Is it safe to administer Ativan (lorazepam) and Benadryl (diphenhydramine) to a 30-week pregnant female patient?

Safety of Ativan (Lorazepam) and Benadryl (Diphenhydramine) at 30 Weeks Gestation

Both medications can be used at 30 weeks gestation when clinically necessary, but require careful risk-benefit assessment and close neonatal monitoring, as both cross the placenta and may cause transient neonatal complications.

Lorazepam (Ativan) Safety Profile

Third Trimester Use

• Lorazepam is not associated with increased risk of major congenital malformations when used in the third trimester, as organogenesis is complete by this gestational age 1, 2
• The critical period for teratogenic concern is the first trimester; at 30 weeks, structural malformation risk is no longer relevant 3
• A prospective registry study of 151 women exposed to benzodiazepines in the first trimester found no increased risk of major malformations (OR 0.92; 95% CI 0.35-2.41) 2

Neonatal Considerations at Delivery

• Late pregnancy exposure may cause "floppy infant syndrome" characterized by hypotonia, hypoactivity, hypothermia, respiratory depression, apnea, feeding problems, and impaired metabolic response to cold stress 1
• Neonatal withdrawal symptoms can occur in infants whose mothers used benzodiazepines for several weeks preceding delivery 1, 4
• Lorazepam exhibits slower placental transfer compared to diazepam, though clinical significance remains uncertain 5
• The newborn's slow elimination of benzodiazepines should be considered when dosing near delivery 5

Clinical Management Algorithm

• Use the lowest effective dose for the shortest duration necessary 6
• Divide daily dosing into 2-3 doses to avoid high peak concentrations 6
• Avoid combining with other CNS depressants when possible, particularly opioids like buprenorphine, though this is not an absolute contraindication if careful monitoring is implemented 3
• Plan for enhanced neonatal monitoring at delivery, informing the pediatric team of maternal benzodiazepine use 1

Diphenhydramine (Benadryl) Safety Profile

Pregnancy Safety Data

• Diphenhydramine has generally good overall safety data with extensive use during pregnancy 3
• However, there is concern from one case-control study suggesting an association with cleft palate, though this has not been sufficiently refuted and applies primarily to first-trimester exposure 3
• At 30 weeks gestation, the cleft palate concern is not relevant as palatal closure occurs by 10 weeks 3

Second-Generation Alternatives

• Second-generation antihistamines now have comparable safety data to first-generation agents like diphenhydramine 3
• The sedative qualities and impaired performance characteristics of diphenhydramine make second-generation antihistamines potentially more desirable choices 3

Combined Use Considerations

Additive CNS Depression

• The combination increases risk of maternal sedation, hypotension, and hypoxia, which can affect both mother and fetus 1
• Lorazepam produces increased CNS-depressant effects when combined with sedative antihistamines like diphenhydramine 1

Risk Mitigation Strategy

• If both medications are necessary, use the minimum effective doses of each 6
• Monitor maternal vital signs and level of sedation closely 1
• Consider whether one agent alone might suffice for the clinical indication
• Ensure the pediatric team is aware of both exposures for appropriate neonatal monitoring 1

Key Clinical Pitfalls to Avoid

• Do not abruptly discontinue lorazepam if the patient has been on chronic therapy, as maternal withdrawal poses greater risks than continued use at 30 weeks 4
• Avoid high-dose administration near delivery to minimize floppy infant syndrome risk 1, 5
• Do not assume safety data from first-trimester studies applies to third-trimester use—the risks differ substantially 3, 1
• Ensure clear documentation and communication with the delivery team about timing of last dose relative to delivery 1

Neonatal Monitoring Plan

• Observe for sedation, respiratory depression, feeding difficulties, temperature instability, and withdrawal symptoms in the first 1-4 weeks of life 7, 1
• Monitor for hypotonia and poor suck reflex immediately after delivery 1
• Extended observation may be warranted given lorazepam's slow neonatal elimination 5