What are the guidelines for using pregabalin (lyrica) during pregnancy?

Pregabalin Use During Pregnancy

Pregabalin should be avoided during pregnancy due to potential risks to the fetus, and alternative treatments should be considered whenever possible. 1

Risk Assessment

Pregabalin carries significant concerns for use during pregnancy based on the FDA drug label and available evidence:

• The FDA label indicates there are no adequate and well-controlled studies with pregabalin in pregnant women 1
• Animal studies show increased incidences of fetal structural abnormalities including:
  • Skeletal malformations
  • Retarded ossification
  • Decreased fetal body weight
  • Premature fusion of jugal and nasal sutures 1

These effects were observed at doses that produced plasma pregabalin exposures (AUC) greater than or equal to 16 times human exposure at the maximum recommended dose of 600 mg/day 1.

Pregnancy Registry

Women who are taking pregabalin during pregnancy should be advised to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 1. This registry helps monitor pregnancy outcomes in women exposed to pregabalin during pregnancy.

Background Risk

The background risk of major birth defects in the U.S. general population is 2-4%, and miscarriage occurs in 15-20% of clinically recognized pregnancies 1. While some studies have not shown a clear signal of increased risk with pregabalin, most analyses have been underpowered 2.

Clinical Decision Algorithm

1. First consideration: Is the medication absolutely necessary?

   • Evaluate if the condition can be managed with non-pharmacological approaches
   • Consider if the condition poses greater risks to maternal health than potential medication risks

2. If medication is necessary:

   • Explore alternative medications with better established safety profiles in pregnancy
   • Consider the lowest effective dose if pregabalin must be used
   • Limit use to circumstances where the risk-benefit ratio is clearly favorable 2

3. Timing considerations:

   • First trimester exposure carries the highest risk for structural malformations
   • Later exposure may still affect fetal growth and development 1

Breastfeeding Considerations

Breastfeeding is not recommended during treatment with pregabalin due to:

• Pregabalin is detected in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma 1
• The estimated average daily infant dose from breast milk is approximately 7% of the maternal dose 1
• There is a potential risk of tumorigenicity with pregabalin exposure via breast milk 1

Monitoring Recommendations

If pregabalin must be used during pregnancy:

• Regular ultrasound monitoring to assess fetal growth and development
• Shared decision-making with the patient after thorough discussion of risks and benefits 2
• Consider consultation with maternal-fetal medicine specialists
• Monitor for neonatal complications after delivery

Conclusion

The evidence suggests caution with pregabalin use during pregnancy. While some studies have not shown definitive harm 2, animal data and FDA labeling indicate potential risks 1, 3. The decision to use pregabalin during pregnancy should involve careful consideration of risks versus benefits, with preference given to safer alternatives when available.