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Coagulation Factor Ix Recombinant, Glycopegylated

FDA Drug Information • Also known as: Rebinyn

Brand Names
Rebinyn
Dosage Form
KIT
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION REBINYN is a sterile, non-pyrogenic, white to off-white lyophilized powder for reconstitution with the provided histidine diluent for intravenous infusion. After reconstitution, the solution appears as a clear and colorless to slightly yellow liquid, free from visible particles and contains the following excipients per mL: sodium chloride, 2.34 mg; histidine, 3.10 mg; sucrose, 10 mg; mannitol, 25 mg; polysorbate 80, 0.05 mg. REBINYN is available in single-dose vials containing the labeled amount of Factor IX activity, expressed in IU. Each vial contains nominally 500 IU, 1000 IU, 2000, or 3000 IU. REBINYN potency is assigned using an in vitro , activated partial thromboplastin time (aPTT)-based, one-stage clotting assay calibrated against the World Health Organization (WHO) international standard for Factor IX concentrates. REBINYN contains no preservatives. REBINYN is a purified recombinant human Factor IX (rFIX) with a 40 kilodalton (kDa) polyethylene-glycol (PEG) conjugated to the protein. The 40 kDa PEG group is selectively attached to specific -N-linked glycans in the rFIX activation peptide, with mono-PEGylated rFIX as the predominant form of REBINYN. The rFIX protein in REBINYN consists of a gamma-carboxylated (Gla) domain, two EGF-like (epidermal growth factor) domains, an activation peptide (which is cleaved off upon activation), and a protease domain. Once activated, the resulting rFIX has structural and functional properties similar to those of endogenous activated Factor IX. The primary amino acid sequence in REBINYN is identical to the Thr148 allelic form of human plasma-derived Factor IX and consists of 415 amino acids. The average molecular weight of REBINYN is approximately 98 kDa and the molecular weight of the protein moiety alone is 56 kDa. The nominal specific activity of REBINYN is 144 IU/mg protein. REBINYN is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells. No additives of human or animal origin are...

What Is Coagulation Factor Ix Recombinant, Glycopegylated Used For?

1 INDICATIONS AND USAGE REBINYN, Coagulation Factor IX (Recombinant), GlycoPEGylated, is a recombinant DNA-derived coagulation Factor IX concentrate indicated for use in adults and children with hemophilia B (congenital Factor IX deficiency) for:

  • On-demand treatment and control of bleeding episodes
  • Perioperative management of bleeding
  • Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use : REBINYN is not indicated for immune tolerance induction in patients with hemophilia B. REBINYN, Coagulation Factor IX (Recombinant), GlycoPEGylated, is a recombinant DNA-derived coagulation Factor IX concentrate indicated for use in adults and children with hemophilia B (congenital Factor IX deficiency) for:
  • On-demand treatment and control of bleeding episodes
  • Perioperative management of bleeding
  • Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use : REBINYN is not indicated for immune tolerance induction in patients with hemophilia B ( 1 ).

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION For intravenous infusion after reconstitution only. For intravenous infusion after reconstitution only ( 2 ).

  • Each carton and vial label for REBINYN states the actual Factor IX potency in international units (IU) ( 2.1 ). On-demand treatment and control of bleeding episodes:
  • 40 IU/kg body weight for minor and moderate bleeds, and 80 IU/kg body weight for major bleeds. Additional doses of 40 IU/kg can be given ( 2.1 ). Perioperative management:
  • Pre-operative dose of 40 IU/kg body weight for minor surgery, and 80 IU/kg body weight for major surgery. As clinically needed for the perioperative management of bleeding, repeated doses of 40 IU/kg (in 1-3 day intervals) within the first week after major surgery may be administered.
  • Frequency may be extended to once weekly after the first week until bleeding stops and healing is achieved ( 2.1 ). Routine prophylaxis :
  • 40 IU/kg body weight once weekly ( 2.1 ). 2.1 Dosing Guidelines
  • Dose and duration of treatment depend on the location and extent of bleeding, and the patient’s clinical condition.
  • If monitoring of Factor IX activity is performed, use a chromogenic assay or selected one-stage clotting assay validated for use with REBINYN [ see Warnings and Precautions ( 5.5 ) ].
  • Each carton and vial label for REBINYN states the actual Factor IX potency in IU. On-demand Treatment and Control of Bleeding Episodes REBINYN dosing for on-demand treatment and control of bleeding episodes is provided in Table 1. Table 1: Dosing for On-demand Treatment and Control of Bleeding Episodes Type of bleeding Recommended dose IU/kg body weight Additional information Minor and moderate For example: Uncomplicated joint bleeds, minor muscular bleeds, mucosal or subcutaneous bleeds 40 A single dose should be sufficient for minor and moderate bleeds. Additional doses of 40 IU/kg can be given. Major For example: Intracranial, retroperitoneal, iliopsoas and neck bleeds, muscle bleeds with compartment syndrome and bleeds associated with a significant decrease in the hemoglobin level 80 Additional doses of 40 IU/kg can be given. Perioperative Management REBINYN dosing for perioperative management is provided in Table 2. Table 2: Dosing for Perioperative Management Type of surgical procedure Recommended dose IU/kg body weight Additional Information Minor For example: Implanting pumps in subcutaneous tissue, skin biopsies or simple dental procedures 40 A single pre-operative dose should be sufficient. Additional doses can be given if needed. Major For example: Body cavity is entered, mesenchymal barrier is crossed, fascial plane is opened, organ is removed, normal anatomy is operatively altered 80 Pre-operative dose 40 As clinically needed for the perioperative management of bleeding, repeated doses of 40 IU/kg (in 1-3 day intervals) within the first week after major surgery may be administered.* Due to the long half-life of REBINYN, the frequency of dosing in the post-surgical setting may...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS Common adverse reactions (incidence ≥ 1%) in PTPs reported in clinical trials for REBINYN were itching and injection site reactions. Common adverse reactions (incidence ≥ 1%) in PUPs reported in clinical trials for REBINYN were rash, FIX inhibitors, hypersensitivity, itching, injection site reaction, and anaphylactic reaction. The most frequently reported adverse reactions (≥ 1%) in previously treated patients (PTPs) and previously untreated patients (PUPs) were itching and injection site reactions ( 6 ). Additional frequently reported adverse reactions (≥ 1%) in PUPs included rash, Factor IX inhibition, hypersensitivity, and anaphylactic reaction ( 6 ). In animals administered repeat doses of REBINYN, accumulation of polyethylene-glycol (PEG) was observed in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons ( 8.4 and 13.2 ). The potential clinical implications of these animal findings are unknown ( 6.3 ). To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-877-668-6777 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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 clinical trials of another drug and may not reflect the rates observed in clinical practice. Previously Treated Patients (PTPs) In five multicenter, prospective, non-controlled, open-label clinical trials, 115 PTPs [0 to 6 years old: 12 subjects (10%); 7 to 12 years old: 13 subjects (11%); 13 to 17 years old: 18 subjects (16%); ≥18 years old: 72 subjects (63%)] received at least one dose of REBINYN as part of routine prophylaxis, on-demand treatment of bleeding episodes, perioperative management of major and minor surgery, or pharmacokinetic evaluation [ see Clinical Studies (14) ]. A PTP was defined as a subject with a history of at least 150 exposure days to other Factor IX products (adolescent/adult subjects) or 50 exposure days to other Factor IX products (pediatric subjects), and no history of inhibitors. A total of 15,167 injections were administered over a median of 733 days (range: 29- 2951 days), equivalent to 15,137 exposure days and 292 patient-years. Adverse reactions in PTPs are listed in Table 3. Table 3: Summary of Adverse Reactions in Previously Treated Patients System Organ Class Adverse Reaction Number of subjects (%) N=115 General disorders and administration site conditions Injection site reactions 4 (4) Immune system disorders Hypersensitivity 1 (1) Skin and subcutaneous tissue disorders Itching 3 (3) Previously Untreated Patients (PUPs) In one multicenter, prospective, non-controlled, open-label clinical trial conducted in PUPs, 50 subjects (≤6 years of age) received at least one dose of REBINYN [see Clinical Studies (14) ]. A PUP was defined as a subject previously untreated or exposed to FIX-containing products less than or equal to 3 exposure days (5 previous exposures to blood components was acceptable). A total of 6,737 injections were administered over a median of 996 days (range: 61- 2,233 days), equivalent to 6,709 exposure days and 142 patient-years. Adverse reactions in PUPs are listed in Table 4. Table 4: Summary of Adverse Reactions in Previously Untreated Patients System Organ Class Adverse Reaction Number of subjects (%) N=50 Blood and lymphatic system disorders Factor IX inhibition 4 (8) General disorders and administration site conditions Injection site reaction 1 (2) Immune system disorders Anaphylactic reaction Hypersensitivty 1 (2) 3 (6) Skin and subcutaneous tissue disorders Rash Itching 9 (18) 2 (4) 6.2 Immunogenicity Subjects were monitored for inhibitory antibodies to factor IX prior to dosing, on a monthly basis for the first three months, every two months up to one year, every three months for an additional year, and then every 6 months until end of trial. No inhibitors were reported in the...

    Contraindications

    4 CONTRAINDICATIONS REBINYN is contraindicated in patients who have known hypersensitivity to REBINYN or its components (including hamster proteins) [ see Warnings and Precautions ( 5.1 ) and Description ( 11 ) ] Do not use in patients who have known hypersensitivity to REBINYN or its components, including hamster proteins ( 4 ).

    Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary There are no data with REBINYN use in pregnant women to determine whether there is a drug-associated risk. Animal reproduction studies have not been conducted with REBINYN. It is unknown whether REBINYN can cause fetal harm when administered to a pregnant woman or can affect fertility. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied

  • REBINYN is supplied in packages comprised of a single-dose vial containing nominally 500, 1000, 2000, or 3000 IU of Factor IX potency; a MixPro ® pre-filled diluent syringe containing 10 mM histidine solution (1.6 mg/mL), and a sterile vial adapter with 25 micrometer filter, which serves as a needleless reconstitution device.
  • The actual Factor IX potency in IU is stated on each REBINYN carton and vial. Table 12: REBINYN Presentations Presentation (Nominal Product Strength; IU) Cap Color Indicator Carton NDC Number Components 500 Red NDC 0169 7905 01
  • REBINYN in single-dose vial [NDC 0169 7955 11]
  • Pre-filled histidine diluent in syringe, 4 mL [NDC 0169 7009 98]
  • Vial adapter 1000 Green NDC 0169 7901 01
  • REBINYN in single-dose vial [NDC 0169 7911 11]
  • Pre-filled histidine diluent in syringe, 4 mL [NDC 0169 7009 98]
  • Vial adapter 2000 Yellow NDC 0169 7902 01
  • REBINYN in single-dose vial [NDC 0169 7922 11]
  • Pre-filled histidine diluent in syringe, 4 mL [NDC 0169 7009 98]
  • Vial adapter 3000 Dark Gray NDC 0169 7903 01
  • REBINYN in single-dose vial [NDC 0169 7933 11]
  • Pre-filled histidine diluent in syringe, 4 mL [NDC 0169 7009 98]
  • Vial adapter
  • The REBINYN vials are made of glass, closed with a chlorobutyl rubber stopper (not made with natural rubber latex), and sealed with an aluminum cap.
  • The pre-filled diluent syringes are made of glass, with a siliconised bromobutyl rubber plunger (not made with rubber latex).
  • The closed vials and pre-filled diluent syringes are equipped with a tamper-evident snap-off cap which is made of polypropylene. Storage and Handling
  • Store REBINYN in the original package in order to protect from light.
  • Store REBINYN under refrigeration at a temperature of 36°F-46°F (2°C – 8°C) for up to 24 months from the date of manufacture until the expiration date stated on the label.
  • REBINYN may be stored at room temperature not to exceed 86°F (30°C) for up to 6 months within the...

    • About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.