The Direct Factor Xa Inhibitor Rivaroxaban Passes Into Human Breast Milk

Abstract

Thromboembolic disorders frequently require antithrombotic treatment during pregnancy and lactation. Vitamin K antagonists and heparins are the treatment options of choice in breastfeeding women. Factors including the route of administration, discomfort during treatment, and fetal and neonatal safety affect women's choices about anticoagulant therapy. Direct-acting oral anticoagulants (DOACs) have emerged as alternatives to these agents and may offer advantages compared with vitamin K antagonists. As breastfeeding women were excluded from clinical trials evaluating DOACs, no safety and efficacy data are available for these special patients and, crucially, estimates for infant exposure are lacking. Therefore, the manufacturer recommends against using DOACs during the lactation period. We present the case of a patient who stopped breastfeeding owing to a diagnosis of postpartum cardiomyopathy. Anticoagulation with enoxaparin that commenced after the diagnosis of postpartum pulmonary embolism was switched to rivaroxaban. At that time, breast milk samples were collected and rivaroxaban concentrations were determined by liquid chromatography tandem-mass spectrometry. Rivaroxaban appears in human breast milk in comparatively small amounts; its safety has not been determined.

Venous thromboembolism and women's health

“…DOACs would, once again, provide an attractive alternative to traditional anticoagulants during the puerperium. Animal studies from all the direct factor Xa inhibitors suggest that they will transfer into breastmilk and, for rivaroxaban, a single case report has confirmed this to be the case in humans (Wiesen et al , ). No animal data for dabigatran exists, however data from the Dalmation study [Eudra CT 2014‐004249‐29] has recently posted results from two subjects of their open‐label phase II clinical trial of dabigatran in breastfeeding women, which suggest that dabigatran does transfer into breastmilk [available at https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004249-29/results].…”

Direct-Acting Oral Anticoagulants (DOACs) in Cirrhosis and Cirrhosis-Associated Portal Vein Thrombosis

“…98 Wiesen et al capitalized on a rare situation when a lactating woman was diagnosed with a lower extremity VTE in their hospital. 99 The patient had ceased breastfeeding due a postpartum cardiomyopathy and was treated initially with enoxaparin followed by rivaroxaban. 99 During weaning, breast milk samples were collected for analysis of rivaroxaban levels.…”

“…99 The patient had ceased breastfeeding due a postpartum cardiomyopathy and was treated initially with enoxaparin followed by rivaroxaban. 99 During weaning, breast milk samples were collected for analysis of rivaroxaban levels. 99 Rivaroxaban concentration in the milk reached 40% of the plasma drug concentration, with the estimated relative infant dose to be 1.3%-well below the proposed acceptable 10% exposure concentration.…”

Liquid chromatographic methods for the determination of direct oral anticoagulant drugs in biological samples: A critical review

“…A recent case study aimed to assess the concentration of rivaroxaban in the breast milk of a single woman in the beginning of the lactation period. It showed that rivaroxaban was able to pass into breast milk but conclusions regarding the infant's exposure cannot be drawn based on a single case and without assessing the infant's plasma or urine rivaroxaban concentrations [65].…”