FDA Approves First Dabigatran Reversal Agent

The FDA has granted accelerated approval for idarucizumab (Praxbind) to reverse the anticoagulant effects of dabigatran (Pradaxa) in emergency situations. Idarucizumab, an injectable monoclonal antibody fragment, binds to dabigatran and thereby neutralizes its effect.

Approval was based on three trials in which some 280 healthy adults who did not require anticoagulant therapy were given dabigatran and, subsequently, idarucizumab. After receipt of the latter agent, participants’ unbound plasma concentration of dabigatran fell immediately and remained reduced for at least 24 hours. In a fourth, ongoing trial, over 120 patients on dabigatran were given idarucizumab because they had problematic bleeding or required emergency surgery. Idarucizumab completely reversed dabigatran’s anticoagulant effect within 4 hours in nearly 90% of participants.

The most common side effects observed included headache (in healthy volunteers), hypokalemia, confusion, constipation, fever, and pneumonia.

Given the risk for blood clots and stroke upon stopping dabigatran, idarucizumab’s label recommends resuming anticoagulant treatment as soon as medically appropriate.

Harlan Krumholz, editor-in-chief of NEJM Journal Watch Cardiology, weighed in: “The introduction of this product is welcome news. Concerns about bleeding are common, and the availability of this agent should improve the safety profile of dabigatran. I hope that it is priced reasonably since it is designed to overcome a risk of the manufacturer’s own drug.” (Note: Physician’s First Watch later reported that the U.S. wholesale acquisition cost would be $3500, according to the manufacturer.)