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Praxbind® - IdarucizumabManufacturer: Boehringer Ingelheim
Pharmaceuticals, Inc.
FDA Approval Date: 10/16/2015
Praxbind® - Idarucizumab
Objectives
• At the end of this presentation participants will be able to:1. Appropriately recommend Praxbind® -
(idarucizumab)
2. Effectively educate patients on the purpose, proper use and potential adverse effects of Praxbind® - (idarucizumab)
Praxbind® - Idarucizumab
Clinical Application
• Indications:• Patient’s treated with Pradaxa (dabigatran)
that require anticoagulation reversal in cases of:• Emergency Surgery or Urgent
Procedure• Life Threatening Bleeding
• Place in therapy:• First in market reversal agent for new oral
anticoagulation dabigatran
Praxbind ® [package insert].
Praxbind® - Idarucizumab
Clinical Application
• Contraindications:• None
• Warnings and Precautions:• Thromboembolic risk
• Re-elevation of coagulation parameters
• Hypersensitivity
• Fructose intolerance
Praxbind ® [package insert].
Praxbind® - Idarucizumab
Clinical Application
• Pregnancy:• No Data
• Lactation:• No Data
Praxbind ® [package insert].
Praxbind® - Idarucizumab
Drug Facts
• Pharmacology:• Humanized monoclonal antibody
fragment (Fab) that binds to dabigatran and its acylglucuronide metabolites with an affinity higher than that of thrombin
• This specific binding neutralizes the anticoagulation effect of dabigatran
• Antibody is lock/key with dabigatran
Praxbind ® [package insert].
Praxbind® - Idarucizumab
Drug Facts
• Pharmacokinetics:• A – t ½ 47 minutes, terminal t ½ 10.3h • D – Multiphasic with limited
extravascular distribution. VoD 8.9 L• M – Biodegradation of the antibody to
small peptides• E – ~30% eliminated in the urine, the rest
is eliminated via degradation
Praxbind ® [package insert].
Praxbind® - Idarucizumab
Drug Interactions
• No remarkable drug interactions determined via a theoretical mechanism, in vitro assessment, or in animal models
Praxbind ® [package insert].
Praxbind® - Idarucizumab
Adverse Effects
• Healthy volunteers• Headache 5%
• REVERSE-AD trial• Hypokalemia: 7%• Delirium: 7%• Constipation 7%• Pyrexia: 6%• Pneumonia: 6%
• Serious Adverse Effects:• 5 of 123 patients in the REVERSE-AD trial had a thrombotic
event
Praxbind ® [package insert].
Praxbind® - Idarucizumab
Monitoring Parameters
• Efficacy Monitoring:• Baseline aPTT, re-evaluation of aPTT at
12 and 24 hours
• Monitor for signs and symptoms of bleed
• Toxicity Monitoring:• Monitor for hypersensitivity or
immunogenic reactions
Praxbind ® [package insert].
Praxbind® - Idarucizumab
Prescription Information
• Dosing: 5 g infusion: provided as two 2.5g/50 mL vials. There is limited data to support a second 5 g infusion
• Cost: – NEJM Journal Watch. November 5, 2015• 2.5g/50 mL vial ~$3500
• Cost per treatment: $7000
Praxbind ® [package insert].
PRAXBIND® - IDARUCIZUMAB
RE-VERSE AD TRIAL
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Praxbind® - Idarucizumab
RE-VERSE AD Trial
• Purpose: Examine efficacy and safety of idarucizumab for dabigatran reversal
• Study Design:• Multicenter, prospective cohort study
• Interim analysis, data on 90 of 300 pts
• Each patient received two 2.5 g infusions 15 minutes apart
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Praxbind® - Idarucizumab
REVERSE-AD Trial
• Inclusion: • 18 y/o, and on dabigatran
• Group A: Life-threatening bleed
• Group B: Urgent surgery or procedure required
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Praxbind® - Idarucizumab
Endpoints
• Primary:• Maximum percentage reversal
• Secondary:• Proportion with normalization of dilute
thrombin time• Proportion with normalization of ecarin
clotting time• Reduction in concentration of unbound
dabigatran
• Safety: • All adverse events captured
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Praxbind® - Idarucizumab
Patient Characteristics
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Baseline CharacteristicsAge 77
Race 87%
CrCL 62 mL/min
Atrial Fibrillation 96%
Last dose of dabigatran 15 hr
Elevated Dilute thrombin time at baseline 76%
Elevated ecarin clotting time at baseline 90%
Praxbind® - Idarucizumab
Results
• 22 patients had dilute thrombin times that were within normal limits and 9 of those patients had normal clotting times excluding these 22 pts from analysis (Group A - 40 patients and Group B - 28 patients).
• 81 of 90 were assessed with ecarin-clotting time test (Group A - 47 patients and Group B - 34 patients).
• All patients received idarucizumab regardless of their inclusion in the efficacy analysis
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Praxbind® - Idarucizumab
Results
• Primary:
• Maximum percentage reversal in Groups A and B was 100%
• Reversal was evident on first sample taken after infusion
• Secondary:
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Normalization of clotting time Dilute Thrombin
TimeEcarin Clotting
TimeGroup A 98% 89%Group B 93% 88%
Praxbind® - Idarucizumab
Safety
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Safety Outcomes
Death 18/90 (20%)
Serious Adverse Event 21/90 (23.3%)
MI 1/90 (1%)
Stroke 1/90 (1%)
DVT/PE 3/90 (3.3%)
Praxbind® - Idarucizumab
Conclusions
• Praxbind® is effective in reversing anticoagulation of dabigatran
• Minimal adverse event profile
• Small population using dabigatran will limit the impact of this medication
Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.
Praxbind® - Idarucizumab
Summary
• Praxbind®, idarucizumab, is a humanized monoclonal antibody that reverses the anticoagulation effect of dabigatran
• Idarucizumab is indicated for patients treated with dabigatran that have a life-threatening or uncontrolled bleed, or require an emergency or urgent procedure
• Idarucizumab is 5g administered as two 2.5g infusions
• There is a risk of rebound anticoagulation 12-24 hours after administration
• Hypersensitivity reactions are possible despite humanization of the antibody
Praxbind® - Idarucizumab
References
1. http://www.praxbind.com/ Accessed 11/20/2015.
2. Praxbind package insert. Boehringer Ingelheim Pharmaceuticals, Inc. Oct 2015.
3. Boehringer Ingelheim Pharmaceuticals Inc. Praxbind ® approval announcement. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm467396.htm. Accessed 11/20/15.
4. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015 Aug 6;373(6):511-20.