Praxbind® (idarucizumab) is indicated in patients treated with Pradaxa® when reversal of the anticoagulant effects of dabigatran is needed:
PRAXBIND has been specifically developed to reverse the anticoagulant effects of dabigatran, the active ingredient in PRADAXA® (dabigatran etexilate).1,2
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.
†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.
‖Based on determination for dTT or ECT.
¶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
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.
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.
Pyrexia, bronchospasm, hyperventilation, rash, and pruritus have been reported in clinical trials with idarucizumab.
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.
PRAXBIND 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 immediately after administration.1
Restores thrombin activity by binding to dabigatran with ~350-fold higher affinity than dabigatran to thrombin5
**Emergency surgery or urgent procedure is defined as a procedure that cannot be delayed for a minimum of 8 hours.4
††Life-threatening or uncontrolled bleeding is defined as overt bleeding that is judged by the treating clinician to require a reversal agent.4
‡‡Cessation and normalization assessments were subjective and based upon investigator visualization or measurement.
§§Click here to learn about the RE-VERSE AD trial.
‖‖Coagulation factors and dialysis have not been evaluated in clinical trials and clinical experience for the management of medical emergencies is limited.
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.
PRAXBIND is a specific reversal agent for PRADAXA, with no impact on the effect of other anticoagulant or antithrombotic therapies.
#These recommendations are not intended to replace clinical judgment or to dictate individual patient care.
*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.
References: 1. PRAXBIND [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2. PRADAXA [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 3. Data on file. Boehringer Ingelheim Pharmaceuticals, Inc. 4. Pollack CV Jr, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal – full cohort analysis. N Engl J Med. 2017;377(5):431-441; 1-13 [suppl appendix]. 5. Schiele F, van Ryn J, Canada K et al. A specific antidote for dabigatran: functional and structural characterization. Blood. 2013;121(18):3554-3562. 6. American College of Cardiology. Update on reversal agents for novel oral anticoagulants. 2015 http://www.acc.org/latest-in-cardiology/articles/2015/12/11/08/20/update-on-reversal-agents-for-novel-oral-anticoagulants. Accessed October 19, 2016. 7. Data on file. Boehringer Ingelheim Pharmaceuticals, Inc. 8. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. [published correction appears in Circulation. 2014;130:e199-e267.] Circulation. 2014;129:1-123.
Pradaxa® (dabigatran etexilate) Capsules is indicated:
Premature discontinuation of any oral anticoagulant, including PRADAXA, increases the risk of thrombotic events. If anticoagulation with PRADAXA is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant
Epidural or spinal hematomas may occur in patients treated with PRADAXA who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:
Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients who are or will be anticoagulated.
PRADAXA is contraindicated in patients with:
Increased Risk of Thrombotic Events after Premature Discontinuation
Premature discontinuation of any oral anticoagulant, including PRADAXA, in the absence of adequate alternative anticoagulation, increases the risk of thrombotic events. If PRADAXA Capsules is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant and restart PRADAXA Capsules as soon as medically appropriate.
Risk of Bleeding
Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves
The use of PRADAXA is contraindicated in all patients with mechanical prosthetic valves due to a higher risk for thromboembolic events, especially in the post-operative period, and an excess of major bleeding for PRADAXA vs. warfarin. Use of PRADAXA for the prophylaxis of thromboembolic events in patients with AFib in the setting of other forms of valvular heart disease, including bioprosthetic heart valve, has not been studied and is not recommended.
Effect of P-gp Inducers & Inhibitors on Dabigatran Exposure
Concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided. P-gp inhibition and impaired renal function are major independent factors in increased exposure to dabigatran. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to increase exposure of dabigatran compared to either factor alone.
Reduction of Risk of Stroke/Systemic Embolism in NVAF in Adult Patients.
Treatment and Reduction in the Risk of Recurrence of DVT/PE & Prophylaxis of DVT/PE Following Hip Replacement Surgery in Adult Patients.
Increased Risk of Thrombosis in Patients with Triple-Positive Antiphospholipid Syndrome
There is an increased risk of thrombosis in patients with triple-positive antiphospholipid syndrome. PRADAXA use is not recommended.
The most common adverse reactions (>15%) reported with PRADAXA are gastrointestinal adverse reactions and bleeding.
Other Measures Evaluated
In NVAF patients, a higher rate of clinical MI was reported in patients who received PRADAXA (0.7/100 patient-years for 150 mg dose) than in those who received warfarin (0.6).
Pregnancy: The limited available data on PRADAXA use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes.
Lactation: Breastfeeding is not recommended.
Females and Males of Reproductive Potential: Discuss pregnancy planning with females of reproductive potential requiring anticoagulation. Assess the risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, in females of reproductive potential and those with abnormal uterine bleeding.
Pediatric Use: The safety and effectiveness of PRADAXA Capsules for the treatment and the reduction in risk of recurrence of venous thromboembolism have been established in pediatric patients 8 to less than 18 years of age. Other age-appropriate pediatric dosage forms of dabigatran etexilate are available for pediatric patients less than 8 years of age for these indications. Safety and effectiveness of PRADAXA Capsules have not been established in pediatric patients with non-valvular atrial fibrillation or those who have undergone hip replacement surgery.
Geriatric: Risk of bleeding increases with age.
CL-PX-100063 06.28.21
Please see full Prescribing Information, including boxed WARNING and Medication Guide.
Praxbind® (idarucizumab) is indicated in patients treated with Pradaxa® when reversal of the anticoagulant effects of dabigatran is needed:
CL-PB-100001 April 2018
Please click here for full Prescribing Information for PRAXBIND.