aAdditional doses may be required post-operatively.1
In all major surgeries studied in adults and adolescents1,b
(N=13 surgeries)
single pre-operative dose1
intraoperative hemostatic effect success rate1
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 be extended to once weekly after the first week until bleeding stops and healing is achieved.
bMajor surgeries are classified as procedures where the body cavity is entered, mesenchymal barrier is crossed, fascial plane is opened, organ is removed, or where the normal anatomy is operatively altered.
See how an initial dose of Rebinyn® was predicted to maintain target FIX levels during major surgery.3
Factor IX activity sustained up to 48 hours post surgery1,2,c
cIn the surgery study, mean FIX activity following an initial preoperative infusion of Rebinyn® 80 IU/kg in 13 procedures was assessed by 1-stage assay with product-specific standard. At 8 and 24 hours, 1 subject who had no FIX activity measurement obtained was excluded. At 48 hours, 2 subjects who had no FIX activity measurement obtained were excluded and 4 subjects re-dosed prior to the second day after surgery for whom FIX activity at 24 hours was 84%, 112%, 131%, and 134%. The FIX activity at 48 hours reflects a measurement on the second day after surgery (range 47 to 57 hours).1
dRange shaded represents the non-hemophilia population FIX activity range of >40% based on World Federation of Hemophilia classification.
Reliable bleed control after surgery1,2
Patients were given postoperative doses of 40 IU/kg at the investigator’s discretion for up to 3 weeks after surgery.1
days after surgery2
- Median of 2 injections administered
- 84.1 IU/kg median consumption
days after surgery2
- Median of 3 injections administered
- 126.1 IU/kg median consumption
Rebinyn® may help Juanita and Oliver
Juanita, whose son Oliver lives with hemophilia B, is concerned about the potential for bleeds during dental surgery. The surgical efficacy of Rebinyn® may make it a good fit for them.
For illustrative purposes.
Study designs
Escobar et al (2017)
paradigm 3: phase 3 clinical trial evaluating major surgery
Patients: 13 male patients aged 13–70 with hemophilia B and FIX activity ≤0.02 IU/mL who were scheduled for major surgery. Patients had at least 150 prior exposure days to standard FIX products and no history of FIX inhibitors.
Study design: On the day of their respective surgeries, patients received 1 infusion of Rebinyn® 80 IU/kg. Postoperatively, subjects received infusions of Rebinyn® 40 IU/kg at the investigator’s discretion for up to 3 weeks after surgery. Across 13 surgical procedures—which included 9 orthopedic, 1 gastrointestinal, and 3 oral cavity procedures—the hemostatic effect during surgery was evaluated on a 4-point scale of excellent, good, moderate, or poor. Treatment success was defined as excellent or good hemostasis. Mean FIX activity following an initial preoperative Rebinyn® 80 IU/kg dose in 13 procedures was assessed by one-stage assay with product-specific standard.1,4
Primary endpoint: Intraoperative hemostatic effect during and after surgery, measured by the investigator or surgeon according to a four-point response scale: excellent, good, moderate, or poor.
Secondary endpoint: Efficacy of Rebinyn®, as measured by hemoglobin levels, Rebinyn® consumption, and number of doses per procedure.
Powerful bleed protection
Studies show Rebinyn® prophylaxis helps prevent spontaneous and traumatic bleeds.1
Simple prophylaxis dosing
Convenient, once-weekly dosing for all patients.
Selected Important Safety Information for Rebinyn®
Contraindications
- Rebinyn® is contraindicated in patients with a known hypersensitivity to Rebinyn® or its components, including hamster proteins.
Warnings and Precautions
- Hypersensitivity Reactions: Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with Rebinyn®. Signs may include angioedema, chest tightness, difficulty breathing, wheezing, urticaria, and itching. Discontinue Rebinyn® if allergic- or anaphylactic-type reactions occur and initiate appropriate treatment.
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, and 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.
Important Safety Information
Contraindications
- Rebinyn® is contraindicated in patients with a known hypersensitivity to Rebinyn® or its components, including hamster proteins.
Warnings and Precautions
- Hypersensitivity Reactions: Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with Rebinyn®. Signs may include angioedema, chest tightness, difficulty breathing, wheezing, urticaria, and itching. Discontinue Rebinyn® if allergic- or anaphylactic-type reactions occur and initiate appropriate treatment.
- Inhibitors: The formation of inhibitors (neutralizing antibodies) to Factor IX has occurred following Rebinyn®. If expected plasma factor IX activity levels are not attained, or if bleeding is not controlled as expected with the administered dose, perform an assay that measures Factor IX inhibitor concentration. Monitor all patients using clinical observations and laboratory tests for the development of inhibitors. Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used.
- Thrombotic Events: The use of Factor IX-containing products has been associated with thromboembolic complications. Monitor for thrombotic and consumptive coagulopathy when administering Rebinyn® to patients with liver disease, post-operatively, to newborn infants, or to patients at risk of thrombosis or disseminated intravascular coagulation (DIC).
- Nephrotic Syndrome: Nephrotic syndrome has been reported following immune tolerance induction therapy with Factor IX products in hemophilia B patients with Factor IX inhibitors, often with a history of allergic reactions to Factor IX. The safety and efficacy of using Rebinyn® for immune tolerance induction have not been established.
Adverse Reactions
- The most common adverse reactions reported in previously treated patients in clinical trials (≥1%) were itching and injection site reactions. The most common adverse reactions (≥1%) in previously untreated patients reported in clinical trials were rash, FIX inhibitors, hypersensitivity, itching, injection site reaction, and anaphylactic reaction.
- Animals administered Rebinyn® showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. The potential clinical implications of these animal findings are unknown. Consider whether the patient is vulnerable to cognitive impairment, such as infants and children who have developing brains, and patients who are cognitively impaired.
Please click here for Rebinyn® Prescribing Information.
References:
- Rebinyn [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2022.
- Escobar MA, Tehranchi R, Karim FA, et al. Low-factor consumption for major surgery in haemophilia B with long-acting recombinant glycoPEGylated factor IX. Haemophilia. 2017;23(1):67-76.
- Simpson M, Kulkarni R, Ettingshausen C, et al. Population pharmacokinetic modeling of on-demand and surgical use of nonacog beta pegol (N9-GP) and rFIXFc based upon the paradigm 7 comparative pharmacokinetic study. J Blood Med. 2019;10:391–398.