What are the first-line medications and dosing for managing hypertension in pregnancy?

First-Line Medications and Dosing for Managing Hypertension in Pregnancy

The first-line medications for managing hypertension in pregnancy are oral methyldopa, labetalol, and extended-release nifedipine, with the goal of maintaining blood pressure between 110-140/85 mmHg to reduce maternal complications while avoiding fetal compromise. 1, 2

Classification of Hypertension in Pregnancy

• Hypertension in pregnancy is classified as: chronic hypertension (present before 20 weeks), gestational hypertension (arising after 20 weeks without proteinuria), or preeclampsia (hypertension with proteinuria after 20 weeks) 1
• Hypertension is diagnosed when systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, measured in the office or hospital; it should be confirmed on 2 separate occasions or at least 15 minutes apart in severe hypertension 3

Treatment Thresholds

• Blood pressure consistently at or above 140/90 mmHg should be treated, aiming for a target diastolic BP of 85 mmHg and systolic BP of 110-140 mmHg 3, 1
• The European Heart Journal recommends initiating drug treatment when systolic BP is ≥140 mmHg or diastolic BP ≥90 mmHg in women with gestational hypertension, pre-existing hypertension with superimposed gestational hypertension, or hypertension with subclinical organ damage 2
• Severe hypertension (BP >160/110 mmHg) requires urgent treatment in a monitored setting 3

First-Line Medications for Non-Severe Hypertension

Methyldopa

• Dosage: Starting dose 250 mg orally 2-3 times daily, maximum 3 g/day 1, 2
• Methyldopa has fallen out of favor in high-income countries due to its side effect profile but is still commonly used in low- and middle-income countries 2
• Should be switched to an alternative medication in the postpartum period 3

Labetalol

• Dosage: Starting dose 100-200 mg orally twice daily, maximum 2.4 g/day 1, 2
• May need to be adjusted to three or four times daily due to accelerated drug metabolism during pregnancy 2
• Contraindicated in patients with history of reactive airway disease 2

Extended-Release Nifedipine

• Dosage: Starting dose 30-60 mg orally once daily, maximum 120 mg/day 4, 1
• Offers the advantage of once-daily dosing, which improves patient adherence during pregnancy 4, 2
• Only the long-acting formulation should be used as maintenance therapy during pregnancy 4, 2

Management of Severe Hypertension (>160/110 mmHg)

• Requires urgent treatment in a monitored setting 3
• First-line medications include:
  • Oral nifedipine: 10 mg (short-acting for acute treatment only) 3
  • IV labetalol: Initial dose 20 mg, followed by 40 mg, then 80 mg every 10-15 minutes as needed (maximum 300 mg) 3, 1
  • IV hydralazine: Initial dose 5 mg, followed by 5-10 mg every 20-30 minutes as needed 3
• Oral labetalol may be used if these treatments are unavailable 3

Medications to Avoid in Pregnancy

• ACE inhibitors, angiotensin receptor blockers (ARBs), direct renin inhibitors, and mineralocorticoid receptor antagonists are contraindicated throughout pregnancy due to fetotoxicity 4, 1, 2
• Atenolol should be avoided due to risk of fetal growth restriction 2
• Diuretics are controversial in pregnancy and should only be used in combination with other drugs 2

Special Considerations

• Avoid sublingual or intravenous nifedipine as rapid and excessive BP reduction has caused myocardial infarction or fetal distress 2
• Be aware that myocardial depression may occur with combination of calcium channel blockers and intravenous magnesium 2
• Short-acting nifedipine should be reserved only for rapid treatment of severe hypertension, not for maintenance therapy 4
• Common side effects of nifedipine include headaches, tachycardia, or edema, which may require switching to an alternative agent like labetalol 4

Postpartum Management

• First-line agents for postpartum hypertension include nifedipine, amlodipine, enalapril, and labetalol 4, 2
• Methyldopa should be switched to an alternative in the postpartum period 3
• Blood pressure should be monitored closely after delivery, with recordings shortly after birth and again within 6 hours 1

Comparative Efficacy

• A systematic review and network meta-analysis found nifedipine to be superior to hydralazine for successful treatment of severe hypertension in pregnancy 5
• A randomized controlled trial comparing oral antihypertensives found that nifedipine resulted in a greater frequency of blood pressure control than methyldopa 6
• A post-hoc analysis of the CHAP trial found no significant difference in maternal or neonatal outcomes between patients taking labetalol compared with nifedipine 4, 2