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Pronunciation: EYE-bri-TOOM-oh-mab tye-UX-e-tan
Class: Monoclonal antibody
- Injection, solution 3.2 mg
Ibritumomab 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).
The mean fraction of injected activity in the blood AUC is 39 h.
The mean effective half-life for yttrium-90 (Y-90) activity in the blood is 30 h. Over 7 days, a median of 7.2% of injected activity is excreted in urine.
At 4 wk, the median number of circulating B cells is zero (range, 0 to 1,084 cells/mm 3 ).
B-cell recovery begins at approximately 12 wk following treatment, and the median level of B cells is within the healthy range (32 to 341 cells/mm 3 ) by 9 mo after treatment.
Indications and Usage
Treatment of relapsed or refractory low-grade or follicular B-cell NHL; treatment of previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy.
None well documented.
Dosage and AdministrationAdults
IV The therapeutic regimen consists of 2 steps. Step 1 includes a single infusion of rituximab 250 mg/m 2 at a rate of 50 mg/h. Escalate the infusion in 50 mg/h increments every 30 min to a max of 400 mg/h. Within 4 h following completion of the rituximab infusion, administer indium-111 (In-111) ibritumomab tiuxetan 5 mCi (1.6 mg total antibody dose) administered as a 10-min IV push. Step 2 follows step 1 by 7 to 9 days and consists of a second infusion of rituximab 250 mg/m 2 at a rate of 100 mg/h. Escalate the infusion in 100 mg/h increments at 30-min intervals to a max of 400 mg/h. Within 4 h following completion of the rituximab infusion, administer Y-90 ibritumomab tiuxetan 0.4 mCi/kg as a 10-min IV push (max, 32 mCi (1,184 MBq). Reduce the Y-90 ibritumomab tiuxetan dose to 0.3 mCi/kg (11.1 MBq/kg) for patients with a baseline platelet count between 100,000 and 149,000 cells/mm 3 . Do not administer to patients with platelets less than 100,000 cells/mm 3 .
- For IV administration only.
- Premedicate with acetaminophen 650 mg and diphenhydramine 50 mg prior to each infusion of rituximab.
- Immediately stop the rituximab infusion for serious infusion reactions and discontinue the ibritumomab tiuxetan therapeutic regimen. Temporarily slow or interrupt the rituximab infusion for less severe infusion reactions. If symptoms improve, continue the infusion at half the previous dose.
- Inject In-111 or Y-90 ibritumomab tiuxetan within 4 h following completion of the rituximab dose.
- Prior to step 2, verify that biodistribution is present 48 to 72 hours after In-111 ibritumomab tiuxetan administration; do not proceed if biodistribution is not acceptable.
- Prior to injection of In-111 or Y-90 ibritumomab tiuxetan, a 0.22-micrometer low-protein-binding filter should be in-line between the syringe and the infusion port. After injection, flush the line with at least 10 mL of isotonic sodium chloride solution.
- Do not mix or dilute rituximab with other drugs.
- Establish a free-flowing IV line prior to Y-90 ibritumomab tiuxetan injection.
Store at 36°F to 46°F. Do not freeze. Administer In-111 ibritumomab tiuxetan within 12 h of radiolabeling. Administer Y-90 ibritumomab tiuxetan within 8 h of radiolabeling.
Drug InteractionsAnticoagulants (eg, enoxaparin, heparin, warfarin), antiplatelet agents (eg, aspirin, clopidogrel, dipyridamole)
Risk of bleeding or hemorrhage, as well as cytopenias, may be increased by concomitant therapy. Avoid coadministration. If coadministered, monitor anticoagulant function and frequently monitor for thrombocytopenia.Hematopoietic growth factors (eg, darbepoetin alfa, epoetin alfa, filgrastim, pegfilgrastim)
May alter the biodistribution pattern by increasing bone marrow uptake of ibritumomab tiuxetan. Reassess biodistribution after correction of underlying factors.Live vaccines
A reduced immune response may occur following administration of live vaccines. Avoid immunization with a live vaccine for 12 mo following ibritumomab therapy.
Laboratory Test Interactions
None well documented.
Fatigue (33%); dizziness (7%).
Night sweats, petechiae (8%); pruritus, rash (7%); cutaneous and mucocutaneous reactions (postmarketing).
Nausea (18%); abdominal pain (17%); diarrhea (11%); anorexia (8%).
Thrombocytopenia (95%); platelet count below 50,000 cells/mm 3 (78%); neutropenia (77%); absolute neutrophil count (ANC) below 1,000 cells/mm 3 (74%); anemia (61%); leukopenia (43%); ANC below 500 cells/mm 3 (35%); lymphopenia (26%); platelet count below 10,000 cells/mm 3 (14%).
Infusion-site erythema and ulceration (postmarketing).
Nasopharyngitis (19%); cough (11%); bronchitis, rhinitis (8%); pharyngolaryngeal pain, sinusitis (7%); epistaxis (5%).
Infection (29%); asthenia (15%); fever (10%); myalgia (9%); flu-like illness (8%); hypertension, UTI (7%); acute myelogenous leukemia/myelodysplastic syndrome (5%); antibody formation (3%); radiation injury (postmarketing).
WarningsSerious infusion reaction
Death within 24 h of rituximab infusion, an essential component of the ibritumomab therapeutic regimen, has occurred. These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, and cardiogenic shock. Approximately 80% of fatal infusion reactions occurred in association with the first rituximab infusion. Discontinue ibritumomab tiuxetan infusions in patients who develop severe infusion reactions.Prolonged and severe cytopenias
Administration of Y-90 ibritumomab tiuxetan results in severe and prolonged cytopenias in most patients. Do not administer the ibritumomab tiuxetan therapeutic regimen to patients with at least 25% lymphoma marrow involvement and/or impaired bone marrow reserve.Severe cutaneous and mucocutaneous reactions
Severe cutaneous and mucocutaneous reactions, some fatal, have been reported in association with the ibritumomab tiuxetan treatment regimen. Discontinue rituximab, In-111 ibritumomab tiuxetan, and Y-90 ibritumomab tiuxetan infusions in patients experiencing severe cutaneous or mucocutaneous reactions.Dosing
Ensure that the dose of Y-90 ibritumomab tiuxetan does not exceed 32 mCi (1,184 MBq). Do not administer Y-90 ibritumomab tiuxetan to patients with altered biodistribution as determined by imaging with In-111 ibritumomab tiuxetan.
Obtain platelet and CBC counts weekly following the ibritumomab tiuxetan therapeutic regimen and continue until levels recover. Monitor platelets and CBC more frequently in patients who develop severe cytopenia, in patients who are receiving medications that interfere with platelet function or coagulation, or as clinically indicated. Monitor patients closely for evidence of extravasation during ibritumomab tiuxetan infusions.
Category D .
Safety and efficacy not established.
The greater sensitivity of some older individuals cannot be ruled out.
Do not administer Y-90 ibritumomab tiuxetan to patients with altered biodistribution of In-111 ibritumomab tiuxetan.
During and after radiolabeling ibritumomab tiuxetan with In-111 or Y-90, take care to minimize radiation exposure of patients and medical personnel.
Acute myelogenous leukemia and myelodysplastic syndrome have been reported following the ibritumomab tiuxetan therapeutic regimen.
Because this product contains albumin, a derivative of human blood, there is a risk of transmitting infectious agents (eg, viruses), including Creutzfeldt-Jakob disease.
- Advise patients to report any signs or symptoms of cytopenias (eg, bleeding, easy bruising, fatigue, pallor, petechiae or purpura, weakness) or infection (eg, fever).
- Advise patients to seek prompt medication attention for diffuse rash, bullae, or desquamation of the skin or oral mucosa.
- Advise patients that immunization with live viral vaccines is not recommended for 12 mo following ibritumomab tiuxetan therapeutic regimen.
- Advise patients to avoid medications that interfere with platelet function, except as directed by health care provider.
- Advise women to avoid becoming pregnant, and to use effective contraceptive methods during treatment and for up to 12 mo following the ibritumomab tiuxetan therapeutic regimen.
- Advise patients to discontinue breast-feeding during and after ibritumomab tiuxetan treatment.
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