Trimethadione in pregnancy and breastfeeding

Trimethadione]]>

Risk Factor: D
Class: Central nervous system drugs/ Anticonvulsants

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References

Fetal Risk Summary

Trimethadione is an oxazolidinedione anticonvulsant used in the treatment of petit mal epilepsy. Several case histories have suggested a phenotype for a fetal trimethadione syndrome of congenital malformations (1,2,3,4,5,6 and 7). The use of trimethadione in nine families was associated with a 69% incidence of congenital defects25 malformed children from 36 pregnancies. Three of these families reported five normal births after the anticonvulsant medication was stopped (1,4). The incidence of fetal loss in these families was also increased compared with that seen in the general epileptic population. Because trimethadione has demonstrated both clinical and experimental fetal risk greater than other anticonvulsants, its use should be abandoned in favor of other medications used in the treatment of petit mal epilepsy (8,9,10 and 11).

Features of Fetal Trimethadione Syndrome (25 cases) Feature No.* % Feature No.* % Growth: Cardiac: Prenatal deficiency 8

  • Septal defect 5
  • Postnatal deficiency 6
  • Not stated 4
  • Performance (19 cases): Patent ductus 4
  • Mental retardation 7
  • arteriosus Vision (myopia) 5
  • Limb: Speech disorder 4
  • Simian crease 7
  • Impaired hearing 2 8 Malformed hand 2 8 Craniofacial: Club foot 1 4 Low-set, cupped, or
  • 72 Genitourinary: abnormal ears Kidney and ureter 5
  • High-arched or cleft
  • 64 abnormalities lip and/or palate Inguinal hernia(s) 3
  • Microcephaly 6
  • Hypospadias 3
  • Irregular teeth 4 6 Ambiguous genitalia 2 8 Feature No.* % Feature No.* % Epicanthic folds 3
  • Clitoral hypertrophy 1 4 Broad nasal bridge 3
  • Imperforate anus 1 4 Strabismus 3
  • Other: Low hairline 2 8 Tracheoesophageal 3
  • Facial hemangiomata 1 4 fistula Unusual facies 3
  • Esophageal 2 8 (details not given) atresia *Not mutually exclusive.

    Breast Feeding Summary

    No data are available.

    References

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    1. German J, Kowan A, Ehlers KH. Trimethadione and human teratogenesis. Teratology 1970;3:34962.
    2. Zackae EH, Mellman WJ, Neiderer B, Hanson JW. The fetal trimethadione syndrome. J Pediatr 1975;87:2804.
    3. Nichols MM. Fetal anomalies following maternal trimethadione ingestion. J Pediatr 1973;82:8856.
    4. Feldman GL, Weaver DD, Lourien EW. The fetal trimethadione syndrome. Report of an additional family and further delineation of this syndrome. Am J Dis Child 1977;131:138992.
    5. Rosen RC, Lightner ES. Phenotypic malformations in association with maternal trimethadione therapy. J Pediatr 1978;92:2404.
    6. Zellweger H. Anticonvulsants during pregnancy: a danger to the developing fetus? Clin Pediatr 1974;13:33845.
    7. Rischbieth RH. Troxidone (trimethadione) embryopathy: case report with review of the literature. Clin Exp Neurol 1979;16:2516.
    8. Fabro S, Brown NA. Teratogenic potential of anticonvulsants. N Engl J Med 1979;300:12801.
    9. National Institute of Health. Anticonvulsants found to have teratogenic potential. JAMA 1981;245:36.
    10. Dansky L, Andermann E, Andermann F. Major congenital malformations in the offspring of epileptic patients. Genetic and environmental risk factors. In Epilepsy, Pregnancy and the Child. Proceedings of a Workshop held in Berlin, September 1980. New York, NY: Raven Press, 1981.
    11. Nakane Y, Okuma T, Takahashi R, Sato Y, Wada T, Sato T, Fukushima Y, Kumashiro H, Ono T, Takahashi T, Aoki Y, Kazamatsuri H, Inami M, Komai S, Seino M, Miyakoshi M, Tanimura T, Hazama H, Kawahara R, Otsuki S, Hosokawa K, Inanaga K, Nakazawa Y, Yamamoto K. Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: a report of a collaborative study group in Japan. Epilepsia 1980;21:66380.

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