Is acetazolamide (carbonic anhydrase inhibitor) safe to use in a pregnant woman at 26 weeks of gestation?

Acetazolamide Use in Pregnancy at 26 Weeks

Acetazolamide should not be used in a pregnant woman at 26 weeks of gestation unless there is imminent risk of vision loss due to idiopathic intracranial hypertension (IIH), as the potential risks to the fetus generally outweigh the benefits. 1

Safety Profile and FDA Classification

Acetazolamide is classified as FDA Pregnancy Category C, indicating that:

• Animal studies have shown adverse effects on the fetus
• There are no adequate well-controlled studies in pregnant women
• The drug should only be given if potential benefits justify potential risks to the fetus 2

Evidence on Risks and Benefits

Risks:

• Acetazolamide has been shown to be teratogenic in animal studies, causing limb defects in mice, rats, hamsters, and rabbits 2
• The manufacturer does not recommend its use during pregnancy 1
• Case reports have suggested possible association with congenital malformations including:
  • Ectrodactyly (absence of digits)
  • Syndactyly (fusion of digits)
  • Oligodontia (missing teeth) 3

Benefits and Limited Safety Data:

• Small observational studies suggest that acetazolamide use in pregnant women with IIH may not cause adverse pregnancy outcomes 4, 5
• A 2024 prospective case series reported 8 pregnancies with acetazolamide treatment without significant adverse outcomes 6

Management Algorithm for IIH in Pregnancy

1. First-line approaches (preferred at 26 weeks):

   • Weight management with appropriate gestational weight gain
   • Serial lumbar punctures for temporary relief if vision is threatened 1
   • Multidisciplinary management involving neurology, ophthalmology, and maternal-fetal medicine 1

2. When to consider acetazolamide:

   • Only if IIH is active with imminent risk of vision loss
   • After other measures have failed
   • After thorough risk-benefit discussion with the patient 1

3. If acetazolamide is deemed necessary:

   • Use lowest effective dose
   • Limit duration of treatment
   • Provide detailed informed consent regarding uncertain fetal risks
   • Increase monitoring of fetal development

Important Considerations

• About 49% of pregnant women with IIH experience worsening symptoms during pregnancy, particularly in the first and second trimesters 6
• Symptoms often improve in the later stages of pregnancy without specific treatment 6
• For hypertension management in pregnancy, safer alternatives include methyldopa, labetalol, and nifedipine 1, 7

Conclusion for Clinical Practice

For a 26-week pregnant woman with IIH, non-pharmacological approaches and serial lumbar punctures should be exhausted before considering acetazolamide. If vision is at imminent risk, the decision to use acetazolamide should involve a thorough discussion of the uncertain risk profile with the patient, acknowledging that while animal studies show teratogenic effects, limited human data has not conclusively demonstrated harm.