Has anyone nationally or internationally done any studies of apixaban, a direct oral factor Xa inhibitor in pregnancy or postpartum? Not sure if it crosses the placenta or not.

Jeffrey Kuller, MD Professor Obstetrics/Gynecology / Maternal-Fetal Medicine
Duke University School of Medicine Durham, NC

The four new oral agents for long-term anticoagulation, the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban have not been studied in pregnancy. Two of the four have been approved by the United States Food and Drug Administration (FDA) - dabigatran for the treatment of atrial fibrillation and rivoroxaban for VTE prophylaxis after orthopedic surgery. There are no published data on edoxaban. For apixaban, unpublished animal studies do not yet indicate direct or indirect harmful effects.[1]  Rivaroxaban reportedly crosses the placenta in animals.[2]  For both rivaroxaban and dabigatran, while there were no structural malformations in rats or rabbits, post-implantation losses were noted in rats.[2,3]  The therapeutic formulation of dabigatran, however, is polar, and prevents it from crossing membranes. The drug has not been found to cross the placenta in the mouse, rat or rabbit (from drug development research). Therefore, while dabigatran does not necessarily need to be stopped prior to conception, there are, nonetheless, insufficient data to justify continuing its use during pregnancy. Even in a non-continuing pregnancy, the lack of a reversing agent for these anticoagulants would preclude their use.

With respect to the four new oral agents for long-term anticoagulation, a high milk to plasma ratio in rats suggests active transport of apixaban into breast milk.[4]   There are no data about the presence of edoxaban, rivaroxaban or dabigatran in breast milk. 

1. ELiquis: summary of product characteristics.  2011  [cited 2011 November 18, 2011]; Available from: http://www.eliquis.com/PDF/ELIQUIS®SmPC.pdf.

2. Prescribing information for Xarelto (rivaroxaban) tablets for oral use.  2011  [cited 2011 November 18, 2011]; Available from:http://www.xareltohcp.com/sites/default/files/pdf/xarelto_0.pdf#zoom=100.

3. Pradaxa prescribing information.  2011  [cited 2011 November 18, 2011]; Available from:http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf.

4. Wang L., et al. Tissue distribution and elimination of [14C]apixaban in rats. Drug Metab Dispos, 2011. 39(2): p. 256-64.

Andra James, MD, MPH
Director/Founder of the Women's Hemostasis and Thrombosis Clinic
Duke University Medical Center
Associate Professor of Obstetrics & Gynecology
Duke University School of Medicine
Durham, NC