AMOBARBITAL

Fetal Risk Summary

Amobarbital is a member of the barbiturate class. The drug crosses the placenta, achieving levels in the cord serum similar to those in the maternal serum (1,2). Single or continuous dosing of the mother near term does not induce amobarbital hydroxylation in the fetus as demonstrated by the prolonged elimination of the drug in the newborn (half-life 2.5 times maternal). An increase in the incidence of congenital defects in infants exposed in utero to amobarbital has been reported (3,4, pp. 336, 344). One survey of 1,369 patients exposed to multiple drugs found 273 who received amobarbital during the 1st trimester (3). Ninety-five of the exposed mothers delivered infants with major or minor abnormalities. Malformations associated with barbiturates, in general, were as follows:   Anencephaly Congenital heart disease Severe limb deformities Cleft lip and palate Intersex Papilloma of the forehead Hydrocele Congenital dislocation of the hip Soft-tissue deformity of the neck Hypospadias Accessory auricle Polydactyly Nevus The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 298 of whom had 1st trimester exposure to amobarbital (4, pp. 336, 344). For use anytime during pregnancy, 867 exposures were recorded (4, p. 438). A possible association was found between the use of the drug in the 1st trimester and the following: Cardiovascular malformations (7 cases) Polydactyly in blacks (2 cases in 29 blacks) Genitourinary malformations other than hypospadias (3 cases) Inguinal hernia (9 cases) Clubfoot (4 cases) In contrast to the above reports, a 1964 survey of 187 pregnant patients who had received various neuroleptics, including amobarbital, found a 3.1% incidence of malformations in the offspring (5). This is approximately the expected incidence of abnormalities in a nonexposed population. Arthrogryposis and multiple defects were reported in an infant exposed to amobarbital during the 1st trimester (6). The defects were attributed to immobilization of the limbs at the time of joint formation, multiple drug use, and active tetanus.

[*Risk Factor B according to manufacturer - Eli Lilly & Co., 1985.

Breast Feeding Summary

No data are available.

References

1. Kraver B, Draffan GH, Williams FM, Calre RA, Dollery CT, Hawkins DF. Elimination kinetics of amobarbital in mothers and newborn infants. Clin Pharmacol Ther 1973;14:442–7.
2. Draffan GH, Dollery CT, Davies DS, Krauer B, Williams FM, Clare RA, Trudinger BJ, Darling M, Sertel H, Hawkins DF. Maternal and neonatal elimination of amobarbital after treatment of the mother with barbiturates during late pregnancy. Clin Pharmacol Ther 1976;19:271–5.
3. Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. Br Med J 1971;1:523–7.
4. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
5. Favre-Tissot M. An original clinical study of the pharmacologic-teratogenic relationship. Ann Med Psychol (Paris) 1967:389.
6. Jago RH. Arthrogryposis following treatment of maternal tetanus with muscle relaxants. Arch Dis Child 1970;45:277–9.