Praxbind (idarucizumab), the first reversal agent for the anticoagulant Pradaxa(dabigatran)

October 16, 2015

FDA approves Praxbind, the first reversal agent for the anticoagulant Pradaxa.

The U.S. Food and Drug Administration granted accelerated approval to Praxbind (idarucizumab) for use in patients who are taking the anticoagulant Pradaxa (dabigatran) during emergency situations when there is a need to reverse Pradaxa’s blood-thinning effects.

Idarucizumab is a humanized monoclonal antibody fragment (Fab) derived from an IgG1 isotype molecule, whose target is the direct thrombin inhibitor dabigatran.

Using recombinant expression technology, idarucizumab is produced in a well characterized recombinant (mammalian) CHO cell line and is purified using standard technology.

Idarucizumab is composed of a light chain of 219 amino acids and a heavy chain fragment of 225 amino acids, covalently linked together by one disulfide bond between cysteine 225 of the heavy chain fragment and cysteine 219 of the light chain, and has an estimated molecular mass of approximately 47,766 Daltons.

CLINICAL PHARMACOLOGY

Mechanism of Action

Idarucizumab is a specific reversal agent for dabigatran. It is a humanized monoclonal antibody fragment (Fab) that binds to dabigatran and its acylglucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing their anticoagulant effect.

INDICATIONS AND USAGE

PRAXBIND is indicated in patients treated with Pradaxa when reversal of the anticoagulant effects of dabigatran is needed:

• For emergency surgery/urgent procedures

• In life-threatening or uncontrolled bleeding

DOSAGE AND ADMINISTRATION

The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing 2.5 g/50 mL idarucizumab  There is limited data to support administration of an additional 5 g of PRAXBIND.

praxbind

 Restarting Antithrombotic Therapy

Patients being treated with dabigatran therapy have underlying disease states that predispose them to thromboembolic events. Reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate.

Idarucizumab is a specific reversal agent for dabigatran, with no impact on the effect of other anticoagulant or antithrombotic therapies.

Pradaxa treatment can be initiated 24 hours after administration of PRAXBIND.

SAFETY & EFFICACY

The safety and effectiveness of Praxbind were studied in three trials involving a total of 283 healthy volunteers taking Pradaxa (i.e., people who did not require an anticoagulant).

In the healthy volunteers who were given Praxbind, there was an immediate reduction in the amount of Pradaxa in participants’ blood (measured as unbound dabigatran plasma concentration) that lasted for a period of at least 24 hours. In this study, the most common side effect from use of Praxbind was headache.

Another trial included 123 patients taking Pradaxa who received Praxbind due to uncontrolled bleeding or because they required emergency surgery. In this ongoing trial, based on laboratory testing, the anticoagulant effect of Pradaxa was fully reversed in 89 percent of patients within four hours of receiving Praxbind. In this patient trial, the most common side effects were low potassium (hypokalemia), confusion, constipation, fever and pneumonia.

WARNINGS AND PRECAUTIONS

Thromboembolic Risk: Reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease. Resume anticoagulant therapy as soon as medically appropriate.

Re-elevation of Coagulation Parameters: In patients with elevated coagulation parameters and reappearance of clinically relevant bleeding or requiring a second emergency surgery/urgent procedure, an additional 5 g dose of PRAXBIND may be considered.

Hypersensitivity reactions: Discontinue administration and evaluate.

Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient: Patients with hereditary fructose intolerance may be at risk of adverse reactions

Praxbind and Pradaxa are both marketed by Boehringer Ingelheim of Ridgefield, Connecticut.

SOURCE:

FDA News