These Highlights Do Not Include All The Information Needed To Use Praxbind Safely And Effectively. See Full Prescribing Information For Praxbind.

Thromboembolic Events

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 [see Warnings and Precautions (5.1)].

Idarucizumab is a humanized monoclonal antibody fragment (Fab) derived from an IgG1 isotype molecule, whose target is the direct thrombin inhibitor dabigatran. Using recombinant expression technology, idarucizumab is produced in a well characterized recombinant (mammalian) CHO cell line and is purified using standard technology. Idarucizumab is composed of a light chain of 219 amino acids and a heavy chain fragment of 225 amino acids, covalently linked together by one disulfide bond between cysteine 225 of the heavy chain fragment and cysteine 219 of the light chain, and has an estimated molecular mass of approximately 47,766 Daltons.

PRAXBIND (idarucizumab) is a sterile, preservative-free, colorless to slightly yellow, clear to slightly opalescent solution for intravenous administration. PRAXBIND (idarucizumab) is supplied in 2 single-dose vials, each containing 2.5 g of idarucizumab in 50 mL formulated as a buffered, isotonic, solution containing acetic acid glacial (10.05 mg), polysorbate 20 (10 mg), sodium acetate (88.82 mg), sorbitol (2004.20 mg), and water for injection with an osmolality of 270-330 mOsm/kg and a pH of 5.3-5.7.

• Remove both vials (each containing 2.5 g/50 mL idarucizumab) from carton.
• 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. The solution in vials may be stored at room temperature, 25°C (77°F), but must be used within 6 hours [see How Supplied/Storage and Handling (16.2)].

• PRAXBIND is a sterile, preservative-free, colorless to slightly yellow, clear to slightly opalescent solution supplied as 2 single-dose vials each containing 2.5 g/50 mL of idarucizumab.
• NDC number 0597-0197-05: Carton containing two 2.5 g/50 mL vials.

Safety and effectiveness have not been established in pediatric patients.

A total of 454 (90%) patients treated with idarucizumab in the case series trial were 65 years of age and older, and 318 (63%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

• Do not mix with other medicinal products. Use aseptic technique when administering PRAXBIND.
• Intravenously administer the dose of 5 g (2 vials, each contains 2.5 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 0.9% 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 (12.2)].

As with all proteins there is a potential for immunogenicity with idarucizumab. Detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to idarucizumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Using an electro-chemiluminescence (ECL) based assay, plasma samples from 283 subjects (224 treated with idarucizumab) in phase I trials and 501 patients were tested for antibodies cross-reacting with idarucizumab. Pre-existing antibodies with cross-reactivity to idarucizumab were detected in approximately 12% (33/283) of the subjects and 4% (19/501) of patients. The majority of pre-existing antibodies were shown to have low titers. No impact on the pharmacokinetics or the reversal effect of idarucizumab or hypersensitivity reactions were observed. Treatment-emergent possibly persisting anti-idarucizumab antibodies with low titers were observed in 4% (10/224) of the subjects and 2% (8/501) of patients treated with idarucizumab. Nine patients were re-dosed with idarucizumab. All nine patients were re-dosed within 6 days after the first idarucizumab dose. None of these patients re-dosed with idarucizumab tested positive for anti-idarucizumab antibodies.

The epitope specificity of antibodies to idarucizumab was characterized using probe molecules. For pre-existing antibodies in patients, 95% (18/19) had specificity for the C-terminus, a region of idarucizumab to which dabigatran does not bind. For treatment emergent antibodies in patients, 67% (6/9) had specificity for the C-terminus, 22% (2/9) had specificity for the variable region, and 11% (1/9) had mixed specificity.

The safety and effectiveness of PRAXBIND was investigated in three randomized placebo-controlled healthy volunteer trials, Trials 1321.1, 1321.2 and 1321.5 (NCT01688830, NCT01955720, NCT02028780), and in RE-VERSE-AD (RE-VERSal Effects of idarucizumab on Active Dabigatran) trial (NCT02104947), a single cohort case series trial with dabigatran-treated patients who have life-threatening or uncontrolled bleeding, or who require emergency surgery or urgent procedure.

None.

The following serious adverse reactions are described in more detail elsewhere in the labeling:

• Thromboembolic Risk [see Warnings and Precautions (5.1)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.3)]
• Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient [see Warnings and Precautions (5.4)]

The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing 2.5 g/50 mL idarucizumab (see Figure 1). Both vials are packaged together in one carton.

For intravenous use only.

There is limited data to support administration of an additional 5 g of PRAXBIND [see Warnings and Precautions (5.2)].

In healthy subjects aged 45 to 64 years, the plasma concentrations of unbound dabigatran were reduced to below the lower limit of quantification immediately after the administration of 5 g idarucizumab. Subjects' diluted thrombin time (dTT), ECT, aPTT, thrombin time (TT), and activated clotting time (ACT) parameters returned to baseline levels (see Figure 4 and Figure 5). This reduction of dabigatran plasma concentration was observed over the entire observation period of at least 24 hours. Similar findings were also observed in elderly subjects (aged 65 to 80 years) as well as subjects with mild and moderate renal impairment [see Clinical Pharmacology (12.3)].

In a limited number of patients, re-distribution of dabigatran from the periphery to plasma led to re-elevation of dTT, ECT, aPTT, and TT [see Warnings and Precautions (5.2)].

Re-dosing with 2.5 g idarucizumab in 6 healthy subjects aged 45-64 years at 2 months after first infusion revealed no differences in safety and no indication of allergic reactions [see Clinical Pharmacology (12.3)].

No changes in the pharmacokinetics or pharmacodynamics of dabigatran were noted upon re-initiation 24 hours after the administration of idarucizumab [see Dosage and Administration (2.4)].

Figure 4 Plasma-Levels of Unbound Dabigatran in the Representative Group of Healthy Subjects (Administration of Idarucizumab or Placebo at 0 h)

Figure 5 Change of ECT from Baseline in the Representative Group of Healthy Subjects (Administration of Idarucizumab or Placebo at 0 h)

There were no obvious differences in the idarucizumab plasma concentration time profiles when idarucizumab was administered alone or after pretreatment with dabigatran. A dose-dependent increase in the fraction of unchanged idarucizumab excreted in urine was observed.

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

Patients being treated with dabigatran therapy have underlying disease states that predispose them to thromboembolic events. 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 [see Dosage and Administration (2.4)].

Idarucizumab is a specific reversal agent for dabigatran. It 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.

• Store PRAXBIND vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.
• PRAXBIND vials may be stored at room temperature, 25°C (77°F), for up to 48 hours in the original carton to protect from light.
• PRAXBIND vials may be stored at room temperature, 25°C (77°F), out of the carton and exposed to light but must be used within 6 hours [see Dosage and Administration (2.2)].

• Thromboembolic Risk: Reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease. Resume anticoagulant therapy as soon as medically appropriate. (2.4, 5.1)
• Re-elevation of Coagulation Parameters: In patients with elevated coagulation parameters and reappearance of clinically relevant bleeding or requiring a second emergency surgery/urgent procedure, an additional 5 g dose of PRAXBIND may be considered. (5.2)
• Hypersensitivity reactions: Discontinue administration and evaluate. (5.3)
• Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient: Patients with hereditary fructose intolerance may be at risk of adverse reactions. (5.4)

For intravenous use only.

• The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing 2.5 g/50 mL idarucizumab. (2.1)
• There is limited data to support administration of an additional 5 g of PRAXBIND. (2.1)

PRAXBIND is a sterile, preservative-free, colorless to slightly yellow, clear to slightly opalescent solution available as:

Injection: 2.5 g/50 mL solution in a single-dose vial.

There is insufficient clinical experience with PRAXBIND in patients to evaluate risk of hypersensitivity to idarucizumab. In clinical studies adverse events possibly indicative of hypersensitivity reactions where a possible relationship could not be excluded were reported [see Adverse Reactions (6.1)]. The risk of using PRAXBIND in patients with known hypersensitivity (e.g., anaphylactoid reaction) to idarucizumab or to any of the excipients needs to be weighed cautiously against the potential benefit of such an emergency treatment. If an anaphylactic reaction or other serious allergic reaction occurs, immediately discontinue administration of PRAXBIND and institute appropriate treatment.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In three healthy volunteer clinical trials, 224 subjects were treated with idarucizumab. In these trials, during the treatment period, the overall frequency of adverse events was similar between idarucizumab-treated subjects (55/224, 25%) and placebo-treated subjects (26/105, 25%). Among those subjects treated with idarucizumab, adverse reactions reported in ≥5% of subjects was headache (12/224, 5%).

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 [see Clinical Studies (14)]. 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.

Patients being treated with dabigatran therapy have underlying disease states that predispose them to thromboembolic events. 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 [see Clinical Pharmacology (12.2)].

In a limited number of patients in the clinical program, between 12 and 24 hours after administration of 5 g idarucizumab, elevated coagulation parameters (e.g., activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT)) have been observed [see Dosage and Administration (2.1)].

If reappearance of clinically relevant bleeding together with elevated coagulation parameters is observed after administration of 5 g PRAXBIND, administration of an additional 5 g dose of PRAXBIND may be considered. Similarly, patients who require a second emergency surgery/urgent procedure and have elevated coagulation parameters may receive an additional 5 g dose of PRAXBIND.

The safety and effectiveness of repeat treatment with PRAXBIND have not been established [see Clinical Pharmacology (12.2)].

NDC 0597-0197-05

Rx only

Praxbind^®

(idarucizumab)

Injection

2.5 g/50 mL

(50 mg/mL)

For Intravenous Use Only

Discard Unused Portion.

Administer 2 vials for complete dose of 5 g

50 mL Single-Dose Vial

Boehringer

Ingelheim

No carcinogenicity or genotoxicity studies have been conducted with idarucizumab. No animal studies have been performed to evaluate the potential effects of idarucizumab on fertility in males or females or on reproduction and development.

In patients with the condition of hereditary fructose intolerance who have received parenteral administration of sorbitol, serious adverse reactions, including fatal reactions, have been reported. Reactions have included hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure with breakdown of excretory and synthetic function.

The recommended dose of PRAXBIND contains 4 g sorbitol as an excipient. When prescribing PRAXBIND to patients with hereditary fructose intolerance, consider the combined daily metabolic load of sorbitol/fructose from all sources, including PRAXBIND and other drugs containing sorbitol. The minimum amount of sorbitol at which serious adverse reactions may occur in these patients is not known.

Thromboembolic Events

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 [see Warnings and Precautions (5.1)].

Idarucizumab is a humanized monoclonal antibody fragment (Fab) derived from an IgG1 isotype molecule, whose target is the direct thrombin inhibitor dabigatran. Using recombinant expression technology, idarucizumab is produced in a well characterized recombinant (mammalian) CHO cell line and is purified using standard technology. Idarucizumab is composed of a light chain of 219 amino acids and a heavy chain fragment of 225 amino acids, covalently linked together by one disulfide bond between cysteine 225 of the heavy chain fragment and cysteine 219 of the light chain, and has an estimated molecular mass of approximately 47,766 Daltons.

PRAXBIND (idarucizumab) is a sterile, preservative-free, colorless to slightly yellow, clear to slightly opalescent solution for intravenous administration. PRAXBIND (idarucizumab) is supplied in 2 single-dose vials, each containing 2.5 g of idarucizumab in 50 mL formulated as a buffered, isotonic, solution containing acetic acid glacial (10.05 mg), polysorbate 20 (10 mg), sodium acetate (88.82 mg), sorbitol (2004.20 mg), and water for injection with an osmolality of 270-330 mOsm/kg and a pH of 5.3-5.7.

• Remove both vials (each containing 2.5 g/50 mL idarucizumab) from carton.
• 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. The solution in vials may be stored at room temperature, 25°C (77°F), but must be used within 6 hours [see How Supplied/Storage and Handling (16.2)].

• PRAXBIND is a sterile, preservative-free, colorless to slightly yellow, clear to slightly opalescent solution supplied as 2 single-dose vials each containing 2.5 g/50 mL of idarucizumab.
• NDC number 0597-0197-05: Carton containing two 2.5 g/50 mL vials.

Safety and effectiveness have not been established in pediatric patients.

A total of 454 (90%) patients treated with idarucizumab in the case series trial were 65 years of age and older, and 318 (63%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

• Do not mix with other medicinal products. Use aseptic technique when administering PRAXBIND.
• Intravenously administer the dose of 5 g (2 vials, each contains 2.5 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 0.9% 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 (12.2)].

As with all proteins there is a potential for immunogenicity with idarucizumab. Detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to idarucizumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Using an electro-chemiluminescence (ECL) based assay, plasma samples from 283 subjects (224 treated with idarucizumab) in phase I trials and 501 patients were tested for antibodies cross-reacting with idarucizumab. Pre-existing antibodies with cross-reactivity to idarucizumab were detected in approximately 12% (33/283) of the subjects and 4% (19/501) of patients. The majority of pre-existing antibodies were shown to have low titers. No impact on the pharmacokinetics or the reversal effect of idarucizumab or hypersensitivity reactions were observed. Treatment-emergent possibly persisting anti-idarucizumab antibodies with low titers were observed in 4% (10/224) of the subjects and 2% (8/501) of patients treated with idarucizumab. Nine patients were re-dosed with idarucizumab. All nine patients were re-dosed within 6 days after the first idarucizumab dose. None of these patients re-dosed with idarucizumab tested positive for anti-idarucizumab antibodies.

The epitope specificity of antibodies to idarucizumab was characterized using probe molecules. For pre-existing antibodies in patients, 95% (18/19) had specificity for the C-terminus, a region of idarucizumab to which dabigatran does not bind. For treatment emergent antibodies in patients, 67% (6/9) had specificity for the C-terminus, 22% (2/9) had specificity for the variable region, and 11% (1/9) had mixed specificity.

The safety and effectiveness of PRAXBIND was investigated in three randomized placebo-controlled healthy volunteer trials, Trials 1321.1, 1321.2 and 1321.5 (NCT01688830, NCT01955720, NCT02028780), and in RE-VERSE-AD (RE-VERSal Effects of idarucizumab on Active Dabigatran) trial (NCT02104947), a single cohort case series trial with dabigatran-treated patients who have life-threatening or uncontrolled bleeding, or who require emergency surgery or urgent procedure.

None.

The following serious adverse reactions are described in more detail elsewhere in the labeling:

• Thromboembolic Risk [see Warnings and Precautions (5.1)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.3)]
• Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient [see Warnings and Precautions (5.4)]

The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing 2.5 g/50 mL idarucizumab (see Figure 1). Both vials are packaged together in one carton.

For intravenous use only.

There is limited data to support administration of an additional 5 g of PRAXBIND [see Warnings and Precautions (5.2)].

In healthy subjects aged 45 to 64 years, the plasma concentrations of unbound dabigatran were reduced to below the lower limit of quantification immediately after the administration of 5 g idarucizumab. Subjects' diluted thrombin time (dTT), ECT, aPTT, thrombin time (TT), and activated clotting time (ACT) parameters returned to baseline levels (see Figure 4 and Figure 5). This reduction of dabigatran plasma concentration was observed over the entire observation period of at least 24 hours. Similar findings were also observed in elderly subjects (aged 65 to 80 years) as well as subjects with mild and moderate renal impairment [see Clinical Pharmacology (12.3)].

In a limited number of patients, re-distribution of dabigatran from the periphery to plasma led to re-elevation of dTT, ECT, aPTT, and TT [see Warnings and Precautions (5.2)].

Re-dosing with 2.5 g idarucizumab in 6 healthy subjects aged 45-64 years at 2 months after first infusion revealed no differences in safety and no indication of allergic reactions [see Clinical Pharmacology (12.3)].

No changes in the pharmacokinetics or pharmacodynamics of dabigatran were noted upon re-initiation 24 hours after the administration of idarucizumab [see Dosage and Administration (2.4)].

Figure 4 Plasma-Levels of Unbound Dabigatran in the Representative Group of Healthy Subjects (Administration of Idarucizumab or Placebo at 0 h)

Figure 5 Change of ECT from Baseline in the Representative Group of Healthy Subjects (Administration of Idarucizumab or Placebo at 0 h)

There were no obvious differences in the idarucizumab plasma concentration time profiles when idarucizumab was administered alone or after pretreatment with dabigatran. A dose-dependent increase in the fraction of unchanged idarucizumab excreted in urine was observed.

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

Patients being treated with dabigatran therapy have underlying disease states that predispose them to thromboembolic events. 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 [see Dosage and Administration (2.4)].

Idarucizumab is a specific reversal agent for dabigatran. It 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.

• Store PRAXBIND vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.
• PRAXBIND vials may be stored at room temperature, 25°C (77°F), for up to 48 hours in the original carton to protect from light.
• PRAXBIND vials may be stored at room temperature, 25°C (77°F), out of the carton and exposed to light but must be used within 6 hours [see Dosage and Administration (2.2)].

• Thromboembolic Risk: Reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease. Resume anticoagulant therapy as soon as medically appropriate. (2.4, 5.1)
• Re-elevation of Coagulation Parameters: In patients with elevated coagulation parameters and reappearance of clinically relevant bleeding or requiring a second emergency surgery/urgent procedure, an additional 5 g dose of PRAXBIND may be considered. (5.2)
• Hypersensitivity reactions: Discontinue administration and evaluate. (5.3)
• Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient: Patients with hereditary fructose intolerance may be at risk of adverse reactions. (5.4)

For intravenous use only.

• The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing 2.5 g/50 mL idarucizumab. (2.1)
• There is limited data to support administration of an additional 5 g of PRAXBIND. (2.1)

PRAXBIND is a sterile, preservative-free, colorless to slightly yellow, clear to slightly opalescent solution available as:

Injection: 2.5 g/50 mL solution in a single-dose vial.

There is insufficient clinical experience with PRAXBIND in patients to evaluate risk of hypersensitivity to idarucizumab. In clinical studies adverse events possibly indicative of hypersensitivity reactions where a possible relationship could not be excluded were reported [see Adverse Reactions (6.1)]. The risk of using PRAXBIND in patients with known hypersensitivity (e.g., anaphylactoid reaction) to idarucizumab or to any of the excipients needs to be weighed cautiously against the potential benefit of such an emergency treatment. If an anaphylactic reaction or other serious allergic reaction occurs, immediately discontinue administration of PRAXBIND and institute appropriate treatment.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In three healthy volunteer clinical trials, 224 subjects were treated with idarucizumab. In these trials, during the treatment period, the overall frequency of adverse events was similar between idarucizumab-treated subjects (55/224, 25%) and placebo-treated subjects (26/105, 25%). Among those subjects treated with idarucizumab, adverse reactions reported in ≥5% of subjects was headache (12/224, 5%).

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 [see Clinical Studies (14)]. 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.

Patients being treated with dabigatran therapy have underlying disease states that predispose them to thromboembolic events. 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 [see Clinical Pharmacology (12.2)].

In a limited number of patients in the clinical program, between 12 and 24 hours after administration of 5 g idarucizumab, elevated coagulation parameters (e.g., activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT)) have been observed [see Dosage and Administration (2.1)].

If reappearance of clinically relevant bleeding together with elevated coagulation parameters is observed after administration of 5 g PRAXBIND, administration of an additional 5 g dose of PRAXBIND may be considered. Similarly, patients who require a second emergency surgery/urgent procedure and have elevated coagulation parameters may receive an additional 5 g dose of PRAXBIND.

The safety and effectiveness of repeat treatment with PRAXBIND have not been established [see Clinical Pharmacology (12.2)].

NDC 0597-0197-05

Rx only

Praxbind^®

(idarucizumab)

Injection

2.5 g/50 mL

(50 mg/mL)

For Intravenous Use Only

Discard Unused Portion.

Administer 2 vials for complete dose of 5 g

50 mL Single-Dose Vial

Boehringer

Ingelheim

No carcinogenicity or genotoxicity studies have been conducted with idarucizumab. No animal studies have been performed to evaluate the potential effects of idarucizumab on fertility in males or females or on reproduction and development.

In patients with the condition of hereditary fructose intolerance who have received parenteral administration of sorbitol, serious adverse reactions, including fatal reactions, have been reported. Reactions have included hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure with breakdown of excretory and synthetic function.

The recommended dose of PRAXBIND contains 4 g sorbitol as an excipient. When prescribing PRAXBIND to patients with hereditary fructose intolerance, consider the combined daily metabolic load of sorbitol/fructose from all sources, including PRAXBIND and other drugs containing sorbitol. The minimum amount of sorbitol at which serious adverse reactions may occur in these patients is not known.