Is hydralazine (antihypertensive medication) safe during pregnancy?

From the Guidelines

Hydralazine should not be considered a first-line treatment for hypertension in pregnancy due to its association with more perinatal adverse effects compared to other drugs, as stated in the 2007 guidelines for the management of arterial hypertension 1. However, according to more recent guidelines, hydralazine may still be considered in the acute management of hypertension in pregnancy or severe preeclampsia 1. The most recent and highest quality study, published in 2020, suggests that intravenous hydralazine is still widely used, particularly in North America, despite being associated with a number of adverse effects, including a greater risk of caesarean section, more frequent placental abruption, more maternal oliguria, and fetal tachycardia 1. Some key points to consider when using hydralazine in pregnancy include:

• Typical dosing starts at 10-25 mg orally every 6-8 hours, which can be gradually increased as needed to a maximum of 300 mg daily.
• For acute blood pressure management, it can be given intravenously at 5-10 mg doses.
• Hydralazine works by directly relaxing vascular smooth muscle, leading to vasodilation and blood pressure reduction.
• The medication crosses the placenta but has not been associated with birth defects or adverse fetal outcomes when used appropriately.
• Common side effects include headache, palpitations, and fluid retention, which should be monitored.
• Hydralazine should only be used under close medical supervision during pregnancy, with regular monitoring of blood pressure and fetal well-being.
• The benefits of treating maternal hypertension typically outweigh the potential risks, as uncontrolled high blood pressure during pregnancy can lead to serious complications for both mother and baby.

From the FDA Drug Label

Animal studies indicate that hydrALAZINE is teratogenic in mice at 20 to 30 times the maximum daily human dose of 200 to 300 mg and possibly in rabbits at 10 to 15 times the maximum daily human dose, but that it is nonteratogenic in rats. There are no adequate and well-controlled studies in pregnant women. Although clinical experience does not include any positive evidence of adverse effects on the human fetus, hydrALAZINE should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus.

Hydralazine is not considered safe for pregnancy due to potential teratogenic effects. The decision to use hydralazine during pregnancy should be made with caution, weighing the potential risk to the fetus against the expected benefit to the mother 2. Key considerations include:

• Lack of adequate and well-controlled studies in pregnant women
• Teratogenic effects observed in animal studies
• Potential risk to the fetus that must be justified by the expected benefit to the mother

From the Research

Safety of Hydralazine in Pregnancy

• Hydralazine is considered safe for use during pregnancy, as stated in a study published in 1981 3, which recommends its use when needed, with proper monitoring.
• A 2022 systematic review and meta-analysis found that hydralazine can be used to treat severe hypertension in pregnancy, although it may have a higher risk of persistent hypertension compared to nifedipine 4.
• Another study published in 2014 found that oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy, with hydralazine being used as a comparator 5.
• A 2022 network meta-analysis compared the efficacy and safety of intravenous hydralazine, oral nifedipine, and intravenous labetalol with different dosage regimens in the treatment of severe hypertension during pregnancy, and found that nifedipine 60,90 mg showed superior effectiveness than intravenous hydralazine 15,25 mg in the successful treatment rate of severe hypertension during pregnancy 6.
• A 2023 retrospective cohort study found that hydralazine was used in 20.5% of patients with hypertensive disorders of pregnancy, with labetalol and nifedipine being the most frequently used medications 7.

Comparison with Other Medications

• Hydralazine has been compared to other antihypertensive medications, such as nifedipine and labetalol, in terms of efficacy and safety in pregnancy 4, 5, 6.
• The studies suggest that while hydralazine can be used to treat severe hypertension in pregnancy, it may not be the first-line agent of choice, with nifedipine being preferred in some cases 4, 6.

Usage in Clinical Practice

• Hydralazine is used in clinical practice to treat severe hypertension in pregnancy, although its usage may vary depending on the specific clinical scenario and patient population 7.
• The choice of antihypertensive medication in pregnancy should be individualized, taking into account the severity of hypertension, the presence of other medical conditions, and the potential risks and benefits of each medication 3, 4, 5, 6, 7.