazine as first-line in non-obstetrical hypertensive emergencies – Nicardipine, labetalol, or clevidipine are preferred due to more predictable responses 4, 5

• Administering without food – Administration with food results in higher plasma levels 2

• Forgetting to add beta-blocker and diuretic in chronic use – This is essential to counteract reflex tachycardia and fluid retention 3

• Inadequate dosing in HFrEF – The mortality benefit in clinical trials was only achieved at target doses of 75 mg with 40 mg isosorbide dinitrate three times daily; lower doses have not demonstrated the same benefit 3