{"entity":{"id":"rituximab-then-ibritumomab-tiuxetan","kind":"pairing","name":"Rituximab pretreatment before ibritumomab tiuxetan (Zevalin)","aka":[],"tldr":"Before giving the radioactive lymphoma treatment Zevalin, doctors first give a dose of the antibody drug rituximab. This clears out normal B-cells in the blood so the radioactivity goes to the lymphoma more precisely, and it is a mandatory step on the drug's official label, not an optional extra.","summary":"Ibritumomab tiuxetan (Zevalin), a yttrium-90-labelled anti-CD20 radioimmunotherapy, is administered only as part of a fixed two-step regimen defined in its FDA label and EMA product information. On day 1, patients receive rituximab 250 mg/m2 by intravenous infusion; seven to nine days later, a second rituximab infusion (250 mg/m2) is given, followed within four hours by the therapeutic yttrium-90 ibritumomab tiuxetan infusion, dosed at 0.4 mCi/kg (14.8 MBq/kg) for patients with platelet counts of 150,000/mm3 or more, or a reduced 0.3 mCi/kg (11.1 MBq/kg) for platelet counts of 100,000-149,000/mm3, with a maximum activity cap of 32 mCi regardless of body weight.\n\nThe pharmacological rationale, stated explicitly in the EMA summary of product characteristics, is that rituximab pretreatment clears circulating and marginal-zone CD20-positive B-cells, which would otherwise act as a radioactivity 'sink' and reduce the fraction of the yttrium-90 dose reaching lymphoma cells; the rituximab dose used in the Zevalin regimen is deliberately lower than the dose used when rituximab is given as monotherapy. Zevalin is approved for relapsed or refractory low-grade or follicular B-cell non-Hodgkin lymphoma, and as consolidation after first-line induction chemotherapy in previously untreated follicular lymphoma (the latter still requiring the same rituximab-then-Zevalin sequence).\n\nBecause rituximab must be ordered and administered separately from the Zevalin kit, this is one of the clearest examples of a mandated, label-level drug sequence in radiopharmaceutical practice: Zevalin cannot be lawfully administered without preceding rituximab, and the labels carry boxed warnings for infusion reactions (during the rituximab step) and for prolonged, severe cytopenias following the radiolabelled step.","asOf":"2026-09-22","links":[{"label":"FDA label: Zevalin (ibritumomab tiuxetan), 2018 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125019s227lbl.pdf"},{"label":"EMA product information: Zevalin (rituximab pretreatment rationale and dosing)","url":"https://ec.europa.eu/health/documents/community-register/2020/20200211147169/anx_147169_en.pdf"}],"tags":["lymphoma","radioimmunotherapy","mandatory sequence"],"related":["cd20","dlbcl","follicular-lymphoma","radioimmunotherapy","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"rituximab","b":"ibritumomab-tiuxetan","rationale":"Rituximab pretreatment clears circulating and marginal-zone CD20-positive B-cells that would otherwise compete for binding, so the radiolabelled antibody given afterwards delivers more of its radiation dose specifically to lymphoma cells.","evidence":"The FDA label and EMA SmPC for Zevalin mandate a fixed two-step regimen: rituximab 250 mg/m2 on day 1, then a second rituximab 250 mg/m2 infusion on day 7-9 followed within 4 hours by yttrium-90 ibritumomab tiuxetan at 0.4 mCi/kg (or 0.3 mCi/kg if platelets 100,000-149,000/mm3), capped at 32 mCi total.","pairingType":"sequence"},"route":"/pairings/rituximab-then-ibritumomab-tiuxetan/","neighbours":{"target":[{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"}],"indication":[{"id":"dlbcl","kind":"indication","name":"Diffuse large B-cell lymphoma","route":"/indications/dlbcl/"},{"id":"follicular-lymphoma","kind":"indication","name":"Follicular lymphoma","route":"/indications/follicular-lymphoma/"}],"technology":[{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/"}],"isotope":[{"id":"y-90","kind":"isotope","name":"Yttrium-90","route":"/isotopes/y-90/"}],"drug":[{"id":"ibritumomab-tiuxetan","kind":"drug","name":"Ibritumomab tiuxetan","route":"/drugs/ibritumomab-tiuxetan/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]}}