This drug should only be given during pregnancy when there are no alternatives and benefit outweighs risk

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

Risk Summary: There are no adequate and well-controlled studies in pregnant women; animal reproduction studies have shown increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity.

Comment:
-Patients should be advised of the potential risk to a fetus.
-Women of childbearing potential should be encouraged to use reliable contraception during treatment.
-Physicians should encourage pregnant patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry; toll free 1-888-233-2334 or http://www.aedpregnancyregistry.org/

Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity including skeletal malformations, retarded ossification, and decreased fetal body weight have been observed in rat and rabbit offspring receiving this drug at 18 times or greater the maximum recommended dose during organogenesis. Lethality, growth retardation, and nervous and reproductive system functional impairment have been observed in rat offspring receiving this drug during gestation and lactation. Rat offspring tested as adults, showed neurobehavioral abnormalities (decreased auditory startle responding). There are no controlled data in human pregnancy.

A clinical trial in healthy male subjects found that 3 months of taking this drug at 600 mg/day did not effect sperm motility. Adverse reproductive and developmental effects have been observed in male rats.

To provide information regarding the effects of in utero exposure to this drug, physicians are advised to recommend that pregnant patients enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

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.

See references

Limited data have shown the estimated average daily infant dose expected from breast milk is about 7% of the maternal weight adjusted dose. An unexpectedly high incidence of hemangiosarcoma was observed in standard preclinical in vivo lifetime carcinogenicity studies in 2 different strains of mice. The clinical significance of this finding is unknown.

Breastfeeding is not recommended

Excreted into human milk: Yes

Comment:
-Because of the potential risk of tumorigenicity, breastfeeding is not recommended during treatment.

See references