Rituxan Hycela

Name: Rituxan Hycela

What Is Rituxan Hycela?

Hyaluronidase is a genetically designed protein.

Rituximab is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Hyaluronidase and rituximab is a combination medicine used to treat follicular lymphoma, diffuse large B-cell lymphoma, or chronic lymphocytic leukemia.

Hyaluronidase and rituximab is sometimes used together with other cancer medicines.

Hyaluronidase and rituximab may also be used for purposes not listed in this medication guide.

Rituximab may cause a serious brain infection that can lead to disability or death. Call your doctor right away if you have changes in your mental state, vision changes, weakness on one side of your body, or problems with speech or walking.

Tell your doctor if you have ever had hepatitis B. Rituximab can cause this condition to come back or get worse.

Severe skin problems can also occur during treatment with rituximab. Call your doctor if you have painful skin or mouth sores, or a severe skin rash with blistering, peeling, or pus.

Some side effects may occur during the injection or within 24 hours afterward. Tell your caregiver right away if you feel itchy, dizzy, weak, light-headed, short of breath, chilled, feverish, or if you have chest pain, wheezing, a sudden cough, or pounding heartbeats or fluttering in your chest.

You should not use hyaluronidase and rituximab if you are pregnant. Avoid getting pregnant for at least 12 months after you stop using this medicine.

You should not be treated with this medicine if you are allergic to hyaluronidase or rituximab.

To make sure hyaluronidase and rituximab is safe for you, tell your doctor if you have ever had:

  • kidney disease;
  • lung disease;
  • a weak immune system (caused by disease or by using certain medicines);
  • an infection such as herpes, shingles, cytomegalovirus, chickenpox, parvovirus, West Nile virus, or hepatitis B or C;
  • heart disease, angina (chest pain), or heart rhythm disorder; or
  • if you recently received any vaccine, or you are are scheduled to receive a vaccine.

Using hyaluronidase and rituximab during pregnancy could harm the unborn baby. Tell your doctor if you are pregnant or if you become pregnant. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 12 months after your last dose.

It is not known whether hyaluronidase and rituximab passes into breast milk or if it could harm a nursing baby. Do not breast-feed while using hyaluronidase and rituximab, and for at least 6 months after your last dose.

What is hyaluronidase and rituximab?

Hyaluronidase is a genetically designed protein.

Rituximab is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Hyaluronidase and rituximab is a combination medicine used to treat follicular lymphoma, diffuse large B-cell lymphoma, or chronic lymphocytic leukemia.

Hyaluronidase and rituximab is sometimes used together with other cancer medicines.

Hyaluronidase and rituximab may also be used for purposes not listed in this medication guide.

Hyaluronidase and rituximab side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection (or within 24 hours afterward). Tell your caregiver right away if you feel itchy, dizzy, weak, light-headed, short of breath, chilled, feverish, or if you have chest pain, wheezing, a sudden cough, or pounding heartbeats or fluttering in your chest.

Serious and sometimes fatal infections may occur during treatment with hyaluronidase and rituximab. Call your doctor right away if you have signs of infection such as:

  • fever, sore throat, cold or flu symptoms;

  • sores or white patches in your mouth or throat;

  • pain or burning when you urinate;

  • earaches, headaches; or

  • painful skin sores with redness, warmth, or swelling.

Rituximab may cause a serious viral infection of the brain or spinal cord that can lead to disability or death. Call your doctor right away if you have any of the following symptoms (which may start gradually and get worse quickly):

  • confusion, memory problems, or other changes in your mental state;

  • weakness on one side of your body;

  • vision changes; or

  • problems with speech or walking.

Call your doctor at once if you have any of these other side effects, even if they occur several months after you are treated with hyaluronidase and rituximab, or after your treatment ends.

  • skin or mouth sores, or a severe skin rash with blistering, peeling, or pus;

  • severe stomach pain, severe vomiting;

  • chest pain, irregular heartbeats;

  • little or no urination;

  • low blood cell counts--fever, chills, flu-like symptoms, swollen gums, mouth sores, skin sores, rapid heart rate, pale skin, easy bruising, unusual bleeding, feeling light-headed; or

  • signs of tumor cell breakdown--vomiting, diarrhea; little or no urination; numbness or tingly feeling; muscle weakness or twitching; fast or slow heart rate; confusion, hallucinations, seizure, feeling restless or irritable.

Common side effects may include:

  • low blood cell counts;

  • nausea, vomiting, constipation;

  • hair loss;

  • feeling tired;

  • cough; or

  • redness where the injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect hyaluronidase and rituximab?

Other drugs may interact with hyaluronidase and rituximab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Uses For Rituxan Hycela

Rituximab and hyaluronidase human, recombinant combination injection is used alone or together with other cancer medicines to treat follicular lymphoma and chronic lymphocytic leukemia (CLL). It is also used together with other medicines to treat diffuse large B-cell lymphoma (DLBCL) in people who have not received previous treatment.

Rituximab and hyaluronidase human, recombinant combination injection is an antineoplastic agent (cancer medicine). It interferes with the growth of cancer cells, which are eventually destroyed by the body.

This medicine is to be given only by or under the direct supervision of your doctor.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Rituxan Hycela is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Rituxan Hycela (rituximab and hyaluronidase) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Rituxan Hycela. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Rituxan Hycela - Clinical Pharmacology

Mechanism 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.

Pharmacodynamics

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.

Pharmacokinetics

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*
Study† Cycle Rituximab
* Pharmacokinetic parameters are presented as geometric mean unless otherwise specified. † For study design information, see Clinical Studies (14). ‡ Rituxan Hycela 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) § Based on predicted values ¶ Rituxan Hycela 1,600 mg/26,800 Units (1,600 mg rituximab and 26,800 Units hyaluronidase human)
FL‡ Cmax, mcg/mL (CV%) SABRINA 7 237 (29.4)
18 156 (24.7)§
Ctrough, mcg/mL (CV%) 7 122.2 (55.3)
18 45.5 (53.6)§
AUCTAU, mcg∙day/mL (CV%) 7 3779 (33.7)
18 5000 (34.3)§
CLL¶ Cmax, mcg/mL (CV%) SAWYER 6 202 (36.1)
Ctrough, mcg/mL (CV%) 5 97.5 (42.6)
AUCTAU, mcg∙day/mL (CV%) 5 4088 (34.2)

In the SABRINA study, the geometric mean Ctrough in the Rituxan Hycela arm was higher than in the rituximab arm with a geometric mean ratio (Ctrough, Rituxan Hycela/Ctrough, 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 Ctrough 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 (14.3)].

Table 5: Pharmacokinetic Parameters of Rituximab following Subcutaneous Administration of Rituxan Hycela*
FL CLL
* Parameters represented as geometric mean (%CV) unless otherwise specified † Compared to a rituximab product administered intravenously ‡ 95% CI § Volume of central compartment and peripheral compartment
Absorption
  Absolute Bioavailability† 0.646
(0.634–0.659‡)
0.634
(0.602–0.665‡)
Distribution
  Volume of Central compartment (L) 4.06 (26) 4.80 (18)
  Apparent Volume of Distribution at steady state§ (L) 8.09 (19) 8.52 (13)
Elimination
  Terminal Half-life (days) 34.1 (27) 32 (24)
  Clearance (L/day) 0.18 (34) 0.204 (31)

Specific Populations

The pharmacokinetics of rituximab and hyaluronidase human in children and adolescents is unknown. The effect of either renal or hepatic impairment on the pharmacokinetics of rituximab and hyaluronidase human is unknown.

Drug Interaction Studies

The drug interaction potential of rituximab and hyaluronidase human is unknown.

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 sign and symptoms of bowel obstruction and perforation, including severe abdominal pain or repeated vomiting [see Warnings and Precautions (5.9)].

Embryo-Fetal Toxicity

Advise a pregnant woman of the potential risk to a fetus. Advise female patients that rituximab containing products can cause fetal harm if taken during pregnancy and to use effective contraception during treatment with Rituxan Hycela and for at least 12 months after the last dose of Rituxan Hycela. Advise patients to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.11) and Use in Specific Populations (8.1, 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)].

Rituxan Hycela™ [rituximab and hyaluronidase human]

Manufactured by:
Genentech, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA 94080-4990
US License No.: 1048

Rituxan Hycela™ is a trademark of Biogen.
Jointly marketed by: Biogen and Genentech USA, Inc.
©2017 Biogen and Genentech USA, Inc.

This Medication Guide has been approved by the U.S. Food and Drug Administration Issued: 6/2017
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 medical conditions, including if you:
  • have had a severe reaction to a rituximab product or Rituxan Hycela
  • have a history of heart problems, irregular heart beat or chest pain
  • have lung or kidney problems
  • have an infection or weakened immune system
  • have or have had any severe infections including:
    • Hepatitis B virus (HBV)
    • Hepatitis C virus (HCV)
    • Cytomegalovirus (CMV)
    • Herpes simplex virus (HSV)
    • Parvovirus B19
    • Varicella zoster virus (chickenpox or shingles)
    • West Nile Virus
  • have had a recent vaccination or are scheduled to receive vaccinations. You should not receive certain vaccines before or during treatment with Rituxan Hycela.
  • are pregnant or plan to become pregnant. Talk to your healthcare provider about the risks to your unborn baby if you receive Rituxan Hycela during pregnancy.
    Females who are able to become pregnant should use effective birth control (contraception) during treatment with Rituxan Hycela and for 12 months after the last dose of Rituxan Hycela. Talk to your healthcare provider about effective birth control.
  • are breastfeeding or plan to breastfeed. It is not known if Rituxan Hycela passes into your breast milk. Do not breastfeed during treatment and for at least 6 months after your last dose of Rituxan Hycela.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How will I receive Rituxan Hycela?
  • Rituxan Hycela is given as an injection under the skin, in the stomach-area (abdomen).
  • Rituxan Hycela is injected over 5 or 7 minutes.
  • Your healthcare provider will prescribe medicines before the injection of Rituxan Hycela to help reduce side effects such as fever and chills.
  • Your healthcare provider should monitor you for side effects for at least 15 minutes after you receive an injection of Rituxan Hycela.
  • If you have CLL, your healthcare provider should prescribe medicines to help prevent certain infections during treatment and for up to 12 months following treatment with Rituxan Hycela.
Before each injection of Rituxan Hycela treatment, your healthcare provider or nurse will ask you questions about your general health. Tell your healthcare provider or nurse about any new symptoms.
What are possible side effects of Rituxan Hycela?
Rituxan Hycela can cause serious side effects, including:
  • See "What is the most important information I should know about Rituxan Hycela?"
  • Tumor Lysis Syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause you to have:
    • kidney failure and the need for dialysis treatment
    • abnormal heart rhythm
    TLS can happen within 12 to 24 hours after an injection of Rituxan Hycela. Your healthcare provider may do blood tests to check you for TLS. Your healthcare provider may give you medicine to help prevent TLS.
    Tell your healthcare provider right away if you have any of the following signs or symptoms of TLS:
  • nausea
  • vomiting
  • diarrhea
  • lack of energy
  • Serious infections. Serious infections can happen during and after treatment with Rituxan Hycela, and can lead to death. Rituximab products can increase your risk of getting infections and can lower the ability of your immune system to fight infections. Types of serious infections that can happen with Rituxan Hycela include bacterial, fungal, and viral infections. After receiving Rituxan Hycela, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these people with low antibody levels developed infections. Tell your healthcare provider right away if you have any symptoms of infection:
    • fever
    • cold symptoms, such as runny nose or sore throat that do not go away
    • flu symptoms, such as cough, tiredness, and body aches
    • earache or headache
    • pain during urination
    • white patches in the mouth or throat
    • cuts, scrapes or incisions that are red, warm, swollen or painful
  • Heart problems. Rituxan Hycela may cause chest pain, irregular heartbeats, and heart attack. Your healthcare provider may monitor your heart during and after treatment with Rituxan Hycela if you have symptoms of heart problems or have a history of heart problems. Tell your healthcare provider right away if you have chest pain or irregular heartbeats during treatment with Rituxan Hycela.
  • Kidney problems Rituxan Hycela can cause severe kidney problems that can lead to death. Your healthcare provider should do blood tests to check how well your kidneys are working.
  • Stomach and serious bowel problems that can sometimes lead to death. Bowel problems, including blockage or tears in the bowel, can happen if you receive Rituxan Hycela with chemotherapy medicines. Tell your healthcare provider right away if you have severe stomach-area (abdomen) pain or repeated vomiting during treatment with Rituxan Hycela.
Your healthcare provider will stop treatment with Rituxan Hycela if you have severe, serious or life-threatening side effects.
The most common side effects of Rituxan Hycela in people with Follicular Lymphoma (FL) include: infections, low white blood cell count, nausea, constipation, cough, and tiredness.
The most common side effects of Rituxan Hycela in people with Diffuse Large B-cell Lymphoma (DLBCL) include: infections, low white blood cell count, loss of hair, nausea, and low red blood cell count.
The most common side effects of Rituxan Hycela in people with Chronic Lymphocytic Leukemia (CLL) include: infections, low white blood cell count, nausea, low platelet count, fever, vomiting, and injection site redness.
These are not all of the possible side effects with Rituxan Hycela.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of Rituxan Hycela.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or healthcare provider for information about Rituxan Hycela that is written for health professionals.
What are the ingredients in Rituxan Hycela?
Active ingredient: rituximab and hyaluronidase human.
Inactive ingredients: L-histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 80, α,α-trehalose dihydrate, and Water for Injection.
Manufactured by: Genentech, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990
US License No.: 1048
Jointly marketed by: Biogen and Genentech USA, Inc.
Rituxan Hycela™ is a trademark of Biogen.
©2017 Biogen and Genentech USA, Inc.
For more information, go to www.RITUXANHYCELA.com or call 1-877-436-3683.

Representative sample of labeling (see the HOW SUPPLIED section for complete listing):

PRINCIPAL DISPLAY PANEL - 13.4 mL Vial Carton

NDC 50242-109-01
Rituxan Hycela™
(rituximab and
hyaluronidase human)
Injection

1,600 mg and
26,800 Units/13.4 mL
(120 mg and 2,000 Units/mL)

For Subcutaneous Use Only.

Single-Dose Vial.
Discard Unused Portion.

Attention Pharmacist: Dispense the
accompanying Medication Guide to
each patient.

1 vial

Rx only

Genentech | Biogen®

10173775

Rituxan Hycela 
rituximab and hyaluronidase injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50242-108
Route of Administration SUBCUTANEOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
rituximab (rituximab) rituximab 120 mg  in 1 mL
hyaluronidase (hyaluronidase) hyaluronidase 2000 U  in 1 mL
Inactive Ingredients
Ingredient Name Strength
Histidine  
Histidine monohydrochloride monohydrate  
Trehalose dihydrate  
Methionine  
Polysorbate 80  
Water  
Packaging
# Item Code Package Description
1 NDC:50242-108-01 1 VIAL, SINGLE-DOSE in 1 CARTON
1 11.7 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA761064 06/22/2017
Rituxan Hycela 
rituximab and hyaluronidase injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50242-109
Route of Administration SUBCUTANEOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
rituximab (rituximab) rituximab 120 mg  in 1 mL
hyaluronidase (hyaluronidase) hyaluronidase 2000 U  in 1 mL
Inactive Ingredients
Ingredient Name Strength
Histidine  
Histidine monohydrochloride monohydrate  
Trehalose dihydrate  
Methionine  
Polysorbate 80  
Water  
Packaging
# Item Code Package Description
1 NDC:50242-109-01 1 VIAL, SINGLE-DOSE in 1 CARTON
1 13.4 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA761064 06/22/2017
Labeler - Genentech, Inc. (080129000)
Establishment
Name Address ID/FEI Operations
Genentech, Inc. (Vacaville) 004074162 API MANUFACTURE(50242-108, 50242-109), ANALYSIS(50242-108, 50242-109)
Revised: 07/2017   Genentech, Inc.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of Rituxan Hycela.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Chest pain or pressure or a fast heartbeat.
  • A heartbeat that does not feel normal.
  • Dizziness or passing out.
  • Feeling very tired or weak.
  • Any unexplained bruising or bleeding.
  • A burning, numbness, or tingling feeling that is not normal.
  • Very bad and sometimes deadly kidney problems have happened with this drug. Call your doctor right away if you are unable to pass urine or if you have blood in the urine or a change in the amount of urine passed.
  • Very bad and sometimes deadly lung problems have happened with this drug. Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.
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