Methodological Limitations in Assessing the Safety of Direct Oral Anticoagulants During Lactation
DOI:
https://doi.org/10.12775/QS.2026.73.75134Keywords
Direct oral anticoagulant, lactation, breastfeeding, Pharmacokinetics, Venous thromboembolismAbstract
Introduction. Direct oral anticoagulants (DOACs) offer superior clinical convenience over traditional therapies. However, their use in postpartum women is heavily constrained, routinely forcing a choice between optimal venous thromboembolism (VTE) prophylaxis, and breastfeeding due to a lack of high-certainty safety data.
Objective. This review synthesizes clinical data regarding DOAC excretion into human breast milk, evaluates current pharmacokinetic indices and outlines the methodological limitations hindering definitive clinical guidelines.
Materials and Methods. A comprehensive literature search was conducted in the PubMed database up to June 2026 to evaluate human clinical data concerning maternal DOAC therapy and subsequent infant exposure metrics.
Results. Available evidence indicates distinct profiles among DOACs. Apixaban exhibits significant accumulation in breast milk driven by active BCRP transport, yielding an unacceptable Relative Infant Dose (RID) of up to 21%. Conversely, rivaroxaban and dabigatran demonstrate promising safety margins, with RIDs substantially below the 10% safety threshold. Data regarding edoxaban remain constrained to an isolated case report.
Conclusion. Contemporary literature is severely undermined by methodological vulnerabilities, including small sample sizes, lack of standardized milk fraction sampling (foremilk vs. hindmilk), and non-steady-state sampling parameters. Due to the suspension of breastfeeding during trials, investigators frequently rely on mathematical proxies like the Relative Infant Dose Daily (RIDD). To establish high-certainty guidelines, future protocols must address these flaws, utilize advanced PBPK modeling and implement long-term observational registries to evaluate infant safety.
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Copyright (c) 2026 Bartosz Pomirski, Anna Wilewska, Agata Pomirska, Julia Biernikiewicz, Konstanty Alabrudziński, Milena Biernikiewicz, Agnieszka Borowiec, Aleksandra Dach, Kinga Borowiec, Paulina Kwaśniewska
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