Temazepam

 Risk Factor: XM
 Class: CENTRAL NERVOUS SYSTEM DRUGS / Sedatives and Hypnotics

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Temazepam is a benzodiazepine that is used as a hypnotic for the short-term management of insomnia. Reproductive studies in rats revealed increased resorptions and an increased incidence of rudimentary ribs, which were considered skeletal variants (1). Exencephaly and fusion or asymmetry of ribs were observed in rabbits (1).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 146 newborns had been exposed to temazepam during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of six (4.1%) major birth defects were observed (six expected), including one cardiovascular defect (one expected) and two oral clefts (none expected). No anomalies were observed in four other categories of defects (spina bifida, polydactyly, limb-reduction defects, and hypospadias) for which specific data were available. Although the two oral clefts suggest a relationship with the drug, other factors, such as the mother's disease, concurrent drug use, and chance, may be involved.

A potential drug interaction between temazepam and diphenhydramine, resulting in the stillbirth of a term female infant, has been reported (2). The mother had taken diphenhydramine 50 mg for mild itching of the skin and approximately 1.5 hours later took 30 mg of temazepam for sleep. Three hours later she awoke with violent intrauterine fetal movements, which lasted several minutes and then abruptly stopped. The stillborn infant was delivered approximately 4 hours later. Autopsy revealed no gross or microscopic anomalies. In an experiment with pregnant rabbits, neither of the drugs alone caused fetal mortality but when combined, 51 (81%) of 63 fetuses were stillborn or died shortly after birth (2). No definite mechanism could be established for the apparent interaction.

Breast Feeding Summary

Temazepam is excreted in human breast milk. Ten mothers, within 15 days of delivery, were administered 1020 mg of temazepam for at least 2 days as a bedtime hypnotic (3). Milk and plasma samples were obtained about 15 hours later corresponding to an infant feeding. Temazepam was detected (limit of detection 5 ng/mL) in the milk of only one woman with before- and after-feed levels of 28 and 26 ng/mL, respectively. The milk:plasma ratio in this patient was 0.12. Although no adverse effects were observed in the nursling, nursing infants of mothers consuming temazepam should be closely observed for sedation and poor feeding. The American Academy of Pediatrics considers the effects of temazepam on the nursing infant to be unknown, but they may be of concern (4).

References

1. Product information. Restoril. Sandoz Pharmaceuticals Corp., 1993.
2. Kargas GA, Kargas SA, Bruyere HJ Jr, Gilbert EF, Opitz JM. Perinatal mortality due to interaction of diphenhydramine and temazepam. N Engl J Med 1985;313:1417.
3. Lepedevs TH, Wojnar-Horton RE, Yapp P, Roberts MJ, Dusci LJ, Hackett LP, Ilett KF. Excretion of temazepam in breast milk. Br J Clin Pharmacol 1992;33:2046.
4. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.