What is the use of Hydralazine (Apresoline)?

From the Guidelines

Hydralazine should be used with caution and is not the first-line treatment for hypertensive emergencies, especially in pregnancy, due to its association with more perinatal adverse effects and unpredictability of response, as noted in the 2020 European Heart Journal study 1.

Key Points

• Hydralazine is a direct vasodilator used to treat high blood pressure (hypertension) by relaxing and dilating blood vessels, improving blood flow and lowering blood pressure.
• The typical starting dose is 10-25 mg orally four times daily, which can be gradually increased to 50-100 mg four times daily if needed.
• For hypertensive emergencies, it can be administered intravenously at 10-20 mg doses, as outlined in the 2018 Journal of the American College of Cardiology study 1.
• Hydralazine is often used in combination with other antihypertensive medications, particularly beta-blockers or diuretics, as it can cause reflex tachycardia when used alone.
• Common side effects include headache, dizziness, flushing, palpitations, and nasal congestion.
• Long-term use requires monitoring for potential development of drug-induced lupus-like syndrome, particularly in slow acetylators.
• Patients should take hydralazine with meals to enhance absorption and report any unusual symptoms like joint pain, fever, or rash, which could indicate an adverse reaction.

Considerations in Pregnancy

• Hydralazine is associated with more perinatal adverse effects than other drugs, such as labetalol, and its use is no longer recommended as the first-line treatment for severe hypertension in pregnancy, as stated in the 2011 European Heart Journal study 1.
• The 2020 European Heart Journal study 1 recommends considering alternative treatments, such as labetalol or nifedipine, for hypertensive emergencies in pregnancy.
• Sodium nitroprusside should be used with caution and only as a last resort due to the risk of fetal cyanide poisoning and increased intracranial pressure in the pregnant woman.

Dosage and Administration

• The initial dose of hydralazine for hypertensive emergencies is 10 mg via slow IV infusion, with repeat doses every 4-6 hours as needed, as outlined in the 2018 Journal of the American College of Cardiology study 1.
• The maximum initial dose is 20 mg, and the drug's effect begins to decrease within 10-30 minutes, lasting 2-4 hours.
• Hydralazine can be administered orally or intravenously, depending on the severity of the hypertensive emergency and the patient's clinical status.

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. In hypertensive patients with normal kidneys who are treated with hydralazine, there is evidence of increased renal blood flow and a maintenance of glomerular filtration rate. However, as with any antihypertensive agent, hydralazine should be used with caution in patients with advanced renal damage.

The use of hydralazine requires caution in patients with:

• Suspected coronary artery disease due to the risk of myocardial infarction and anginal attacks
• Cardiovascular inadequacies that may be accentuated by the "hyperdynamic" circulation caused by hydralazine
• Advanced renal damage, as with any antihypertensive agent 2

From the Research

Hydralazine Overview

• Hydralazine is a direct-acting vasodilator used to treat hypertension, including severe hypertension in pregnancy 3, 4, 5.
• It has been used since the 1950s, but its use has largely been replaced by newer antihypertensive drugs with more acceptable tolerability profiles 6.

Efficacy and Safety

• Studies have compared the efficacy and safety of hydralazine with other antihypertensive agents, including nifedipine and labetalol 3, 4, 5.
• A systematic review and network meta-analysis found that nifedipine was superior to hydralazine for successful treatment of severe hypertension in pregnancy, but not associated with an increased risk for caesarean delivery or maternal side effects 3.
• Another systematic review and meta-analysis found that nifedipine had a lower risk of persistent hypertension compared to hydralazine and labetalol 4.
• A meta-analysis of randomized controlled trials found that hydralazine was associated with more maternal hypotension, caesarean sections, placental abruption, and adverse effects on fetal heart rate compared to other antihypertensive agents 5.

Adverse Effects

• Hydralazine has been reported to cause adverse effects, including reflex tachycardia, hemolytic anemia, vasculitis, glomerulonephritis, and a lupus-like syndrome 6.
• Studies have also reported side effects, such as flushing and headaches, in patients taking nifedipine in combination with hydralazine 7.

Clinical Use

• Hydralazine is still widely used in developing countries due to its lower cost, but its use is not recommended as first-line treatment for severe hypertension in pregnancy 5.
• Nifedipine may be preferred as the first-line agent for treating severe hypertension in pregnancy, based on its efficacy and safety profile 3, 4.