Remimazolam in Pregnancy and Breastfeeding: Placental Transfer and Safety

When considering the use of remimazolam during pregnancy, several important factors must be evaluated to ensure the safety of both the mother and the fetus. Benzodiazepines, including remimazolam, cross the placenta, meaning they can potentially impact fetal development. While there have been some observations of teratogenic effects (birth defects), there is no clear consensus or definitive evidence linking remimazolam use in pregnancy to significant harm. More data are needed to establish a firm connection between the drug and teratogenicity. However, caution is still warranted due to the potential for neonatal sedation or withdrawal symptoms when exposed to benzodiazepines late in pregnancy. These symptoms can include hypotonia (low muscle tone), lethargy, respiratory depression, feeding difficulties, hyperreflexia (exaggerated reflexes), irritability, restlessness, and tremors. Furthermore, long-term neurodevelopmental effects remain inconclusive, with ongoing research required to better understand these risks.

In cases where pregnant patients require surgery, the American College of Obstetricians and Gynecologists (ACOG) advises that medically necessary procedures should not be withheld, regardless of the trimester. If the surgery is elective, delaying the procedure until after delivery is recommended. When remimazolam is administered during pregnancy, the newborn should be carefully monitored post-delivery for any signs of respiratory depression, sedation, and withdrawal symptoms. Based on animal data, repeated or prolonged exposure to anesthetic agents that block NMDA receptors or enhance GABA activity, like remimazolam, may interfere with brain development in the fetus, emphasizing the importance of cautious use during pregnancy.

For breastfeeding mothers, the presence of remimazolam in breast milk is not well-established. The drug manufacturer suggests weighing the risks of infant exposure through breastfeeding against the benefits of breastfeeding for both the mother and child. If remimazolam must be used, lactating mothers are advised to express and discard their milk for five hours post-administration to minimize potential infant exposure. Infants should be monitored closely for sedation, respiratory issues, and feeding problems during this period. The Academy of Breastfeeding Medicine recommends postponing elective surgeries until breastfeeding and milk supply are well-established. If possible, mothers should express milk ahead of surgery to ensure a backup supply. Generally, breastfeeding may resume once the mother has recovered from the procedure, though caution is advised for infants at risk of apnea, hypotension, or hypotonia. In such cases, expressed milk may be stored and used at a later time when the child is at lower risk.

From a safety perspective, remimazolam can cause modest hypotension (low blood pressure) and hypoventilation (reduced breathing), although these cardiorespiratory effects are usually mild when used for sedation. However, more severe complications, such as anaphylactic shock, have been reported. A critical consideration is the risk of “re-sedation” in patients who receive flumazenil as a reversal agent after remimazolam anesthesia. If the effects of remimazolam last longer than the flumazenil antagonism, patients may experience sedation again. This can be an entirely preventable issue with careful monitoring and judicious use of flumazenil, which should only be administered to patients with delayed emergence from anesthesia.

Decision flow for remimazolam use in pregnant and breastfeeding patients, with the flumazenil re-sedation caution.