Benefit should outweigh risk

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

Risk Summary: Cases of birth defects have been reported with this drug; however, assigning causality to these reports is not possible as the epileptic condition itself may be a more important factor leading to birth defects. The risk of a mother with epilepsy giving birth to a baby with birth defects is about 3 times that of the general population.

Comments:
-Women on antiepileptic drugs (AEDs) should receive pre-pregnancy counseling with regard to the risk of fetal abnormalities.
-Discontinuing anticonvulsant drugs is not without risks as the possibility of precipitating seizures and associated hypoxia pose risks to the developing embryo/fetus.
-Information regarding the safety of antiepileptic drugs is being collected and shared through the North American Antiepileptic Drug Pregnancy Registry (NAAED); this may be accessed at http://www.aedpregnancyregistry.org/ or by calling 1-888-233-2334

This drug crosses the placenta. Animal studies have not been reported. There are no controlled data in human pregnancy. An increased risk of congenital malformations has been associated with use of anticonvulsants (including ethosuximide) in women with epilepsy during pregnancy. Abnormalities reported have included spontaneous hemorrhage in the neonate, patent ductus arteriosus, cleft lip and/or palate, mongoloid facies, short neck, altered palmar crease, an accessory nipple, and hydrocephalus. Anomalies associated with anticonvulsant use in pregnancy have included neural tube defects, cleft lips, cleft palates, cardiac defects, and microcephaly. Anticonvulsant drugs should generally be continued in patients who require treatment to prevent major seizures due to the strong possibility of precipitating status epilepticus with attendant hypoxia with discontinuation. In individual cases where the severity and frequency of the seizure disorder is such that the stopping the anticonvulsant does not pose a serious threat to the patient, discontinuation may be considered prior to and during pregnancy, although it cannot be said that even minor seizures do not pose some hazard. Folic acid supplementation (5 mg) is recommended starting 4 weeks prior to and continue for 12 weeks after conception.

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.

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In published reports of anticonvulsant use while breastfeeding, it is often difficult to determine the relationship of the maternal dose to breastmilk concentrations as anticonvulsants are often used in combination. One authority states that no adverse effects have been attributed solely to this drug, while another authority reports sedation, poor suckling and irritability in breastfed infants. It is estimated that average concentrations in breastmilk may be 50% to 60% of the maternal weight-adjusted dose and infant plasma levels 25% to 30% of the maternal levels. In 2001, the America Academy of Pediatrics considered this drug compatible with breastfeeding.

Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-Monitor for infant drowsiness, adequate weight gain, and developmental milestones.
-If there is a concern with toxicity, infant serum level can be measured.
-Some authorities advise against breastfeeding during maternal use.

See references