Animal models have revealed evidence of teratogenicity, decreased number of pregnancies, lower surviving offspring numbers, and long-term changes in cellular immune responses, brain neurochemistry, and behavior. Cleft palate, central nervous system malformations/encephalopathy, and permanent functional disturbances occurred in animal models at maternally toxic doses. Neonatal flaccidity, respiratory/feeding difficulties, and hypothermia have been reported in humans. Use during the first and third trimesters may be associated with an increased risk of teratogenicity and withdrawal symptoms in the newborn, respectively.

Human data and animal models have revealed evidence of possible genotoxicity. Aneuploidy was induced in men at doses of 10 mg/m2/day.

To monitor maternal-fetal outcome of pregnant women exposed to antiepileptic drugs, an Antiepileptic Drug (AED) Pregnancy Registry has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: http://www.aedpregnancyregistry.org/

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. 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 not be used during pregnancy unless the benefit outweighs the risk to the fetus.

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

Risk Summary: An increase in congenital malformations has been suggested with minor tranquilizer use, especially during the first trimester.

Comments:
-If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
-Neonates exposed to single high doses during labor and delivery should be monitored for irregularities in fetal heart rate, hypotonia, poor sucking, hypothermia, and moderate respiratory depression.
-If used during pregnancy, monitor the newborn for acute withdrawal syndrome symptoms during the postnatal period.
-A pregnancy exposure registry is available.

See references

The milk to plasma ratio ranged between 0.2 and 2.7. This drug may accumulate in breastfed infants, especially with repeated dosing or with acute use of rectal gel formulations.

Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Yes

Comments:
-Sedation, weight loss, and feeding difficulties have occurred in nursing infants.
-The American Academy of Pediatrics considers this agent a drug for which the effect on nursing infants is unknown but may be of concern if exposure is prolonged.
-The WHO considers this drug compatible with breastfeeding if given in a single dose; repeated doses should be avoided, if possible. Breastfed infants should be monitored for drowsiness. Short-acting benzodiazepines (e.g., oxazepam, lorazepam) may be preferred.

See references