Praxbind Drug Information

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 PRAXBIND is a humanized monoclonal antibody fragment (Fab) 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

Preparation

Remove both vials (each containing 2.5 g/50 mL idarucizumab) from carton. Ensure aseptic handling when preparing the infusion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Once solution has been removed from the vial, administration should begin promptly. The solution in vials may be stored at room temperature, 25°C (77°F), but must be used within 6 hours.

Administration

Do not mix with other medicinal products. Use aseptic technique when administering PRAXBIND. A pre-existing intravenous line may be used for administration of PRAXBIND.

The line must be flushed with sterile 0.9% Sodium Chloride Injection, USP solution prior to infusion. No other infusion should be administered in parallel via the same intravenous access. PRAXBIND treatment can be used in conjunction with standard supportive measures, which should be considered as medically appropriate.

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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In three healthy volunteer clinical trials, 224 subjects were treated with idarucizumab. Among those subjects treated with idarucizumab, adverse reactions reported in ≥5% of subjects was headache (12/224, 5%).

In the RE-VERSE-AD ® (RE-VERSal Effects of idarucizumab on Active Dabigatran) trial, a total of 503 dabigatran-treated patients were administered idarucizumab either because they required an emergency surgery or urgent procedure, or because they presented with life-threatening or uncontrolled bleeding. Of the 503 dabigatran-treated patients in the entire study period, 101 patients died, 19 within the first day after idarucizumab dosing; each of these deaths could be attributed either as a complication of the index event or associated with co-morbidities. Most of these patients were not on antithrombotic therapy at the time of the event, and in each of these cases, the thrombotic event could be attributed to the underlying medical condition of the patient.

Hypersensitivity Pyrexia, bronchospasm, hyperventilation, rash, and pruritus have been reported in clinical trials with idarucizumab.

Immunogenicity As with all proteins there is a potential for immunogenicity with idarucizumab. Detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease.

For these reasons, comparison of the incidence of antibodies to idarucizumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. Using an electro-chemiluminescence (ECL) based assay, plasma samples from 283 subjects (224 treated with idarucizumab) in phase I trials and 501 patients were tested for antibodies cross-reacting with idarucizumab. The majority of pre-existing antibodies were shown to have low titers.

No impact on the pharmacokinetics or the reversal effect of idarucizumab or hypersensitivity reactions were observed. Nine patients were re-dosed with idarucizumab. All nine patients were re-dosed within 6 days after the first idarucizumab dose.

None of these patients re-dosed with idarucizumab tested positive for anti-idarucizumab antibodies. The epitope specificity of antibodies to idarucizumab was characterized using probe molecules. For pre-existing antibodies in patients, 95% (18/19) had specificity for the C-terminus, a region of idarucizumab to which dabigatran does not bind.

Pregnancy Risk Summary There are no available data on PRAXBIND use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproductive and development studies have not been conducted with idarucizumab. It is also not known whether PRAXBIND can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

PRAXBIND should be given to a pregnant woman only if clearly needed. The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Pediatric Use Safety and effectiveness have not been established in pediatric patients.