Is lorazepam (Ativan) safe to use during pregnancy?

Lorazepam Use During Pregnancy

Lorazepam can be used during pregnancy when clinically necessary, particularly in the second and third trimesters as part of antiemetic regimens for chemotherapy, but should be avoided in the first trimester when possible and used at the lowest effective dose for the shortest duration due to theoretical risks of congenital malformations and neonatal withdrawal syndrome.

Evidence-Based Safety Profile

First Trimester Considerations

The FDA label for lorazepam notes that increased risk of congenital malformations has been suggested with minor tranquilizers (including benzodiazepines) during the first trimester, and states that "the use of lorazepam during this period should be avoided" unless clinically essential 1.

However, the actual magnitude of risk appears modest:

• Case-control studies suggest a slightly increased risk of oral cleft, while cohort studies have not identified a notable association with major malformations 2
• Animal studies showed occasional anomalies (reduction of tarsals, tibia, metatarsals, malrotated limbs, gastroschisis, malformed skull, and microphthalmia) in rabbits, though without clear dose-relationship 1
• Current evidence is insufficient to definitively determine whether benefits outweigh risks, but the theoretical concerns warrant caution 3

Second and Third Trimester Use

The NCCN guidelines explicitly state that ondansetron, lorazepam, and dexamethasone can be used as part of prechemotherapy antiemetic regimens during pregnancy 4. This represents guideline-level endorsement for specific clinical indications in later pregnancy.

Neonatal Effects at Delivery

The most clinically significant concern is neonatal effects when lorazepam is used near delivery:

• "Floppy infant syndrome" (hypoactivity, hypotonia, hypothermia, respiratory depression, apnea, feeding problems) has been reported in neonates born to mothers receiving benzodiazepines during late pregnancy or at delivery 1
• Neonatal withdrawal symptoms can occur in infants whose mothers used benzodiazepines for several weeks or more preceding delivery 1
• Lorazepam and its glucuronide cross the placenta, with detectable levels in umbilical cord blood 1

Clinical Management Algorithm

When Lorazepam is Being Considered

1. Assess the clinical necessity: Is this for a clear medical indication (e.g., chemotherapy-related nausea, severe anxiety disorder) where untreated maternal illness poses significant risks? 5

2. Timing matters:

   • First trimester: Avoid if possible; if essential, use lowest dose for shortest duration and arrange level 2 ultrasonography to rule out oral cleft 2
   • Second/third trimester: Can be used when medically indicated (e.g., as antiemetic with chemotherapy) 4
   • Near delivery: Minimize use in final weeks to reduce risk of floppy infant syndrome 1

3. Dosing strategy:

   • Use the lowest effective dose 3
   • Divide daily dosage into 2-3 doses to avoid high peak concentrations 3
   • Use as monotherapy when possible 3
   • Shortest possible duration 3

If Patient is Already Taking Lorazepam

1. Do not abruptly discontinue if the patient has been on chronic therapy, as withdrawal can be dangerous 1

2. Weigh risks of untreated maternal psychiatric illness (poor prenatal care, substance use, adverse pregnancy outcomes) against medication risks 5

3. Consider switching to agents with longer safety records if time permits and clinically appropriate 3

4. If continuing through delivery, prepare neonatal team for potential floppy infant syndrome or withdrawal 1

Breastfeeding Considerations

Lorazepam should not be administered to breastfeeding women unless expected benefit outweighs potential risk 1:

• Lorazepam is detected in human breast milk 1
• Sedation and inability to suckle have occurred in nursing neonates 1
• If breastfeeding continues, monitor infant closely for sedation, lethargy, and weight loss 3

Critical Pitfalls to Avoid

1. Do not use high doses near delivery without neonatal intensive care availability, as floppy infant syndrome can cause respiratory depression requiring intervention 1

2. Do not assume all benzodiazepines are equivalent: Lorazepam has specific pharmacokinetic properties (slower placental transfer than diazepam but still significant) 6

3. Do not forget to counsel about pregnancy planning: Women of childbearing potential should be advised to communicate with their physician if they become pregnant 1

4. Do not overlook the slow neonatal elimination: Newborns eliminate benzodiazepines slowly, prolonging effects 6

5. Do not combine with other CNS depressants (especially opioids) without careful monitoring, as this increases risk of neonatal respiratory depression 1