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10/19/2015

Idarucizumab Approved to Reverse Anticoagulant Effects of Dabigatran

Kate Traynor

Kate TraynorNews Writer
News Center

FDA and Boehringer Ingelheim on October 16 announced the approval of idarucizumab injection to reverse the anticoagulant effects of dabigatran.

The reversal agent will be available through U.S. hospital distributors as quickly as possible under the brand name Praxbind, according to the company.

Labeling for idarucizumab states that it is a recombinant humanized monoclonal antibody that binds to dabigatran and its acylglucuronide metabolites, inhibiting the binding of dabigatran to thrombin and neutralizing that drug’s antithrombotic effects.

Idarucizumab is indicated for use in patients taking dabigatran who require emergency surgery or urgent procedures and during episodes of life-threatening or uncontrolled bleeding.

Idarucizumab was licensed under FDA’s accelerated approval pathway on the basis of preliminary data from studies of healthy volunteers. Boehringer Ingelheim must submit additional clinical data to FDA confirm the preliminary findings.

The recommended dosage of idarucizumab is two consecutively administered 2.5-g doses. The monoclonal antibody may be infused directly from the vials or injected as i.v. boluses.

Idarucizumab may be administered through a previously placed i.v. line that has been flushed with 0.9% Sodium Chloride Injection, USP. No other medications should be coadministered through the i.v. line along with the reversal agent.

A second 5-g dose may be considered if clinically relevant bleeding persists or additional surgical or urgent procedures are required, although the safety and efficacy of the second dose have not been established, according to the labeling.

The labeling warns that the underlying factors that led to the use of dabigatran remain after the anticoagulant’s effects are reversed. Anticoagulant therapy should be restarted as soon as possible after the administration of idarucizumab, according to the labeling.

Idarucizumab contains sorbitol and may cause adverse events in patients with hereditary fructose intolerance.

Headache was the most frequently reported adverse event in healthy volunteers treated with idarucizumab in clinical studies.

Among the 123 dabigatran-treated patients who received idarucizumab as part of the reversal agent’s major clinical trial, hypokalemia, delirium, constipation, fever, and pneumonia were the most frequently reported adverse events.

According to an interim analysis, 26 of these patients, all of whom received idarucizumab for the now-approved indications, died, including 11 who died within 24 hours of receiving the reversal agent. The labeling states that the deaths could be attributed to a complication of the index event or a comorbid condition.

Idarucizumab will be supplied in cartons containing two 2.5-g vials that should be refrigerated at 2–8 °C and never frozen or shaken. The vials, each containing 50 mL of idarucizumab solution, may be brought to room temperature for up to 48 hours before administration if kept in the original packaging. After exposure to light, the vials should be administered within six hours.

[This news story appears in the December 1, 2015, issue of AJHP.]