Coagulation factor ix recombinant

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.

Patients with hemophilia B are deficient in coagulation Factor IX, which is required for effective hemostasis. Treatment with REBINYN temporarily replaces the missing coagulation Factor IX. The Factor IX in REBINYN is conjugated to a 40-kDa polyethylene glycol molecule, which slows down its removal from the blood circulation.

For intravenous infusion after reconstitution only. For intravenous infusion after reconstitution only. • Each carton and vial label for REBINYN states the actual Factor IX potency in international units (IU). 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. 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. Routine prophylaxis: • 40 IU/kg body weight once weekly.

REBINYN is contraindicated in patients who have known hypersensitivity to REBINYN or its components (including hamster proteins) Do not use in patients who have known hypersensitivity to REBINYN or its components, including hamster proteins.

• Hypersensitivity reactions, including anaphylaxis, have occurred. Should hypersensitivity reactions occur, discontinue REBINYN and administer appropriate treatment. • Neutralizing antibodies (inhibitors) to Factor IX have occurred following administration of REBINYN. Perform an assay that measures Factor IX inhibitor concentration if bleeding is not controlled with the recommended dose of REBINYN or if plasma Factor IX activity level fails to increase as expected. • The use of Factor IX- products has been associated with the development of thromboembolic complications. • Nephrotic syndrome has been reported following immune tolerance induction with Factor IX-containing products in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions to Factor IX.

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. Additional frequently reported adverse reactions (≥ 1%) in PUPs included rash, Factor IX inhibition, hypersensitivity, and anaphylactic reaction. 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 ).

• 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 24-month time period. Record the date when the product was removed from the refrigerator in the space provided on the outer carton. The total time of storage at room temperature should not exceed 6 months. Do not return the product to the refrigerator.