Photo by Nina Matthews
New research suggests the anticoagulant rivaroxaban can cross the placenta in pregnant women, raising concerns that the drug might
cause side effects in unborn children.
The ex vivo study, published in the American Journal of Obstetrics & Gynecology, showed that rivaroxaban can rapidly cross the human placenta in both directions.
The researchers did not draw any conclusions about the potential link between rivaroxaban and birth defects, but they said additional research is needed to explore this possibility.
Gideon Koren, MD, of the Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study using an ex vivo placenta perfusion model.
They added rivaroxaban (250 ng/mL) to the maternal circulation, the fetal circulation, or both and observed the effects over 3 hours. They measured rivaroxaban concentrations via liquid chromatography-tandem mass spectrometry.
The researchers said they saw “rapid transfer” of rivaroxaban across the placenta, both in the maternal-to-fetal and fetal-to-maternal directions.
Three hours after they added rivaroxaban to the maternal reservoir, the median fetal concentration of the drug was 69.5 ng/mL, and the median fetal-to-maternal ratio was 0.69.
Three hours after they added rivaroxaban to the fetal reservoir, the maternal concentration of rivaroxaban was 58.2 ng/mL, and the maternal-to-fetal ratio was 0.69.
When the researchers added equal concentrations of rivaroxaban to both reservoirs, the fetal-to-maternal ratio remained relatively constant over the 3-hour period. And the rate of rivaroxaban disappearance was similar in both reservoirs—1.51 ng/mL/min in the maternal reservoir and 1.86 ng/mL/min in the fetal reservoir.
The researchers said this is the first direct evidence of rivaroxaban transfer across the placenta from both directions.
However, they also noted that, because rivaroxaban is highly bound to plasma proteins, the amount of unbound drug that may reach the fetus is likely much lower than observed in these experiments.
Nevertheless, additional studies should be conducted before rivaroxaban can be safely administered to pregnant women.
