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Concerns regarding Sugammadex Use During Pregnancy and Lactation

March 12, 2025

by Sarah Dodd, MD; Hans Sviggum, MD; Emily Sharpe, MD, FASA
Related Article: Safety of Sugammadex in Pregnancy, Pediatrics, and Renal Failure

TO THE EDITOR

Dear Drs. Methangkool and Banayan,

We reach out with utmost respect to the Anesthesia Patient Safety Foundation (APSF) in response to the article “Safety of Sugammadex in Pregnancy, Pediatrics, and Renal Failure.“1 While we understand the intention was to simplify complex information, it unfortunately resulted in inaccuracies, particularly concerning pregnant and lactating patients.

Regarding pregnant and lactating patients, we have three main areas where we differ in opinion with the information provided in this recent article.

  1. Sugammadex use in pregnancy: In the text, the authors lay out the paucity of evidence of harm for sugammadex use in pregnant patients and cite the editorial by Gaston et al.2 that questioned SOAP3 and Merck4 recommendations to avoid sugammadex for reversal in pregnancy. Yet, the infographic does not convey these nuances. Further, teratogenicity has been demonstrated in the one rabbit study and not in rat or human studies. Given the available evidence for superiority over neostigmine and frankly the lack of evidence for harm, we do not think a blanket recommendation to avoid sugammadex in pregnancy is best for patients.
  2. Sugammadex compatibility with uninterrupted breastfeeding. Medical decisions require evaluation of risks, benefits and alternatives, and it cannot be overstated that the benefit of breastfeeding is high. Not only is breast milk the ideal nutrition to support growth and development in infants, but it can also protect against infection, reduce the risk of sudden infant death syndrome, and lower the risk of heart disease and breast and ovarian cancer in mothers. Supporting initiation and maintenance of lactation is crucial for individual and public health. Providing accurate, consistent information to healthcare providers and patients is essential for success. Multiple expert bodies support uninterrupted breastfeeding after a patient has received sugammadex5, 6, 7 based on its low transfer to milk, low oral bioavailability for the infant, and minimal risk of harm to the infant, even if exposed to trace levels of the drug. Additionally, there have been no reported cases of infant harm attributed to sugammadex in breast milk5. There are also reports of neonates and infants receiving sugammadex following difficult airway management requiring muscle relaxant and reversal without harm attributable to the sugammadex8. The APSF recommendation that sugammadex is incompatible with lactation is incongruent with current expert opinion and available data.
  3. Breast milk production and composition change over time. The APSF article groups pregnant and lactating patients together without distinguishing that lactating patients will also present for anesthesia care beyond the post-partum period. The source articles explain that in early lactation the junctions between lactocytes are leaky and sugammadex molecules may cross into breastmilk at a higher rate during this period9. This is presented as the major reason to avoid sugammadex in lactating patients, despite oral bioavailability being low and no reported instances of harm. This explanation is also featured in the SOAP guideline3, although with a different conclusion. Even if one were to avoid sugammadex in this population for this reason, this physiology would be expected to last only for the first few days up to 2 weeks. No distinction was made in this article between recommendations for early and late lactation when sugammadex is extremely unlikely to pass into mature breastmilk.

In addition to potential revisions within the article, we request changes to the infographic as some readers may refer to it without reading the article in its entirety. We recommend:

  • Change “Interaction with progesterone” to “Potential interaction with progesterone”
  • Remove “Potential teratogenicity”
  • Change “Discourage during breastfeeding” to “Safe in established lactation” (judicious use in early postpartum period) OR remove summary recommendation for lactation as we feel that it would be better to be absent than inaccurate.

 

Respectfully,

Sarah Dodd, MD

Hans Sviggum, MD

Emily Sharpe, MD, FASA

The authors have no conflicts of interest.

REFERENCES

  1. Safety of sugammadex in pregnancy, pediatrics, and renal failure. Anesthesia Patient Safety Foundation. February 2025
  2. Gaston IN, Lange EMS, Farrer JR, Toledo P. Sugammadex use for reversal in nonobstetric surgery during pregnancy: a reexamination of the evidence. Anesth Analg. 2023;136:1217–1219. PMID: 37205805.
  3. Society for Obstetric Anesthesia and Perinatology. Statement on Sugammadex during pregnancy and lactation. Society for Obstetric Anesthesia and Perinatology. 2019
  4. Bridion (sugammadex) {prescribing information]. Rahway, NJ: Merck & Co., Inc.; 2022.
  5. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006-. Sugammadex. [Updated 2023 Apr 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500924/
  6. Reece-Stremtan S, Campos M, Kokajko L, et al. Abm clinical protocol #15: analgesia and anesthesia for the breastfeeding mother, revised 2017. Breastfeeding Medicine. 2017;12(9):500-506.
  7. Hale TW, Rowe HE. Medications & Mothers Milk. Seventeenth edition. Springer Publishing Company; 2017.
  8. Franz AM, Chiem J, Martin LD, Rampersad S, Phillips J, Grigg EB. Case series of 331 cases of sugammadex compared to neostigmine in patients under 2 years of age. Paediatr Anaesth. 2019 Jun;29(6):591-596. doi: 10.1111/pan.13643. Epub 2019 Apr 29. PMID: 30934160.
  9. Do W, Cho AR. What we need to know and do on sugammadex usage in pregnant and lactating women and those on hormonal contraceptives. Anesth Pain Med (Seoul). 2023;18:114–122. PMID: 37183279.

REPLY

Response to Letter to the Editor: Concerns Regarding Sugammadex Use During Pregnancy and Lactation

Dear Drs. Dodd, Sviggum, and Sharpe,

Thank you for your thoughtful critique of our APSF article, “Safety of Sugammadex in Pregnancy, Pediatrics, and Renal Failure.” We welcome the opportunity to reinforce the evidence-based conclusions of our article and address the points of contention regarding sugammadex use in pregnant and lactating patients. Our objective remains to present a thorough and accurate analysis based on the best available data.

1. Sugammadex Use in Pregnancy

Our article accurately reflects the current state of the evidence and prevailing clinical guidelines regarding sugammadex use in pregnancy. While no definitive studies in humans have demonstrated harm, the potential for sugammadex to bind progesterone remains an area of concern. This has been supported by in vitro studies and animal models, with one rabbit study demonstrating teratogenic effects. Given the critical role of progesterone in maintaining pregnancy, and the lack of large-scale human studies, we maintain that a cautious approach remains warranted. Furthermore, we acknowledge that the use of sugammadex for rescue reversal in cannot-intubate/cannot-ventilate scenarios is merited as the sequelae of severe hypoxia could be more detrimental than the potential risks that may arise from sugammadex exposure.

Current recommendations, including those from the Society for Obstetric Anesthesia and Perinatology (SOAP) and the prescribing information from Merck, advise against routine use of sugammadex in pregnancy. While we appreciate alternative viewpoints, we believe that our position aligns with the best available data and clinical guidance at this time.

2. Sugammadex Compatibility with Breastfeeding

We recognize that the transfer of sugammadex into breast milk is expected to be minimal and that its low oral bioavailability suggests negligible systemic exposure for nursing infants. However, our discussion highlights an important physiological consideration—during early lactation, the increased permeability of lactocyte junctions could allow for greater drug transfer. Given the limited human data, this remains a relevant factor in clinical decision-making.

While expert opinions on this issue vary, we believe that our article provides a balanced review of the available literature, emphasizing the need for individualized risk-benefit assessments when considering sugammadex in lactating patients. The lack of reported adverse events does not equate to definitive safety, and it is prudent to acknowledge the gaps in current research.

3. Differentiation Between Pregnant and Lactating Patients

Our discussion appropriately acknowledges the evolving physiology of lactation and its potential implications for drug transfer. While later-stage breast milk may have reduced permeability to medications, early postpartum lactation is characterized by increased junctional permeability, which could theoretically allow for greater sugammadex transfer. This is a well-documented physiological process and remains a relevant consideration for clinical decision-making.

It is important to recognize that recommendations regarding medication use in lactation are based not only on direct evidence of harm but also on an understanding of drug pharmacokinetics, infant physiology, and the precautionary principle. While no reported cases of harm exist, the absence of data is not equivalent to proof of safety. Our article presents a balanced discussion of these factors, ensuring that anesthesia professionals are aware of the full context when considering sugammadex use in lactating patients.

We maintain that our article provides a well-reasoned, evidence-based discussion of sugammadex safety in special populations. The recommendations align with current guidelines and the best available data. While differing interpretations exist, our cautious approach reflects standard principles in perinatal pharmacology—prioritizing patient safety in the absence of definitive human studies. We appreciate the ongoing dialogue on this topic and welcome further research to expand our understanding of sugammadex use in pregnancy and lactation.

 

Respectfully,

Kevin Yang, BS
Christina Ratto, MD
Joseph Szokol, MD
Ashley Osumi, MD

Authors, “Safety of Sugammadex in Pregnancy, Pediatrics, and Renal Failure”
Published in APSF Newsletter, February 2025

The authors have no conflicts of interest.