Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations.

Knowledge of the pharmacokinetic properties of the benzodiazepines is playing an increasingly important role in their use during pregnancy, labour and lactation. All of the benzodiazepine derivatives are lipophilic, undissociated agents which readily penetrate membranes. Thus, they exhibit rapid placental transfer with significant fetal uptake of the drug. In the first trimester of pregnancy there is seldom a clear indication for the use of benzodiazepines. In late pregnancy and at parturition there may be more clear indications for their use. During delivery, the lowest effective dose should be used, since after high doses the so-called 'floppy infant syndrome' may occur, and the slow elimination of these agents by the newborn should be considered. Oxazepam, lorazepam, nitrazepam and, especially, flunitrazepam, appear to penetrate the human placenta more slowly than diazepam, but the clinical significance of this phenomenon remains uncertain. All of these derivatives appear in human milk, but only high clinical doses might be expected to exert a possible effect on the nursing newborn.