Is apixaban (direct oral anticoagulant) safe to use during lactation?

Apixaban in Lactation: Safety Considerations

Apixaban is not recommended during breastfeeding, and alternative anticoagulants should be used instead. 1

Evidence-Based Recommendations

The American College of Chest Physicians (ACCP) provides clear guidance on the use of direct oral anticoagulants (DOACs) during lactation:

• For breastfeeding women, alternative anticoagulants rather than factor Xa inhibitors (including apixaban) are strongly recommended (Grade 1C) 1
• Preferred alternatives for breastfeeding women include:
  • Warfarin (Grade 1A) 1
  • Low molecular weight heparin (LMWH) (Grade 1B) 1
  • Unfractionated heparin (UFH) (Grade 1A) 1

Rationale and Evidence

Animal Studies

• In animal studies, apixaban showed extensive lacteal excretion in rats, with greater than 96% of sample radioactivity appearing in milk 1
• The high milk-to-maternal plasma ratio may be due to active transport into breast milk 1

Human Data

• The FDA drug label for apixaban states there are no data on the presence of apixaban or its metabolites in human milk, the effects on the breastfed child, or effects on milk production 2
• The drug label specifically notes that "breastfeeding is not recommended during treatment with apixaban tablets" 2
• Animal data shows that apixaban can accumulate in milk with a milk-to-plasma AUC ratio of 30:1 2

Comparative DOAC Data

While apixaban specifically lacks human lactation data, limited research on other DOACs suggests:

• Rivaroxaban has shown milk-to-plasma ratios of 0.27-0.32 with relative infant doses of 0.82-1.79% 3, 4
• Among DOACs, dabigatran appears to have the least excretion in human breast milk, while apixaban milk excretion may be greater than the maximum allowed range 5

Clinical Decision Algorithm

1. Identify need for anticoagulation in breastfeeding woman

2. Select appropriate anticoagulant based on ACCP recommendations:

   • First-line options:
     • Warfarin (if not contraindicated)
     • LMWH
     • UFH
   • Avoid:
     • Apixaban and other DOACs
     • Fondaparinux (Grade 2C) 1

3. If patient is currently on apixaban:

   • Switch to recommended alternative anticoagulant
   • Do not discontinue anticoagulation without replacement if clinically indicated

Important Considerations

• The recommendation against apixaban during breastfeeding is based on safety concerns and lack of human data, not proven harm
• The potential risks of apixaban to the breastfed infant must be weighed against the mother's need for anticoagulation
• Medication concerns can become barriers to breastfeeding 6, so clear communication about safe alternatives is essential
• When switching from apixaban to an alternative anticoagulant, ensure appropriate dosing and monitoring of the new agent

Common Pitfalls to Avoid

• Do not continue apixaban during breastfeeding based on limited data from other DOACs
• Do not discontinue anticoagulation without providing an appropriate alternative if clinically indicated
• Avoid making assumptions about drug safety in human milk based solely on animal studies
• Do not confuse the safety profile of warfarin in breastfeeding (safe) with its contraindication in pregnancy (teratogenic)