MEPROBAMATE

Fetal Risk Summary

Meprobamate is used in the treatment of anxiety disorders or for the short-term treatment of the symptoms of anxiety. The drug crosses the placenta to the fetus and has been measured in umbilical cord blood at or near maternal plasma levels (1).

Meprobamate use in pregnancy has been associated with an increased risk of congenital anomalies (1.9%–12.1%) (2,3). In one study of 395 patients, 8 defects were observed (2): Congenital heart disease (2 with multiple other defects) (5 cases) Down's syndrome (1 case) Deafness (partial) (1 case) Deformed elbows and joints (1 case) Another report described multiple anomalies, including congenital heart defects, in a newborn exposed to meprobamate (4). The mother of this patient was treated very early in the 1st trimester with meprobamate and propoxyphene. Malformations observed were omphalocele, defective anterior abdominal wall, defect in diaphragm, congenital heart disease with partial ectopic cordis secondary to sternal cleft, and dysplastic hips.

Multiple defects of the eye and central nervous system were observed in a newborn exposed to multiple drugs, including meprobamate and LSD (5).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 356 of which were exposed in the 1st trimester to meprobamate (6,7). No association of meprobamate with large classes of malformations or to individual defects was found. Others have also failed to find a relationship between the use of meprobamate and congenital malformations (8).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 75 newborns had been exposed to meprobamate during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Three (4.0%) major birth defects were observed (three expected), including (observed/expected) 1/0 oral clefts and 2/0 polydactyly. No anomalies were observed in four other defect categories (cardiovascular defects, spina bifida, limb reduction defects, and hypospadias) for which specific data were available. Only with the cases of polydactyly is there a suggestion of a possible association, but other factors, such as the mother's disease, concurrent drug use, and chance, may be involved.

Because few indications exist for this drug in the pregnant woman, it should be used with extreme caution, if at all, during pregnancy. Use during the first 6 weeks of pregnancy may be correlated with an increased risk for fetal malformations.

Breast Feeding Summary

Meprobamate is excreted into breast milk (1,9). Milk concentrations are 2–4 times that of maternal plasma. The effect on the nursing infant is unknown.

References

1. Product information. Miltown. Wallace Laboratories, 2000.
2. Milkovich L, van den Berg BJ. Effects of prenatal meprobamate and chlordiazepoxide hydrochloride on human embryonic and fetal development. N Engl J Med 1974;291:1268–71.
3. Crombie DL, Pinsent RJ, Fleming DM, Rumeau-Rouguette C, Goujard J, Huel G. Fetal effects of tranquilizers in pregnancy. N Engl J Med 1975;293:198–9.
4. Ringrose CAD. The hazard of neurotropic drugs in the fertile years. Can Med Assoc J 1972;106:1058.
5. Bogdanoff B, Rorke LB, Yanoff M, Warren WS. Brain and eye abnormalities: possible sequelae to prenatal use of multiple drugs including LSD. Am J Dis Child 1972;123:145–8.
6. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:336–7.
7. Hartz SC, Heinonen OP, Shapiro S, Siskind V, Slone D. Antenatal exposure to meprobamate and chlordiazepoxide in relation to malformations, mental development, and childhood mortality. N Engl J Med 1975;292:726–8.
8. Belafsky HA, Breslow S, Hirsch LM, Shangold JE, Stahl MB. Meprobamate during pregnancy. Obstet Gynecol 1969;34:378–86.
9. Wilson JT, Brown RD, Cherek DR, Dailey JW, Hilman B, Jobe PC, Manno BR, Manno JE, Redetzki HM, Stewart JJ. Drug excretion in human breast milk: principles, pharmacokinetics and projected consequences. Clin Pharmacokinet 1980;5:1–66.