-This drug has caused serious birth defects when administered during pregnancy. There have been reports of congenital abnormalities including congenital heart disease, cleft palate, and conditions associated with maternal folate deficiency, including spina bifida, microencephaly, and anencephaly.

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 D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

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.

This drug should be used during pregnancy only if the benefit outweighs the risk.

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Risk Summary: Reports suggest an association between the use of anticonvulsant drugs by pregnant women and an elevated incidence of birth defects in children born to these women. Data are more extensive with respect to diphenylhydantoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs.

Comments:
-The risk of a mother taking antiepileptic drugs (AEDs) giving birth to a baby with an abnormality is about 3 times that of the general population.
-The risk of having an abnormal child because of antiepileptic medication is outweighed by the dangers to the mother and fetus of uncontrolled epilepsy; therefore, it is recommended that:
1) Women taking AEDs should receive prepregnancy counseling regarding the risk of fetal abnormalities.
2) AEDs should be continued during pregnancy and monotherapy should be used if possible at the lowest effective dose as risk of abnormality is greater in women taking combined medication.
3) Folic acid supplementation (5 mg) should be started 4 weeks prior to and continued for 12 weeks after conception.
4) Specialist prenatal diagnosis including detailed mid-trimester ultrasound should be offered.
-Anticonvulsant therapy in pregnancy has occasionally been associated with coagulation disorders in the neonates; therefore, pregnant patients should be given Vitamin K1 through the last month of pregnancy up to the time of delivery.
-Withdrawal symptoms may occur in newborns whose mothers have received this drug during late pregnancy.

See references

Caution is recommended.

Excreted into human milk: Yes (in substantial amounts)

Comments:
-Some experts believe if this drug is required by the mother, it is not a reason to discontinue breastfeeding; however, the infant should be monitored for drowsiness, weight gain, and developmental milestones, especially in younger, exclusively breastfed infants, and when using combinations of anticonvulsant drugs.
-Measurement of infant serum levels of this drug may help rule out toxicity.

See references