Praxbind

— THERAPEUTIC CATEGORIES —
  • Bleeding disorders
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Praxbind Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Idarucizumab 2.5g/50mL; soln for IV inj; preservative-free; contains sorbitol.

    Pharmacological Class

    Humanized monoclonal antibody fragment.

    How Supplied

    Single-use vials—2

    How Supplied

    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.

    Storage

    Store Praxbind vials in the refrigerator at 2ºC to 8ºC (36ºF to 46ºF) 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.

    Manufacturer

    Boehringer Ingelheim Pharmaceuticals

    Generic Availability

    NO

    Praxbind Indications

    Indications

    Reversal of the anticoagulant effects of dabigatran in emergency surgery/urgent procedures and in life-threatening or uncontrolled bleeding.

    Praxbind Dosage and Administration

    Adult

    For IV use only. Administer 5g (2 vials) as 2 consecutive infusions or as bolus injection of both vials consecutively via syringe. Other additional dose: see Warnings/Precautions.

    Children

    Not established.

    Praxbind Contraindications

    Not Applicable

    Praxbind Boxed Warnings

    Not Applicable

    Praxbind Warnings/Precautions

    Warnings/Precautions

    Thromboembolic risk; consider resuming anticoagulant therapy as soon as medically appropriate; can initiate dabigatran 24hrs after Praxbind administration. In patients having a reappearance of bleeding with elevated coagulation parameters or those requiring a second emergency surgery/urgent procedure and have elevated coagulation parameters, consider repeat administration of Praxbind 5g dose. Discontinue immediately if hypersensitivity reactions occur and treat appropriately. Hereditary fructose intolerance. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Thromboembolic Risk

    • 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.

    • Dabigatran therapy can be initiated 24 hours after administration of Praxbind.

    Re-elevation of Coagulation Parameters

    • May consider administration of an additional 5 g dose of Praxbind if reappearance of clinically relevant bleeding together with elevated coagulated parameters is observed or patients who require a second emergency surgery/urgent procedure and have elevated coagulation. 

    • Safety and efficacy of repeat treatment with Praxbind has not been established.

    Hypersensitivity Reactions

    • Cautiously weigh the risk of using Praxbind in patients with known hypersensitivity (e.g., anaphylactoid reaction) to idarucizumab or to any excipients against the potential benefit of such an emergency treatment.

    • Discontinue immediately the Praxbind administration and institute appropriate treatment if anaphylactic reaction or other serious allergic reaction occurs.

    Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient

    • Patients with hereditary fructose intolerance who have received parenteral administration of sorbitol may experience serious adverse reactions including hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, and acute liver failure with breakdown of excretory and synthetic function.

    • In these patients, consider the combined daily metabolic load of sorbitol/fructose from all sources. The minimum amount of sorbitol at which serious adverse reactions may occur in these patients is not known.

    Pregnancy Considerations

    Risk Summary

    • No available data on Praxbind use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage.

    • Only administer to pregnant women if clearly needed.

    Nursing Mother Considerations

    Risk Summary

    • No data on the effects of Praxbind on the breastfed child or on milk production.

    • Not known whether idarucizumab is excreted in human milk.

    • Consider the mother’s clinical need for Praxbind and any potential adverse effects on the breastfed child from Praxbind or from the underlying maternal condition. 

    Pediatric Considerations

    Safety and effectiveness have not been established in pediatric patients.

    Geriatric Considerations

    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.

    Praxbind Pharmacokinetics

    Distribution

    Idarucizumab exhibited multiphasic disposition kinetics and limited extravascular distribution. Following the intravenous infusion of a 5 g dose, the geometric mean volume of distribution at steady state (Vss) was 8.9 L (geometric coefficient of variation (gCV 24.8%)).

    Metabolism

    Several pathways have been described that may contribute to the metabolism of antibodies. All of these pathways involve biodegradation of the antibody to smaller molecules, i.e., small peptides or amino acids which are then reabsorbed and incorporated in the general protein synthesis.

    Elimination

    Idarucizumab was rapidly eliminated with a total clearance of 47.0 mL/min (gCV 18.4%), an initial half-life of 47 minutes (gCV 11.4%), and a terminal half-life of 10.3 h (gCV 18.9%). After intravenous administration of 5 g idarucizumab, 32.1% (gCV 60.0%) of the dose was recovered in urine within a collection period of 6 hours and less than 1% in the following 18 hours. The remaining part of the dose is assumed to be eliminated via protein catabolism, mainly in the kidney.

    Praxbind Interactions

    Not Applicable

    Praxbind Adverse Reactions

    Adverse Reactions

    Headache, constipation, nausea; hypersensitivity reactions.

    Praxbind Clinical Trials

    Clinical Trials

    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. 

    In RE-VERSE AD, 5 grams of idarucizumab was administered to patients treated with dabigatran who presented with dabigatran-related life-threatening or uncontrolled bleeding (Group A) or who required emergency surgery or urgent procedures (Group B). The primary endpoint was the maximum percentage reversal of the pharmacodynamic anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, based on central laboratory determination of dTT or ECT. 

    Among evaluable patients, idarucizumab immediately reversed the anticoagulant effect of Pradaxa. Complete reversal was seen within 4 hours in the majority of patients, as measured by ecarin clotting time (ECT 82%), activated partial thromboplastin time (aPTT 93%) or diluted thrombin time (dTT 99%). In addition, there was a low rate of thrombotic events and no new safety events were reported. Findings were similar for Groups A and B.

    Praxbind Note

    Not Applicable

    Praxbind Patient Counseling

    Patient Counseling

    Thromboembolic Risk

    • Inform patients that reversing dabigatran therapy exposes them to the thromboembolic risk of their underlying disease. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as the patient is sufficiently stable.

    Recurrence of Bleeding   

    • Inform patients to get immediate medical attention for any signs or symptoms of bleeding.

    Hypersensitivity Reactions

    • Inform patients of signs and symptoms of allergic hypersensitivity reactions such as anaphylactoid reactions that may be experienced during or after injection of Praxbind.

    Risk of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient

    • Inform patients with hereditary fructose intolerance (HFI) that Praxbind contains sorbitol. Parenteral administration of sorbitol in patients who have HFI has been associated with reports of hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure with breakdown of excretory and synthetic function, and death and may occur during or after injection of Praxbind.

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