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REBINYN coagulation factor IX recombinant, GlycoPEGylated Kit — NDC 00169-7901-97 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

REBINYN coagulation factor IX recombinant, GlycoPEGylated Kit — NDC 0169-7901-97 (Billing 00169-7901-97)

by Novo Nordisk · 1 KIT in 1 KIT * 4 mL in 1 VIAL, GLASS * 4 mL in 1 SYRINGE, GLASS * 4 mL in 1 VIAL, GLASS

This is a package of REBINYN coagulation factor IX recombinant, GlycoPEGylated Kit from Novo Nordisk, marketed since Dec 2017 and currently FDA-listed.

NDC 00169-7901-97
🏷️ FDA NDC (as labeled) 0169-7901-97 billing pads the labeler segment with a zero
This package
Contains1 kit in 1 kit * 4 mL in 1 vial, glass * 4 mL in 1 syringe, glass * 4 mL in 1 vial, glass Pack sizes2 compare ↓
Product page 00169-7901-01 Also comes in: 1 kit 0169-7901-01
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

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Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 0169-7901-97 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
0169 labeler · 7901 product · 97 package
Package marketed since
May 5, 2022
Sample package
Yes — professional sample, not for sale
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 0169790197 8
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0169-7901-97
Product NDC 0169-7901
11-digit billing NDC 00169790197
RxCUI 1990857, 1990862
Application # BLA125611
SPL Set ID 0ea37235-35fd-410d-b8c4-40ba15fe1294
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2017-12-01
Dosage form KIT
Biologic (Purple Book) 351(a)

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 85100028452130
GPI class Rebinyn
GCN Seq No 077459
GCN 43483
HICL code 044322
Ingredient (HICL) Factor Ix Human Rec,Pegylated
HIC1 code M
Therapeutic class — broad (HIC1) Blood
HIC2 code M0
Therapeutic class — intermediate (HIC2) Blood And Blood Replacement Preparations
HIC3 code M0F
Therapeutic class — specific (HIC3) Factor Ix Preparations
AHFS code 20:28.16.00
AHFS class Hemostatics
FDB label name REBINYN 1,000 UNIT VIAL
FDB brand name Rebinyn
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 077459
  • GCN: 43483
  • GPI-14 (Medi-Span): 85100028452130
  • HICL (First Databank): 044322
  • AHFS class code: 20:28.16.00
  • RxCUI (RxNorm): 1990857
Why two NDCs? The FDA registers this code as 0169-7901-97 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00169-7901-97. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Human Blood Coagulation Factor class.

Pharmacologic class Human Blood Coagulation Factor
Drug family (ATC) Blood coagulation factors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name REBINYN 1,000 UNIT VIAL Ingredient Factor Ix Human Rec,Pegylated

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 1 kit
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
00169-7901-01 0169-7901-01 Main listing 1 KIT in 1 KIT * 4 mL in 1 VIAL, GLASS * 4 mL in 1 SYRINGE, GLASS * 4 mL in 1 VIAL, GLASS 2017-12-01 — Active
00169-7901-97 You're viewing this 1 KIT in 1 KIT * 4 mL in 1 VIAL, GLASS * 4 mL in 1 SYRINGE, GLASS * 4 mL in 1 VIAL, GLASS Sample 2022-05-05 — Active

Pack size FAQ

What quantity is in this package?
This package is listed by the FDA — 1 kit in 1 kit * 4 ml in 1 vial, glass * 4 ml in 1 syringe, glass * 4 ml in 1 vial, glass.
What NDC number is used to bill for this package of REBINYN coagulation factor IX recombinant, GlycoPEGylated Kit?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Rebinynthis 00169-7901-97 Novo 1 kit — — FDA listed —
Rebinyn 00169-7902-01 Novo 1 kit — — FDA listed —
Rebinyn 00169-7903-01 Novo 1 kit — — FDA listed —
Rebinyn 00169-7905-01 Novo 1 kit — — FDA listed —
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & biosimilar status

🏛️
2017
First FDA approval
May 2017
📍
2026
Currently FDA-listed
9 years listed
🛡️
2029
Latest patent/protection listed
not a guaranteed launch date
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through May 2029. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.
📅 FDA approved May 31, 2017 ⏳ ~2.7 yr to latest listed protection

Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.

Patents & exclusivity — FDA Purple Book
Exclusivity RefProduct
2017 2019 2021 2023 2025 2027 2029
Today
LOE
Biologic patent Exclusivity
🏛️Reference-product exclusivity
A flat 12 years of FDA market protection from first licensure. No biosimilar can be licensed before it ends — regardless of patents.
🧪Listed biologic patents
Patents the reference maker lists covering the molecule, formulation, or manufacturing. A biosimilar generally can’t launch until these resolve.
🔁Interchangeability
An interchangeable biosimilar may be substituted at the pharmacy (state laws vary). The first one can earn its own exclusivity period.
🛈 What do these terms mean?
Biologic patent
A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
Reference-product exclusivity
A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
Interchangeable exclusivity
The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
Earliest biosimilar (LOE)
The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.

Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.

FDA exclusivity
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateMay 31, 2029
Common questions
Is there a biosimilar for REBINYN 1,000 UNIT VIAL?
No FDA-licensed biosimilar is currently listed for this biologic in the FDA Purple Book.
Why do different websites show different biosimilar dates?
Biosimilar availability isn’t based on one single date. Some sources use the reference-product exclusivity, some use the last listed patent, and patent litigation, settlements, and licenses can all change the real-world launch date. This page shows the underlying Purple Book dates so you can see why estimates differ.
Can a biosimilar launch before the last patent expires?
Sometimes. A biosimilar maker may settle with the reference manufacturer or receive a license to launch earlier. In other cases, the last listed protection delays competition.
What does “current Purple Book estimate” mean?
It means we’re using the latest patent and exclusivity dates currently listed in the FDA Purple Book. It is not a guaranteed launch date.
What does “FDA listed” mean?
It means the product appears in the FDA’s official directory. That’s a good sign a product exists for the U.S. market, but on its own it does not confirm a pharmacy can get it today. Where we have recent retail pricing data, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Purple Book for a patent or exclusivity on the reference biologic. It can affect when a biosimilar becomes widely available — but it is not a guaranteed launch date. Settlements and licenses can move the real date earlier or later.
Built from the FDA Purple Book Patent List (patents the reference-product sponsor has publicly listed under the BPCIA) plus reference-product exclusivity. Biosimilars cannot launch until these clear; patent litigation and settlements can shift the real date. Biologics have no small-molecule generics — competition comes from FDA-licensed biosimilars, not the Orange Book.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerNovo Nordisk
FDA applicationBLA125611 (BLA)
Labeler code00169
First marketedDec 2017
Product typeHuman Prescription Drug
Portfolio74 products on file

More NDCs from Novo Nordisk labeler code 00169

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 145 words ▾

1 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 • 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. REBINYN, Coagulation Factor IX (Recombinant), GlycoPEGylated, is a recombinant DNA-derived coagulation Factor IX concentrate indicated for use in adults and children with hemophilia B (congenital Factor IX deficiency) for: • On-demand treatment and control of bleeding episodes • Perioperative management of bleeding • Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use : REBINYN is not indicated for immune tolerance induction in patients with hemophilia B ( 1 ).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For intravenous infusion after reconstitution only. For intravenous infusion after reconstitution only ( 2 ). • Each carton and vial label for REBINYN states the actual Factor IX potency in international units (IU) ( 2.1 ). On-demand treatment and control of bleeding episodes: • 40 IU/kg body weight for minor and moderate bleeds, and 80 IU/kg body weight for major bleeds.

Additional doses of 40 IU/kg can be given ( 2.1 ). Perioperative management: • Pre-operative dose of 40 IU/kg body weight for minor surgery, and 80 IU/kg body weight for major surgery. As clinically needed for the perioperative management of bleeding, repeated doses of 40 IU/kg (in 1-3 day intervals) within the first week after major surgery may be administered. • Frequency may be extended to once weekly after the first week until bleeding stops and healing is achieved ( 2.1 ).

Routine prophylaxis : • 40 IU/kg body weight once weekly ( 2.1 ).

2.1Dosing Guidelines • Dose and duration of treatment depend on the location and extent of bleeding, and the patient’s clinical condition. • If monitoring of Factor IX activity is performed, use a chromogenic assay or selected one-stage clotting assay validated for use with REBINYN [ see Warnings and Precautions ( 5.5 ) ]. • Each carton and vial label for REBINYN states the actual Factor IX potency in IU. On-demand Treatment and Control of Bleeding Episodes 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.

Perioperative Management 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

12.3Pharmacokinetics, Table 8 Routine Prophylaxis 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.

2.2Reconstitution • Always wash hands and ensure that the area is clean before performing the reconstitution procedures. • Use aseptic technique during the reconstitution procedures. • If the patient uses more than one vial of REBINYN per infusion, reconstitute each vial according to the following instructions. Overview of REBINYN Package 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.

Reconstitution 1. Bring the REBINYN vial and the pre-filled diluent syringe to room temperature. 2.

Remove the plastic cap from the REBINYN vial. 3. Wipe the ru… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 87 words ▾

3 DOSAGE FORMS AND STRENGTHS 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.

REBINYN is available as a lyophilized powder in single-dose vials of 500, 1000, 2000, and 3000 IU ( 3 ).

⛔ Contraindications 53 words ▾

4 CONTRAINDICATIONS REBINYN is contraindicated in patients who have known hypersensitivity to REBINYN or its components (including hamster proteins) [ see Warnings and Precautions ( 5.1 ) and Description ( 11 ) ] Do not use in patients who have known hypersensitivity to REBINYN or its components, including hamster proteins ( 4 ).

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Hypersensitivity reactions, including anaphylaxis, have occurred. Should hypersensitivity reactions occur, discontinue REBINYN and administer appropriate treatment ( 5.1 ). • Neutralizing antibodies (inhibitors) to Factor IX have occurred following administration of REBINYN. Perform an assay that measures Factor IX inhibitor concentration if bleeding is not controlled with the recommended dose of REBINYN or if plasma Factor IX activity level fails to increase as expected (5.2 , 5.5 ). • The use of Factor IX- products has been associated with the development of thromboembolic complications ( 5.3 ). • Nephrotic syndrome has been reported following immune tolerance induction with Factor IX-containing products in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions to Factor IX.

( 5.4 ) • Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used ( 5.5 ).

5.1Hypersensitivity Reactions Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with REBINYN. The product may contain traces of hamster proteins which in some patients may cause allergic reactions. 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 REBINYN if allergic- or anaphylactic - type reactions occur, and initiate appropriate treatment.

5.2Inhibitors 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 [ see Warnings and Precautions (5.5) ].

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.

5.3Thrombotic Events The use of Factor IX-containing products has been associated with thromboembolic complications. Due to the potential risk of thromboembolic 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 REBINYN should be weighed against the risk of these complications.

5.4Nephrotic 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.

5.5Monitoring Laboratory Tests If monitoring of Factor IX activity is performed, use a chromogenic assay or selected one-stage clotting assay validated for use with REBINYN [ see Dosage and Administration ( 2 ) ]. 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 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 recommen… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS Common adverse reactions (incidence ≥ 1%) in PTPs reported in clinical trials for REBINYN were itching and injection site reactions. Common adverse reactions (incidence ≥ 1%) in PUPs reported in clinical trials for REBINYN were rash, FIX inhibitors, hypersensitivity, itching, injection site reaction, and anaphylactic reaction. The most frequently reported adverse reactions (≥ 1%) in previously treated patients (PTPs) and previously untreated patients (PUPs) were itching and injection site reactions ( 6 ).

Additional frequently reported adverse reactions (≥ 1%) in PUPs included rash, Factor IX inhibition, hypersensitivity, and anaphylactic reaction ( 6 ). In animals administered repeat doses of REBINYN, accumulation of polyethylene-glycol (PEG) was observed in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons ( 8.4 and 13.2 ). The potential clinical implications of these animal findings are unknown ( 6.3 ).

To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-877-668-6777 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. Previously Treated Patients (PTPs) 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 (14) ].

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) Previously Untreated Patients (PUPs) 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 (14) ].

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 Hypersensitivty 1 (2) 3 (6) Skin and subcutaneous tissue disorders Rash Itching 9 (18) 2 (4)

6.2Immunogenicity 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 cl… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS Pediatric Use: No dose adjustment is needed ( 8.4 ).

8.1Pregnancy Risk Summary 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 can cause fetal harm when administered to a pregnant woman or can affect fertility.

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.

8.2Lactation Risk Summary 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 considered along with the mother’s clinical need for REBINYN and any potential adverse effects on the breastfed infant from REBINYN or from the underlying maternal condition.

8.4Pediatric Use Safety and efficacy of REBINYN were evaluated in four clinical trials that included 43 PTPs and in one clinical trial that included 50 pediatric PUPs [ see Adverse Reactions ( 6 ) and Clinical Studies ( 14 ) ]. Twelve of these subjects were ≤ 6 years of age; 13 subjects were 7 to 12 years of age; and 18 subjects were 13 to 17 years of age. Pharmacokinetic parameters were evaluated for 28 of the pediatric PTPs who were treated with REBINYN 40 IU/kg [ see Clinical Pharmacology ( 12.3 ) ].

Body weight-adjusted clearance was observed to be higher for pediatric subjects than for adult subjects. However, in clinical trials, no dose adjustment was needed in pediatric subjects who received a fixed dose of 40 IU/kg every week for routine prophylaxis. Juvenile Animal Toxicity Data A juvenile animal neurotoxicity study was conducted to evaluate the potential neurotoxicity of REBINYN when intravenously administered 120-1200 IU/kg/twice weekly in immature male rats from 3 to 13 weeks of age, followed by a 13-week treatment-free period.

Accumulation of PEG was observed in the choroid plexus, pituitary, circumventricular organs, and the cranial motor neurons. PEG levels in these tissues increased with dose and dose duration (10 weeks) and remained detectable after the 13-week treatment-free period. Treatment-related PEG-positive vacuolated macrophages were observed in the pituitary.

The accumulation of PEG was not associated with neurobehavioral changes, fertility, or functional effects.

8.5Geriatric Use Clinical studies of 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 REBINYN showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. [ see Use in Specific Populations ( 8.4 ) and Animal Toxicology and/or Pharmacology ( 13.2 ) ]. The potential clinical implications of these animal findings are unknown.

No adverse neurologic effects of PEG have been reported in adults exposed to REBINYN during clinical trials, however, use in older adults with baseline cognitive dysfunction has not been fully evaluated [ see Neurologic Considerations ( 6.3 ) ].

🤰 Pregnancy 74 words ▾

8.1Pregnancy Risk Summary 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 can cause fetal harm when administered to a pregnant woman or can affect fertility.

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.

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use Safety and efficacy of REBINYN were evaluated in four clinical trials that included 43 PTPs and in one clinical trial that included 50 pediatric PUPs [ see Adverse Reactions ( 6 ) and Clinical Studies ( 14 ) ]. Twelve of these subjects were ≤ 6 years of age; 13 subjects were 7 to 12 years of age; and 18 subjects were 13 to 17 years of age. Pharmacokinetic parameters were evaluated for 28 of the pediatric PTPs who were treated with REBINYN 40 IU/kg [ see Clinical Pharmacology ( 12.3 ) ].

Body weight-adjusted clearance was observed to be higher for pediatric subjects than for adult subjects. However, in clinical trials, no dose adjustment was needed in pediatric subjects who received a fixed dose of 40 IU/kg every week for routine prophylaxis. Juvenile Animal Toxicity Data A juvenile animal neurotoxicity study was conducted to evaluate the potential neurotoxicity of REBINYN when intravenously administered 120-1200 IU/kg/twice weekly in immature male rats from 3 to 13 weeks of age, followed by a 13-week treatment-free period.

Accumulation of PEG was observed in the choroid plexus, pituitary, circumventricular organs, and the cranial motor neurons. PEG levels in these tissues increased with dose and dose duration (10 weeks) and remained detectable after the 13-week treatment-free period. Treatment-related PEG-positive vacuolated macrophages were observed in the pituitary.

The accumulation of PEG was not associated with neurobehavioral changes, fertility, or functional effects.

🧓 Geriatric Use 117 words ▾

8.5Geriatric Use Clinical studies of 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 REBINYN showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. [ see Use in Specific Populations ( 8.4 ) and Animal Toxicology and/or Pharmacology ( 13.2 ) ]. The potential clinical implications of these animal findings are unknown.

No adverse neurologic effects of PEG have been reported in adults exposed to REBINYN during clinical trials, however, use in older adults with baseline cognitive dysfunction has not been fully evaluated [ see Neurologic Considerations ( 6.3 ) ].

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism 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.

12.2Pharmacodynamics 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.

12.3Pharmacokinetics 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 (14) ]. 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 Recovery 30min (IU/dL per IU/kg) 1.82 (28.2) 1.92 (19.6) AUC 0-168 (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 ≥18years 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) Min, Max** 15.4 (13.2; 17.9) 9.2; 24.5 18.7 (16.2; 21.6) 8.3; 28.3 23.7 (19.9; 28.2) 18.6; 34.6 29.3 (26.0; 33.0) 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 Recovery 30min (IU/dL per IU/kg) 1.51 (7.31) 1.59 (16.2) 1.96 (14.7) 2.34 (11.3) AUC inf (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/m 2 ) and 4 were overweight (BMI 25 to <29.9 kg/m 2 ). 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 hours 1 24 hours 1 48 ho… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 52 words ▾

12.1Mechanism 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.

📦 How Supplied / Storage and Handling ~2 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied • REBINYN is supplied in packages comprised of a single-dose vial containing nominally 500, 1000, 2000, or 3000 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. Table 12: REBINYN Presentations Presentation (Nominal Product Strength; IU) Cap Color Indicator Carton NDC Number Components 500 Red NDC 0169 7905 01 • REBINYN in single-dose vial [NDC 0169 7955 11] • Pre-filled histidine diluent in syringe, 4 mL [NDC 0169 7009 98] • Vial adapter 1000 Green NDC 0169 7901 01 • REBINYN in single-dose vial [NDC 0169 7911 11] • Pre-filled histidine diluent in syringe, 4 mL [NDC 0169 7009 98] • Vial adapter 2000 Yellow NDC 0169 7902 01 • REBINYN in single-dose vial [NDC 0169 7922 11] • Pre-filled histidine diluent in syringe, 4 mL [NDC 0169 7009 98] • Vial adapter 3000 Dark Gray NDC 0169 7903 01 • REBINYN in single-dose vial [NDC 0169 7933 11] • Pre-filled histidine diluent in syringe, 4 mL [NDC 0169 7009 98] • Vial adapter • 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 and Handling • 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.

📋 Description ~2 min read ▾

11 DESCRIPTION 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 to slightly yellow 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-dose vials containing the labeled amount of Factor IX activity, expressed in IU.

Each vial contains nominally 500 IU, 1000 IU, 2000, or 3000 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 144 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.

💬 Information for Patients 216 words ▾

17 PATIENT COUNSELING INFORMATION • Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use). • 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.

Version: 4 License Number: 1261 REBINYN ® and MixPro ® are trademarks of Novo Nordisk A/S. For Patent Information, refer to: http://novonordisk-us.com/patients/products/product-patents.html Clave ® and MicroClave ® are registered trademarks of ICU Medical Inc. InVision-Plus ® , InVision-Plus CS ® , Invision-Plus ® Junior ® are registered trademarks of RyMed Technologies, Inc.

Bionector ® is a registered trademark of Vygon. © 2022 Novo Nordisk For information contact: Novo Nordisk Inc. 800 Scudders Mill Road Plainsboro, NJ 08536, USA 1-844-REB-INYN Manufactured by: Novo Nordisk A/S Novo Allé, DK-2880 Bagsvaerd

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics 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 (14) ]. 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 Recovery 30min (IU/dL per IU/kg) 1.82 (28.2) 1.92 (19.6) AUC 0-168 (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 ≥18years 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) Min, Max** 15.4 (13.2; 17.9) 9.2; 24.5 18.7 (16.2; 21.6) 8.3; 28.3 23.7 (19.9; 28.2) 18.6; 34.6 29.3 (26.0; 33.0) 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 Recovery 30min (IU/dL per IU/kg) 1.51 (7.31) 1.59 (16.2) 1.96 (14.7) 2.34 (11.3) AUC inf (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/m 2 ) and 4 were overweight (BMI 25 to <29.9 kg/m 2 ). 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 hours 1 24 hours 1 48 hours 2 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) 1 Excludes one subject with no Factor IX activity measurement obtained. 2 Excludes 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).

🧬 Pharmacodynamics 30 words ▾

12.2Pharmacodynamics 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.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES 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)]. • Adult/adolescent trial: The trial included 74 adolescent and adult subjects.

There were two routine prophylaxis 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 adolescent and adult subjects 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. • Pediatric trial: The main phase of the pediatric trial included 25 PTPs (1 to 12 years old) in which subjects received routine prophylaxis with REBINYN 40 IU/kg once weekly for approximately 52 weeks until 50 EDs were reached.

Treatment of Bleeding Episodes 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 Total 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).

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.

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 effec… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 179 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Studies in animals to evaluate the carcinogenic or genotoxic potential of REBINYN, or dedicated studies to determine the effects of REBINYN on fertility, have not been performed. In a juvenile rat study (3 to 13 week old male rats), fertility was unaffected following 9 weeks of twice weekly administrations of up to 1200 IU/kg [ see Use in Specific Populations ( 8.4 ) ].

13.2Animal Toxicology and/or Pharmacology 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 ( 8.4 ) ].

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 70 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Studies in animals to evaluate the carcinogenic or genotoxic potential of REBINYN, or dedicated studies to determine the effects of REBINYN on fertility, have not been performed. In a juvenile rat study (3 to 13 week old male rats), fertility was unaffected following 9 weeks of twice weekly administrations of up to 1200 IU/kg [ see Use in Specific Populations ( 8.4 ) ].

📄 Patient Package Insert ~3 min read ▾

Patient Package Insert Patient Product Information REBINYN (reh-bē-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 • are allergic to Factor IX or any of the other ingredients of REBINYN • if you are allergic to hamster proteins 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 • Have or have had any medical conditions. • Take any medicines, including non-prescription medicines and dietary supplements. • Are nursing. It is not known if REBINYN passes into breast milk or if it can harm your baby. • Are pregnant or planning to become pregnant. It is not known if REBINYN may harm your unborn baby. • Have been told that you have inhibitors to Factor IX (because REBINYN may not work for 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 produc… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 14 words ▾

Indications and Usage ( 1 ) ……………………………… ………07/2022 Dosage and Administration ( 2.1 )…………………………………07/2022

📄 Package Label / Principal Display Panel ~2 min read ▾

PRINCIPAL DISPLAY PANEL NDC 0169 7905 01 List: 790501 500 IU Range REBINYN ® (Coagulation Factor IX (Recombinant), GlycoPEGylated) 500 IU Intravenous use, after reconstitution. Single-dose. Discard unused portion. Contains no preservatives. Rx Only Includes MixPro ® a vial adapter and pre-filled diluent syringe Image of 500 IU Range carton

Principal Display Panel NDC 0169 7901 01 List: 790101 1000 IU Range REBINYN ® (Coagulation Factor IX (Recombinant), GlycoPEGylated) 1000 IU Intravenous use, after reconstitution. Single-dose. Discard unused portion. Contains no preservatives. Rx Only Includes MixPro ® a vial adapter and pre-filled diluent syringe Image of 1000 IU Range carton

Principal Display Panel NDC 0169 7902 01 List: 790201 2000 IU Range REBINYN ® (Coagulation Factor IX (Recombinant), GlycoPEGylated) 2000 IU Intravenous use, after reconstitution. Single-dose. Discard unused portion.

Contains no preservatives. Rx Only Includes MixPro ® a vial adapter and pre-filled diluent syringe NDC 0169 7955 11 REBINYN ® (Coagulation Factor IX (Recombinant), GlycoPEGylated) 500 IU Store in a refrigerator 36°F - 46°F (2°C-8°C) Do not freeze Rx Only Reconstitution with 4 mL histidine diluent only NDC 0169 7911 11 REBINYN ® (Coagulation Factor IX (Recombinant), GlycoPEGylated) 1000 IU Store in a refrigerator 36°F - 46°F (2°C-8°C) Do not freeze Rx Only Reconstitution with 4 mL histidine diluent only NDC 0169 7922 11 REBINYN ® (Coagulation Factor IX (Recombinant), GlycoPEGylated) 2000 IU Store in a refrigerator 36°F - 46°F (2°C-8°C) Do not freeze Rx Only Reconstitution with 4 mL histidine diluent only NDC 0169 7009 98 Histidine (10 mM Solution) 4 mL For reconstitution of Tradename Store in a refrigerator 36°F to 46°F (2°C to 8°C) Do not freeze Rx Only Single Use Only Image of 2000 IU Range carton 500 IU Vial 1000 IU Vial 2000 IU VIal Histidine Syringe

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0169 7903 01 List: 790301 REBINYN ® 3000 IU Range Coagulation Factor IX (Recombinant), GlycoPEGylated 3000 IU Intravenous use, after reconstitution. Single-dose. Discard unused portion.

Contains no preservatives. Rx Only Includes MixPro ® a vial adapter and pre-filled diluent syringe NDC 0169 7933 11 REBINYN ® 3000 IU Range Coagulation Factor IX (Recombinant), GlycoPEGylated Store in a refrigerator 36°F - 46°F (2°C-8°C) Do not freeze Rx Only Reconstitution with 4 mL histidine diluent only 3000 IU Carton - 8-9040-31-301-1 3000 IU Vial

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

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FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Novo Nordisk. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 1 kit (00169-7901-01). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Novo Nordisk is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 00169-7850-01 · Novo 00169-7902-01 · Novo →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.