Trade Names:Rituxan- Injection, solution, concentrate 10 mg/mL
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).
C max increases with each successive infusion and was 486 mcg/mL following the fourth infusion. Peak and trough serum levels are inversely correlated with pretreatment circulating CD19-positive B cells and tumor burden.
Binds to lymphoid cells in thymus, white pulp of spleen, and a majority of B lymphocytes in peripheral blood and lymph nodes. In rheumatoid arthritis (RA) patients, the Vd was 3.1 L.
The wide range of half-lives reflect the variable tumor burden and changes in CD19-positive B-cell populations. In RA patients, the Cl was 0.335 L/day and the mean half-life was 18 days. In NHL patients, the half-life was 22 days.
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.
No formal pharmacokinetic studies have been conducted.Hepatic Function Impairment
No formal pharmacokinetic studies have been conducted.Elderly
Age had no effect on rituximab pharmacokinetics.Children
The pharmacokinetics of rituximab have not been studied in children and adolescents.Gender
Gender had no effect on rituximab pharmacokinetics.Weight
Weight had no effect on rituximab pharmacokinetics.
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 nonprogressing (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 for the treatment of adult patients with moderately to severely active RA who have had an inadequate response to 1 or more tumor necrosis factor (TNF)–antagonist therapies.
Neuropathy/polyneuropathy; peripheral ulcerative keratitis; relapsed or refractory chronic lymphocytic leukemia; relapsed or refractory Waldenström macroglobulinemia; thrombocytopenic purpura.
None well documented.
IV 375 mg/m 2 on day 1 of each chemotherapy cycle for up to 8 infusions.Nonprogressing, Low-Grade, CD20-Positive, B-cell NHLAdults
IV Following completion of 6 to 8 cycles of CVP chemotherapy, 375 mg/m 2 infused once weekly for 4 doses at 6-mo intervals to a max of 16 doses.Premedication
Premedicate before each infusion with acetaminophen and an antihistamine. For RA patients, methylprednisolone 100 mg IV or its equivalent is recommended 30 min prior to each infusion.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 once weekly for 4 or 8 doses.Re-treatment
375 mg/m 2 IV once weekly for 4 doses.Rheumatoid ArthritisAdults
IV 2 infusions of 1,000 mg separated by 2 wk in combination with methotrexate. Subsequent courses should be administered every 24 wk, but no sooner than every 16 wk.Rituximab as a Component of Ibritumomab Tiuxetan Therapeutic RegimenAdults
IV As a required component of the ibritumomab tiuxetan therapeutic regimen, 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.
Rituximab vials are stable at 36° to 46°F. 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.
Limited data are available on the safety of the use of biologic agents or disease modifying antirheumatic drugs (DMARDs), other than methotrexate, in patients exhibiting peripheral B-cell depletion following treatment with rituximab. Risk for infection may be increased. Closely observe patients for signs of infection if biologic agents and/or DMARDs are coadministered with rituximab.Cisplatin
Renal toxicity has occurred in patients receiving rituximab and cisplatin concomitantly in clinical trials. Coadministration of these agents is not an approved treatment regimen. If this non-approved combination is used in clinical trials, administer with extreme caution and closely monitor for signs of renal failure.Live virus vaccines
The safety of immunization with live viral vaccines following rituximab has not been studied, and vaccination with live virus vaccines is not recommended. If a non-live vaccine is administered, give at least 4 wk prior to a course of rituximab.
None well documented.
Hypotension (10%); hypertension (6%); fatal cardiac failure, systemic vasculitis (postmarketing).
Asthenia (26%); headache (19%); dizziness (10%); anxiety (5%).
Night sweats, rash (15%); pruritus (14%); urticaria (8%); flushing (5%); severe mucocutaneous reactions (postmarketing).
Throat irritation (9%); optic neuritis, uveitis (postmarketing).
Nausea (23%); abdominal pain (14%); diarrhea, vomiting (10%); bowel obstruction and perforation (postmarketing).
Lymphopenia (48%); leukopenia, neutropenia (14%); thrombocytopenia (12%); anemia (8%); hyperviscosity syndrome in Waldenström macroglobulinemia, late-onset neutropenia, marrow hypoplasia, prolonged pancytopenia (postmarketing).
Hypophosphatemia (21%); angioedema (11%); hyperglycemia (9%); peripheral edema (8%); LDH increase (7%); hyperuricemia (2%).
Arthralgia, back pain, myalgia (10%); polyarticular arthritis (postmarketing).
Increased cough (13%); rhinitis (12%); bronchospasm (8%); dyspnea (7%); sinusitis (6%); fatal bronchiolitis obliterans and pneumonitis, including interstitial pneumonitis (postmarketing).
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, grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection, lupus-like syndrome, pleuritis, serum sickness, vasculitis with rash, viral infections, including progressive multifocal leukoencephalopathy (PML) (postmarketing).
Deaths within 24 h of infusion have been reported. Reaction complex consists of acute respiratory distress syndrome, anaphylactoid events, angioedema, bronchospasm, cardiogenic shock, hypotension, hypoxia, MI, pulmonary infiltrates, urticaria, or ventricular fibrillation. 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, acetaminophen, bronchodilators, diphenhydramine, IV fluids, oxygen, vasopressors).Mucocutaneous reactions (severe)
Reported with fatal outcomes.Progressive multifocal leukoencephalopathy
JC virus infection resulting in PML and death can occur.Tumor lysis syndrome
Rapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hyperphophatemia, hyperuricemia, or hypocalcemia has been reported within 12 to 24 h after the first rituximab infusion.
Obtain CBC and platelet counts at regular intervals and more frequently in patients developing cytopenias. Perform cardiac monitoring during and after all infusions of rituximab for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina. Monitor patients closely for signs of renal failure, especially when the combination of rituximab and cisplatin is used. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active hepatitis B virus infection and for signs of hepatitis during and for up to several months following therapy.
Category C .
Safety and efficacy not established.
No differences in efficacy were observed between patients 65 yr of age and older compared with younger patients. Cardiac adverse reactions (eg, supraventricular arrhythmias) and serious pulmonary adverse reactions (eg, pneumonia, pneumonitis) were more common among elderly patients.Low-grade or follicular NHL
Studies did not include sufficient numbers of patients 65 yr of age and older to determine whether they respond differently from younger patients.Rheumatoid arthritis
Response rates and adverse reactions were similar in patients 65 yr of age and older compared with patients younger than 65 yr of age. The rate of serious adverse reactions (eg, CV events, malignancies, serious infections) were higher in elderly patients.
Abdominal pain and bowel obstruction and perforation, sometimes leading to death, have been reported in patients concurrently receiving chemotherapy.
Discontinue infusions in the event of serious or life-threatening cardiac arrhythmias.
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 with fulminant hepatitis, hepatic failure, and death has been reported in patients with hematologic malignancies.
Vaccination with live virus vaccines is not recommended.
As with all therapeutic proteins, there is a potential for immunogenicity.
Not recommended in patients with severe active infections.
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.
Safety and efficacy of re-treatment have not been established.
Use of rituximab in patients with RA who have not had prior inadequate response to 1 or more TNF antagonists is not recommended.
No experience with overdosage in humans.
Copyright © 2009 Wolters Kluwer Health.