Developmental toxicities have been observed in pregnant rats receiving this drug during pregnancy including increased perinatal mortality and decreased body weights. In rats and rabbits administered this drug during the period of organogenesis, no effects on fetal structure were observed however, doses were limited by maternal toxicity and embryofetal death in rats. Administration to rats during the neonatal and juvenile periods of development (generally thought to correspond to late pregnancy in humans in terms of brain development) resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). In vitro data has shown this drug interferes with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential adverse effects on CNS development related to this interference cannot be ruled out. There are no controlled data in human pregnancy.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

Use is not recommended unless clearly needed

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned

Risk Summary: There are no adequate data on the developmental risks associated with use in pregnant women; developmental toxicity (e.g., increased embryofetal and perinatal mortality, growth deficit) has been observed in animal studies.

Comments:
-There are risks related to epilepsy and antiepileptic products; effective antiepileptic therapy should not be interrupted since aggravation of the illness is detrimental to both mother and fetus.
-Pregnancy Registries:
--The North American Antiepileptic Drug (NAAED) visit http://www.aedpregnancyregistry.org or call 1-888-233-2334.
--Australian Pregnancy Register for Women on Antiepileptic Medication with Epilepsy and Allied Conditions, call 1800 069 722

See references

Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-There is limited data available on use of this drug during lactation; published reports have reported this drug is excreted in breastmilk.
-Some authorities advise against maternal use while breastfeeding as a precautionary measure.

Limited data indicates low levels of this drug in human milk following a maternal dose of 200 mg/day. As with most antiepileptic drugs (AED), the relationship of maternal dose to breastmilk concentration may be variable due to need to take a combination of AEDs. Maternal weight-adjusted dosages of 1.8% and 22% have been reported. Three infants who were breastfed for 7 to 9 months while their mothers received dosages up to 400 mg/day, developed normally. Until more data are available, this drug should be used with careful monitoring, especially while nursing a newborn or preterm infant.

See references