CLORAZEPATE

Fetal Risk Summary

Clorazepate is a member of the benzodiazepine class of agents. No teratogenic effects were observed in two species of animals fed large doses of the drug during gestation. However, cases of congenital malformations in humans after in utero exposure to other benzodiazepines (e.g., see Chlordiazepoxide and Diazepam) have been reported.

One report described multiple anomalies in an infant exposed to clorazepate during the 1st trimester (1). Exposure may have commenced as early as the 3rd week of gestation (5th week after the last menstrual period). The woman reportedly consumed 23 doses of the drug during the 1st trimester. Deformities present in the infant at birth were distended abdomen, oval mass in the suprapubic area, skin tag at site of penis without a urethral opening, absent scrotum and anus, marked shortening of the right thigh, bifid distal part of left foot, left great toe abnormality, right foot with four toes and an abnormal great toe, short digit attached to right finger in place of the thumb on left hand, deformities of the sacrum and fourth and fifth lumbar vertebrae with a narrowed pelvis, underdeveloped right femur, absent right fibula, absence of two left metacarpal bones, hypoplasia of first right metacarpal bone, patent ductus arteriosus, absence of right lung lobe, cecum, rectum, and right kidney, and the presence of several supernumerary spleens. The infant expired 24 hours after birth.

In an unconfirmed, retrospective report of oral contraceptive drug interactions, one woman became pregnant while taking a combination tablet of ethinyl estradiol 80 µg/norethindrone 1 mg (2). The only other medications consumed immediately prior to the pregnancy were clorazepate and an unidentified cold tablet. The authors speculated that a possible interaction may have occurred between the antihistamine in the cold tablet and the contraceptive. Although the woman claimed she did not miss any doses of the oral contraceptive, there was no confirmation of compliance. Interpretation of this interaction, if it exists, is not possible.

Breast Feeding Summary

No data are available. Other benzodiazepines accumulate in human milk, and adverse effects in the nursing infant have been reported (see Diazepam). The excretion of clorazepate in milk should be expected. The American Academy of Pediatrics considers other benzodiazepines (e.g., diazepam) to be drugs whose effect on the nursing infant is unknown but may be of concern (3).

References

1. Patel DA, Patel AR. Clorazepate and congenital malformations. JAMA 1980;244:135–6.
2. DeSano EA Jr, Hurley SC. Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness. Fertil Steril 1982;37:853–4.
3. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.