PRAXBIND is a Specific Reversal Agent for PRADAXA1

Praxbind® (idarucizumab) 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 has been specifically developed to reverse the anticoagulant effects of dabigatran, the active ingredient in PRADAXA® (dabigatran etexilate).1,2

  • Ready-to-Use: Learn more about dosing and administration. View now >
  • Available Nationwide: PRAXBIND is stocked in 3400+ locations across all 50 states3*

There are serious risks and adverse reactions to consider when treating patients with PRAXBIND, including warnings and precautions for thromboembolic risk, re-elevation of coagulation parameters, hypersensitivity reactions and risks of serious adverse reactions in patients with hereditary fructose intolerance due to sorbitol excipient. Please see the Important Safety Information and Adverse Reactions sections below.

*Accurate as of 01/03/20, based on the current information provided to Boehringer Ingelheim Pharmaceuticals, Inc. The company cannot guarantee the availability of PRAXBIND at all facilities in every state.

In RE-VERSE AD™, PRAXBIND Reversed the Anticoagulant Effect of PRADAXA in Emergency Situations4

RE-VERSE AD™ Trial: A Study of the RE-VERSal Effects of Idarucizumab on Active Dabigatran

Methods4

  • Study Design: Multicenter, prospective, open-label study
  • Patients: Final study analysis included 503 patients taking dabigatran who were administered PRAXBIND. The patients were divided into two groups:
    • Group A (n=301): Patients who presented with life-threatening or uncontrolled bleeding
    • Group B (n=202): Patients who required emergency surgery or urgent procedures
  • Study Treatment: All patients were to receive 5 g of intravenous PRAXBIND which was administered as two 50-mL bolus infusions, each containing 2.5 g of PRAXBIND, no more than 15 minutes apart
  • Primary Endpoint: To determine the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours of administration of PRAXBIND, based on central laboratory determination of diluted thrombin time (dTT) or ecarin clotting time (ECT) in patients who presented with Pradaxa® (dabigatran etexilate)-related life‑threatening or uncontrolled bleeding (Group A) or who required emergency surgery or urgent procedures (Group B)
    • Reversal was evaluable only for those patients showing prolonged coagulation times prior to idarucizumab treatment1

Median age was 78 years and median creatinine clearance (CrCl) was 53 mL/min. Approximately 62% of patients in Group A and 62% of patients in Group B had been treated with dabigatran 110 mg BID.

Results

REVERSAL OF CLOTTING TIME4‡§

Prolongation in the RE-VERSE AD Finalized Analysis: ECT

Reversal was evident seconds after administration

Change of ECT From Baseline in PRADAXA-Treated Patients From RE-VERSE AD (GROUP A)

Pradaxa + Praxbind 10th/90th percentilesUpper limit normal 5th/95th percentiles n=(293) 375350325300275250225200175150125100755025 Baseline Between vials 10-30min 1h 2h 4h 12h 24h Time post PRAXBIND ECT (seconds) Administration of 1st vial Administration of 2nd vial

Change of ECT From Baseline in PRADAXA-Treated Patients From RE-VERSE AD (GROUP B)

375350325300275250225200175150125100755025 Baseline Between vials 10-30min 1h 2h 4h 12h 24h Time post PRAXBIND ECT (seconds) Pradaxa + Praxbind 10th/90th percentilesUpper limit normal 5th/95th percentiles n=(194) Administration of 1st vial Administration of 2nd vial
  • In a limited number of patients, elevation of coagulation parameters have been observed between 12 and 24 hours after administration of 5 g PRAXBIND4

REVERSAL OF CLOTTING TIME4‡§

Prolongation in the RE-VERSE AD Finalized Analysis: aPTT

Up to 99% of patients achieved complete reversal

Change of aPTT From Baseline in PRADAXA-Treated Patients From RE-VERSE AD

16014012010080604020 Pradaxa + Praxbind 10th/90th percentilesUpper limit normal 5th/95th percentiles n=(486) aPTT (seconds) Baseline Between vials 10-30min 1h 2h 4h 12h 24h Time post PRAXBIND Administration of 1st vial Administration of 2nd vial

Key Findings4

  • Rapid: PRAXBIND rapidly reversed the anticoagulant effect of dabigatran in emergency situations
  • Complete: Median maximum reversal in evaluable patients was 100% in the first 4 hours (primary endpoint; n=503). Most patients achieved complete reversal as measured by ECT (82%), or dTT (99%)

Based on determination for dTT or ECT.

Additional Findings4

  • Cessation of bleeding: 134 (n=203, 67.7%) of the non-ICH patients who had uncontrolled bleeding had confirmed bleeding cessation within 24 hours, with a median time of 2.5 hours
  • Clotting: Among the patients who underwent emergency surgery or urgent procedures (n=197), periprocedural hemostasis was assessed as normal in 93.4% (n=184) of patients, mild abnormal in 5.1% (n=10), and moderately abnormal in 1.5% (n=3)

The time to the cessation of bleeding could not be assessed in the 98 patients with intracranial bleeding, because there is dissociation between the clinical course and the extent of bleeding.

Clinical relevance of findings from
Group A and B is undetermined.

aPTT=activated partial thromboplastin time; ECT=ecarin clotting time; dTT=dilute thrombin time; ULN=upper limit of normal
Determined by mean clotting time below the ULN as measured by ECT and aPTT.
§Blood samples were obtained at baseline, after the first infusion, at 10-30 min after the second infusion, and at 1, 2, 4, 12, and 24 hours.4

Adverse Reactions1

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. The adverse reactions reported in ≥5% of patients were constipation (33/503, 7%) and nausea (23/503, 5%).

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.

Thromboembolic Events1

In the RE-VERSE AD trial, 33 of 503 patients reported thrombotic events, 11 patients within 5 days after treatment with idarucizumab and 22 patients 6 days or more after treatment with idarucizumab. 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.

Patients being treated with PRADAXA therapy have underlying disease states that predispose them to thromboembolic events. Reversing PRADAXA 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.1

PRADAXA treatment can be re-initiated 24 hours after administration of PRAXBIND.

Hypersensitivity1

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. Treatment-emergent possibly persisting anti-idarucizumab antibodies with low titers were observed in 4% (10/224) of healthy subjects and 2% (8/501) of patients treated with idarucizumab.1

There are serious risks and adverse reactions to consider when treating patients with PRAXBIND, including warnings and precautions for thromboembolic risk, re-elevation of coagulation parameters, hypersensitivity reactions and risks of serious adverse reactions in patients with hereditary fructose intolerance due to sorbitol excipient. Please see more complete details of these risks in the Important Safety Information below.

The RE-VERSE AD™ Trial

Click here to see full trial results

INDICATIONS AND USAGE FOR PRAXBIND

Praxbind® (idarucizumab) 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

IMPORTANT SAFETY INFORMATION FOR PRAXBIND

WARNINGS AND PRECAUTIONS

Thromboembolic Risk

  • Dabigatran-treated patients have underlying diseases predisposing them to thromboembolic events. Reversing dabigatran therapy exposes patients to thrombotic risk. Consider resumption of anticoagulant therapy as soon as medically appropriate.

Re-elevation of Coagulation Parameters

  • Elevated coagulation parameters (eg, activated partial thromboplastin time or ecarin clotting time) have been observed in a limited number of PRAXBIND-treated patients. If reappearance of clinically relevant bleeding together with elevated coagulation parameters is observed, or if patients requiring a second emergency surgery/urgent procedure have elevated coagulation parameters, an additional full dose may be considered.

Hypersensitivity Reactions

  • There is insufficient clinical experience evaluating risk of hypersensitivity to idarucizumab, but a possible relationship could not be excluded. Risk of hypersensitivity (eg, anaphylactoid reaction) to idarucizumab or excipients needs to be weighed cautiously against the potential benefit. If serious allergic reaction occurs, immediately discontinue PRAXBIND and institute appropriate treatment.

Risk in Patients With Hereditary Fructose Intolerance

  • PRAXBIND contains 4 g sorbitol as an excipient. When prescribing PRAXBIND in patients with hereditary fructose intolerance, consider the total daily amount of sorbitol/fructose consumption from all sources, as serious adverse reactions (eg, hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure, and death) may occur.

ADVERSE REACTIONS

  • The most frequently reported adverse reaction in ≥5% of idarucizumab-treated healthy volunteers was headache (5%). The most frequently reported adverse reactions in ≥5% of patients were constipation (7%) and nausea (5%).
  • Treatment-emergent antibodies with low titers were observed in 4% of healthy subjects and 2% of patients treated with idarucizumab.

USE IN SPECIFIC POPULATIONS

Pregnancy and Lactation

  • PRAXBIND should be given to a pregnant woman only if clearly needed. Caution should be exercised when PRAXBIND is administered to a nursing woman.

CL-PB-100001 April 2018

Please click here for full Prescribing Information for PRAXBIND.