Sedative
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in the 1st and 3rd Trimesters
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible* *Potential toxicity if combined with other CNS depressants
PREGNANCY SUMMARY
Lorazepam is a benzodiazepine indicated for the treatment of status epilepticus and as a preanesthetic sedative. One report found a significant association with anal atresia. When used close to delivery, “floppy infant” syndrome has been reported. The long-term effects of in utero exposure on neurobehavior, especially when the exposure occurs in the latter half of pregnancy, have not been studied but are of concern.
FETAL RISK SUMMARY
Reproduction studies with lorazepam have been conducted in mice, rats, and two strains of rabbits. Occasional, non-dose-related malformations (reduction of tarsals, tibia, metatarsals, malrotated limbs, gastroschisis, malformed skull, and microphthalmia) were observed in rabbits, but these defects have also randomly occurred in controls. Fetal resorptions and increased fetal loss occurred in rabbits at oral (40 mg/kg) and IV (4 mg/kg) doses and higher (1).
Lorazepam crosses the placenta, achieving cord levels similar to maternal serum concentrations (2–5). Placental transfer is slower than that of diazepam, but high IV doses may produce the “floppy infant” syndrome (3). (See Diazepam for a description of this syndrome.)
A case reported in 1996 described an otherwise healthy male infant, exposed throughout gestation to lorazepam (7.5–12.5 mg/day) and clozapine (200–300 mg/day), who developed transient, mild floppy infant syndrome after delivery at 37 weeks’ gestation (6). The mother had taken the combination therapy for the treatment of schizophrenia. The hypotonia, attributed to lorazepam because of the absence of such reports in pregnancies exposed to clozapine alone, resolved 5 days after birth.
An abstract published in 1999 found an association between lorazepam and anal atresia (7). Using data from a French pregnancy registry, the investigators reported that among infants exposed to benzodiazepines 5 of 6 cases of anal atresia were exposed to lorazepam (p = 0.01).
Lorazepam has been used in labor to potentiate the effects of narcotic analgesics (8). Although not statistically significant, a higher incidence of respiratory depression occurred in the exposed newborn infants.
BREASTFEEDING SUMMARY
Lorazepam is excreted into breast milk in low concentrations (9,10). In one study, no effects on the nursing infant were reported (9), but the slight delay in establishing feeding was a cause for concern (11). Milk:plasma ratios in four women who had received 3.5 mg orally of lorazepam 4 hours earlier ranged from 0.15 to 0.26 (9). The mean milk concentration was 8.5 ng/mL. In another study, 5 mg of oral lorazepam was given 1 hour before labor induction and the effects on feeding behavior were measured in the newborn infants (12). During the first 48 hours, no significant effect was observed on volume of milk consumed or duration of feeding.
The effects of exposure to benzodiazepines during breastfeeding were reported in a 2012 study (13). In a 15-month period spanning 2010–2011, 296 women called the Motherisk Program in Toronto, Ontario, seeking advice on the use of these drugs during lactation and 124 consented to the study. The most commonly used benzodiazepines were lorazepam (52%), clonazepam (18%), and midazolam (15%). Neonatal sedation was reported in only two infants. Lorazepam was not used by either mother. There was no significant difference between the characteristics of these 2 and the 122 that reported no sedation in terms of maternal age, gestational age at birth, daily amount of time nursing, amount of time infant slept each day, and the benzodiazepine dose (mg/kg/day). The only difference was in the number of CNS depressants that the mothers were taking: 3.5 vs. 1.7 (p = 0.0056). The investigators concluded that their results supported the recommendation that the use benzodiazepines was not a reason to avoid breastfeeding (13).
The American Academy of Pediatrics classifies the effects of lorazepam on the nursing infant as unknown but may be of concern if exposure is prolonged (14).
References
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14.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.