Xarelto Pregnancy Risks Require Further Studies, After Evidence Drug Crosses Placenta

New research suggests that the controversial anticoagulant Xarelto may cross the placenta in pregnant women, potentially causing side effects for unborn children, leading to calls for further studies to clarify the pregnancy risks of Xarelto.

Potential questions about the safety of Xarelto in pregnancy were raised in a study published last week in the American Journal of Obstetrics & Gynecology, which found that the medication rapidly transfers across the human placenta in both directions.

Xarelto (rivaroxaban) is a new-generation anticoagulant used for reduction of blood clots among individuals suffering from atrial fibrillation. However, concerns about the potential side effects of Xarelto have emerged, with a large number of adverse event reports involving uncontrollable bleeding and other problems seen since the drug was introduced in 2011.

In this latest study, researchers with The Motherisk Program at the Hospital for Sick Children in Toronto looked at the ability of Xarelto to cross the placenta, which is often seen as the first evidence that a drug’s side effects may impact a developing fetus. Such impacts can be minimal or negligible, but they also could result in Xarelto birth defects, developmental problems later in life or even spontaneous abortions.

Researchers did not draw any conclusions about the potential link between Xarelto and birth defects when the medication is used during pregnancy, but indicated that further studies are needed to explore the potential Xarelto pregnancy risks.

The study used an ex-vivo placenta perfusion model, adding Xarelto to either the maternal or fetal circulation only. They then conducted experiments to detect whether the drug had cross the placenta. Researchers found that there was “rapid transfer” of Xarelto from the mother to the fetus, and from the fetus to the mother, with both having a 69% transfer ratio after just three hours.

“This is the first direct evidence of rivaroxaban transfer across the term human placenta from both the mother to the fetus and fetus to mother,” the researchers concluded. “Our results document that unbound rivaroxaban rapidly crosses the placental barrier via passive diffusion. However, since rivaroxaban is highly bound to plasma proteins (up to 95%), this suggests that the amount of unbound drug that may reach the fetus is likely much lower. Additional studies will need to explore its safety before administering rivaroxaban to a pregnant woman.”

Xarelto Bleeding Concerns

Xarelto was introduced in 2011 as a superior replacement for Coumadin (warfarin), designed to reduce the risk of blood clots among individuals at risk for deep vein thrombosis or pulmonary embolism. Since it hit the market, the drug has been aggressively marketed and has quickly grown to become one of the top selling medications in the United States.

While all blood thinners carry a risk of bleeding problems, Xarelto and other members of this new generation of anticoagulants currently lack an approved antidote that doctors can use to reverse the effects of the drug. While doctors can quickly stop the blood thinning effects of warfarin, there is no Xarelto antidote, leaving physicians unable to stop bleeding problems that may occur during use, which may increase the risk of more severe injury or death.

Hundreds of Xarelto lawsuits are now being pursued against the drug makers, alleging that inadequate warnings were provided about the bleeding risks, and that all potential reversal agents should have been explored before the drug was introduced, which would have made the medication safer.

In December 2014, a panel of federal judges ordered the centralization of all Xarelto bleeding lawsuits, transferring cases filed throughout the federal court system to before U.S. District Judge Eldon Fallon in the Eastern District of Louisiana for coordinated pretrial proceedings.

The first federal Xarelto trials are expected to begin in August 2016, to help gauge how juries may respond to certain evidence and testimony that is likely to be repeated throughout the litigation.