Rituximab
Pronunciation: (ri-TUX-i-mab)Class: Monoclonal antibody
Trade Names:
Rituxan
- Injection, solution, concentrate 10 mg/mL
Pharmacology
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Rituximab is a monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The CD20 antigen is also expressed on more than 90% of B-cell non-Hodgkin lymphomas (NHL).
Pharmacokinetics
Absorption
IV absorption is immediate and results in a rapid and sustained depletion of circulating and tissue-based cells.
Distribution
Binds to lymphoid cells in thymus, white pulp of spleen, and a majority of B lymphocytes in peripheral blood and lymph nodes.
Elimination
Mean serum half-life is 59.8 h after first infusion and 174 h after fourth infusion. Wide range of half-lives reflect the variable tumor burden and changes in CD20-positive B-cell populations.
Duration
Detectable in serum 3 to 6 mo after completion of treatment. B-cell recovery began at about 6 mo following completion of treatment. Median B-cell levels returned to normal by 12 mo after completion of treatment.
Indications and Usage
Treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent; treatment of previously untreated follicular, CD20-positive, B-cell NHL in combination with cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy; treatment of non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy; treatment of previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other anthracycline-based chemotherapy regimens; in combination with methotrexate to reduce signs and symptoms and to slow the progression of structural damage in adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to 1 or more tumor necrosis factor (TNF) antagonist therapies.
Unlabeled Uses
Relapsed or refractory chronic lymphocytic leukemia; relapsed or refractory Waldenström macroglobulinemia; thrombocytopenic purpura.
Contraindications
None.
Dosage and Administration
Diffuse Large B-Cell NHLAdults
IV 375 mg/m 2 infused on day 1 of each chemotherapy cycle for up to 8 infusions.
Non-Progressing, Low-Grade, CD20-Positive, B-cell NHL, After First-Line CVP ChemotherapyAdults
IV Following completion of 6 to 8 cycles of CVP chemotherapy, administer 375 mg/m 2 once weekly for 4 doses at 6-mo intervals to a max of 16 doses.
Previously Untreated, Follicular, CD20-Positive, B-Cell NHLAdults
IV 375 mg/m 2 infusion, given on day 1 of each cycle of CVP chemotherapy, for up to 8 doses.
Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHLAdults
IV 375 mg/m 2 infused once weekly for 4 or 8 doses.
Retreatment375 mg/m 2 IV infusion once/wk for 4 doses.
RAAdults
IV 2 infusions of 1,000 mg separated by 2 wk.
Rituximab as a Component of Ibritumomab Tiuxetan Therapeutic RegimenAdults
IV As a required component of the ibritumomab tiuxetan therapeutic regimen, infuse 250 mg/m 2 within 4 h prior to administration of indium-111 (In-111) ibritumomab tiuxetan and within 4 h prior to administration of yttrium-90 (Y-90) ibritumomab tiuxetan. Rituximab and In-111 ibritumomab tiuxetan should precede rituximab and Y-90 ibritumomab tiuxetan by 7 to 9 days.
General Advice
- Do not administer as an IV push or bolus.
- Because infusion reactions may occur, consider premedication with acetaminophen and an antihistamine prior to each rituximab infusion.
- Because transient hypotension may occur during rituximab infusion, consider withholding antihypertensive medications 12 h prior to rituximab infusion.
- First infusion: Infuse rituximab solution at an initial rate of 50 mg/h. Do not mix or dilute with other drugs. If infusion reactions do not occur, escalate infusion rate in 50 mg/h increments every 30 min, to a max of 400 mg/h. If an infusion reaction develops, temporarily slow or interrupt infusion. Upon improvement of patient's symptoms, continue infusion at one-half the previous rate.
- Subsequent infusions: If the first infusion is well tolerated, subsequent rituximab infusions can be given at an initial rate of 100 mg/h, and increased in 100 mg/h increments at 30-min intervals, to a max of 400 mg/h as tolerated. If the first infusion is not tolerated, follow the guidelines for first infusion.
Storage/Stability
Rituximab vials are stable at 36° to 46°F. Do not use beyond expiration date stamped on carton. Protect vials from direct sunlight. Do not freeze or shake. Rituximab solutions for infusion may be stored at 36° to 46°F for 24 h, and are stable at room temperature for an additional 24 h. However, because rituximab solutions do not contain a preservative, store diluted solutions refrigerated at 36° to 46°F.
Drug Interactions
Live virus vaccinesThe safety of immunization with live viral vaccines following rituximab has not been studied, and vaccination with live virus vaccines is not recommended.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Hypotension (10%); hypertension (6%); fatal cardiac failure, systemic vasculitis (postmarketing).
CNS
Asthenia (26%); headache (19%); dizziness (10%); anxiety (5%).
Dermatologic
Night sweats, rash (15%); pruritus (14%); urticaria (8%); flushing (5%); severe mucocutaneous reactions (postmarketing).
EENT
Throat irritation (9%); optic neuritis, uveitis (postmarketing).
GI
Nausea (23%); abdominal pain (14%); diarrhea, vomiting (10%); bowel obstruction and perforation (postmarketing).
Hematologic-Lymphatic
Lymphopenia (48%); leukopenia, neutropenia (14%); thrombocytopenia (12%); anemia (8%); hyperviscosity syndrome in Waldenström macroglobulinemia, late-onset neutropenia, marrow hypoplasia, prolonged pancytopenia (postmarketing).
Metabolic-Nutritional
Angioedema (11%); hyperglycemia (9%); peripheral edema (8%); LDH increase (7%).
Musculoskeletal
Arthralgia, back pain, myalgia (10%).
Respiratory
Increased cough (13%); rhinitis (12%); bronchospasm (8%); dyspnea (7%); sinusitis (6%); fatal bronchiolitis obliterans and pneumonitis, including interstitial nephritis (postmarketing).
Miscellaneous
Fever (53%); chills (33%); infection (31%); infusion reactions, including angioedema, bronchospasm (with or without hypotension or hypertension), chills, cough, fever, pruritus, rigors, sneezing, throat irritation, and urticaria/rash (27%); pain (12%); disease progression of Kaposi sarcoma, fatal infections in HIV-associated lymphoma, lupus-like syndrome, pleuritis, polyarticular arthritis, serum sickness, vasculitis with rash, viral infections, including progressive multifocal leukoencephalopathy (PML) (postmarketing).
Precautions
WarningsInfusion reactionDeaths within 24 h of infusion have been reported. Reaction complex consists of hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, or cardiogenic shock. Approximately 80% of fatal infusion reactions occur with first infusion. Interrupt the rituximab infusion for severe reactions and institute supportive care measures as medically indicated (eg, IV fluids, vasopressors, oxygen, bronchodilators, diphenhydramine, acetaminophen). Mucocutaneous reactions (severe)Reported with fatal outcomes. Progressive multifocal leukoencephalopathyJohn Cunningham (JC) virus infection resulting in PML and death can occur. Tumor lysis syndromeRapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatasemia has been reported within 12 to 24 h after the first rituximab infusion. |
MonitorObtain CBC and platelet counts at regular intervals and more frequently in patients developing cytopenias. |
Pregnancy
Category C .
Lactation
Undetermined.
Children
Safety and efficacy have not been established.
Elderly
Diffuse large B-cell NHLNo differences in efficacy were observed between patients who where 65 yr of age and older compared with younger patients.
Low-grade or follicular NHLStudies did not include sufficient numbers of patients 65 yr of age and older to determine whether they respond differently from younger patients.
Rheumatoid arthritisResponse rates and adverse reactions were similar in patients 65 yr of age and older compared with patients younger than 65 yr of age.
Hypersensitivity
Rituximab is associated with hypersensitivity reactions, which may respond to adjustments in the infusion rate and in medical management.
Renal Function
Severe, including fatal, renal toxicity can occur after rituximab administration in patients with hematologic malignancies. Consider discontinuing rituximab in patients with rising serum creatinine or oliguria.
Bowel obstruction
Abdominal pain and bowel obstruction and perforation, sometimes leading to death, have been reported in patients concurrently receiving chemotherapy.
Cardiac arrhythmias
Discontinue infusions in the event of serious or life-threatening cardiac arrhythmias.
Coadministration with biologic agents or disease modifying anti-rheumatic drugs (DMARDs)
There are limited data available on the safety of use of biologic agents or DMARDs other than methotrexate in patients exhibiting peripheral B-cell depletion following treatment with rituximab. Observe patients closely for signs of infection if biologic agents or DMARDs are coadministered with rituximab.
Hepatitis B reactivation
Hepatitis B reactivation with fulminant hepatitis, hepatic failure, and death has been reported in patients with hematologic malignancies.
Retreatment in RA patients
Safety and efficacy of retreatment have not been established.
RA patients
Use of rituximab in patients with RA who have not had prior inadequate response to 1 or more TNF antagonists is not recommended.
Overdosage
Symptoms
No experience with overdosage in humans.
Patient Information
- Advise patient to read the patient information leaflet before using product the first time and with each refill.
- Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
- Review dosing schedule with patient, family, or caregiver.
- Advise patient, family, or caregiver to immediately report any of the following to health care provider: chest pain; decreased urine output; fever, chills, or other signs of infection; hives; itching; persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness; rash; shortness of breath or difficulty breathing; sores in mouth; unusual bleeding or bruising.
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More Rituximab resources
rituximab Intravenous - Includes detailed dosage instructions.
Compare Rituximab with other medications for the treatment of:
Rheumatoid Arthritis, Non-Hodgkin's Lymphoma, Pemphigus, Chronic Lymphocytic Leukemia, Idiopathic Thrombocytopenic Purpura, Evan's Syndrome, Bullous Pemphigoid, Pemphigoid
