REVIEW OF IDARUCIZUMAB, THE REVERSAL AGENT FOR DABIGATRAN

Transcription

1 REVIEW OF IDARUCIZUMAB, THE REVERSAL AGENT FOR DABIGATRAN Joyce Tsang RPh, PharmD (Candidate), BScPhm, HonsBSc Clinical Pharmacist, Surgery, University Health Network Adjunct Lecturer, Leslie Dan Faculty of Pharmacy CSHP Ontario Branch Education Committee Member

2 Presenter Disclosure Disclosure I have no current or past relationships with commercial entities I have received no speaker s fee for this learning activity Commercial Support Disclosure This program has received no financial or in-kind support from any commercial or other organization

3 Learning Objectives 1. Briefly review the clinical properties and the availability of idarucizumab. 2. Summarize the available evidence for the efficacy and safety of idarucizumab. 3. Discuss the clinical implications and suggested place in therapy of idarucizumab.

4 Idarucizumab (Praxbind ) Humanized monoclonal antibody fragment Specific binding to dabigatran Not procoagulant Dosing: 5 grams Divided into two 2.5 grams IV bolus Eikelboom JW, Quinlan DJ, Van Ryn, J et al. Idarucizumab The antidote for Reversal of Dabigatran. Circulation. 2015; 132:

5 Mechanism of Action Eikelboom JW, Quinlan DJ, Van Ryn, J et al. Idarucizumab The antidote for Reversal of Dabigatran. Circulation. 2015; 132:

6 Clinical Properties Onset Half-life Metabolism Immediate Distribution phase: 47 mins Terminal phase: 10 hrs Protein catabolism Elimination Urine: 32% Storage Fridge (2ºC to 8ºC) Protect from light Praxbind Idarucizumab Product Monograph. Boehringer Ingelheim INC p 1 to 15

7 Availability of Idarucizumab Conditionally approved by Health Canada in April 2016 for rapid reversal of dabigatran in the following scenarios: Emergency surgery or Life threatening/uncontrolled bleeding Conditional pending full clinical trial Cost: ~$2000 for 2.5g/50mL vial Health Canada Notice of Compliance Database. Idarucizumab. Accessed June 6, 2016

8 Phase III trial: RE-VERSE AD Eikelboom JW, Quinlan DJ, Van Ryn, J et al. Idarucizumab The antidote for Reversal of Dabigatran. Circulation. 2015; 132:

9 Efficacy: Phase III interim report Pollack CV, Reilly, PA, Eikelboom J et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373(6):

10 Efficacy: Phase III interim report Pollack CV, Reilly, PA, Eikelboom J et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373(6):

11 1. Pollack CV, Reilly, PA, Eikelboom J et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373(6): Eikelboom JW, Quinlan DJ, Van Ryn, J et al. Idarucizumab The antidote for Reversal of Dabigatran. Circulation. 2015; 132: Adverse reactions Safety Phase III (n = 123) Healthy Volunteers (n = 224) Thromboembolism 4% None observed Hypersensitivity reactions Immunogenicity reaction Hereditary Fructose Intolerance Pyrexia, Bronchospasm, rash, pruritus Not studied Not studied None observed Pre-existing & Post-dose antibodies Not studied Proteinuria Not studied Peak in 4hrs

12 Clinical Implications Reversal for dabigatran at a high cost Renal impairment does not affect reversal Dabigatran can be restarted in 24 hours Elevated coagulation parameters hours Repeat 5g dose? Look alike sound alike to idarubicin

13 Suggested Place in Therapy Eikelboom JW, Quinlan DJ, Van Ryn, J et al. Idarucizumab The antidote for Reversal of Dabigatran. Circulation. 2015; 132:

14 Summary Idarucizumab is available in the Canadian market. Idarucizumab specifically reverses the anticoagulant activity of dabigatran reliably for 12 hours. Questions remaining: Safety of giving a second 5 gram dose of idarucizumab Time to bleeding cessation despite rapid reversal

15 References Eikelboom JW, Quinlan DJ, Van Ryn, J et al. Idarucizumab The antidote for Reversal of Dabigatran. Circulation. 2015; 132: Praxbind Idarucizumab Product Monograph. Boehringer Ingelheim INC p 1 to 15 Dosage and Administration Canadian Agency for Drugs and Technologies in Health. Antidote Treatments for the Reversal of Direct Oral Anticoagulants. Issues in Emerging Health Technologies. June pp1-11 Dager WE, Gosselin RC, Kitchen S et al. Dabigatran Effects on the International Normalized Ratio, Activated Partial Thromboplastin Time, Thrombin Time, and Fibrinogen: A Multicenter, In Vitro Study. Anticoagulation. 2012; 46: Gosselin R, Hawes E, Moll S, and Adcock D. Performance of Various Laboratory Assays in the Measurement of Dabigatran in Patients Receiving Therapeutic Doses. A Prospective Study Based on Peak and Trough Plasma Levels. Am J Clin Patho. 2014; 141 (2): Health Canada Notice of Compliance Database. Idarucizumab. Accessed June 6, 2016 ISMP. Warning: Don t confuse idarucizumab and IDArubicin. Acute care ISMP Medication Safety Alert! Nov (22):1-5 Pollack CV, Reilly, PA, Eikelboom J et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373(6): Tummala R, Kevtaradze A, Gupta A, et al. Review: Specific antidotes against direct oral anticoagulant: A comprehensive review of clinical trials data. Int J Cardiol. 2016;214 (2016)

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