Rituxan

What is Rituxan?

Rituxan is a prescription medicine used to treat Adults with Non-Hodgkin’s Lymphoma (NHL): alone or with other chemotherapy medicines.

It is also used in following conditions.

• Adults with Chronic Lymphocytic Leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide.
• Adults with Rheumatoid Arthritis (RA): with another prescription medicine called methotrexate, to reduce the signs and symptoms of moderate to severe active RA in adults, after treatment with at least one other medicine called a Tumor Necrosis Factor (TNF) antagonist has been used and did not work well enough.
• People with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) ages 2 years and above: with glucocorticoids, to treat GPA and MPA.
• Adults with Pemphigus Vulgaris (PV): to treat moderate to severe PV.

Rituxan is not indicated in children less than 2 years of age with GPA or MPA or in children with conditions other than GPA or MPA.

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.

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.

What is the most important information I should know about Rituxan?

Rituxan can cause serious side effects that can lead to death, including:

• Infusion-related reactions. Infusion-related reactions are very common side effects of Rituxan treatment. Serious infusion-related reactions can happen during your infusion or within 24 hours after your infusion of Rituxan. Your healthcare provider should give you medicines before your infusion of Rituxan to decrease your chance of having a severe infusion-related reaction. Tell your healthcare provider or get medical help right away if you get any of these symptoms during or after an infusion of Rituxan:
  • 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
• 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:
  • 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 your Rituxan treatment, your healthcare provider 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 could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems including liver failure, and death. You should not receive Rituxan if you have active hepatitis B liver disease. Your healthcare provider will monitor you for hepatitis B infection during and for several months after you stop receiving Rituxan. 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.
• Progressive Multifocal Leukoencephalopathy (PML). PML is a rare, serious brain infection caused by a virus that can happen in people who receive Rituxan. 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

See “What are the possible side effects of Rituxan?” below for more information about side effects.

What should I tell my healthcare provider before taking Rituxan?

Before you receive Rituxan, tell your healthcare provider about all of your medical conditions, including if you:

• have had a severe reaction to Rituxan or a rituximab product
• have a history of heart problems, irregular heart beat or chest pain
• have lung or kidney problems
• have an infection or weakened immune system.
• If you have or have had any severe infections including:
  • Hepatitis B virus (HBV)
  • Hepatitis C virus (HCV)
  • Cytomegalovirus (CMV)
  • 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.
• are pregnant or plan to become pregnant. Talk to your healthcare provider about the risks to your unborn baby if you receive Rituxan during pregnancy. Females who are able to become pregnant should use effective birth control (contraception) during treatment with Rituxan and for 12 months after the last dose of Rituxan. Talk to your healthcare provider about effective birth control. Tell your healthcare provider right away if you become pregnant or think that you are pregnant during treatment with Rituxan.
• are breastfeeding or plan to breastfeed. It is not known if Rituxan passes into your breast milk. Do not breastfeed during treatment and for at least 6 months after your last dose of Rituxan.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your doctor if you take or have taken:

• a Tumor Necrosis Factor (TNF) inhibitor medicine
• a Disease Modifying Anti-Rheumatic Drug (DMARD)

If you are not sure if your medicine is one listed above, ask your healthcare provider.

How should I take Rituxan?

• Rituxan is given by infusion through a needle placed in a vein (intravenous infusion), in your arm. Talk to your healthcare provider about how you will receive Rituxan.
• Your healthcare provider may prescribe medicines before each infusion of Rituxan to reduce infusion side effects such as fever and chills.
• Your healthcare provider should do blood tests regularly to check for side effects to Rituxan.
• Before each Rituxan 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 the possible side effects of Rituxan?

Rituxan can cause serious side effects, including:

• See “What is the most important information I should know about Rituxan?”
• 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 rhythmTLS can happen within 12 to 24 hours after an infusion of Rituxan. 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, and can lead to death. Rituxan 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 include bacterial, fungal, and viral infections. After receiving Rituxan, 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. People with serious infections should not receive Rituxan. 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
  • cold sores in the mouth or throat
  • cuts, scrapes or incisions that are red, warm, swollen or painful
• Heart problems. Rituxan may cause chest pain, irregular heartbeats, and heart attack. Your healthcare provider may monitor your heart during and after treatment with Rituxan 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.
• Kidney problems, especially if you are receiving Rituxan for NHL. Rituxan can cause severe kidney problems that 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 with chemotherapy medicines. Tell your healthcare provider right away if you have any severe stomach-area (abdomen) pain or repeated vomiting during treatment with Rituxan.

Your healthcare provider will stop treatment with Rituxan if you have severe, serious or life-threatening side effects.

The most common side effects of Rituxan include:

• infusion-related reactions (see “What is the most important information I should know about Rituxan?”)
• infections (may include fever, chills)
• body aches
• tiredness
• nausea

In adult patients with GPA or MPA the most common side effects of Rituxan also include:

• low white and red blood cells
• swelling
• diarrhea
• muscle spasms

Other side effects with Rituxan include:

• aching joints during or within hours of receiving an infusion
• more frequent upper respiratory tract infection

These are not all of the possible side effects with Rituxan.

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.

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 that is written for healthcare professionals.

What are the ingredients in Rituxan?

Active ingredient: rituximab

Inactive ingredients: polysorbate 80, sodium chloride, sodium citrate dihydrate, and Water for Injection, USP.

Label

PRINCIPAL DISPLAY PANEL – 11.7 ML VIAL CARTON

• Rx only
• NDC 50242-108-01
• Rituxan Hycela®
  (rituximab and
  hyaluronidase human)
  Injection
• 1,400 mg and
  23,400 Units/11.7 mL
  (120 mg and 2,000 Units/mL)
• For Subcutaneous Use Only.
  Give the subcutaneous
  injection over 5 to 7 minutes.
• Single-Dose Vial.
  Discard Unused Portion.
• Attention Pharmacist: Dispense the
  accompanying Medication Guide to
  each patient.
• 1 vial
• Genentech | Biogen®
• 10214985

PRINCIPAL DISPLAY PANEL – 13.4 ML VIAL CARTON

• Rx only
• 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.
  Give the subcutaneous
  injection over 5 to 7 minutes.
• Single-Dose Vial.
  Discard Unused Portion.
• Attention Pharmacist: Dispense the
  accompanying Medication Guide to
  each patient.
• 1 vial
• Genentech | Biogen®
• 10214988

SRC: NLM .