Product Monograph - Pradaxa® Reversal Agent

1 Product Monograph1 Please see safety information throughout. Please see complete Important Safety Information on page 14 and full Prescribing ..3 Indications and Usage ..3 Dosage and Administration ..4 Description ..5 Clinical Pharmacology ..5 Clinical Studies ..7 Contraindications ..9 Warnings and Precautions ..10 Adverse Reactions ..10 Use in Specific Populations ..12 Nonclinical Toxicology ..12 Dosage Forms and Strengths ..13 How Supplied/Storage and Handling ..13 Patient Counseling Information ..13 Important Safety Information ..142 Please see safety information throughout. Please see complete Important Safety Information on page 14 and full Prescribing PRAXBIND is an immediate and specific Reversal Agent for PRADAXA 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 This indication is approved under accelerated approval based on a reduction in unbound dabigatran and normalization of coagulation parameters in healthy volunteers.

2 Continued approval for this indication may be contingent upon the results of an ongoing cohort case series study The recommended dose of PRAXBIND is 5 g, provided as 2 separate 50-mL vials, each containing g In an interim analysis of an ongoing trial in actively treated PRADAXA patients, PRAXBIND immediately reversed the anticoagulant activity of dabigatran in all patients with complete Reversal occurring in 9 out of 10 PRAXBIND is a humanized monoclonal antibody fragment (Fab) that binds to dabigatran and its acyl glucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing their anticoagulant effect Most frequently reported adverse events in 5% of healthy volunteers was headache and in 5% of patients were: hypokalemia, delirium, constipation, pyrexia, and pneumonia Low potential for immune reactions 4% of volunteers had low levels of possibly persisting treatment-emergent antibodies (low titers) PRAXBIND alone has shown no procoagulant effect measured as endogenous thrombin potential (ETP) Patients being treated with PRADAXA therapy have underlying disease states that predispose them to thromboembolic events.

3 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 PRADAXA can be reinitiated 24 hours after administration of PRAXBINDI ndications and UsagePRAXBIND 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 bleedingThis indication is approved under accelerated approval based on a reduction in unbound dabigatran and normalization of coagulation parameters in healthy volunteers. Continued approval for this indication may be contingent upon he results of an ongoing cohort case series is an immediate and specific Reversal Agent for PRADAXA3 Please see safety information throughout.

4 Please see complete Important Safety Information on page 14 and full Prescribing PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE PRAXBIND is indicated in patients treated with Pradaxa when rapid Reversal of the anticoagulant effects of dabigatran is required: For emergency surgery/urgent procedures In life-threatening or uncontrolled bleeding This indication is approved under accelerated approval based on a reduction in unbound dabigatran and coagulation parameters in healthy volunteers and based on interim analyses of a single cohort study in dabigatran-treated patients with life-threatening or uncontrolled bleeding, or who require emergency surgery or urgent procedure (RE-VERSE AD) [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon XXXXXXX. 2 DOSAGE AND ADMINISTRATION For intravenous use only.

5 Recommended Dose The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing g/50 mL idarucizumab (see Figure 1).There is limited data to support administration of an additional 5 g of PRAXBIND [see Warnings and Precautions ( )] Preparation 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 or within 1 hour. Administration Do not mix with other medicinal products. Use aseptic technique when administering PRAXBIND. Intravenously administer the dose of 5 grams (2 vials, each contains g) as oTwo consecutive infusions (see Figure 2) or oBolus injection by injecting both vials consecutively one after another via syringe (see Figure 3).

6 A pre-existing intravenous line may be used for administration of PRAXBIND. The line must be flushed with sterile 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[see Clinical Pharmacology ( )].Figure 1 Recommended dose of PRAXBIND provided as two vials Figure 2 Two consecutive infusions by hanging vials Figure 3 Two consecutive bolus injections via syringe Restarting Antithrombotic Therapy Patients being treated with dabigatran therapy have underlying disease states that predispose them to thromboembolic events.

7 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. Dosage and AdministrationFor intravenous use DoseThe recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing g/50 mL idarucizumab (see Figure 1). There is limited data to support administration of an additional 5 g of 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.

8 Once solution has been removed from the vial, administration should begin promptly or within 1 Do not mix with other medicinal products. Use asepctic technique when administering PRAXBIND. Intravenously administer the dose of 5 g (2 vials, each contains g) as Two consecutive infusions (see Figure 2) or Bolus injection by injecting both vials consecutively one after another via syringe (see Figure 3). A pre-existing intravenous line may be used for administration of PRAXBIND. The line must be flushed with sterile 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 Antithrombotic TherapyPatients being treated with dabigatran therapy have underlying disease states that predispose them to thromboembolic events.

9 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 is a specific Reversal Agent for dabigatran, with no impact on the effect of other anticoagulant or antithrombotic treatment can be initiated 24 hours after administration of recommended dose of PRAXBIND is 5 g, provided as 2 separate 50-mL vials, each containing gPRADAXA can be reinitiated 24 hours after administration of PRAXBINDFULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE PRAXBIND is indicated in patients treated with Pradaxa when rapid Reversal of the anticoagulant effects of dabigatran is required: For emergency surgery/urgent procedures In life-threatening or uncontrolled bleeding This indication is approved under accelerated approval based on a reduction in unbound dabigatran and coagulation parameters in healthy volunteers and based on interim analyses of a single cohort study in dabigatran-treated patients with life-threatening or uncontrolled bleeding, or who require emergency surgery or urgent procedure (RE-VERSE AD) [see Clinical Studies (14)].

10 Continued approval for this indication may be contingent upon XXXXXXX. 2 DOSAGE AND ADMINISTRATION For intravenous use only. Recommended Dose The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing g/50 mL idarucizumab (see Figure 1).There is limited data to support administration of an additional 5 g of PRAXBIND [see Warnings and Precautions ( )] Preparation 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 or within 1 hour. Administration Do not mix with other medicinal products. Use aseptic technique when administering PRAXBIND.