Coagulation factor IX, GlycoPEGylated (Rebinyn)

Coagulation factor IX, GlycoPEGylated (Rebinyn)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yashasvi Aryaputra[2];

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Black Box Warning

Warning Title See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Overview

Coagulation factor IX, GlycoPEGylated (Rebinyn) is a Acetylcholine release inhibitor, Adrenergic receptor agonist that is FDA approved for the (type of indication of drug) of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition 1

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Condition 2

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Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition 1

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

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Condition 2

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

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Non–Guideline-Supported Use

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Condition 3

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Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition 1

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Condition 2

• Dosing Information

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Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition 1

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Condition 2

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

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Non–Guideline-Supported Use

Condition 1

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Condition 2

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Condition 3

• Dosing Information

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Contraindications

CONTRAINDICATIONS

Warnings

Warning Title See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Conidition 1

(Description)

Conidition 2

(Description)

Conidition 3

(Description)

Adverse Reactions

Clinical Trials Experience

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

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Respiratory

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Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

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Miscellaneous

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Condition 2

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Postmarketing Experience

(Description)

Drug Interactions

• Drug 1
• Drug 2
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Drug 1

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Drug 2

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Drug 3

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Drug 4

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Drug 5

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Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): (Description)
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

(Description)

Nursing Mothers

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Pediatric Use

(Description)

Geriatic Use

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Gender

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Race

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Renal Impairment

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Hepatic Impairment

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Females of Reproductive Potential and Males

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Immunocompromised Patients

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Others

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Administration and Monitoring

Administration

(Oral/Intravenous/etc)

Monitoring

Condition 1

(Description regarding monitoring, from Warnings section)

Condition 2

(Description regarding monitoring, from Warnings section)

Condition 3

(Description regarding monitoring, from Warnings section)

IV Compatibility

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

Overdosage

Acute Overdose

Signs and Symptoms

(Description)

Management

(Description)

Chronic Overdose

Signs and Symptoms

(Description)

Management

(Description)

Pharmacology

Coagulation factor IX, GlycoPEGylated (Rebinyn)
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Mechanism of Action

• 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.

Structure

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

Pharmacodynamics

• The administration of 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 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 REBINYN 40 IU/kg are shown in Table 5.

This image is provided by the National Library of Medicine.

• 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.

This image is provided by the National Library of Medicine.

• Single-dose pharmacokinetic parameters of REBINYN in children, adolescents and adults are listed in Table 7.

This image is provided by the National Library of Medicine.

• 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.

This image is provided by the National Library of Medicine.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• Studies in animals to evaluate the carcinogenic or genotoxic potential of REBINYN, or studies to determine the effects of REBINYN on fertility, have not been performed.

Animal Toxicology and/or Pharmacology

• 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 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/μL, 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 REBINYN 80 IU/kg on the day of surgery, and post-operatively received infusions of 40 IU/kg, at the investigator’s 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 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 REBINYN 40 IU/kg once-weekly for approximately 52 weeks.

Treatment of Bleeding Episodes

• 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 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.

This image is provided by the National Library of Medicine.

• 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.

Perioperative Management

• In the surgery trial, the efficacy analysis of 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 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 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 REBINYN in previously treated patients. The hemostatic effect during major and minor surgery was confirmed with a success rate of 100%.

How Supplied

• 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 REBINYN carton and vial.

This image is provided by the National Library of Medicine.

• 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

• 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.

• Do not use 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 REBINYN.

• Use 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

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Package and Label Display Panel

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This image is provided by the National Library of Medicine.

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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

References

The contents of this FDA label are provided by the National Library of Medicine.