Is Ativan (lorazepam) safe to use during pregnancy?

Is Ativan (Lorazepam) Safe in Pregnancy?

Lorazepam should be avoided during pregnancy, particularly in the first trimester, due to potential risks of congenital malformations and neonatal complications, and should only be used when benefits clearly outweigh risks to both mother and fetus.

Key Safety Concerns

Congenital Malformations

• The FDA drug label explicitly states that "an increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam, and meprobamate) during the first trimester of pregnancy has been suggested in several studies" and recommends that "the use of lorazepam during this period should be avoided" 1.
• Case-control studies show a slightly increased risk of oral cleft, though cohort studies have not consistently identified a notable association with major malformations 2.
• Animal studies revealed occasional anomalies including reduction of tarsals, tibia, metatarsals, malrotated limbs, gastroschisis, malformed skull, and microphthalmia in drug-treated rabbits, along with evidence of fetal resorption at higher doses 1.

Neonatal Complications

• Floppy infant syndrome can occur after high doses during delivery, characterized by hypoactivity, hypotonia, hypothermia, respiratory depression, apnea, feeding problems, and impaired metabolic response to cold stress 1.
• Infants born to mothers taking benzodiazepines for several weeks or more before delivery have been reported to have withdrawal symptoms during the postnatal period 1.
• Lorazepam exhibits rapid placental transfer with significant fetal uptake, and blood levels from umbilical cord blood confirm placental transfer of both lorazepam and its glucuronide metabolite 1.
• The slow elimination of benzodiazepines by newborns is a critical consideration, as neonatal metabolism is significantly impaired 3.

Clinical Decision-Making Algorithm

First Trimester

• Avoid lorazepam entirely unless there is a life-threatening psychiatric emergency where no safer alternative exists 1.
• The FDA label states "because the use of these drugs is rarely a matter of urgency, the use of lorazepam during this period should be avoided" 1.
• If a patient has already used lorazepam just after conception, recommend level 2 ultrasonography to rule out visible forms of cleft lip 2.

Second and Third Trimesters

• Consider alternative anxiolytics with better safety profiles before resorting to lorazepam 4.
• If lorazepam must be used, prescribe the lowest effective dose for the shortest possible duration 4.
• Divide daily dosage into 2-3 doses to avoid high peak concentrations 4.
• Use as monotherapy rather than in combination with other CNS depressants 4.

At Delivery

• Use the lowest effective dose if needed during labor 3.
• Be prepared to monitor the newborn for floppy infant syndrome and respiratory depression 1.
• Anticipate potential neonatal withdrawal symptoms requiring observation and possible treatment 1.

Common Pitfalls to Avoid

• Failing to counsel patients of childbearing potential: Women should be advised that if they become pregnant while taking lorazepam, they should communicate with their physician about discontinuing the drug 1.
• Not considering safer alternatives: Chlordiazepoxide appears to have a safer profile during pregnancy and lactation compared to lorazepam 4.
• Using during lactation: Lorazepam is detected in breast milk and should not be administered to breastfeeding women unless expected benefits outweigh risks, as it can cause sedation and inability to suckle in neonates 1.
• Prescribing high doses near delivery: This significantly increases risk of floppy infant syndrome 3.

Context from Related Guidelines

While the provided guidelines discuss benzodiazepine use in the context of opioid use disorder treatment, they note that methadone may be more appropriate than buprenorphine when there is concurrent benzodiazepine use, highlighting the concern about CNS depressant combinations 5. This underscores the general caution surrounding benzodiazepine use in pregnancy across multiple clinical contexts.