What are the safe antihypertensive (high blood pressure) medications for use in pregnancy?

From the Guidelines

Labetalol and nifedipine are the safest antihypertensive medications for use during pregnancy, as recommended by the most recent and highest quality study 1.

Key Considerations

• Methyldopa, labetalol, and nifedipine are considered safe for use in pregnancy, with labetalol and nifedipine being the preferred first-line agents due to their efficacy and safety profile 1.
• ACE inhibitors, ARBs, and direct renin inhibitors should be strictly avoided during pregnancy as they can cause fetal kidney damage, growth restriction, and even fetal death 1.
• Diuretics are generally not recommended as first-line therapy as they can reduce placental perfusion 1.
• Blood pressure should be maintained below 150/100 mmHg but not lowered too aggressively (avoid below 120/80 mmHg) to ensure adequate placental blood flow 1.

Medication Dosage

• Labetalol (100-400 mg twice daily) is an effective alternative that works as both an alpha and beta-blocker 1.
• Extended-release nifedipine (30-60 mg daily) is a calcium channel blocker that can be used when additional medication is needed 1.

Monitoring and Management

• Regular monitoring of blood pressure, fetal growth, and maternal symptoms is essential throughout pregnancy for women on antihypertensive therapy 1.
• Women with preeclampsia should be assessed in hospital when first diagnosed, and thereafter, some may be managed as outpatients once it is established that their condition is stable and they can be relied on to report problems and monitor their BP 1.

From the FDA Drug Label

Pregnancy Teratogenic Effects. Reproduction studies performed with methyldopa at oral doses up to 1000 mg/kg in mice, 200 mg/kg in rabbits and 100 mg/kg in rats revealed no evidence of harm to the fetus. Published reports of the use of methyldopa during all trimesters indicate that if this drug is used during pregnancy the possibility of fetal harm appears remote. In five studies, three of which were controlled, involving 332 pregnant hypertensive women, treatment with methyldopa was associated with an improved fetal outcome

Safe antihypertensive medications for use in pregnancy include:

• Methyldopa: The FDA drug label for methyldopa indicates that it can be used during pregnancy if clearly needed, and published reports suggest that the possibility of fetal harm appears remote 2.

Pregnancy:Teratogenic Effects: Pregnancy Category C: Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Labetalol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

• Labetalol: The FDA drug label for labetalol indicates that it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 3.

From the Research

Safe Antihypertensive Medications in Pregnancy

The following antihypertensive medications are considered safe for use in pregnancy:

• Labetalol
• Nifedipine
• Methyldopa
• Hydralazine

Efficacy and Safety of Antihypertensive Medications

Studies have shown that:

• Nifedipine is superior to hydralazine in treating severe hypertension in pregnancy 4
• Labetalol is effective in treating severe hypertension in pregnancy, but its efficacy compared to nifedipine is unclear 5, 4
• Methyldopa is a viable option for treating severe hypertension in pregnancy, but its use is less common compared to labetalol and nifedipine 5, 6
• Hydralazine is also used to treat severe hypertension in pregnancy, but its efficacy compared to nifedipine and labetalol is lower 4, 7

Pharmacokinetics of Antihypertensive Medications

The pharmacokinetics of antihypertensive medications during pregnancy are not well understood, with limited studies available:

• Methyldopa, labetalol, and nifedipine do not accumulate in the fetus 8
• Further studies are needed to understand the pharmacokinetics and pharmacodynamics of antihypertensive medications during pregnancy 8

Real-World Use of Antihypertensive Medications

In a real-world setting, antihypertensive medication use among patients with hypertensive disorders of pregnancy is common:

• Labetalol is the most frequently used medication, followed by nifedipine and hydralazine 6
• Methyldopa is used less frequently 6
• The choice of antihypertensive medication depends on the severity of the hypertensive disorder and other factors 6