Apixaban and Breastfeeding

Summary of use during lactation

Information from four mothers indicates that apixaban levels in milk are high, potentially resulting in infant anticoagulation and bleeding. An alternate drug is preferred, especially while nursing a newborn or preterm infant.[1-4]

Drug levels in milk and infant serum

Maternal Levels. A nursing mother who was 23 months postpartum received 2 doses of 5 mg of oral apixaban 12 hours apart. Blood and milk samples were obtained before the first dose and at 3.5, 7, 12 (before the second dose), 16, and 24 hours after the first dose. Peak apixaban milk levels of about 230 mcg/L occurred at 3.5 to 4 hours after each dose. The average milk level over 24 hours was 113.6 mcg/L, which corresponds to a daily infant dosage of 17 mcg/kg daily and a relative infant dose of 12.8% of the maternal weight-adjusted dosage.[3] Three lactating women were taking 5 mg of apixaban twice daily by mouth and were at steady-state. They extracted milk and provided samples at 0, 1, 2, 4, 6, 8, 10, and 12 hours after a dose. Peak milk levels of apixaban occurred at 1 hours after the dose in one woman and 2 hours after the dose in the others two. Peak levels ranged from 0.2 to 0.25 mg/L and average milk levels ranged from 0.134 to 0.16 mg/L. The absolute infant dosage was calculated to be 10 mcg/kg every 12 hours, which amounted to weight adjusted infant dosages of 14%, 20% and 21% in the three infants.[2] A physiologically based pharmacokinetic (PBPK) model was constructed to simulate breastmilk and infant serum apixaban concentrations and compared to published data. The model predicted peak milk levels of 212 and 416 mcg/L for dosages of 2.5 and 5 mg twice daily, respectively. Results indicate that the worst-case relative infant dosage in infants would be about 140%.[4] Infant Levels. Relevant published information was not found as of the revision date.

Effects in breastfed infants

Relevant published information was not found as of the revision date.

Effects on lactation and breastmilk

Relevant published information was not found as of the revision date.

Alternative drugs to consider

Acenocoumarol, Dabigatran, Dalteparin, Enoxaparin, Heparin, Rivaroxaban, Warfarin

References

1. Daei M, Khalili H, Heidari Z. Direct oral anticoagulant safety during breastfeeding: A narrative review. Eur J Clin Pharmacol 2021;77:1465–71.33963877 PubMed
2. Datta P, Bramnik A, Rewers-Felkins K, et al. Transfer of apixaban into human milk. Obstet Gynecol 2021;137:1080–2.33957661 PubMed
3. Zhao Y, Arya R, Couchman L, et al. Are apixaban and rivaroxaban distributed into human breast milk to clinically relevant concentrations? Blood 2020;136:1783–5.32488251 PubMed
4. Butler AS, Cole S, Arya R, et al. Considerations of safety for women prescribed apixaban or rivaroxaban who breastfeed? - a physiologically based pharmacokinetic analysis. J Thromb Haemost 202541161415 PubMed