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Rituxan Hycela rituximab and hyaluronidase 120 mg/mL; 2000 U/mL Injection, Solution, 1 vial — NDC 50242-0108-86 package photo

Rituxan Hycela rituximab and hyaluronidase 120 mg/mL; 2000 U/mL Injection, Solution, 1 vial

by Genentech, Inc. · 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-108-86) / 11.7 mL in 1 VIAL, SINGLE-DOSE
NDC 50242-0108-86
🏷️ FDA NDC (as labeled) 50242-108-86 billing pads the product segment with a zero
This package
Contains1 vial Pack sizes2 compare ↓
Also comes in: 11.7 mL 50242-0108-01
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

🆔 Identity & classification

FDA NDC (as labeled) 50242-108-86
Product NDC 50242-108
11-digit billing NDC 50242010886
RxCUI 1927885, 1927890, 1927893, 1927894
UNII 743QUY4VD8, 4F4X42SYQ6
Application # BLA761064
SPL Set ID 3e5b7e82-f018-4eaf-ae78-d6145a906b20
Established class (EPC) Endoglycosidase; CD20-directed Cytolytic Antibody
Mechanism of action CD20-directed Antibody Interactions
Chemical class Glycoside Hydrolases
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2017-06-22
Route SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance RITUXIMAB; HYALURONIDASE (HUMAN RECOMBINANT)
GPI-14 21990002642020
GPI class Rituxan Hycela
GCN Seq No 072319
GCN 36469
HICL code 044378
Ingredient (HICL) Rituximab/Hyaluronidase,Human
HIC1 code Z
Therapeutic class — broad (HIC1) Body As A Whole
HIC2 code Z2
Therapeutic class — intermediate (HIC2) Antihistamines, Antiserotonins, Immunosuppressants
HIC3 code Z2W
Therapeutic class — specific (HIC3) Anti-Cd20 (B Lymphocyte) Monoclonal Antibody
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name RITUXAN HYCELA 1,400 MG-23,400
FDB brand name Rituxan Hycela
Legend status F — Federal legend — prescription drug or device
Biologic (Purple Book) 351(a)
Why two NDCs? The FDA registers this code as 50242-108-86 — a 5-3-2 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 product segment → 50242-0108-86. 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 CD20-directed Cytolytic Antibody class.

Pharmacologic class CD20-directed Cytolytic Antibody
Drug family (ATC) CD20 (Clusters of Differentiation 20) inhibitors
How it works CD20-directed Antibody Interactions
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.

🏭 Manufacturer & labeler

LabelerGenentech, Inc.
FDA applicationBLA761064 (BLA)
Labeler code50242
First marketedJun 2017
Product typeHuman Prescription Drug
Portfolio93 products on file
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.

🩺 Clinical

Label name RITUXAN HYCELA 1,400 MG-23,400 Ingredient Rituximab/Hyaluronidase,Human
📖 What it is MedlinePlus · NLM

Rituximab and hyaluronidase human injection is used alone or with other medications to treat various types of non-Hodgkin's lymphoma (NHL; a type of cancer that begins in a type of white blood cells that normally fights infection). Rituximab and hyaluronidase human injection is also used with other medications to treat chronic lymphocytic leukemia (CLL; a type of cancer of the white blood cells). Rituximab and hyaluronidase human injection is in a class of medications called monoclonal antibodies. It treats the various types of NHL and CLL by killing cancer cells.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • That's a really common question. The IV dose is given first so your care team can monitor how you respond to rituximab in a controlled setting — since serious reactions are more li...
  • Why do I have to get an IV infusion first before switching to the injection?
  • No — this one has to be given by a healthcare professional in a clinical setting every time. After each injection you'll be observed for at least 15 minutes, because serious reacti...
  • Is the injection something I can do at home?
📖 Read our full Rituximab and Hyaluronidase Human Injection guide →

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.

🧪 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 4QD397987E
    An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
  • UNII X573657P6P
    Histidine monohydrochloride monohydrate is an amino acid salt used as a buffer in medicines. It helps maintain the proper acidity level of liquid formulations to keep the drug stable and effective.
  • UNII AE28F7PNPL
    Methionine is an amino acid used as a nutrient supplement and pH buffer in medicines. It helps stabilize the formulation and supports the product's overall composition.
  • UNII 6OZP39ZG8H
    Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
  • UNII 7YIN7J07X4
    A natural sugar derived from plants and microorganisms. It acts as a filler to give the medication bulk and stability, and helps preserve the active ingredient during storage and manufacturing.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

6 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

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.

💲 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 mLPer 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: 11.7 mL
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Rituxan Hycela 120 mg/mL; 2000 U/mLthis 50242-0108-86 Genentech, 1 vial — — FDA listed —
Rituxan Hycela 120 mg/mL; 2000 U/mL 50242-0109-01 Genentech, 1 vial — — 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
Jun 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 Jun 2029. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.
📅 FDA approved Jun 22, 2017 ⏳ ~2.8 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 dateJun 22, 2029
Common questions
Is there a biosimilar for RITUXAN HYCELA 1,400 MG-23,400?
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.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
1 vial50242-0108-01 68 Rx · $203,198
1 vial this page50242-0108-86 No Medicaid data
Drug total (last 4 qtrs): 68 Rx · 598 units · $203,198 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Rituxan Hycela — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Rituxan Hycela. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$294K
Claims incl. refills
41
Beneficiaries
25
Spend / beneficiary
$11,760.60
Spend / claim
$7,171.10
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Rituxan Hycela (this brand).

Top reported reactions

Rash50
Fatigue36
Nausea35
Pain33
Headache28
Dizziness27
Pneumonia27

Age at onset

Adult30
Elderly30

Reporter sex

448 reports
Male · 39%
Female · 61%
Reports over time (by year) — tap or hover for the count & year
2020 2022 2024 2026 72 14
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
50242-0108-01 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-108-01) / 11.7 mL in 1 VIAL, SINGLE-DOSE 2017-06-22 Active
50242-0108-86 You're viewing this 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-108-86) / 11.7 mL in 1 VIAL, SINGLE-DOSE 2017-06-23 Active

Pack size FAQ

What quantity is in NDC 50242-0108-86?
NDC 50242-0108-86 contains 1 vial — 1 vial, single-dose in 1 carton / 11.7 ml in 1 vial, single-dose.
What is the difference between NDC 50242-0108-86 and NDC 50242-0108-01?
Both are Rituxan Hycela rituximab and hyaluronidase 120 mg/mL; 2000 U/mL Injection, Solution — the drug itself is identical. NDC 50242-0108-86 is the 1 vial package, while NDC 50242-0108-01 is the 1 vial package.
What NDC number is used to bill for this package of Rituxan Hycela rituximab and hyaluronidase 120 mg/mL; 2000 U/mL Injection, Solution?
Bill NDC 50242-0108-86 — the 11-digit billing format is 50242010886. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ 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 FDA registers it as 50242-108-86, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 50242-0108-86, written without dashes as 50242010886. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 50242-0108-86, the first segment (50242) is the labeler code FDA assigned to Genentech, Inc.; the middle segment (0108) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (86) identifies this exact package size and type. Together they name one specific package of one specific product.
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 Genentech, Inc.. 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 vial (50242-0108-01). 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?
Genentech, Inc. 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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide
🚨 Boxed Warning 187 words ▾

WARNING: SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY WARNING: SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY See full prescribing information for complete boxed warning. Severe mucocutaneous reactions, some with fatal outcomes ( 5.1 ). Hepatitis B virus reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death ( 5.2 ).

Progressive multifocal leukoencephalopathy resulting in death ( 5.3 ). Severe Mucocutaneous Reactions Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab-containing products, including RITUXAN HYCELA [see Warnings and Precautions (5.1) ]. Hepatitis B Virus (HBV) Reactivation HBV reactivation can occur in patients treated with rituximab-containing products, including RITUXAN HYCELA, in some cases resulting in fulminant hepatitis, hepatic failure, and death.

Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RITUXAN HYCELA. Discontinue RITUXAN HYCELA and concomitant medications in the event of HBV reactivation [see Warnings and Precautions (5.2) ] . Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving rituximab-containing products, including RITUXAN HYCELA [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ].

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE RITUXAN HYCELA is a combination of rituximab, a CD20-directed cytolytic antibody, and hyaluronidase human, an endoglycosidase, indicated for the treatment of adult patients with: Follicular Lymphoma (FL) ( 1.1 ) Relapsed or refractory, follicular lymphoma as a single agent Previously untreated follicular lymphoma in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy Non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy Diffuse Large B-cell Lymphoma (DLBCL) ( 1.2 ) Previously untreated diffuse large B-cell lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens Chronic Lymphocytic Leukemia (CLL) ( 1.3 ) Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide (FC) Limitations of Use: Initiate treatment with RITUXAN HYCELA only after patients have received at least one full dose of a rituximab product by intravenous infusion.

( 1.4 , 2.1 , 5.4 ). RITUXAN HYCELA is not indicated for the treatment of non-malignant conditions. ( 1.4 )

1.1Follicular Lymphoma (FL) RITUXAN HYCELA is indicated for the treatment of adult patients with: Relapsed or refractory, follicular lymphoma as a single agent. Previously untreated follicular lymphoma in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy. Non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.

1.2Diffuse Large B-Cell Lymphoma (DLBCL) RITUXAN HYCELA is indicated for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.

1.3Chronic Lymphocytic Leukemia (CLL) RITUXAN HYCELA is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of adult patients with previously untreated and previously treated CLL.

1.4Limitations of Use Initiate treatment with RITUXAN HYCELA only after patients have received at least one full dose of a rituximab product by intravenous infusion [see Dosage and Administration (2.1) and Warnings and Precautions (5.4) ]. RITUXAN HYCELA is not indicated for the treatment of non-malignant conditions.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For subcutaneous use only ( 2.1 ) All patients must receive at least one full dose of a rituximab product by intravenous infusion before receiving RITUXAN HYCELA by subcutaneous injection ( 2.1 ). FL/DLBCL: Administer 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously according to recommended schedule ( 2.2 , 2.3 ). CLL: Administer 1,600 mg/26,800 Units (1,600 mg rituximab and 26,800 Units hyaluronidase human) subcutaneously according to recommended schedule ( 2.4 ).

Premedicate with acetaminophen and antihistamine before each dose; in addition, consider premedication with glucocorticoids ( 2.5 , 5.4 ) Administer specified volume into subcutaneous tissue of abdomen: ( 2.6 ) 11.7 mL from 1,400 mg/23,400 Units vial over approximately 5 minutes. 13.4 mL from 1,600 mg/26,800 Units vial over approximately 7 minutes. Observe 15 minutes following administration

2.1Important Dosing Information RITUXAN HYCELA is for subcutaneous use only. RITUXAN HYCELA should only be administered by a healthcare professional with appropriate medical support to manage severe reactions that can be fatal if they occur. All patients must first receive at least one full dose of a rituximab product by intravenous infusion without experiencing severe adverse reactions before starting treatment with RITUXAN HYCELA.

If patients are not able to receive one full dose by intravenous infusion, they should continue subsequent cycles with a rituximab product by intravenous infusion and not switch to RITUXAN HYCELA until a full intravenous dose is successfully administered [see Warnings and Precautions (5.4) ]. Refer to the prescribing information for a rituximab product for intravenous infusion for additional information. Premedicate before each dose of RITUXAN HYCELA [see Dosage and Administration (2.5) ] .

Dose reductions of RITUXAN HYCELA are not recommended. When RITUXAN HYCELA is given in combination with chemotherapy dose, reduce the chemotherapeutic drugs to manage adverse reactions.

2.2Recommended Dosage for Follicular Lymphoma (FL) All patients must receive at least one full dose of a rituximab product by intravenous infusion before starting treatment with RITUXAN HYCELA [see Dosage and Administration (2.1) and Warnings and Precautions (5.4) ]. Premedicate before each dose [see Dosage and Administration (2.5) ]. The recommended dose is RITUXAN HYCELA 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously at a fixed dose irrespective of patient's body surface area according to the following schedules: Relapsed or Refractory, Follicular Lymphoma Administer once weekly for 3 or 7 weeks following a full dose of a rituximab product by intravenous infusion at week 1 (i.e., 4 or 8 weeks in total).

Retreatment for Relapsed or Refractory, Follicular Lymphoma Administer once weekly for 3 weeks following a full dose of a rituximab product by intravenous infusion at week 1 (i.e., 4 weeks in total). Previously Untreated, Follicular Lymphoma Administer on Day 1 of Cycles 2–8 of chemotherapy (every 21 days), for up to 7 cycles following a full dose of a rituximab product by intravenous infusion on Day 1 of Cycle 1 of chemotherapy (i.e., up to 8 cycles in total). In patients with complete or partial response, initiate RITUXAN HYCELA maintenance treatment 8 weeks following completion of RITUXAN HYCELA in combination with chemotherapy.

Administer RITUXAN HYCELA as a single-agent every 8 weeks for 12 doses. Non-progressing, Follicular Lymphoma after first line CVP chemotherapy Following completion of 6–8 cycles of CVP chemotherapy and a full dose of a rituximab product by intravenous infusion at week 1, administer once weekly for 3 weeks (i.e., 4 weeks in total) at 6 month intervals to a maximum of 16 doses.

2.3Recommended Dosage for Diffuse Large B-Cell Lymphoma (DLBCL) All patients must receive at least one full dose of a rituximab product by intravenous infusi…

💊 Dosage Forms and Strengths 107 words ▾

3 DOSAGE FORMS AND STRENGTHS RITUXAN HYCELA is a colorless to yellowish, clear to opalescent solution for subcutaneous injection: Injection: 1,400 mg rituximab and 23,400 Units hyaluronidase human per 11.7 mL (120 mg/2,000 Units per mL) in a single-dose vial. Injection: 1,600 mg rituximab and 26,800 Units hyaluronidase human per 13.4 mL (120 mg/2,000 Units per mL) in a single-dose vial. Injection: ( 3 ) 1,400 mg rituximab and 23,400 Units hyaluronidase human per 11.7 mL (120 mg/2,000 Units per mL) solution in a single-dose vial 1,600 mg rituximab and 26,800 Units hyaluronidase human per 13.4 mL (120 mg/2,000 Units per mL) solution in a single-dose vial

⛔ Contraindications 4 words ▾

4 CONTRAINDICATIONS None None.

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Hypersensitivity and other administration reactions: Local cutaneous reactions may occur more than 24 hours after administration. Interrupt injection if severe reaction develops. Premedicate before injection.

( 5.4 ) Tumor lysis syndrome: Administer aggressive intravenous hydration, anti hyperuricemic agents, monitor renal function. ( 5.5 ) Infections: Withhold and institute appropriate anti-infective therapy. ( 5.6 ) Cardiac adverse reactions: Discontinue in case of serious or life-threatening events.

( 5.7 ) Renal toxicity: Discontinue in patients with rising serum creatinine or oliguria. ( 5.8 ) Bowel obstruction and perforation: Consider and evaluate for abdominal pain, vomiting, or related symptoms. ( 5.9 ) Immunizations: Live virus vaccinations prior to or during treatment not recommended.

( 5.10 ) Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.11 )

5.1Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with rituximab-containing products, including RITUXAN HYCELA. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. Discontinue RITUXAN HYCELA in patients who experience a severe mucocutaneous reaction.

The safety of re-administration of a rituximab-containing product, including RITUXAN HYCELA, to patients with severe mucocutaneous reactions has not been determined .

5.2Hepatitis B Virus Reactivation Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies, including rituximab-containing products. HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA levels or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis, i.e., increase in transaminase levels.

In severe cases increase in bilirubin levels, liver failure, and death can occur. Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with a rituximab-containing product. For patients who show evidence of prior hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during treatment with a rituximab-containing product.

Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following RITUXAN HYCELA. HBV reactivation has been reported up to 24 months following completion of therapy containing rituximab. In patients who develop reactivation of HBV while on RITUXAN HYCELA, immediately discontinue treatment and any concomitant chemotherapy, and institute appropriate treatment.

Insufficient data exist regarding the safety of resuming RITUXAN HYCELA treatment in patients who develop HBV reactivation. Resumption of RITUXAN HYCELA treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing HBV.

5.3Progressive Multifocal Leukoencephalopathy (PML) JC virus infection resulting in PML and death has been observed in patients receiving rituximab-containing products, including RITUXAN HYCELA. Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture.

Discontinue RITUXAN HYCELA and consider discontinuation or reduction of any concomitant…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Mucocutaneous reactions [see Warnings and Precautions (5.1) ] Hepatitis B reactivation including fulminant hepatitis [see Warnings and Precautions (5.2) ] Progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.3) ] Hypersensitivity and other administration reactions [see Warnings and Precautions (5.4) ] Tumor lysis syndrome [see Warnings and Precautions (5.5) ] Infections [see Warnings and Precautions (5.6) ] Cardiac arrhythmias [see Warnings and Precautions (5.7) ] Renal toxicity [see Warnings and Precautions (5.8) ] Bowel obstruction and perforation [see Warnings and Precautions (5.9) ] Most common adverse reactions (incidence of ≥ 20%) are: ( 6.1 ) FL: infections, neutropenia, nausea, constipation, cough, and fatigue DLBCL: infections, neutropenia, alopecia, nausea, and anemia CLL: infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 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 the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data described below reflect exposure to RITUXAN HYCELA in 892 patients in four controlled trials with exposures ranging from a single injection up to 27 months of treatment. The population included 382 patients with follicular lymphoma (FL), 369 patients with diffuse large B-cell lymphoma (DLBCL), and 141 patients with chronic lymphocytic leukemia (CLL).

The median age was 60 years (range: 18–85 years, 53% were male, and 84% were White. In the SABRINA study patients with FL received a full dose of a rituximab product by intravenous infusion, followed by RITUXAN HYCELA (1,400 mg rituximab/23,400 Units hyaluronidase human), in combination with chemotherapy for up to 7 doses (i.e., total of 8 doses in combination with chemotherapy), or as monotherapy for up to 12 doses (maintenance treatment). In the MabEase study patients with DLBCL received a full dose of a rituximab product by intravenous infusion, followed by RITUXAN HYCELA (1,400 mg rituximab/23,400 Units hyaluronidase human), given in combination with chemotherapy for up to 7 doses (i.e., up to a total of 8 doses).

In the SAWYER study patients with CLL on part 2 received a full dose of a rituximab product by intravenous infusion, followed by RITUXAN HYCELA (1,600 mg rituximab/26,800 Units hyaluronidase human) for up to 5 doses, in combination with fludarabine and cyclophosphamide (i.e., total of 6 doses). The most common adverse reactions (≥ 20%) of RITUXAN HYCELA observed in patients with FL on the SABRINA study were: infections, neutropenia, nausea, constipation, cough, and fatigue. The most common adverse reactions (≥ 20%) of RITUXAN HYCELA observed in patients with DLBCL on the MabEase study were: infections, neutropenia, alopecia, nausea, and anemia.

The most common adverse reactions (≥ 20%) of RITUXAN HYCELA observed in patients with CLL on part 2 of the SAWYER study were: infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema. Administration-related reactions (ARRs) Administration-related reactions (ARRs) with RITUXAN HYCELA were defined as all the adverse reactions related to the administration of RITUXAN HYCELA within the 24 hours post injection. The incidence of ARRs with RITUXAN HYCELA was 34% in FL/DLBCL in combination with chemotherapy with injection site erythema (5%), chills (3%), dyspnea, erythema, flushing, injection site pain, nausea, pruritus, pyrexia, rash, and throat irritation (2% each) being the most common ARRs.

The incidence of ARRs in FL maintenance setting was 20%. The…

🔄 Drug Interactions 11 words ▾

Renal toxicity when used in combination with cisplatin. ( 5.8 )

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )

8.1Pregnancy Risk Summary Based on human data, rituximab-containing products can cause fetal harm due to B-cell lymphocytopenia in infants exposed to rituximab in-utero (see Clinical Considerations ) . There are no available data on RITUXAN HYCELA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, intravenous administration of a rituximab product to pregnant cynomolgus monkeys during the period of organogenesis caused lymphoid B cell depletion in the newborn offspring at doses resulting in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans.

Reduced fetal weight and increased fetal lethality were observed following subcutaneous administration of hyaluronidase human in mice at a dose > 2700 times higher than the human dose. Comparable systemic exposure levels could occur in a pregnant patient following accidental intravenous administration of an entire vial of RITUXAN HYCELA (see Data ) . Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk in the U.S. general population of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies.

Clinical Considerations Fetal/Neonatal Adverse Reactions Observe newborns and infants for signs of infection and manage accordingly. Data Human Data Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than 6 months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero.

Animal Data RITUXAN HYCELA for subcutaneous injection contains rituximab and hyaluronidase human [see Description (11) ] . Rituximab Product: An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received rituximab via the intravenous route during early gestation (organogenesis period; post coitum days 20 through 50).

Rituximab was administered as loading doses on post coitum (PC) Days 20, 21 and 22, at 15, 37.5 or 75 mg/kg/day, and then weekly on PC Days 29, 36, 43 and 50, at 20, 50 or 100 mg/kg/week. The 100 mg/kg/week dose resulted in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans. Rituximab crosses the monkey placenta.

Exposed offspring did not exhibit any teratogenic effects but did have decreased lymphoid tissue B cells. A subsequent pre-and postnatal reproductive toxicity study in cynomolgus monkeys was completed to assess developmental effects including the recovery of B cells and immune function in infants exposed to rituximab in utero. Animals were treated with a loading dose of 0, 15, or 75 mg/kg every day for 3 days, followed by weekly dosing with 0, 20, or 100 mg/kg dose.

Subsets of pregnant females were treated from PC Day 20 through postpartum Day 78, PC Day 76 through PC Day 134, and from PC Day 132 through delivery and postpartum Day 28. Regardless of the timing of treatment, decreased B cells and immunosuppression were noted in the offspring of rituximab-treated pregnant animals. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months postpartum.

Hyaluronidase Human: In an embryo-fetal study, mice have been dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase human at dose levels up to 2,200,000 U/kg, which is > 2700 times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is > 450 times higher than the human dose.

In a peri-and…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Based on human data, rituximab-containing products can cause fetal harm due to B-cell lymphocytopenia in infants exposed to rituximab in-utero (see Clinical Considerations ) . There are no available data on RITUXAN HYCELA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, intravenous administration of a rituximab product to pregnant cynomolgus monkeys during the period of organogenesis caused lymphoid B cell depletion in the newborn offspring at doses resulting in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans.

Reduced fetal weight and increased fetal lethality were observed following subcutaneous administration of hyaluronidase human in mice at a dose > 2700 times higher than the human dose. Comparable systemic exposure levels could occur in a pregnant patient following accidental intravenous administration of an entire vial of RITUXAN HYCELA (see Data ) . Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk in the U.S. general population of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies.

Clinical Considerations Fetal/Neonatal Adverse Reactions Observe newborns and infants for signs of infection and manage accordingly. Data Human Data Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than 6 months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero.

Animal Data RITUXAN HYCELA for subcutaneous injection contains rituximab and hyaluronidase human [see Description (11) ] . Rituximab Product: An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received rituximab via the intravenous route during early gestation (organogenesis period; post coitum days 20 through 50).

Rituximab was administered as loading doses on post coitum (PC) Days 20, 21 and 22, at 15, 37.5 or 75 mg/kg/day, and then weekly on PC Days 29, 36, 43 and 50, at 20, 50 or 100 mg/kg/week. The 100 mg/kg/week dose resulted in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans. Rituximab crosses the monkey placenta.

Exposed offspring did not exhibit any teratogenic effects but did have decreased lymphoid tissue B cells. A subsequent pre-and postnatal reproductive toxicity study in cynomolgus monkeys was completed to assess developmental effects including the recovery of B cells and immune function in infants exposed to rituximab in utero. Animals were treated with a loading dose of 0, 15, or 75 mg/kg every day for 3 days, followed by weekly dosing with 0, 20, or 100 mg/kg dose.

Subsets of pregnant females were treated from PC Day 20 through postpartum Day 78, PC Day 76 through PC Day 134, and from PC Day 132 through delivery and postpartum Day 28. Regardless of the timing of treatment, decreased B cells and immunosuppression were noted in the offspring of rituximab-treated pregnant animals. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months postpartum.

Hyaluronidase Human: In an embryo-fetal study, mice have been dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase human at dose levels up to 2,200,000 U/kg, which is > 2700 times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is > 450 times higher than the human dose.

In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous…

🧒 Pediatric Use 17 words ▾

8.4Pediatric Use The safety and effectiveness of RITUXAN HYCELA in pediatric patients have not been established.

🧓 Geriatric Use 70 words ▾

8.5Geriatric Use Of the total number of subjects in the SABRINA, MabEase, and SAWYER studies, 37% were 65 and over, while 10% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC).

Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a half-life of approximately 0.5 days.

Hyaluronidase human increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan. In the doses administered, hyaluronidase human in RITUXAN HYCELA acts locally. The effects of hyaluronidase human are reversible and permeability of the subcutaneous tissue is restored within 24 to 48 hours.

Hyaluronidase human has been shown to increase the absorption rate of a rituximab product into the systemic circulation when given in the subcutis of Göttingen Minipigs.

12.2Pharmacodynamics Peripheral B-cell counts declined to levels below normal following a dose of rituximab by intravenous infusion. In patients treated with rituximab for hematological malignancies, B cell recovery began within 6 months of treatment and generally returned to normal levels within 12 months after completion of therapy, although in some patients this may take longer. Follicular Lymphoma (FL) Peripheral B-cell counts decline to levels below normal following the first cycle of rituximab and are maintained during treatment with RITUXAN HYCELA.

After stopping RITUXAN HYCELA treatment, B-cell repletion followed similar kinetics to that of rituximab with B-cell repletion beginning after 6 months of stopping treatment, although in some patients this may take longer. Chronic Lymphocytic Leukemia (CLL) Following the first cycle of treatment of rituximab, B-cells begin to deplete, with 28% of patients B-cell depleted at pre-dose Cycle 2 in the SAWYER study. An increase in the proportion of B-cell depleted patients was observed with subsequent cycles of RITUXAN HYCELA and by Cycle 6, 96% of patients were depleted.

Patients remained B-cell depleted until the month 9 follow-up visit, where signs of repletion were seen.

12.3Pharmacokinetics The geometric mean rituximab exposures are provided in Table 4 . The pharmacokinetic properties of rituximab following the administration of RITUXAN HYCELA in the approved indications are provided in Table 5 . The elimination of rituximab was characterized by a time-dependent process that occurred early in therapy and a time-independent process.

Table 4: Rituximab Exposure Values following Subcutaneous Administration of RITUXAN HYCELA Pharmacokinetic parameters are presented as geometric mean unless otherwise specified. Study For study design information, see Clinical Studies (14) . Cycle Rituximab FL RITUXAN HYCELA 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) C max , mcg/mL (CV%) SABRINA 7 237 (29.4) 18 156 (24.7) Based on predicted values C trough , mcg/mL (CV%) 7 122.2 (55.3) 18 45.5 (53.6) AUC TAU , mcg∙day/mL (CV%) 7 3779 (33.7) 18 5000 (34.3) CLL RITUXAN HYCELA 1,600 mg/26,800 Units (1,600 mg rituximab and 26,800 Units hyaluronidase human) C max , mcg/mL (CV%) SAWYER 6 202 (36.1) C trough , mcg/mL (CV%) 5 97.5 (42.6) AUC TAU , mcg∙day/mL (CV%) 5 4088 (34.2) In the SABRINA study, the geometric mean C trough in the RITUXAN HYCELA arm was higher than in the rituximab arm with a geometric mean ratio (C trough , RITUXAN HYCELA/C trough , rituximab) of 1.52 (90% CI: 1.36, 1.70) at Cycle 7 [see Clinical Studies (14.1) ] .

In the SAWYER study, the geometric mean C trough in the RITUXAN HYCELA arm was higher than in the rituximab arm with an adjusted geometric mean ratio of 1.53 (90% CI: 1.27–1.85) at Cycle 5 [see Clinical Studies (14…

🧬 Mechanism of Action 156 words ▾

12.1Mechanism of Action Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC).

Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a half-life of approximately 0.5 days.

Hyaluronidase human increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan. In the doses administered, hyaluronidase human in RITUXAN HYCELA acts locally. The effects of hyaluronidase human are reversible and permeability of the subcutaneous tissue is restored within 24 to 48 hours.

Hyaluronidase human has been shown to increase the absorption rate of a rituximab product into the systemic circulation when given in the subcutis of Göttingen Minipigs.

📦 How Supplied / Storage and Handling 100 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING RITUXAN HYCELA (rituximab and hyaluronidase human) injection, for subcutaneous use is supplied as a sterile preservative-free liquid solution in a single-dose vial. The following configurations are available: Individually packaged single-dose vials: RITUXAN HYCELA 1,400 mg/23,400 Units (NDC 50242-108-01) providing 1,400 mg rituximab and 23,400 Units hyaluronidase human per 11.7 mL RITUXAN HYCELA 1,600 mg/26,800 Units (NDC 50242-109-01) providing 1,600 mg rituximab and 26,800 Units hyaluronidase human per 13.4 mL Storage Store RITUXAN HYCELA vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

Do not freeze.

📦 Storage and Handling 26 words ▾

Storage Store RITUXAN HYCELA vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze.

📋 Description 209 words ▾

11 DESCRIPTION RITUXAN HYCELA is a combination of rituximab and hyaluronidase human. Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. Rituximab has an approximate molecular weight of 145 kD.

Rituximab has a binding affinity for the CD20 antigen of approximately 8.0 nM. Rituximab is produced by mammalian cell (Chinese Hamster Ovary) suspension. Recombinant human hyaluronidase is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously.

It is produced by mammalian (Chinese Hamster Ovary) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). It is a glycosylated single-chain protein with an approximate molecular weight of 61 kD. RITUXAN HYCELA (rituximab and hyaluronidase human) injection is a colorless to yellowish, clear to opalescent solution supplied in sterile, preservative-free, single-dose vials for subcutaneous use.

RITUXAN HYCELA is supplied as 1,400 mg rituximab and 23,400 Units hyaluronidase human per 11.7 mL in single-dose vials or 1,600 mg rituximab and 26,800 Units hyaluronidase human per 13.4 mL in single-dose vials. Each mL of solution contains rituximab (120 mg), hyaluronidase human (2,000 Units), L-histidine (0.53 mg), L-histidine hydrochloride monohydrate (3.47 mg), L-methionine (1.49 mg), polysorbate 80 (0.6 mg), α,α-trehalose dihydrate (79.45 mg), and Water for Injection.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Severe Mucocutaneous Reactions Advise patients to contact their healthcare provider immediately for symptoms of severe mucocutaneous reactions, including painful sores or ulcers on the lips or mouth, blisters, peeling skin, rash, and pustules [see Warnings and Precautions (5.1) ]. Hepatitis B Virus Reactivation Advise patients to contact their healthcare provider immediately for symptoms of hepatitis including worsening fatigue or yellow discoloration of skin or eyes [see Warnings and Precautions (5.2) ].

Progressive Multifocal Leukoencephalopathy (PML) Advise patients to contact their healthcare provider immediately for signs and symptoms of PML, including new or changes in neurological symptoms such as confusion, dizziness or loss of balance, difficulty talking or walking, decreased strength or weakness on one side of the body, or vision problems [see Warnings and Precautions (5.3) ]. Hypersensitivity and Other Administration Reactions Inform patients about the signs and symptoms of hypersensitivity and administration-related reactions.

Advise patients to contact their healthcare provider immediately to report symptoms of administration-related reactions including dizziness, nausea, chills, fever, vomiting, diarrhea, urticaria, angioedema, breathing problems, or chest pain [see Warnings and Precautions (5.4) ] . Tumor Lysis Syndrome (TLS) Advise patients to contact their healthcare provider immediately for signs and symptoms of tumor lysis syndrome such as nausea, vomiting, diarrhea, and lethargy [see Warnings and Precautions (5.5) ]. Infections Advise patients to contact their healthcare provider immediately for signs and symptoms of infections including fever, cold symptoms (e.g., rhinorrhea or laryngitis), flu symptoms (e.g., cough, fatigue, body aches), earache or headache, dysuria, cold sores, and painful wounds with erythema [see Warnings and Precautions (5.6) ] Cardiovascular Adverse Reactions Advise patients of the risk of cardiovascular adverse reactions, including ventricular fibrillation, myocardial infarction, and cardiogenic shock.

Advise patients to contact their healthcare provider immediately to report chest pain and irregular heartbeats. [see Warnings and Precautions (5.7) ] Renal Toxicity Advise patients of the risk of renal toxicity. Inform patients of the need for healthcare providers to monitor kidney function [see Warnings and Precautions (5.8) ]. Bowel Obstruction and Perforation Advise patients to contact their healthcare provider immediately for signs and symptoms of bowel obstruction and perforation, including severe abdominal pain or repeated vomiting [see Warnings and Precautions (5.9) ].

Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus. Advise femalesof reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.11) , Use in Specific Populations (8.1 , 8.3) ]. Advise females of reproductive potential to use effective contraception during treatment with RITUXAN HYCELA and for 12 months after the last dose of of rituximab-containing products, including RITUXAN HYCELA [see Use in Specific Populations (8.3) ] .

Lactation Advise women not to breastfeed during treatment with RITUXAN HYCELA and for 6 months after the last dose [see Use in Specific Populations (8.2) ].

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 6/2021 MEDICATION GUIDE RITUXAN HYCELA ® [rih-TUKS-an hye-SELL-uh] (rituximab and hyaluronidase human) injection What is the most important information I should know about RITUXAN HYCELA? RITUXAN HYCELA can cause serious side effects that can lead to death, including: Severe skin and mouth reactions.

Tell your healthcare provider or get medical help right away if you get any of these symptoms at any time during your treatment with RITUXAN HYCELA: painful sores or ulcers on your skin, lips or in your mouth blisters peeling skin rash pustules Hepatitis B virus (HBV) reactivation. Before you receive RITUXAN HYCELA, your doctor will do blood tests to check for HBV infection. If you have had hepatitis B or are a carrier of hepatitis B virus, receiving RITUXAN HYCELA could cause the virus to become an active infection again.

Hepatitis B reactivation may cause serious liver problems including liver failure, and death. Your healthcare provider will monitor you for hepatitis B infection during and for several months after you stop receiving RITUXAN HYCELA. Tell your healthcare provider right away if you get worsening tiredness, or yellowing of your skin or white part of your eyes during treatment with RITUXAN HYCELA.

Progressive Multifocal Leukoencephalopathy (PML) . PML is a rare, serious brain infection caused by a virus that can happen in people who receive RITUXAN HYCELA. People with weakened immune systems can get PML.

PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML. Tell your healthcare provider right away if you have any new or worsening symptoms or if anyone close to you notices these symptoms: confusion dizziness or loss of balance difficulty walking or talking decreased strength or weakness on one side of your body vision problems, such as blurred vision or loss of vision Serious allergic reactions and other severe reactions.

Serious allergic reactions, and reactions due to release of certain substances by your body that can lead to death, can happen with rituximab products, including RITUXAN HYCELA. Skin reactions at or near the injection site (local), including injection site reactions, can happen with RITUXAN HYCELA. Symptoms at or near the injection site may include: pain, swelling, hardness, redness, bleeding, itching, and rash.

These reactions sometimes happen more than 24 hours after an injection of RITUXAN HYCELA. Tell your healthcare provider or get medical help right away if you get any of these symptoms during or after an injection of RITUXAN HYCELA: hives (red itchy welts) or rash itching swelling of your lips, tongue, throat or face sudden cough shortness of breath, difficulty breathing, or wheezing weakness dizziness or feel faint palpitations (feel like your heart is racing or fluttering) chest pain fever chills or shaking chills See " What are the possible side effects of RITUXAN HYCELA? " for more information about side effects.

What is RITUXAN HYCELA? RITUXAN HYCELA is a prescription medicine used to treat adults with: Follicular Lymphoma (FL): alone or with certain chemotherapy medicines. Diffuse Large B-Cell Lymphoma (DLBCL): with certain other chemotherapy medicines in people who have not had previous treatment for their DLBCL.

Chronic Lymphocytic Leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide. You can only receive RITUXAN HYCELA after you receive at least 1 full dose of a rituximab product by IV infusion. Read the rituximab by IV infusion Medication Guide for more information about severe infusion reactions, which usually happen during the first dose with a rituximab product given by IV infusion.

RITUXAN HYCELA is not for use to treat medical conditions other than cancers. It is not known if RITUXAN HYCELA is safe and effective in children. Before you receive RITUXAN HYCELA, tell your healthcare provider about all of your medica…

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