ETHOSUXIMIDE

Fetal Risk Summary

Ethosuximide is a succinimide anticonvulsant used in the treatment of petit mal epilepsy. The use of ethosuximide has been reported in 163 pregnancies (1,2,3,4,5,6,7,8,9,10 and 11). Because of the lack of specific information on the observed malformations, multiple drug therapies, and differences in study methodology, conclusions linking the use of ethosuximide with congenital defects are difficult. Spontaneous hemorrhage in the neonate following in utero exposure to ethosuximide has been reported (see also Phenytoin and Phenobarbital) (6). Abnormalities identified with ethosuximide use in 10 pregnancies include: Patent ductus arteriosus (8 cases) Cleft lip and/or palate (7 cases) Mongoloid facies, short neck, altered palmar crease and an accessory nipple (1 case) Hydrocephalus (1 case) Ethosuximide has a much lower teratogenic potential than the oxazolidinedione class of anticonvulsants (see also Trimethadione and Paramethadione) (11,12). The succinimide anticonvulsants should be considered the anticonvulsants of choice for the treatment of petit mal epilepsy during the 1st trimester.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 18 newborns had been exposed to ethosuximide during the 1st trimester (F. Rosa, personal communication, FDA, 1993). No major birth defects were observed (one expected).

Breast Feeding Summary

Ethosuximide freely enters the breast milk in concentrations similar to the maternal serum (13,14 and 15). Two reports measured similar milk:plasma ratios of 1.0 and 0.78 (13,14). No adverse effects on the nursing infant have been reported. The American Academy of Pediatrics considers ethosuximide to be compatible with breast feeding (16).

References

1. Speidel BD, Meadow SR. Maternal epilepsy and abnormalities of the fetus and newborn. Lancet 1972;2:839–43.
2. Fedrick J. Epilepsy and pregnancy: a report from the Oxford Record Linkage Study. Br Med J 1973;2:442–8.
3. Lowe CR. Congenital malformations among infants born to epileptic women. Lancet 1973;1:9–10.
4. Starreveld-Zimmerman AAE, van der Kolk WJ, Meinardi H, Elshve J. Are anticonvulsants teratogenic? Lancet 1973;2:48–9.
5. Kuenssberg EV, Knox JDE. Teratogenic effect of anticonvulsants. Lancet 1973;2:198.
6. Speidel BD, Meadow SR. Epilepsy, anticonvulsants and congenital malformations. Drugs 1974;8:354–65.
7. Janz D. The teratogenic risk of antiepileptic drugs. Epilepsia 1975;16:159–69.
8. Nakane Y, Okuma T, Takahashi R. Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: a report of a collaborative study group in Japan. Epilepsia 1980;21:663–80.
9. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977:358–9.
10. Dansky L, Andermann E, Andermann F. Major congenital malformations on the offspring of epileptic patients: genetic and environment risk factors. In Epilepsy, Pregnancy and the Child. Proceedings of a workshop held in Berlin, September 1980. New York:Raven Press, 1981.
11. Fabro S, Brown NA. Teratogenic potential of anticonvulsants. N Engl J Med 1979;300:1280–1.
12. The National Institute of Health. Anticonvulsants found to have teratogenic potential. JAMA 1981;241:36.
13. Koup JR, Rose JQ, Cohen ME. Ethosuximide pharmacokinetics in pregnant patient and her newborn. Epilepsia 1978;19:535.
14. Kaneko S, Sato T, Suzuki K. The levels of anticonvulsants in breast milk. Br J Clin Pharmacol 1979;7:624–6.
15. Horning MG, Stillwell WG, Nowlin J, Lertratanangkoon K, Stillwill RN, Hill RM. Identification and quantification of drugs and drug metabolites in human breast milk using GC-MS-COM methods. Mod Probl Paediatr 1975;15:73–9.
16. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137-50.