What are the side effects of methyldopa (alpha-2 adrenergic agonist) in pregnancy?

Side Effects of Methyldopa in Pregnancy

Methyldopa is generally considered safe during pregnancy, but it has several important side effects that clinicians should monitor, including drowsiness, dizziness, fatigue, and risk of postnatal depression when used postpartum.

Common Side Effects

• Lack of energy and dizziness are the most common side effects, affecting approximately 14.5% of pregnant women taking methyldopa 1
• Drowsiness, headache, and postural hypotension have been reported in pregnant patients receiving methyldopa 2
• Peripheral edema, dry mouth, and lightheadedness can occur and may affect medication adherence 3
• Mood disturbances can occur during treatment, with methyldopa specifically being contraindicated in the postpartum period due to increased risk of postnatal depression 3

Serious Adverse Effects

• Acute reactive hepatitis is a rare but serious side effect of methyldopa that can occur during pregnancy 4, 5

  • Monitoring of serum aminotransferases is recommended during methyldopa therapy in pregnancy 4
  • Elevated maternal serum alpha-fetoprotein may be a sign of methyldopa-induced maternal hepatitis 5

• As pregnancy advances, increasing doses of methyldopa may be needed to maintain blood pressure control, which can increase the risk of side effects 1

Fetal and Neonatal Considerations

• Long-term follow-up studies of children born to methyldopa-treated pregnant women have failed to uncover significant adverse effects on development 6
• At 4 years of age, developmental delay commonly seen in children born to hypertensive mothers was less evident in those whose mothers were treated with methyldopa during pregnancy 6
• At age 7.5 years, developmental scores and intelligence indices showed no significant differences in children of treated or untreated hypertensive women 6

Comparison with Other Antihypertensives

• Labetalol has been associated with higher rates of small for gestational age (SGA), neonatal hypotension, and neonatal hyperbilirubinemia compared to methyldopa 7
• Beta-blockers and calcium channel blockers are more effective than methyldopa for the prevention of severe hypertension in pregnancy 3
• Nifedipine and labetalol are currently preferred as first-line agents in high-income countries due to better tolerability and efficacy 8, 9

Dosing Considerations

• The standard dose of methyldopa is 750 mg to 4 g per day in three or four divided doses 3
• As pregnancy advances, increasing daily doses of methyldopa may be needed to maintain blood pressure control 1

Important Precautions

• Methyldopa should be avoided in the postpartum period due to increased risk of postnatal depression 3, 10
• Methyldopa appears in breast milk, so caution should be exercised when given to nursing women 6
• Regular monitoring of liver function is recommended during methyldopa therapy in pregnancy 4, 5

Clinical Decision Algorithm

1. Consider methyldopa as a potential first-line agent for hypertension in pregnancy, particularly when other agents are contraindicated or unavailable 3
2. Start with lower doses (250-500 mg twice daily) and titrate as needed 3
3. Monitor for common side effects like drowsiness, dizziness, and fatigue 1, 2
4. Perform regular liver function tests to detect potential hepatotoxicity 4, 5
5. Consider switching to alternative agents if side effects are intolerable 1
6. Discontinue methyldopa after delivery and switch to alternative agents for postpartum hypertension management 3, 10