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rituximab (Rituxan, Mabthera, Truxima, Ruxience, Riabni)

Indications: - treatment of patients with relapsed or refractory, low-grade or CD20-positive - B-cell non-Hodgkin's follicular lymphoma - diffuse large B-cell lymphoma - mantle cell lymphoma - Burkitt's lymphoma [14] - treatment of Waldenstrom's macroglobulinemia [14] - treatment of chronic lymphocytic leukemia [4] - treatment of autoimmune disorders: - rheumatoid arthritis unresponsive to TNF-alpha inhibitor - adjunct to methotrexate [17] - as effective as TNF-alpha inhibitor [17] - ANCA-associated vasculitis [7,10] - systemic lupus erythematosus (off label) - in conjunction with dexamethasone for treatment of immune thrombocytopenic purpura (ITP), but high risk of adverse effects [9] - microscopic polyangitis [14] - IgG4-related disease [7] - myasthenia gravis Contraindications: - concurrent use of other biologic agent (TNF inhibitor, anakinra, abatacept) Pregnancy category: C [7] Dosage: 1) administer by slow IV infusion (50 mg/hour 1st infusion); maximum infusion rate 400 mg/hour 2) 375 mg/m2 weekly for 4 doses (days 1, 8, 15 & 22) Injection: 100 mg (preservative free) (10 mL) 500 mg (10 mL) Monitor: - serum IgG, CBC, basic metabolic panel, LFTs at baseline, at 2 weeks, & every 3-6 months thereafter - CD20 cells [7] Adverse effects: 1) infusion-related effects a) 80% 1st infusion; 40% therafter b) fever/chills/rigors, hypotension, bronchospasm, angioedema c) interrupt infusion; resume at 1/2 rate after resolution of symptoms d) medications for treatment of hypersensitivity reactions (epinephrine, antihistamines, corticosteroids) should be available for immediate use 2) common (> 10%) a) headache (14%) b) nausea (18%) c) leukopenia (11%) d) fever (49%) e) chills (32%) f) asthenia (16%) g) angioedema (13%) h) hypotension (10%) i) pruritus (10%) j) rash (10%) 3) less common - myalgia, dizziness, urticaria, vomiting, abdominal pain, thrombocytopenia (8%), bronchospasm (8%), throat irritation, rhinitis 4) uncommon (< 1%) a) arrhythmias, angina, myocardial infarction, aplastic anemia, hemolytic anemia b) progressive multifocal leukoencephalopathy (PML) [5,6] - reversible posterior leukoencephalopathy [7] 3) reactivation of viral infection (hepatitis B) 5) serum sickness-like reaction to murine light & heavy chain variable regions 6) hypogammaglobulinemia - opportunistic infection - Pneumocystis pneumonia [8] - poor humoral response to influenza vaccine [11] 7) associated with severe COVID-19 infection [19] 8) Boxed warning: - risk of reactivation of hepatitis B infection [2] - hepatitis B core IgG in serum positive Mechanism of action: 1) binds specifically to CD20, a B-cell restricted differentiation antigen 2) chimeric mouse + human monoclonal Ab [7] - the monoclonal Ab contains murine light & heavy chain variable regions & human constant region (Fc) 3) complement or antibody-dependent cell mediated cytotoxicity 4) in cultured cells, rituximab induces apoptosis 5) vitamin D may enhance antibody-dependent cellular cytotoxicity by rituximab [18] Management: - whenever possible bring patients up to date on vaccinations prior to initiating biologic immunosuppressive agent [7]

Interactions

drug adverse effects of immunosuppressive agents monitor with immunosuppressive agents

General

biologic immunosuppressive agent (biologic agent, biologic immune modulator) antineoplastic monoclonal antibody

References

  1. Kaiser Permanente Northern California Pharmacy update, 11/2000
  2. PDR 2000
  3. Rituximab Plus Chemo More Effective in Elderly Lymphoma Patients http://www.nci.nih.gov/clinicaltrials/results/rituximab-plus-chemo0202
  4. Van Oers MHJ et al, Rituximab maintenance improves clinical outcome of relapsed/ resistance follicular non-Hodgkin lymphoma in patients with and without rituximab during induction: Results of a prospective randomized phase 3 intergroup trial. Blood 2006, 108:3295 PMID: 16873669
  5. FDA Medwatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Rituxan
  6. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Rituxan
  7. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2022.
  8. Martin-Garrido I et al. Pneumocystis pneumonia in patients treated with rituximab. Chest 2012 Dec 20 PMID: 23258406 http://journal.publications.chestnet.org/article.aspx?articleid=1486940
  9. Gudbrandsdottir S et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood 2013 Mar 14; 121:1976. PMID: 23293082
  10. Specks U et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med 2013 Aug 1; 369:417 PMID: 23902481 http://www.nejm.org/doi/full/10.1056/NEJMoa1213277
  11. van Assen S, Holvast A, Benne CA et al Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum. 2010 Jan;62(1):75-81 PMID: 20039396
  12. Bingham CO 3rd, Looney RJ, Deodhar A et al Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010 Jan;62(1):64-74 PMID: 20039397
  13. FDA Drug Safety Communication: Boxed Warning and new recommendations to decrease risk of hepatitis B reactivation with the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and Rituxan (rituximab). September 25, 2013 http://www.fda.gov/Drugs/DrugSafety/ucm366406.htm
  14. Deprecated Reference
  15. Jones RB, Tervaert JW, Hauser T et al Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20 PMID: 20647198
  16. Oddis CV, Reed AM, Aggarwal R et al Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo- phase trial. Arthritis Rheum. 2013 Feb;65(2):314-24. PMID: 23124935
  17. Coblyn JS Head-to-Head Comparison of Rituximab vs. TNF Inhibitors for Rheumatoid Arthritis. NEJM Journal Watch. June 21, 2016 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Porter D, van Melckebeke J, Dale J et al. Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): An open-label, randomised controlled, non-inferiority, trial. Lancet. 2016 May 16. PMID: 27197690
  18. Minerd J. Expert critique by Taylor J Hodgkin Lymphoma Risk: 'Intriguing' Early Links Suggestive of Season Patterns, Role for Vitamin D Relates to biological evidence that vitamin D enhances antibody-dependent cellular cytotoxicity by rituximab. MedPage Today. ASCO Reading Room 06.06.2018 https://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/73311 - Hohaus S, Tisi MC, Bellesi S et al. Vitamin D deficiency and supplementation in patients with aggressive B-cell lymphomas treated with immunochemotherapy. Cancer Medicine 2018; 7: 270-281. PMID: 29271084 Free PMC Article
  19. Ingram I Anti-CD20 Drugs Tied to Severe COVID in Cancer Patients - Plus: Active chemo treatment may not be a COVID risk factor. MedPage Today February 5, 2021 https://www.medpagetoday.com/hematologyoncology/lymphoma/91092
  20. Medscape: rituximab (Rx) https://reference.medscape.com/drug/rituxan-truxima-rituximab-342243

Component-of

cyclophosphamide/pentostatin/rituximab (PCR regimen) hylenex/rituximab N-PEP-12 (MemoProve) cyclophosphamide/pentostatin/rituximab (PCR regimen) rituximab/cyclophosphamide/doxorubicin/vincristine (Oncocin)/dexamethasone (R-CVAD) rituximab/cyclophosphamide/doxorubicin/vincristine (Oncocin)/prednisone (R-CHOP) rituximab/cyclophosphamide/vincristine (Oncocin)/prednisone (R-CVP)