TEGRETOL PRENATAL EXPOSURE LINKED TO DEVELOPMENTAL DELAY

TEGRETOL PRENATAL EXPOSURE LINKED TO DEVELOPMENTAL DELAY observed in 20% or five of 25 children undergoing formal neurobehavioral assessments, Kenneth Jones, University of California-San Diego, et al., reported in the June 22 issue of the New England Journal of Medicine. Of the study's total 35 children born to women who had taken the Tegretol (carbamazepine) and no other anticonvulsant agent during their pregnancy, the incidence of fingernail hypoplasia was 26% and cranofacial effects 11%, the authors report. "Although the data presented in this report do not permit definitive conclusions about the frequency of adverse outcomes of pregnancy among women treated with carbamazepine . . . this drug may well present a significant risk to the unborn baby," the study concludes. In attempting to determine the drug's teratogenicity, researchers first evaluated eight children identified retrospectively as having had prenatal exposure to carbamazepine alone or in combination with a variety of anticonvulsants other than phenytoin (Parke-Davis' Dilantin). In a prospective study they then documented the outcome of the pregnancies of 72 women who had been concerned about the drug and contacted the researchers. The pattern of malformation and developmental delay retrospectively identified in the eight children was later confirmed through the evaluation of the 48 children born to the 72 women in the prospective study. Jones, et al., noted the similarities of the malformations to those observed in earlier studies in children exposed to Dilantin. "That phenytoin and carbamazepine are metabolized through a common pathway probably explains the similarity between the two syndromes," they said. While labeling for Dilantin and as well as for another antiepileptic, Abbott's Depakene, notes the association between antiepileptic drugs and birth defects, Tegretol's labeling only refers to birth defects in lab animals given large doses. In contrast, Dilantin's labeling states: "A number of reports suggest an association between the use of antiepileptic drugs by women with epilepsy and a higher incidence of birth defects in children born to these women." Tegretol manufacturer Ciba-Geigy said it does not have any plans to change the product's labeling based on Jones' study. "Unfortunately, Dr. Jones' data is hard to interpret because of serious methodological problems," Ciba-Geigy said in a prepared response to the journal article. "Specifically, the study uses mothers without epilepsy for the control group. Since the risk of minor malformations increases in mothers with epilepsy, whether or not they are on anticonvulsants, the study cannot, in our view, provide meaningful information regarding any relationship between the use of Tegretol in pregnant women and the incidence of minor malformations." Carbamazepine is also marketed generically by Lederle, Warner Chilcott and Martec.