Ambien During Labor: Pregnancy and Breastfeeding Safety Data

What does the Ambien label say about pregnancy and labor?

The Ambien label (effective February 2025) states that zolpidem crosses the placenta and may produce respiratory depression and sedation in neonates [1]. Its clinical considerations section directs that neonates exposed to Ambien during pregnancy and labor be monitored for signs of excess sedation, hypotonia and respiratory depression, and managed accordingly [1]. The Ambien CR label carries the same pregnancy and lactation language [4].

There are limited postmarketing reports of severe to moderate respiratory depression occurring after birth in neonates whose mothers took zolpidem during pregnancy; these cases required artificial ventilation or intratracheal intubation, and most newborns recovered within hours to a few weeks after birth once treated [1].

For scale, the label gives US background rates in clinically recognized pregnancies: major birth defects 2% to 4% and miscarriage 15% to 20% [1].

Do published data show a birth-defect risk?

Published data from observational studies, birth registries and case reports do not report a clear association between zolpidem and major birth defects, according to the label [1].

The animal data in that same label are specific: rats given 5, 25 and 120 times the maximum recommended human dose (MRHD) based on body surface area, and rabbits given 2.5, 10 and 40 times the MRHD, showed delayed fetal development (incomplete skeletal ossification) at the maternally toxic doses of 25 and 120 times the MRHD in rats and 40 times in rabbits; the rabbits also had embryo-fetal death at 40 times the MRHD [1]. The label states that oral zolpidem in pregnant rats and rabbits did not indicate a risk for adverse effects on fetal development at clinically relevant doses [1].

Does zolpidem raise the risk of preterm birth or low birth weight?

One nationwide population-based study from Taiwan compared 2,497 mothers who received zolpidem during pregnancy with 12,485 randomly selected mothers who did not, linking the National Health Insurance Research Dataset to the birth-certificate registry [3]. Adjusted odds ratios were higher in the zolpidem group for low birth weight (1.39, 95% CI 1.17 to 1.64), preterm delivery (1.49, 95% CI 1.28 to 1.74), small for gestational age (1.34, 95% CI 1.20 to 1.49) and cesarean delivery (1.74, 95% CI 1.59 to 1.90) after adjustment for characteristics of the mothers and infants [3].

The study compared women who received zolpidem with women who did not; it did not assign treatment, so the results describe an association rather than proof that the drug caused these outcomes [3].

Breastfeeding: how much zolpidem reaches breast milk?

The most detailed measurement used five healthy lactating women who took a single 20 mg tablet of zolpidem three to four days after a full-term delivery, with milk sampled before dosing and at 3, 13 and 16 hours [2]. The amount excreted in milk at 3 hours ranged from 0.76 to 3.88 micrograms, which was 0.004% to 0.019% of the administered dose; no zolpidem was detectable in milk (below 0.5 ng/mL) at the later sampling times [2]. The milk-to-plasma concentration ratio at 3 hours was 0.13, and the plasma half-life estimated in those women was 2.6 hours [2]. That 20 mg dose is above the maximum recommended adult dose of 10 mg for immediate-release Ambien and well above the 5 mg recommended starting dose for women [1].

The Ambien label's lactation section states that a lactating woman may pump and discard breast milk during treatment and for 23 hours after Ambien administration [1]. The Ambien CR label states the same for Ambien CR, with the same 23-hour window [4].

What is tried first for insomnia, including in pregnancy?

The American College of Physicians recommends cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia disorder in all adults (strong recommendation, moderate-quality evidence), with medication added through shared decision-making when CBT-I alone is unsuccessful (weak recommendation, low-quality evidence) [6]. That guideline covers adults generally and is not specific to pregnancy.

A randomized trial tested CBT-I specifically in pregnancy: 194 women between 18 and 32 weeks of gestation with insomnia disorder were assigned to CBT-I or to a control intervention of imagery exercises, and 179 were analyzed (89 CBT-I, 90 control) [7]. Insomnia Severity Index scores fell from 15.4 to 8.0 with CBT-I versus 15.9 to 11.2 with the control intervention (P<.001, effect size 0.5) [7]. Women meeting criteria for major psychiatric disorders, including depression, were not eligible for that trial [7].