Rituximab

Rituximab is used alone or with other medications to treat certain types of cancer (e.g., non-Hodgkin's lymphoma, chronic lymphocytic leukemia). It is a type of medication called a monoclonal antibody. It works by attaching to certain blood cells from your immune system (B cells) and killing them. It is also used with other monoclonal antibodies and radioactive drugs to treat certain cancers.

Rituximab is also used with methotrexate to treat moderate-to-severe forms of rheumatoid arthritis. It is usually used for arthritis only after other medications have not worked. It can decrease joint pain and swelling. It is also used to treat certain types of blood vessel disease (such as Wegener's granulomatosis, microscopic polyangiitis).

Rituximab is available under the following different brand names: Rituxan.

Dosage Forms and Strengths

Injectable solution

• 10 mg/mL

Dosage Considerations – Should be Given as Follows:

Non-Hodgkin Lymphoma (NHL)

Indications

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
• Previously untreated follicular, CD20-positive, B-cell NHL 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), low-grad, CD20-positive, B-cell NHL as a single agent after first-line CVP (cyclophosphamide, vincristine, and prednisolone) chemotherapy
• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

Recommended Dose for Non-Hodgkin Lymphoma

• 375 mg/m² intravenous (IV) infusion according to the following schedules
• Relapsed or refractory low-grade or follicular, CD20-positive, B-cell NHL: Once weekly for 4-8 doses
• Retreatment for relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL: Once weekly for 4 doses
• Previously untreated, follicular, CD20-positive, B-cell NHL: Administer on Day 1 of each chemotherapy cycle for up to 8 doses; with complete or partial response, initiate maintenance 8 weeks following completion of combination chemotherapy as a single-agent every 8 weeks for 12 doses
• Nonprogressing, low-grade, CD20-positive, B-cell NHL, after first-line CVP chemotherapy: Following completion of 6-8 cycles of CVP chemotherapy, administer once weekly for 4 doses at 6-month intervals to a maximum of 16 doses
• Diffuse large B-cell NHL: Administer on Day 1 of each cycle of chemotherapy for up to 8 infusions

Chronic Lymphocytic Leukemia (CLL)

• Indicated for untreated and previously treated CD20-positive CLL; combined therapy with fludarabine and cyclophosphamide (FC)
• 375 mg/m² intravenous (IV) infusion on day 1 of 1st cycle (for 1st cycle, administer 1 day before chemotherapy with FC), THEN
• 500 mg/m² IV on day 1 of subsequent cycles (administer on same day as chemotherapy with FC)
• Repeat every 28 days for 6 cycles

Fludarabine & cyclophosphamide dosage

• Fludarabine: 25 mg/m² intravenously (IV) once/day x 3 days
• Cyclophosphamide: 250 mg/m² IV once/day x3 days
• Repeat q28 days x 6 cycles

Rheumatoid Arthritis

• 1000 mg intravenous (IV) infusion, repeat after 2 week (2 infusions separated by 2 week is 1 course)
• Repeat course every 24 weeks or based on clinical evaluation (but no sooner than 16 weeks)
• Used in combo with methotrexate
• Pre-medicate with glucocorticoids 30 minutes before infusion to reduce infusion reaction
• Not to exceed 1000 mg/dose

Wegener Granulomatosis

• 375 mg/m² intravenously (IV) once/week for 4 weeks

Administration

• Premedicate with acetaminophen and antihistamine before rituximab infusion
• Administer methylprednisolone 1 g intravenously (IV)/day for 1-3 days, then prednisone 1 mg/kg/day orally; not to exceed 80 mg/day and taper as clinically needed
• Initiate glucocorticoids within 14 days prior to or with initiation or rituximab; may continue during and after the 4-week rituximab treatment course
• Concomitant use of immunosuppressants other than corticosteroids has not been studied in Wegener granulomatosis
• Safety and efficacy of subsequent courses of rituximab not established

Microscopic Polyangiitis

• 375 mg/m² intravenously (IV) once/week for 4 weeks

Administration

• Premedicate with acetaminophen and antihistamine before rituximab infusion
• Administer methylprednisolone 1 g intravenously (IV)/day x1-3 days, then prednisone 1 mg/kg/day orally; not to exceed 80 mg/day and taper as clinically needed
• Initiate glucocorticoids within 14 days prior to or with initiation or rituximab; may continue during and after the 4-week rituximab treatment course
• Concomitant use of immunosuppressants other than corticosteroids has not been studied in microscopic polyangiitis
• Safety and efficacy of subsequent courses of rituximab not established

Pediatric

• Safety and efficacy not established
• Rheumatoid Arthritis: Safety and effectiveness not established; FDA has not required pediatric studies in polyarticular juvenile idiopathic arthritis (PJIA) patients under 16 years due to concerns regarding the potential for prolonged immunosuppression as a result of B-cell depletion in the developing juvenile immune system
• Wegener Granulomatosis: Safety and effectiveness not established

Common side effects of rituximab include:

• Skin swelling
• Low blood pressure (hypotension)
• Weakness/lack of energy
• Chills
• Dizziness
• Fever
• Headache
• Itching
• Rash
• Abdominal/stomach pain
• Diarrhea
• Nausea
• Vomiting
• Low white blood cell count (leukopenia, neutropenia)
• Low lymphocyte count (lymphopenia)
• Low platelet count (thrombocytopenia)
• Back pain
• Muscle pain
• Cough
• Runny nose
• Infection
• Night sweats
• Swelling (edema)
• Flushing
• High blood pressure (hypertension)
• Anxiety
• Anemia
• Elevated LDH
• Hyperglycemia
• Bronchospasm
• Shortness of breath
• Sinus infection (sinusitis)
• Sore throat
• Hives
• Heartburn
• Joint pain

RA (Rituximab+Methotrexate vs Methotrexate Alone)

• High blood pressure (hypertension)
• Anxiety
• Weakness/lack of energy
• Chills, migraine
• Numbness and tingling
• Fever
• Itching
• Hives
• Indigestion
• Nausea
• Upper abdominal pain
• Hypercholesterolemia
• Joint pain
• Runny or stuffy nose
• Sore throat
• Upper respiratory infection

Serious side effects of rituximab include:

• Increased thirst or urination
• Swelling of the hands or feet
• Tingling of the hands or feet

Other side effects of rituximab include:

• Tumor lysis syndrome
• Lymphoid malignancies
• Hypogammaglobulinemia

Postmarketing side effects of rituximab reported include:

• Grade 3-4 prolonged or late-onset neutropenia

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

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Rituximab has no known severe interactions with other drugs.
• Serious interactions of rituximab include:
  • certolizumab pegol
• Moderate interactions of rituximab include:
  • amphotericin B deoxycholate
  • belatacept
  • cholera vaccine
  • cisplatin
  • denosumab
  • fingolimod
  • ioversol
  • sipuleucel-T
• Rituximab has no known mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Fatal infusion reaction:

• Can result in serious, including fatal reactions
• Deaths within 24 hours of infusion have occurred
• Approximately 80% of fatal infusion reactions occurred in association with the first infusion
• Carefully monitor patients during infusion
• Discontinue infusion and provide medical treatment for grade 3 or 4 reactions

Mucocutaneous reactions (severe):

• Severe, including fatal, mucocutaneous reactions reported including paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis

Progressive multifocal leukoencephalopathy:

• John Cunningham virus infection resulting in progressive multifocal leukoencephalopathy and death has been reported in patients treated with rituximab

Reactivation of hepatitis B:

• Reactivation of hepatitis B virus (HBV) infection reported, including deaths
• Screen all patients for HBV infection before initiating drug by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc)
• Consult with hepatitis experts regarding monitoring and use of HBV antiviral therapy when screening identifies patients at risk of HBV reactivation due to evidence of prior HBV infection
• Monitor patients with evidence of prior HBV infection for clinical and laboratory signs of hepatitis B or HBV reactivation during therapy and for several months thereafter, since reactivations have occurred several months following completion of therapy
• In patients who develop reactivation of HBV, immediately discontinue the drug and start appropriate HBV treatment, also discontinue any chemotherapy until the HBV infection is controlled or resolved
• Because of insufficient data, no recommendation can be made regarding the resumption of the drug in patients who develop HBV reactivation hepatitis

This medication contains rituximab. Do not take Rituxan if you are allergic to rituximab or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity to any component, murine proteins

Effects of Drug Abuse

• None

Short-Term Effects

• May cause sudden daytime "sleep attacks;" inquire about factors that may increase risk of falling asleep, including sleep disorders or taking sedating medications; caution patients about performing tasks requiring mental alertness; discontinue if there is evidence of sleep attacks; if decision is made to continue therapy, advice patient not to perform dangerous activities requiring mental alertness.
• See "What Are Side Effects Associated with Using Rituximab?"

Long-Term Effects

• Possibility of unusual behavioral impulse patterns (e.g., compulsive gambling) may occur; hallucinations and psychotic-like behavior may occur.
• See "What Are Side Effects Associated with Using Rituximab?"

Cautions

• Cardiac arrhythmia, angina, high tumor burden, concomitant cisplatin.
• Infusion reactions may occur and are potentially fatal; reactions may resolve with slowing or suspending infusion; risk diminishes with subsequent infusions.
• Risk of potentially fatal mucocutaneous reactions.
• Risk of potentially fatal tumor lysis syndrome.
• Increased risk of potentially fatal hepatitis B virus reactivation.
• Potential risk of progressive multifocal leukoencephalopathy.

Pregnancy and Lactation

Use rituximab with caution during pregnancy if benefits outweigh risks. Animal studies show risk and human studies are not available or neither animal nor human studies were done.

It is not known if rituximab is excreted in breast milk. Do not nurse while using rituximab.