Pharmacology and toxicology

Vigabatrin, a so-called "add-on" or supplementary antiepileptic, irreversibly inhibits the GABA-aminotransferase and thereby increases the concentration of the inhibiting neurotransmitter, GABA, in the central nervous system. As a result, abnormal discharges, which cause seizure activity, are suppressed.

Ncuropathological effects have been reported in the developing rat brain (Qiao 2000). Transplacental passage of vigabatrin has been demonstrated in animal experiments (Aboulrazzaq 2001). In the few reported instances of human fetal exposure to vigabatrin monotherapy, no congenital malformations have resulted. Cases of diaphragmatic hernia (Kramer 1992) and hypospadias (Lindhout 1994) were reported in children also exposed to carbamazepine. Two cases of hypocalcemia were also mentioned. Vajda (2003) found no teratogenic effects among 8 pregnancies reported to the Australian Epilepsy Register. Congenital anomalies have been reported in 14.5% (of these, two-thirds were major malformations) of 196 pregnancies exposed to vigabatrin (Committee for Proprietary Medicinal Products 1999), but most cases were polytherapies. Vigabatrin is under discussion bccause it has been found to cause concentric visual-field defects in 30-40% of the users (Spencer 2003, Kalviainen 1999), but there is insufficient information available on visual-field defects in children who have been exposed prenatally (Sorri 2005).

Recommendation. There is, to date, insufficient experience with humans to rule out a teratogenic effect of vigabatrin. When vigabatrin treatment occurs in the first trimester, termination of pregnancy is not indicated. As with other anticonvulsants, especially with combination therapy, an increased risk of birth defects must be anticipated. An expanded prenatal diagnosis with a detailed fetal ultrasound during the second trimester should be performed to rule out major disturbances of structural development. To decrease the risk of coagulation disturbances in the fetus and newborn, the newborn should receive 1 mg of vitamin K (preferably intramuscularly) at birth and 1 mg orally every 3 days in the first 2 weeks of life (see also section 1.10,6).

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