Rituximab (Rituxan)

==General information==
Class/mechanism: Anti-CD20 antibody, chimeric murine/human monoclonal IgG1 kappa, which binds to CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35), which is expressed on B-cells. The Fc domain recruits immune effector functions to mediate B-cell lysis. Possible mechanisms of cell lysis include complement-dependent cytotoxicity (CDC) and antibody-dependent cell mediated cytotoxicity (ADCC).Rituximab (Rituxan) package insert Rituximab (Rituxan) package insert (locally hosted backup)Rituxan manufacturer's site
Route: IV
Extravasation: neutral
*Rituximab (Rituxan) desensitization protocol
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, or the prescribing information. 
==Diseases for which it is established (work in progress)==
*Chronic lymphocytic leukemia
*Diffuse large B-cell lymphoma
*Indolent lymphoma (FDA)
**Follicular lymphoma
*Mantle cell lymphoma
*Marginal zone lymphoma
*Waldenström macroglobulinemia
==Diseases for which it is used==
*Acquired hemophilia A
*Acquired thrombotic thrombocytopenic purpura
*Immune thrombocytopenia
*B-cell acute lymphoblastic leukemia
*B-cell lymphoma of mucosa-associated lymphoid tissue
*Burkitt lymphoma
*Castleman disease
*CNS lymphoma
*Cold agglutinin disease
*Hairy cell leukemia
*High-grade B-cell lymphoma
*HIV-associated lymphoma
*Classical Hodgkin lymphoma
*Hodgkin lymphoma, nodular lymphocyte-predominant
*Inherited coagulopathy with inhibitor
*Mediastinal gray-zone lymphoma
*Non-Hodgkin lymphoma, pediatric
*Post-transplant lymphoproliferative disorder
*Primary mediastinal B-cell lymphoma
*Acquired thrombotic thrombocytopenic purpura
*Transformed lymphoma
*Warm autoimmune hemolytic anemia
==Patient drug information==
*Rituximab (Rituxan) package insert
*Rituximab (Rituxan) patient drug information (Chemocare)Rituximab (Rituxan) patient drug information (Chemocare)
*Rituximab (Rituxan) patient drug information (UpToDate)Rituximab (Rituxan) patient drug information (UpToDate)
==History of changes in FDA dosing recommendations==
*2012-10-19: Approved for 90-minute infusion in previously untreated diffuse large B-cell lymphoma (DLBCL) and follicular Non-Hodgkin lymphoma (NHL) starting with cycle 2:FDA Approves New Dosing and Administration Information for Rituximab (2012-10-19) Hematology.org, accessed 2012-10-19
**Patients who do not experience a grade 3 or 4 infusion related adverse event during cycle 1 may undergo a 90-minute infusion when used as part of a glucocorticoid-containing chemotherapy regimen. In cycle 2, 20% of the total dose is to be given over the first 30 minutes, and the remaining 80% of the total dose is to be given over the last 60 minutes. If this 90-minute infusion is tolerated, the same rate can be used for remaining cycles of the treatment.Atmar J. Review of the safety and feasibility of rapid infusion of rituximab. J Oncol Pract. 2010 Mar;6(2):91-3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMCSehn LH, Donaldson J, Filewich A, Fitzgerald C, Gill KK, Runzer N, Searle B, Souliere S, Spinelli JJ, Sutherland J, Connors JM. Rapid infusion rituximab in combination with corticosteroid-containing chemotherapy or as maintenance therapy is well tolerated and can safely be delivered in the community setting. Blood. 2007 May 15;109(10):4171-3. Epub 2007 Jan 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMCDakhil S, Hermann R, Schreeder MT, Gregory SA, Monte M, Windsor KS, Hurst D, Chai A, Brewster M, Richards P. Phase III safety study of rituximab administered as a 90-minute infusion in patients with previously untreated diffuse large B-cell and follicular lymphoma. Leuk Lymphoma. 2014 Oct;55(10):2335-40. Epub 2014 Mar 7. EuroPMC
==History of changes in FDA indication==
Note: there is a gap in FDA labels between 1997 and 2006 on the FDA website; there are likely missing indications issued during that time period.
===Chronic lymphocytic leukemia===
*2010-02-18: Approved in combination with fludarabine and cyclophosphamide (FC), for the treatment of previously untreated and previously treated patients with chronic lymphocytic leukemia (CLL). (New disease entity; based on GCLLSG CLL8 & REACH)
===Diffuse large B-cell lymphoma===
*2006-02-10: Approved for use in the first-line treatment of patients with diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma in combination with CHOP or other anthracycline-based chemotherapy regimens. (new disease entity added; scope expanded to first-line treatment; combination therapy required; based on ECOG E4494, LNH 98-5, NCIC-CTG LY.9)
===Follicular lymphoma===
*1997-11-26: Initial FDA approval for the treatment of patients with relapsed or refractory follicular, CD20 positive, B-cell non-Hodgkin’s lymphoma. (Based on Maloney et al. 1997a & McLaughlin et al. 1998)
*2006-09-29: Approved for the first-line treatment of patients with follicular, CD20-positive B-cell non-Hodgkin’s lymphoma. (scope expanded to first-line treatment; based on M39021)
*2011-01-28: Approved for maintenance therapy for patients with previously untreated follicular, CD-20 positive, B-cell non-Hodgkin lymphoma who achieve a response to rituximab in combination with chemotherapy. (Approval extended to maintenance setting; based on ECOG E1496 & PRIMAFL)
===Indolent lymphoma===
*1997-11-26: Initial FDA approval for the treatment of patients with relapsed or refractory low-grade, CD20 positive, B-cell non-Hodgkin’s lymphoma. (Based on Maloney et al. 1997a & McLaughlin et al. 1998)
*2006-09-29: Approved for the first-line treatment of patients with low grade, CD20-positive B-cell non-Hodgkin’s lymphoma. (scope expanded to first-line treatment; based on M39021)
===Pediatric lymphoma/leukemia===
*2021-12-02: Approved in combination with chemotherapy for pediatric patients (at least 6 months to less than 18 years) with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL). (Based on Inter-B-NHL Ritux 2010)
==History of changes in EMA indication==
*1998-06-02: Initial marketing authorization as MabThera.
==History of changes in PMDA indication==
*2013-06-14: New additional indication and a new dosage for the treatment of CD 20-positive B-cell lymphoproliferative disorders in immunocompromised patients.
*2017-06-26: New additional indication and a new dosage for the treatment of chronic idiopathic thrombocytopenic purpura.
*2019-03-26: New additional indication and a new dosage for the treatment of CD20-positive chronic lymphocytic leukemia.
*2020-02-21: New indication and a new dosage for the treatment of acquired thrombotic thrombocytopenic purpura.
==Also known as==
*Code names: BI-695500, IDEC-102, IDEC-C2B8, RTXM-83
*Brand names: Ikgdar, Mabtas, MabThera, Reditux, Ristova, Rituxan, Rituxim, Transera-Kit
==References==
Category:Drugs
Category:Intravenous medications
Category:Neutral
Category:Protein expression-specific medications
Category:Anti-CD20 antibodies
Category:Acquired hemophilia A medications
Category:Acquired thrombotic thrombocytopenic purpura medications
Category:B-cell acute lymphoblastic leukemia medications
Category:Burkitt lymphoma medications
Category:Castleman disease medications
Category:Classical Hodgkin lymphoma medications
Category:CNS lymphoma medications
Category:Chronic lymphocytic leukemia medications
Category:Cold agglutinin disease medications
Category:Diffuse large B-cell lymphoma medications
Category:Follicular lymphoma medications
Category:Hairy cell leukemia medications
Category:High-grade B-cell lymphoma medications
Category:HIV-associated lymphoma medications
Category:Hodgkin lymphoma, nodular lymphocyte-predominant medications
Category:Immune thrombocytopenia medications
Category:Indolent lymphoma medications
Category:Inherited coagulopathy medications
Category:MALT lymphoma medications
Category:Mantle cell lymphoma medications
Category:Marginal zone lymphoma medications
Category:Mediastinal gray-zone lymphoma medications
Category:Post-transplant lymphoproliferative disorder medications
Category:Primary mediastinal B-cell lymphoma medications
Category:Transformed lymphoma medications
Category:Waldenström macroglobulinemia medications
Category:Warm autoimmune hemolytic anemia medications
Category:EMA approved in 1998
Category:FDA approved in 1997
Category:PMDA approved drugs
Category:WHO Essential Cancer Medicine