Coagulation factor IX, GlycoPEGylated (Rebinyn)

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# Overview
Coagulation factor IX, GlycoPEGylated (Rebinyn) is a recombinant DNA-derived coagulation Factor IX concentrate that is FDA approved for the on-demand treatment and control of bleeding episodes and perioperative management of bleeding.   Common adverse reactions include itching and injection site reactions.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Coagulation factor IX, GlycoPEGylated (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 for:
- On-demand treatment and control of bleeding episodes
- Perioperative management of bleeding
- Dosage and duration of therapy depend on location and extent of bleeding and clinical conditions.
- Minor and moderate bleeding: 40 international units/kg IV as a single dose; additional doses of 40 international units/kg may be given.
- Major bleeding: 80 international units/kg IV as a single dose; additional doses of 40 international units/kg may be given.
- Minor surgery: 40 international units/kg IV as a single preoperative dose; additional doses may be given as needed.
- Major surgery: 80 international units/kg as a single preoperative dose; repeat doses of 40 international units/kg may be given as clinically indicated at 1 to 3 day intervals within the first week after surgery. Frequency may be extended to once-weekly after the first week to achieve hemostasis and healing.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.

### NonGuideline-Supported Use
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
- Coagulation factor IX, GlycoPEGylated (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 for:
- On-demand treatment and control of bleeding episodes
- Perioperative management of bleeding
- Dosage and duration of therapy depend on location and extent of bleeding and clinical condition.
- Minor and moderate bleeding: 40 international units/kg IV as a single dose; additional doses of 40 international units/kg may be given.
- Major bleeding: 80 international units/kg IV as a single dose; additional doses of 40 international units/kg may be given.
- Minor surgery: 40 international units/kg IV as a single preoperative dose; additional doses may be given as needed.
- Major surgery: 80 international units/kg IV as a single preoperative dose; repeat doses of 40 international units/kg may be given as clinically indicated at 1 to 3 day intervals within the first week after surgery. Frequency may be extended to once-weekly after the first week to achieve hemostasis and healing.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.

### NonGuideline-Supported Use
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.

# Contraindications
- Coagulation factor IX, GlycoPEGylated (Rebinyn) is contraindicated in patients who have known hypersensitivity to Coagulation factor IX, GlycoPEGylated (Rebinyn) or its components (including hamster proteins).

# Warnings
- Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with Coagulation factor IX, GlycoPEGylated (Rebinyn). The product may contain traces of hamster proteins which in some patients may cause allergic reactions. Early signs of allergic reactions, which can progress to anaphylaxis, may include angioedema, chest tightness, difficulty breathing, wheezing, urticaria, and itching. Observe patients for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of exposure to the product. Discontinue use of Coagulation factor IX, GlycoPEGylated (Rebinyn) if allergic- or anaphylactic - type reactions occur, and initiate appropriate treatment.
- The formation of inhibitors (neutralizing antibodies) to Factor IX may occur during Factor replacement therapy in the treatment of hemophilia B. Monitor all patients using clinical observations and laboratory tests for the development of inhibitors.
- An association between the development of Factor IX inhibitors and allergic reactions has been reported. Evaluate patients experiencing allergic reactions for the presence of an inhibitor. Patients with Factor IX inhibitors may be at an increased risk of severe allergic reactions with subsequent exposure to Factor IX.
- The use of Factor IX-containing products has been associated with thrombotic complications. Due to the potential risk of thrombotic complications, monitor patients for early signs of thrombotic and consumptive coagulopathy when administering this product to patients with liver disease, post-operatively, to newborn infants, or to patients at risk of thrombosis or disseminated intravascular coagulation (DIC). In each of these situations, the benefit of treatment with Coagulation factor IX, GlycoPEGylated (Rebinyn) should be weighed against the risk of these complications.
- 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 Coagulation factor IX, GlycoPEGylated (Rebinyn) for immune tolerance induction have not been established.
- If monitoring of Factor IX activity is performed, use a chromogenic assay or selected one-stage clotting assay validated for use with Coagulation factor IX, GlycoPEGylated (Rebinyn).
- The one-stage clotting assay results can be significantly affected by the type of activated partial thromboplastin time (aPTT) reagent used, which can result in over- or under-estimation of Factor IX activity. Avoid the use of silica-based reagents, as some may overestimate the activity of Coagulation factor IX, GlycoPEGylated (Rebinyn). If a validated one-stage clotting or chromogenic assay is not available locally, then use of a reference laboratory is recommended.
- If bleeding is not controlled with the recommended dose of Coagulation factor IX, GlycoPEGylated (Rebinyn), or if the expected Factor IX activity levels in plasma are not attained, then perform a Bethesda assay to determine if Factor IX inhibitors are present.

# Adverse Reactions

## 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.
- During the clinical development program, 115 previously treated male patients received at least one dose of Coagulation factor IX, GlycoPEGylated (Rebinyn). A previously treated patient 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. There were a total of 8801 exposure days, equivalent to 170 patient-years. A total of 40 patients (35%) were treated for more than 2 years.
- Adverse reactions are shown in Table 3.
- 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 clinical trials in previously treated patients.
- In an ongoing trial in previously untreated patients, anaphylaxis has occurred with development of a factor IX inhibitor following treatment with Coagulation factor IX, GlycoPEGylated (Rebinyn). Inhibitor development and anaphylactic reactions are more likely to occur during the early phases of factor IX replacement therapy.
- The 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.
- Animals administered repeat doses of Coagulation factor IX, GlycoPEGylated (Rebinyn) showed accumulation of PEG in the choroid plexus. The potential clinical implications of these animal findings are unknown. The physician should consider whether the patient may be vulnerable, such as infants and children who have developing brains and patients who are cognitively impaired. Physicians discretion is advised with regard to neurocognitive assessments, taking into consideration factors such as duration of use, cumulative dose, age of the patient and related comorbidities that are likely to increase the risks to patients. Adverse neurologic reactions should be reported.

## Postmarketing Experience
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) Postmarketing Experience in the drug label.

# Drug Interactions
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): 
Risk Summary
- There are no data with Coagulation factor IX, GlycoPEGylated (Rebinyn) use in pregnant women to determine whether there is a drug-associated risk. Animal reproduction studies have not been conducted with Coagulation factor IX, GlycoPEGylated (Rebinyn). It is unknown whether Coagulation factor IX, GlycoPEGylated (Rebinyn) can cause fetal harm when administered to a pregnant woman or can affect fertility. Coagulation factor IX, GlycoPEGylated (Rebinyn) should be given to a pregnant woman only if clearly needed. 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.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Coagulation factor IX, GlycoPEGylated (Rebinyn) in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Coagulation factor IX, GlycoPEGylated (Rebinyn) during labor and delivery.

### Nursing Mothers
Risk Summary
- There is no information regarding the presence of Coagulation factor IX, GlycoPEGylated (Rebinyn) in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for Coagulation factor IX, GlycoPEGylated (Rebinyn) and any potential adverse effects on the breastfed infant from Coagulation factor IX, GlycoPEGylated (Rebinyn) or from the underlying maternal condition.

### Pediatric Use
- Safety and efficacy of Coagulation factor IX, GlycoPEGylated (Rebinyn) were evaluated in 43 previously treated pediatric patients. Twelve of these subjects (28%) were 1 to 6 years of age; 13 subjects (30%) were 7 to 12 years of age; and 18 subjects (42%) were 13 to 17 years of age. Pharmacokinetic parameters were evaluated for 28 of these subjects who were treated with Coagulation factor IX, GlycoPEGylated (Rebinyn) 40 IU/kg.
- No difference in the safety profile of Coagulation factor IX, GlycoPEGylated (Rebinyn) was observed between previously treated pediatric subjects and adult subjects. Body weight-adjusted clearance was higher for pediatric subjects than for adult subjects. Fixed doses were studied in the clinical trials and no dose adjustment was required for pediatric subjects.
- Twenty-eight of the forty-three previously treated pediatric subjects (1 to 17 years old) were treated with Coagulation factor IX, GlycoPEGylated (Rebinyn) for 137 bleeding episodes. Results are provided in Table 4.
- Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single injection; Good: Noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection;
- Moderate: Probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one injection within 8 hours;
- Poor: No improvement, or worsening of symptoms within 8 hours after the second of two injections.
- Animals administered repeat doses of Coagulation factor IX, GlycoPEGylated (Rebinyn) showed accumulation of PEG in the choroid plexus. The potential clinical implications of these animal findings are unknown. No adverse neurologic effects of PEG have been reported in infants, children, and adolescents exposed to Coagulation factor IX, GlycoPEGylated (Rebinyn) during clinical trials. The potential consequences of long term exposure have not been fully evaluated.

### Geriatic Use
- Clinical studies of Coagulation factor IX, GlycoPEGylated (Rebinyn) did not include sufficient numbers of subjects age 65 and over to determine whether or not they respond differently than younger subjects.
- Animals administered repeat doses of Coagulation factor IX, GlycoPEGylated (Rebinyn) showed accumulation of PEG in the choroid plexus. The potential clinical implications of these animal findings are unknown. No adverse neurologic effects of PEG have been reported in adults exposed to Coagulation factor IX, GlycoPEGylated (Rebinyn) during clinical trials, however use in older adults with baseline cognitive dysfunction has not been fully evaluated.

### Gender
There is no FDA guidance on the use of Coagulation factor IX, GlycoPEGylated (Rebinyn) with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Coagulation factor IX, GlycoPEGylated (Rebinyn) with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Coagulation factor IX, GlycoPEGylated (Rebinyn) in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Coagulation factor IX, GlycoPEGylated (Rebinyn) in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Coagulation factor IX, GlycoPEGylated (Rebinyn) in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Coagulation factor IX, GlycoPEGylated (Rebinyn) in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Bring vial and prefilled diluent syringe to room temperature prior to use.
- Slowly add diluent from the prefilled syringe to the vial and then swirl the assembly gently until powder in vial is dissolved.
- Resulting solution should be clear and have no particles.
- Administer immediately or store in the vial with the vial adapter and syringe attached for up to 4 hours at room temperature, 30 degrees C (86 degrees F) or lower.
- Do not administer in same tubing or container with other medicinal products.
- The prefilled diluent syringe is made of glass with an internal tip diameter of 0.037 inches, and is compatible with a standard Luer-lock connector.
- Reconstituted product may be also withdrawn into standard 10 mL Luer-lock plastic syringe for use with need<ss connectors for IV catheders that are incompatible with the diluent syringe.
- Attach the syringe to Luer end of infusion needle set and administer reconstituted product IV slowly over 1 to 4 minutes.
- Dispose of any unused product.

### Monitoring
- Control of bleeding episodes and management of perioperative bleeding in patients with hemophilia B indicates efficacy.
- Factor IX activity: Use a chromogenic assay or selected one-stage clotting assay validated for use with Coagulation factor IX, GlycoPEGylated (Rebinyn)(R) to avoid over- or under-estimation of Factor IX activity; Avoid the use of silica-based reagents, which may result in an over-estimation.
- Development of inhibitors (neutralizing antibodies): Use both clinical evaluation and laboratory testing; if bleeding is not controlled with the recommended dosage, or if the expected Factor IX activity levels in plasma are not attained, used  a Bethesda assay to determine if Factor IX inhibitors are present.
- Early signs of thrombotic and consumptive coagulopathy: When administering to patients with liver disease, postoperatively, to newborn infants, or to patients at risk of thrombosis or disseminated intravascular coagulation.
- Signs and symptoms of an acute hypersensitivity reaction: Especially during the early phases of exposure.

# IV Compatibility
There is limited information regarding the compatibility of Coagulation factor IX, GlycoPEGylated (Rebinyn) and IV administrations.

# Overdosage
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) overdosage.  If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

# Pharmacology

## Mechanism of Action
- Patients with hemophilia B are deficient in coagulation Factor IX, which is required for effective hemostasis. Treatment with Coagulation factor IX, GlycoPEGylated (Rebinyn) temporarily replaces the missing coagulation Factor IX.
- The Factor IX in Coagulation factor IX, GlycoPEGylated (Rebinyn) is conjugated to a 40-kDa polyethylene glycol molecule, which slows down its removal from the blood circulation.

## Structure
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) Structure in the drug label.

## Pharmacodynamics
- The administration of Coagulation factor IX, GlycoPEGylated (Rebinyn) increases plasma levels of Factor IX and can temporarily correct the coagulation defect in hemophilia B patients, as reflected by a decrease in aPTT.

## Pharmacokinetics
- Pharmacokinetic (PK) parameters of Coagulation factor IX, GlycoPEGylated (Rebinyn) were evaluated in previously treated subjects, including a subset of subjects in the adult/adolescent trial and all subjects in the main phase of the pediatric trial. PK samples were collected prior to dosing and at multiple time points up to 168 hours after dosing. The analysis of plasma samples was conducted using the one-stage clotting assay.
- Steady state pharmacokinetic parameters for adolescents and adults following once-weekly prophylactic treatment of Coagulation factor IX, GlycoPEGylated (Rebinyn) 40 IU/kg are shown in Table 5.
- The mean steady state pre-dose trough levels and post-dose peak levels across the clinical trials for all previously treated subjects are shown in Table 6.
- Single-dose pharmacokinetic parameters of REBINYN in children, adolescents and adults are listed in Table 7.
- Pharmacokinetics were investigated in 9 subjects in the adult/adolescent trial, of which 5 were normal weight (body mass index (BMI) 18.5 to 24.9 kg/m2) and 4 were overweight (BMI 25 to <29.9 kg/m2). The pharmacokinetic parameters were not affected by BMI.
- The Factor IX activity following 80 IU/kg infusion in major surgery is shown in Table 8.

## Nonclinical Toxicology
- Studies in animals to evaluate the carcinogenic or genotoxic potential of Coagulation factor IX, GlycoPEGylated (Rebinyn), or studies to determine the effects of Coagulation factor IX, GlycoPEGylated (Rebinyn) on fertility, have not been performed.
- Coagulation factor IX, GlycoPEGylated (Rebinyn) was intraveneously administered in repeat-dose toxicity studies in immune-deficient rats (40-1200 IU/kg/week for 26 weeks) and immune-competent monkeys (350-3750 IU/kg/week for four weeks). Accumulation of the 40-kDa polyethylene-glycol (PEG) was detected by immunohistochemical staining in epithelial cells of the choroid plexus in the brain of the majority of animals. This finding was not associated with morphological changes or abnormal clinical signs.

# Clinical Studies
- Four multicenter, non-controlled trials were conducted to evaluate the safety and efficacy of Coagulation factor IX, GlycoPEGylated (Rebinyn) in routine treatment, on-demand treatment and control of bleeding episodes, and perioperative management in previously treated male patients with hemophilia B (Factor IX activity  2%). Previously treated patients were defined as patients receiving treatment with other Factor IX products for 150 exposure days for adolescents and adults, and 50 exposure days for pediatric patients. The key exclusion criteria across trials included known or suspected hypersensitivity to trial or related products, known history of Factor IX inhibitors or current inhibitor 0.6 BU, HIV-positive with a viral load 400,000 copies/mL or CD4+ lymphocyte count 200/L, additional congenital or acquired coagulation disorders, previous arterial thrombotic events, and recipients of immune modulating or chemotherapeutic medication.
- The efficacy evaluation included 105 subjects: 62 adults (18 to 65 years old), 18 adolescents (13 to 17 years old), and 25 children (1 to 12 years old).
- Adult/adolescent trial: The trial included 74 adolescent and adult previously treated patients. There were two routine treatment arms, with single-blind randomization to either 10 IU/kg or 40 IU/kg once-weekly for approximately 52 weeks, and an open-label on-demand treatment arm for approximately 28 weeks.
- Surgery trial: The surgery trial included 13 previously treated adolescent and adult patients who received one infusion of Coagulation factor IX, GlycoPEGylated (Rebinyn) 80 IU/kg on the day of surgery, and post-operatively received infusions of 40 IU/kg, at the investigators discretion, for up to 3 weeks after surgery.
- Adult/adolescent extension trial: There were 71 subjects from the adult/adolescent trial and surgery trial who continued routine treatment or on-demand treatment with Coagulation factor IX, GlycoPEGylated (Rebinyn) in an open-label extension trial, with the possibility to switch regimens during the trial.
- Pediatric trial: The main phase of the pediatric trial included 25 pediatric previously treated patients (1-12 years old) in which subjects received routine treatment with Coagulation factor IX, GlycoPEGylated (Rebinyn) 40 IU/kg once-weekly for approximately 52 weeks.
- A total of 597 bleeding episodes were reported in 79 out of 105 subjects in the clinical program in previously treated patients. Bleeding episodes were treated with Coagulation factor IX, GlycoPEGylated (Rebinyn) at 40 IU/kg for minor or moderate bleeds or 80 IU/kg for major bleeds, with additional doses of 40 IU/kg as needed. The median dose to treat a bleeding episode was 42.3 IU/kg.
- An overall assessment of efficacy was performed by the subject (for home treatment) or the study site investigator (for treatment under medical supervision) using a 4-point scale of excellent, good, moderate, or poor. The overall success rate (defined as excellent or good) for treatment of bleeding episodes was 93.2% as shown in Table 9.
- The success rate and dose needed for treatment of bleeding episodes were independent of the location of the bleeding. The success rate for treatment of bleeding episodes was also independent of whether the bleed was traumatic or spontaneous.
- Efficacy assessment was based on 591 evaluated bleeding episodes (data missing for six bleeding episodes). Efficacy was assessed according to a four-point scale using:
- Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single injection; Good: Noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection;
- Moderate: Probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one injection within 8 hours;
- Poor: No improvement, or worsening of symptoms within 8 hours after the second of two injections.
- In the on-demand arm there were 143 bleeding episodes in 14 of 15 subjects. The overall success rate was 95.1% (135 of 142 evaluated bleeds). A total of 120 bleeds (83.9%) of the 143 bleeding episodes were treated with one injection, and 20 (14.0%) were treated with two injections.
- In the surgery trial, the efficacy analysis of Coagulation factor IX, GlycoPEGylated (Rebinyn) in perioperative management included 13 surgical procedures of which 9 were major and performed in 13 previously treated adolescent and adult patients. The procedures included 9 orthopedic, 1 gastrointestinal and 3 in the oral cavity.
- The hemostatic effect during surgery was evaluated on a four-point scale of excellent, good, moderate, or poor. The intraoperative hemostatic effect was rated as excellent or good for the 13 surgeries, for a success rate of 100%. A pre-operative dose of 80 IU/kg Coagulation factor IX, GlycoPEGylated (Rebinyn) was effective, and no subjects required additional doses on the day of surgery. The median number of additional 40 IU/kg doses in the post-operative period was 2.0 for Days 1 to 6, 1.5 for Days 7-13, and 3.0 for Days 1 to 13. The mean total consumption of Coagulation factor IX, GlycoPEGylated (Rebinyn) in the pre- and post-operative period was 241 IU/kg (range: 81 to 460 IU/kg). There was no unexpected postoperative bleeding.
- Three additional major surgeries and 18 minor surgery procedures were evaluated in the extension trial for Coagulation factor IX, GlycoPEGylated (Rebinyn) in previously treated patients. The hemostatic effect during major and minor surgery was confirmed with a success rate of 100%.

# How Supplied
- Coagulation factor IX, GlycoPEGylated (Rebinyn) is supplied in packages comprised of a single-use vial containing nominally 500, 1000, or 2000 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 Coagulation factor IX, GlycoPEGylated (Rebinyn) carton and vial.
- The Coagulation factor IX, GlycoPEGylated (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
- Store Coagulation factor IX, GlycoPEGylated (Rebinyn) in the original package in order to protect from light.
- Store Coagulation factor IX, GlycoPEGylated (Rebinyn) under refrigeration at a temperature of 36F-46F (2C  8C) for up to 24 months from the date of manufacture until the expiration date stated on the label.
- Coagulation factor IX, GlycoPEGylated (Rebinyn) may be stored at room temperature not to exceed 86F (30C) 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.
- Do not use Coagulation factor IX, GlycoPEGylated (Rebinyn) after the end of the 6-month period at room temperature storage, or after the expiration date stated on the vial, whichever occurs earlier.
- Do not freeze Coagulation factor IX, GlycoPEGylated (Rebinyn).
- Use Coagulation factor IX, GlycoPEGylated (Rebinyn) within 4 hours after reconstitution when stored at room temperature. Store the reconstituted product in the vial.
- Discard any unused reconstituted product stored at room temperature for more than 4 hours.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
- Inform patients of the early signs of hypersensitivity reactions including rash, hives, itching, facial swelling, tightness of the chest and wheezing. Advise patients to discontinue use of the product and contact their healthcare provider if these symptoms occur.
- Advise patients to contact their healthcare provider for further treatment and/or assessment if they experience a lack of a clinical response to Factor IX therapy, as in some cases this may be a manifestation of an inhibitor.
- Advise patients to contact their healthcare provider if they experience any thrombotic complications.
- Advise patients to follow the recommendations regarding proper sharps disposal provided in the FDA-approved Instructions for Use.

# Precautions with Alcohol
Alcohol-Coagulation factor IX, GlycoPEGylated (Rebinyn) interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

# Brand Names
- Rebinyn

# Look-Alike Drug Names
There is limited information regarding Coagulation factor IX, GlycoPEGylated (Rebinyn) Look-Alike Drug Names in the drug label.

# Drug Shortage Status
Drug Shortage

# Price