What is the recommended use and dosage of Metildopa (Methyldopa) for treating hypertension?

Methyldopa for Hypertension Management

Methyldopa is primarily recommended as a first-line antihypertensive medication for treating hypertension during pregnancy, but is rarely used in non-pregnant adults due to its side effect profile and the availability of more effective alternatives. 1

Use in Pregnancy

Indications and Recommendations

• Methyldopa is a preferred first-line agent for hypertension during pregnancy due to its established safety profile from long-term follow-up studies 1
• Women with pre-existing hypertension who become pregnant should be transitioned to methyldopa, nifedipine, and/or labetalol during pregnancy 1
• ACE inhibitors, ARBs, and direct renin inhibitors are contraindicated during pregnancy due to potential fetal harm 1

Dosing in Pregnancy

• Initial dose: 250 mg/day 2
• Typical maintenance dose: 500-2000 mg/day, divided into 2-3 doses
• Dose should be titrated weekly based on blood pressure response 2
• Average effective dose in clinical studies: 685 mg/day 2
• As pregnancy advances, increasing daily doses may be needed 3

Treatment Thresholds in Pregnancy

• Initiate treatment when:
  • BP ≥140/90 mmHg in women with gestational hypertension (with/without proteinuria), pre-existing hypertension with superimposed gestational hypertension, or hypertension with subclinical organ damage 1
  • BP ≥150/95 mmHg in other pregnant women 1
• BP ≥170/110 mmHg is considered an emergency requiring hospitalization 1

Efficacy and Safety in Pregnancy

• Controls blood pressure effectively in approximately 97% of pregnant women 2
• Reduces risk of severe hypertension by approximately 50% compared to placebo 4
• No significant adverse effects on labor, delivery, or newborn outcomes 2
• Long-term follow-up shows no unfavorable consequences on child development up to 3 years of age 2

Important Caution

• Methyldopa should be avoided post-partum due to the risk of post-natal depression 1

Use in Non-Pregnant Adults

Methyldopa is rarely used as a first-line agent for non-pregnant adults with hypertension due to:

• Significant side effects (sedation, fatigue, dizziness)
• Need for multiple daily dosing
• Availability of more effective and better-tolerated alternatives

Side Effects and Monitoring

Common Side Effects

• Lack of energy/fatigue (most common) 3
• Dizziness 3
• Sedation
• Dry mouth
• Nasal congestion

Monitoring

• Regular blood pressure measurements
• Periodic laboratory evaluation including:
  • Complete blood count
  • Liver function tests
  • Renal function tests

Special Considerations

Pregnancy Planning

• Women planning pregnancy should be transitioned to methyldopa or other pregnancy-safe antihypertensives prior to conception 1
• ACE inhibitors and ARBs should be discontinued prior to conception or as soon as pregnancy is confirmed 1

Breastfeeding

• Alternative antihypertensives are preferred during breastfeeding due to methyldopa's association with post-partum depression 1

Dosage Adjustments

• Dose increases may be needed as pregnancy progresses 3
• Renal impairment may require dose reduction

Algorithm for Hypertension Management in Pregnancy

1. Confirm hypertension diagnosis (BP ≥140/90 mmHg on multiple occasions)
2. Assess severity:
   • Mild to moderate: SBP 140-169 mmHg or DBP 90-109 mmHg
   • Severe: SBP ≥170 mmHg or DBP ≥110 mmHg
3. For mild to moderate hypertension:
   • Start methyldopa 250 mg twice daily
   • Titrate weekly based on BP response
   • Maximum dose: 3 g/day in 2-4 divided doses
4. For severe hypertension (emergency):
   • Hospitalize patient
   • Consider IV labetalol, oral methyldopa, or oral nifedipine 1
5. Post-partum:
   • Discontinue methyldopa due to depression risk
   • Transition to alternative antihypertensive if needed

Methyldopa remains a cornerstone of hypertension management during pregnancy due to its proven safety record, despite having been largely replaced by newer agents in the general hypertensive population.