Enter drug's generic or brand name below. Results will appear here. Note: all drug related information obtained on this page is provided by RX List.
Using the RX LIST database:
(1) Enter the drug name in the search box below and hit ENTER
(2) The rx list web site will open here with the drug search completed. Next, scroll down the page to locate the link to the drug you are searching for and then click on the link.
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 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-use vials containing the labeled amount of Factor IX activity, expressed in IU. Each vial contains nominally 500 IU, 1000 IU or 2000 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 152 IU/mg protein.
REBINYN is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells. No additives of human or animal origin are used in the cell culture, purification, conjugation, or formulation of REBINYN. The rFIX protein is purified by a series of chromatographic steps, including an affinity chromatography step using a monoclonal antibody (produced in CHO cells), to selectively isolate rFIX from the cell culture medium. The production process includes two dedicated viral clearance steps, namely a detergent treatment step for inactivation and a 20 nm filtration step for removal of viruses. The conjugation of the PEG-group is done by an enzymatic reaction during the purification process, followed by final purification of REBINYN.
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:
REBINYN® is not indicated for immune tolerance induction in patients with hemophilia B.
For intravenous infusion after reconstitution only.
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. |
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 be extended to once weekly after the first week until bleeding stops and healing is achieved. |
|
| *See Pharmacokinetics, Table 8 | ||
For prophylaxis use, the recommended dose is 40 IU/kg body weight once weekly.
Adjust dosing regimen based on individual patient’s bleeding pattern, and physical activity.
 |
The instructions below serve as a general guideline for reconstitution of REBINYN®. For full instructions, refer to the FDA-approved patient information and Instructions for Use.
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
For intravenous infusion only.
 |
Caution: The pre-filled diluent syringe is made of glass with an internal tip diameter of 0.037 inches, and is compatible with a standard Luer-lock connector.
Some needleless connectors for intravenous catheters are incompatible with the glass diluent syringes (for example, certain connectors with an internal spike, such as Clave® /MicroClave®, InVision-Plus®, InVision-Plus CS®, Invision-Plus Junior®, Bionector®), and their use can damage the connector and affect administration. To administer REBINYN® through incompatible needleless connectors, withdraw the reconstituted product into a standard 10 mL sterile Luer-lock plastic syringe.
If you encounter any problems with attaching the pre-filled histidine-diluent syringe to any Luer-lock compatible device, please contact Novo Nordisk at (844) 303-4448.
REBINYN® is available as a white to off-white lyophilized powder in single-dose vials containing nominally 500, 1000, 2000, or 3000 IU per vial. Each carton and vial label for REBINYN® states the actual Factor IX potency in IU.
After reconstitution with 4 mL of histidine diluent, the reconstituted solution contains approximately 125, 250, 500, or 750 IU per mL of REBINYN® respectively.
Table 12: REBINYN® Presentations
| Presentation (Nominal Product Strength; IU) | Cap Color Indicator | Carton NDC Number | Components |
| 500 | Red | NDC 0169 7905 01 |
|
| 1000 | Green | NDC 0169 7901 01 |
|
| 2000 | Yellow | NDC 0169 7902 01 |
|
| 3000 | Dark Gray | NDC 0169 7903 01 |
|
Manufactured by: Novo Nordisk A/S DK-2880 Bagsvaerd, Denmark. Revised: Sep 2022.
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.
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.
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]. 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) |
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]. 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 | 1 (2) |
| Hypersensitivity | 3 (6) | |
| Skin and subcutaneous tissue disorders | Rash | 9 (18) |
| Itching | 2 (4) |
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, one anaphylactic reaction has occurred with development of a factor IX inhibitor following treatment with REBINYN®. Inhibitor development and anaphylactic reactions are more likely to occur during the early phases of factor IX replacement therapy [see WARNINGS AND PRECAUTIONS].
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 REBINYN® showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons [see Use In Specific Populations and Animal Toxicology And/Or Pharmacology]. The potential clinical implications of these animal findings are unknown.
In the pediatric studies, 47 PUPs and 25 PTPs receiving routine prophylaxis with REBINYN® at a weekly dose of 40 IU/kg were followed for central nervous system (CNS)-related ADRs for 6 and 8 years, respectively. The median duration of follow up of ADRs in the PUP and PTP studies were 2 and 7 years, respectively. Furthermore, neurological examinations were prospectively conducted in 44 PUPs and 17 PTPs with a median follow up of 2 years, and neurocognitive assessments were prospectively performed in 38 PUPs and 16 PTPs with a median follow up of 1 year.
Although no clear clinical implications of the animal findings are known and no clear clinical neurologic or neurocognitive safety signal has emerged, the physician should consider whether the patient is vulnerable to cognitive impairment, such as infants and children who have developing brains, and patients who are cognitively impaired. Factors such as duration of use, cumulative dose, age of the patient and co-morbidities that may increase risk of adverse neurologic and/or neurocognitive events should be considered when prescribing REBINYN®. Report adverse neurocognitive and neurologic reactions.
The following adverse reactions have been identified during post-approval use of REBINYN®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: Factor IX inhibitor development.
No Information Provided
Included as part of the "PRECAUTIONS" Section
Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with REBINYN. The product maycontain traces of hamster proteins which in some patients may cause allergic reactions. Early signs of allergicreactions, 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 REBINYN if allergic- oranaphylactic - type reactions occur, and initiate appropriate treatment.
The formation of inhibitors (neutralizing antibodies) to Factor IX may occur during Factor replacement therapyin the treatment of hemophilia B. Monitor all patients using clinical observations and laboratory tests for thedevelopment of inhibitors [ see Monitoring Laboratory Tests].
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 IXinhibitors 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 thepotential risk of thrombotic complications, monitor patients for early signs of thrombotic and consumptivecoagulopathy when administering this product to patients with liver disease, post-operatively, to newborninfants, or to patients at risk of thrombosis or disseminated intravascular coagulation (DIC). In each of thesesituations, the benefit of treatment with REBINYN should be weighed against the risk of these complications.
Nephrotic syndrome has been reported following immune tolerance induction therapy with Factor IX products inhemophilia B patients with Factor IX inhibitors, often with a history of allergic reactions to Factor IX. The safetyand efficacy of using 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 assayvalidated for use with REBINYN [ see DOSAGE AND ADMINISTRATION].
The one-stage clotting assay results can be significantly affected by the type of activated partial thromboplastintime (aPTT) reagent used, which can result in over- or under-estimation of Factor IX activity. Avoid the use ofsilica-based reagents, as some may overestimate the activity of REBINYN. If a validated one-stage clotting orchromogenic assay is not available locally, then use of a reference laboratory is recommended.
If bleeding is not controlled with the recommended dose of REBINYN, or if the expected Factor IX activitylevels in plasma are not attained, then perform a Bethesda assay to determine if Factor IX inhibitors are present.
Studies in animals to evaluate the carcinogenic or genotoxic potential of REBINYN, or studies to determine theeffects of REBINYN on fertility, have not been performed.
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 cancause fetal harm when administered to a pregnant woman or can affect fertility. REBINYN should be given to apregnant woman only if clearly needed. In the U.S. general population, the estimated background risk of majorbirth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
There is no information regarding the presence of 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 consideredalong with the mother’s clinical need for REBINYN and any potential adverse effects on the breastfed infantfrom REBINYN or from the underlying maternal condition.
Safety and efficacy of REBINYN were evaluated in 43 previously treated pediatric patients [see Clinical Studies]. Twelve of these subjects (28%) were 1 to 6 years of age; 13 subjects (30%) were 7 to 12 years of age; and18 subjects (42%) were 13 to 17 years of age. Pharmacokinetic parameters were evaluated for 28 of thesesubjects who were treated with REBINYN 40 IU/kg [ see CLINICAL PHARMACOLOGY ].
No difference in the safety profile of REBINYN was observed between previously treated pediatric subjects andadult subjects. Body weight-adjusted clearance was higher for pediatric subjects than for adult subjects. Fixeddoses 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 withREBINYN for 137 bleeding episodes. Results are provided in Table 4.
Table 4: Efficacy in treatment of bleeding episodes in pediatric subjects by age
| ≤ 6 years | 7-12 years | 13-17 years | |
| New bleedingepisodes | n=11 | n=31 | n=95* |
| Efficacyassessment** | |||
| Excellent or good | 10 (91%) | 29 (94%) | 91 (97%) |
| Moderate or poor | 1 (9%) | 2 (6%) | 3 (3%) |
| Number of injectionsto treat a bleedingepisode | |||
| 1 injection | 9 (82%) | 27 (87%) | 78 (82%) |
| 2 injection | 1 (9%) | 4 (13%) | 12 (13%) |
| > 2 injections | 1 (9%) | - | 5 (5%) |
| *Efficacy assessment was missing for one bleeding episode. **Efficacy assessment [Response] 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. |
|||
Animals administered repeat doses of REBINYN showed accumulation of PEG in the choroid plexus [ see Animal Toxicology And/Or Pharmacology]. The potential clinical implications of these animal findings areunknown. No adverse neurologic effects of PEG have been reported in infants, children, and adolescentsexposed to REBINYN during clinical trials. The potential consequences of long term exposure have not beenfully evaluated [see Section 6.3].
Clinical studies of REBINYN did not include sufficient numbers of subjects age 65 and over to determinewhether or not they respond differently than younger subjects.
Animals administered repeat doses of REBINYN showed accumulation of PEG in the choroid plexus [ see Animal Toxicology And/Or Pharmacology]. The potential clinical implications of these animal findings areunknown. No adverse neurologic effects of PEG have been reported in adults exposed to REBINYN duringclinical trials, however use in older adults with baseline cognitive dysfunction has not been fully evaluated [ see Section 6.3].
No Information Provided
REBINYN® is contraindicated in patients who have known hypersensitivity to REBINYN® or its components (including hamster proteins) [see WARNINGS AND PRECAUTIONS and DESCRIPTION]
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.
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.
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 [see Clinical Studies]. 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.
Table 5: Steady-state pharmacokinetic parameters of REBINYN® (40 IU/kg) in adolescents and adults (geometric mean (CV))
| PK Parameter | 13-17 years N=3 |
≥ 18 years N=6 |
| Half-life (hours) | 103.1 (14.2) | 114.9 (9.7) |
| Incremental Recovery30min (IU/dL per IU/kg) | 1.82 (28.2) | 1.92 (19.6) |
| AUC0-168 (IU*hours/dL) | 9072 (22) | 9280 (15) |
| Clearance (mL/hour/kg) | 0.4 (16.7) | 0.4 (11.4) |
| Mean residence time (hours) | 144.4 (15.3) | 158.1 (9.6) |
| Vss (mL/kg) | 60.5 (31.1) | 65.8 (11.9) |
| Factor IX activity 168 h after dosing (%) | 28.9 (18.6) | 32.4 (17.1) |
| Abbreviations: AUC = area under plasma concentration-time curve; Vss= volume of distribution at steady state; CV=coefficient of variation. | ||
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.
Table 6: Factor IX peak and trough levels of REBINYN® (40 IU/kg) by age at steady state
| ≤ 6 years N=12 |
7-12 years N=13 |
13-17 years N=9 |
≥18 years N=20 |
|
| Mean Factor IX peak level (%) (95% CI) | 65.5 (60.6; 70.7) |
71.4 (66.3; 77.0) |
82.8 (70.7; 96.9) |
97.9 (87.7; 109.3) |
| Mean Factor IX trough level* (%) (95% CI) | 15.4 (13.2; 17.9) |
18.7 (16.2; 21.6) |
23.7 (19.9; 28.2) |
29.3 (26.0; 33.0) |
| Min, Max** | 9.2; 24.5 | 8.3; 28.3 | 18.6; 34.6 | 21.3; 42.2 |
| * Factor IX activity from samples collected at clinical site visits just prior to administration of next weekly dose **Individual geometric mean trough values |
||||
Single-dose pharmacokinetic parameters of REBINYN® in children, adolescents and adults are listed in Table 7.
Table 7: Single Dose Pharmacokinetic Parameters of REBINYN® (40 IU/kg) in children, adolescents and adults (geometric mean (CV))
| PK Parameter | ≤ 6 years N=12 |
7-12 years N=13 |
13-17 years N=3 |
≥18 years N=6 |
| Half-life (hours) | 69.6 (15.8) | 76.3 (25.5) | 89.4 (24.1) | 83.0 (22.5) |
| Incremental Recovery30min (IU/dL per IU/ kg) | 1.51 (7.31) | 1.59 (16.2) | 1.96 (14.7) | 2.34 (11.3) |
| AUCinf (IU*h/ dL) | 4617 (14) | 5618 (19) | 7986 (35) | 9063 (16) |
| Clearance (mL/hour/kg) |
0.8 (13.0) | 0.6 (21.9) | 0.5 (30.4) | 0.4 (14.7) |
| Mean residence time (hours) | 95.4 (15.3) | 105.1 (24.2) | 124.2 (24.4) | 115.5 (21.8) |
| Vss (mL/kg) | 72.3 (14.8) | 68.3 (21.7) | 58.6 (7.8) | 47.0 (15.9) |
| Factor IX activity 168 h after dosing (%) | 8.4 (16.3) | 10.9 (18.9) | 14.6 (59.6) | 16.8 (30.6) |
| Abbreviations: AUC = area under plasma concentration-time curve; Vss = volume of distribution at steady state; CV = coefficient of variation. | ||||
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.
Table 8: Factor IX activity following 80 IU/kg bolus for major surgery
| 30 minutes | 8 hours1 | 24 hours1 | 48 hours2 | |
| N=13 | N=12 | N=12 | N=7 | |
| Factor IX activity (%) Median (Range) | 143 (123-224) |
138 (101-175) |
112 (62-146) |
73 (40-110) |
| 1Excludes one subject with no Factor IX activity measurement obtained. 2Excludes two subjects with no Factor IX activity measurement obtained and additionally 4 subjects re-dosed prior to second day after surgery for whom the Factor IX activity at 24 hours were 84%, 112%, 131% and 134%. The 48 hours measurement reflects a measurement on the 2nd day after surgery (range 47-57 hours). |
||||
REBINYN® was intravenously administered in repeat-dose toxicity studies in adult immune-deficient rats (40-1200 IU/kg/week for 26 weeks), immune-competent monkeys (350-3750 IU/kg/week for 4 weeks), and juvenile immune-competent rats (120-1200 IU/ kg/twice weekly for 10 weeks). Accumulation of PEG was detected in epithelial cells of the choroid plexus in the brain of the adult rats and monkeys. This finding was not associated with morphological changes or abnormal clinical signs. In juvenile rats, more comprehensive assessment of brain tissues demonstrated PEG accumulation in the choroid plexus, pituitary, circumventricular organs, and the cranial motor neurons [see Use In Specific Populations].
Safety and efficacy of REBINYN® was evaluated in five multicenter, non-controlled, open-label trials in on-demand treatment of bleeding episodes, perioperative management of major and minor surgery, and routine prophylaxis or pharmacokinetic evaluation in PTPs with hemophilia B (Factor IX activity ≤ 2%). The efficacy evaluation included 105 PTPs [62 adults (18 to 65 years old), 18 adolescents (13 to 17 years old), and 25 children (1 to 12 years old)].
Previously Treated Patients
A total of 250 bleeding episodes were reported in 45 out of 69 PTPs receiving either REBINYN® 40 IU/kg prophylaxis or on-demand treatment in the clinical program. 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 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 95% 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.
Table 9: Treatment of Bleeding Episodes in PTPs Receiving Either 40 IU/kg Prophylaxis or On-Demand Treatment
| Treatment | Prophylaxis with 40 IU/kg | On-Demand | Totals |
| New Bleeding Episodes | 107 | 143 | 250 |
| Efficacy assessment* | |||
| Excellent or Good | 101 (95%) | 135 (95%) | 236 (95%) |
| Moderate or Poor | 5 (5%) | 7 (5%) | 12 (5%) |
| Number of injections to treat a bleeding episode | |||
| 1 injection | 100 (93%) | 120 (84%) | 220 (88%) |
| 2 injections | 5 (5%) | 20 (14%) | 25 (10%) |
| >2 injections | 2 (2%) | 3 (2%) | 5 (2%) |
| *Efficacy assessment was based on 248 evaluated bleeding episodes (data missing for two bleeding episodes). 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 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%.
Adult/Adolescent PTP Trial
In the main phase of the adult/adolescent PTP trial, 29 subjects (13 to 65 years old) received REBINYN® 40 IU/kg once weekly for approximately 52 weeks. The annualized bleeding rate for these subjects in the main phase is presented in Table 10. Eighteen of 20 (90%) target joints per ISTH definition (≥ 3 spontaneous bleeds into a single joint within a consecutive 6-month period) reported in 13 subjects in the 40 IU/kg once weekly arm at baseline were considered resolved at the end of the main phase.
Table 10: Annualized Bleeding Rate (ABR) in the Adult/ Adolescent PTP Trial (40 IU/kg Once Weekly Arm) – Main Phase
| Age of patient | Main Phase | ||
| 13-17 years N=9 |
18-65 years N=20 |
Overall ≥ 13 years N=29 |
|
| Total ABR | |||
| Poisson-estimated mean (95% CI) | 2.19 (0.73 ; 6.54) |
2.68 (1.34 ; 5.35) |
2.52 (1.40; 4.52) |
| Median (Q1; Q3) | 1.93 (0.00 ; 4.01) |
1.03 (0.00 ; 4.01) |
1.04 (0.00; 4.01) |
| ABR for spontaneous bleeds | |||
| Poisson-estimated mean (95% CI) | 0.11 (0.00; 13.23) |
1.77 (0.77; 4.07) |
1.22 (0.46; 3.25) |
| Median (Q1; Q3) | 0.00 (0.00; 0.00) |
0.00 (0.00; 1.51) |
0.00 (0.00; 0.99) |
| ABR for traumatic bleeds | |||
| Poisson-estimated mean (95% CI) | 2.08 (0.98; 4.42) |
0.91 (0.41; 2.02) |
1.29 (0.74; 2.25) |
| Median (Q1; Q3) | 1.93 (0.00; 3.87) |
0.00 (0.00; 1.01) |
0.00 (0.00; 2.05) |
| ABR for joint bleeds | |||
| Poisson-estimated mean (95% CI) | 1.42 (0.36; 5.57) |
2.19 (1.02; 4.73) |
1.94 (0.97; 3.88) |
| Median (Q1; Q3) | 0.97 (0.00; 2.17) |
0.51 (0.00; 2.04) |
0.97 (0.00; 2.07) |
| CI = confidence interval; Q1 = first quartile; Q3 = third quartile. | |||
Pediatric PTP Trial In the main phase of the pediatric PTP trial, 25 subjects 0 to 12 years of age received routine prophylactic administration of REBINYN® 40 IU/kg once weekly for 52 weeks. The patients were stratified into two age groups: 0 to 6 years and 7 to 12 years, with a least 10 subjects in each arm. Two target joints in 2 subjects in the 7 to 12 years age group at baseline were considered resolved during the main phase.
Table 11: Annualized Bleeding Rate (ABR) in the Pediatric PTP Trial - Main Phase
| Age of patient | Main Phase | |
| ≤ 6 years N=12 |
7-12 years N=13 |
|
| Mean treatment period (years) | 0.93 | 1.01 |
| Total ABR | ||
| Poisson-estimated mean (95% CI) | 0.90 (0.43 ; 1.89) |
2.06 (1.31 ; 3.24) |
| Median (Q1; Q3) | 0.00 (0.00 ; 1.98) |
2.00 (0.96 ; 3.00) |
| ABR for spontaneous bleeds | ||
| Poisson-estimated mean (95% CI) | 0.27 (0.06 ; 1.26) |
0.61 (0.24 ; 1.57) |
| Median (Q1; Q3) | 0.00 (0.00 ; 0.00) |
0.00 (0.00 ; 0.96) |
| ABR for traumatic bleeds | ||
| Poisson-estimated mean (95% CI) | 0.63 (0.28 ; 1.43) |
1.14 (0.65 ; 2.01) |
| Median (Q1; Q3) | 0.00 (0.00 ; 1.00) |
0.98 (0.00 ; 1.93) |
| ABR for joint bleeds | ||
| Poisson-estimated mean (95% CI) | 0.18 (0.04 ; 0.72) |
0.92 (0.52 ; 1.62) |
| Median (Q1; Q3) | 0.00 (0.00 ; 0.00) |
0.96 (0.00 ; 1.93) |
| CI = confidence interval; Q1 = first quartile; Q3 = third quartile. | ||
REBINYN®
(reh-be-NINE)
Coagulation Factor IX (Recombinant), GlycoPEGylated
Read the Patient Product Information and the Instructions For Use that come with REBINYN® before you start taking this medicine and each time you get a refill, as there may be new information.
This Patient Product Information does not take the place of talking with your healthcare provider about your medical condition or treatment. If you have questions about REBINYN® after reading this information, ask your healthcare provider.
What is the most important information I need to know about REBINYN®?
Do not attempt to do an infusion yourself unless you have been taught how by your healthcare provider or hemophilia treatment center.
You must carefully follow your healthcare provider’s instructions regarding the dose and schedule for infusing REBINYN® so that your treatment will work best for you.
What is REBINYN®?
REBINYN® is an injectable medicine used to replace clotting Factor IX that is missing in patients with hemophilia B.
Hemophilia B is an inherited bleeding disorder in all age groups that prevents blood from clotting normally.
REBINYN® is used to treat, prevent, or reduce the frequency (number) of bleeding episodes in people with hemophilia B.
Your healthcare provider may give you REBINYN® when you have surgery.
Who should not use REBINYN®?
You should not use REBINYN® if you
If you are not sure, talk to your healthcare provider before using this medicine.
Tell your healthcare provider if you are pregnant or nursing because REBINYN® might not be right for you.
What should I tell my healthcare provider before I use REBINYN®?
You should tell your healthcare provider if you
How should I use REBINYN®?
Treatment with REBINYN® should be started by a healthcare provider who is experienced in the care of patients with hemophilia B.
REBINYN® is given as an infusion into the vein.
You may infuse REBINYN® at a hemophilia treatment center, at your healthcare provider’s office or in your home. You should be trained on how to do infusions by your hemophilia treatment center or healthcare provider. Many people with hemophilia B learn to infuse the medicine by themselves or with the help of a family member.
Your healthcare provider will tell you how much REBINYN® to use based on your weight, the severity of your hemophilia B, and where you are bleeding. Your dose will be calculated in international units, IU.
Call your healthcare provider right away if your bleeding does not stop after taking REBINYN®.
If your bleeding is not adequately controlled, it could be due to the development of Factor IX inhibitors. This should be checked by your healthcare provider. You might need a higher dose of REBINYN® or even a different product to control bleeding. Do not increase the total dose of REBINYN® to control your bleeding without consulting your healthcare provider.
Use in children
REBINYN® can be used in children. Your healthcare provider will decide the dose of REBINYN® you will receive.
If you forget to use REBINYN®
If you forget a dose, infuse the missed dose when you discover the mistake. Do not infuse a double dose to make up for a forgotten dose. Proceed with the next infusions as scheduled and speak to your healthcare provider if you have any questions or concerns.
If you stop using REBINYN®
Do not stop using REBINYN® without consulting your healthcare provider.
If you have any further questions on the use of this product, ask your healthcare provider.
What if I take too much REBINYN®?
Always take REBINYN® exactly as your healthcare provider has told you. You should check with your healthcare provider if you are not sure. If you infuse more REBINYN® than recommended, tell your healthcare provider as soon as possible.
What are the possible side effects of REBINYN®?
Common Side Effects Include:
Your body can also make antibodies called “inhibitors” against Factor IX, including REBINYN®, which may stop REBINYN® from working properly. Your healthcare provider may need to test your blood for inhibitors from time to time.
You could have an allergic reaction to coagulation Factor IX products. Call your healthcare provider right away or get emergency treatment right away if you get, for example, any of the following signs of an allergic reaction: hives, chest tightness, wheezing, difficulty breathing, and/or swelling of the face.
You may be at an increased risk of forming blood clots in your body, especially if you have risk factors for developing blood clots. Call your healthcare provider if you have chest pain, difficulty breathing, leg tenderness or swelling.
These are not all of the possible side effects from REBINYN®.
Ask your healthcare provider for more information. You are encouraged to report side effects to FDA at 1-800-FDA-1088.
Tell your healthcare provider about any side effect that bothers you or that does not go away.
What are the REBINYN® dosage strengths?
REBINYN® comes in four different dosage strengths. The actual number of international units (IU) of Factor IX in the vial will be imprinted on the label and on the box. The four different strengths are as follows:
| Cap Color Indicator | Nominal Strength |
| Red | 500 IU per vial |
| Green | 1000 IU per vial |
| Yellow | 2000 IU per vial |
| Dark Gray | 3000 IU per vial |
Always check the actual dosage strength printed on the label to make sure you are using the strength prescribed by your healthcare provider.
How should I store REBINYN®?
Prior to Reconstitution (mixing the dry powder in the vial with the diluent):
Store in original package in order to protect from light. Do not freeze REBINYN®.
REBINYN® vials can be stored in the refrigerator (36-46°F [2°C- 8°C]) for up to 24 months until the expiration date, or at room temperature (up to 86°F [30°C]) for a single period not more than 6 months.
If you choose to store REBINYN® at room temperature:
Do not use this medicine after the expiration date which is on the outer carton and the vial. The expiration date refers to the last day of that month.
After Reconstitution:
The reconstituted (the final product once the powder is mixed with the diluent) REBINYN® should appear clear without visible particles.
The reconstituted REBINYN® should be used immediately.
If you cannot use the reconstituted REBINYN® immediately, it should be used within 4 hours when stored at or below 86ºF (30°C). Store the reconstituted product in the vial.
Keep this medicine out of the sight and out of reach of children.
What else should I know about REBINYN® and hemophilia B?
Medicines are sometimes prescribed for purposes other than those listed here. Do not use REBINYN® for a condition for which it is not prescribed. Do not share REBINYN® with other people, even if they have the same symptoms that you have.
INSTRUCTIONS FOR USE
REBINYN® MixPro®
READ THESE INSTRUCTIONS CAREFULLY BEFORE USING REBINYN®.
REBINYN® is supplied as a powder. Before infusion (administration) it must be mixed (reconstituted) with the liquid diluent supplied in the syringe. The liquid diluent is a histidine solution. The mixed REBINYN® must be infused into your vein (intravenous infusion). The equipment in this package is designed to mix and infuse REBINYN®.
You will also need an infusion set (tubing and butterfly needle), sterile alcohol swabs, gauze pads, and bandages.
Don’t use the equipment without proper training from your doctor or nurse.
Always wash your hands and ensure that the area around you is clean.
When you prepare and infuse medication directly into the veins, it is important to use a clean and germ free (aseptic) technique. Improper technique can introduce germs that can infect the blood.
Don’t open the equipment until you are ready to use it.
Don’t use the equipment if it has been dropped, or if it is damaged. Use a new package instead.
Don’t use the equipment if it is expired. Use a new package instead. The expiration date is printed on the outer carton and on the vial, the vial adapter and the pre-filled syringe.
Don’t use the equipment if you suspect it is contaminated. Use a new package instead.
Don’t dispose of any of the items until after you have infused the mixed solution.
The equipment is for single use only.
Single-dose container. Discard unused portion.
Content
The package contains:
 |
1. Prepare the vial and the syringe
 |
 |
2. Attach the vial adapter
 |
Don’t take the vial adapter out of the protective cap with your fingers. If you touch the spike on the vial adapter germs from your fingers can be transferred.
If the protective paper is not fully sealed or if it is broken, don’t use the vial adapter.
Once attached, don’t remove the vial adapter from the vial.
 |
Don’t lift the vial adapter from the vial when removing the protective cap.
 |
3. Attach the plunger rod and the syringe
 |
Don’t touch the syringe tip under the syringe cap. If you touch the syringe tip germs from your fingers can be transferred.
If the syringe cap is loose or missing, don’t use the pre-filled syringe.
 |
 |
4. Mix the powder with the diluent
 |
 |
REBINYN® is recommended to be used immediately after it is mixed.
If you cannot use the mixed REBINYN® solution immediately, it should be used within 4 hours when stored at room temperature at or below 86°F (30°C). Store the reconstituted product in the vial.
Do not freeze mixed REBINYN® solution or store it in syringes.
Keep mixed REBINYN® solution out of direct light.
If your dose requires more than one vial, repeat step A to J with additional vials, vial adapters and pre-filled syringes until you have reached your required dose.
 |
Don’t touch the syringe tip. If you touch the syringe tip germs from your fingers can be transferred.
 |
Caution: The pre-filled diluent syringe is made of glass with an internal tip diameter of 0.037 inches, and is compatible with a standard Luer-lock connector.
Some needleless connectors for intravenous catheters are incompatible with the glass diluent syringes (for example, certain connectors with an internal spike, such as Clave® /MicroClave®, InVision-Plus®, InVision- Plus CS®, Invision-Plus® Junior®, Bionector®).
The use of these needleless connectors can damage the connector and affect administration.
To administer REBINYN® through incompatible needleless connectors, withdraw reconstituted product into a standard 10 mL sterile Luer-lock plastic syringe.
If you have encountered any problems with attaching the pre-filled histidine diluent syringe to any Luer-lock compatible device, please contact Novo Nordisk at (844) 303-4448.
5. Infuse the mixed solution
REBINYN® is now ready to infuse into your vein.
Infusing the solution via a central venous access device (CVAD) such as a central venous catheter or subcutaneous port:
The peel-off label found on the REBINYN® vial can be used to record the lot number.
Disposal
Don’t throw it out with the ordinary household trash.
 |
Don’t disassemble the vial and vial adapter before disposal.
Don’t reuse the equipment.
Important information
Contact your healthcare provider or local hemophilia treatment center if you experience any problems.
For full Prescribing Information please read the other insert included in this package.
