Animal studies have shown developmental toxicity at doses estimated to be lower than those used clinically. Pregnant rats administered 3 doses (5, 10 or 20 mg/kg) during the latter part of gestation had increased offspring mortality (including stillbirths) at all doses. The lowest effect dose for peri/postnatal developmental toxicity was less than the human dose of 400 mg/day on mg/m2 basis. Maternal toxicity was observed at the 2 highest doses. Studies in rats have shown a decrease in folic acid during pregnancy, and since this drug is a weak inhibitor of dihydrofolate reductase, there is a theoretical risk of malformation due to folate deficiency. Anti-epileptic drugs should generally be continued during pregnancy with the goal of monotherapy at the lowest effective dose, however, the risk to the mother and fetus of uncontrolled epilepsy should be considered when deciding on treatment options. Data from several international pregnancy registries have not shown an increased risk for malformations overall. The frequency of major congenital malformations was similar to estimates from the general population. The North American Antiepileptic Drug Pregnancy (NAAED) Registry has reported an increased risk of isolated oral clefts, although this finding has not been observed in other large international pregnancy registries. Several meta-analyses have not reported an increased risk of major congenital malformations following lamotrigine exposure in pregnancy compared with healthy and disease-matched controls. No patterns of specific malformation types were observed. As with other antiepileptic drugs, decreased lamotrigine concentrations have been reported during pregnancy with a return to pre-pregnancy concentrations after delivery. Appropriate clinical management should include monitoring drug concentrations and adjusting doses as indicated. There are no adequate and well-controlled studies in pregnant women.

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.

Benefit should outweigh risk

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

Risk Summary: Several prospective pregnancy exposure registries and epidemiological studies have not detected an increased frequency of major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared with the general population; animal studies have shown developmental toxicities at doses administered clinically.

Comments:
-Women with epilepsy who are planning to become pregnant should receive pre-pregnancy counseling; folate supplementation should be considered before conception and for the first 12 weeks of pregnancy.
-Abrupt discontinuation of anti-epileptic therapy during pregnancy is not advised as this may lead to breakthrough seizures in mother and fetus.
-Physiologic changes during pregnancy may affect drug concentrations and/or therapeutic effect; dose adjustments may be necessary to maintain clinical response.
-Women should be advised to notify their healthcare provider if they plan to start or stop oral contraceptive use or other female hormonal preparations as this may significantly affect lamotrigine drug concentrations.
-A pregnancy registry is available to provide information on the effects of in utero exposure; pregnant patients should be encouraged to enroll: North American AED Pregnancy Registry: US toll free number: 1-888-233-2334; Website: http://www.aedpregnancyregistry.org/

See references

Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-Adverse reactions have occasionally been reported in breastfed babies, but long-term exposure does not appear to affect infant growth and development.
-Breastfed infants should be carefully monitored for side effects; serum levels may be measured to rule out toxicity.
-If infant rash occurs, breastfeeding should be discontinued until cause can be established.

Drug concentrations in human milk may be as high as 50% of the maternal serum levels. Neonates are at risk for high plasma levels due to plasma protein binding being relatively low and decreased ability to clear drug (immaturity of glucuronidation capacity). Additionally, similar to other antiepileptic drugs, the maternal dose should generally be reduced after delivery to the pre-pregnancy dosage, and failure to reduce dose may lead to higher milk concentrations. Apnea, rash, drowsiness, and poor sucking have been reported in breastfed infants. If an adverse event occurs, a serum level can be measured to rule out toxicity. Consider monitoring platelet counts and liver function. Breastfeeding should be discontinued in infants with lamotrigine toxicity

See references