Introduction
Rituxan (rituximab) is a revolutionary chimeric monoclonal antibody that has transformed the treatment landscape for B-cell malignancies and autoimmune disorders. First approved by the FDA in 1997 for relapsed or refractory low-grade or follicular CD20-positive B-cell non-Hodgkin lymphoma, Rituxan represents one of the most successful targeted cancer therapies developed. This biologic agent specifically targets the CD20 antigen expressed on the surface of pre-B and mature B lymphocytes, leading to selective depletion of these cells while largely sparing other immune components.
Mechanism of Action
Rituxan exerts its therapeutic effects through multiple mechanisms targeting CD20-positive B cells:
- Antibody-dependent cellular cytotoxicity (ADCC): Binds to CD20 antigen, facilitating recognition and destruction by immune effector cells
- Complement-dependent cytotoxicity (CDC): Activates complement cascade leading to formation of membrane attack complexes
- Direct induction of apoptosis: Cross-linking of CD20 molecules triggers programmed cell death
- Sensitization to chemotherapy: Enhances cytotoxicity of concomitant chemotherapeutic agents
The CD20 antigen is an ideal therapeutic target as it is expressed on over 90% of B-cell non-Hodgkin lymphoma cells but is not present on hematopoietic stem cells, plasma cells, or other normal tissues.
Indications
FDA-Approved Oncology Indications:- Relapsed or refractory, low-grade or follicular CD20-positive, B-cell non-Hodgkin lymphoma (NHL)
- Previously untreated follicular CD20-positive NHL in combination with chemotherapy
- Non-progressing low-grade CD20-positive NHL after first-line chemotherapy
- Previously untreated diffuse large B-cell CD20-positive NHL with CHOP chemotherapy
- Previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL)
- Moderately-to-severely active rheumatoid arthritis (RA) with inadequate response to TNF antagonists
- Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) with glucocorticoids
- Pemphigus vulgaris
Dosage and Administration
Oncology Dosing:- NHL: 375 mg/m² IV weekly for 4-8 doses
- CLL: 375 mg/m² first dose, then 500 mg/m² for subsequent doses (in combination with chemotherapy)
- RA: Two 1000 mg IV infusions separated by 2 weeks
- GPA/MPA: 375 mg/m² IV once weekly for 4 weeks
- Pemphigus vulgaris: Two 1000 mg IV infusions separated by 2 weeks, with subsequent maintenance doses
- Premedicate with acetaminophen and diphenhydramine 30-60 minutes prior to infusion
- Administer initial infusion at 50 mg/hr; may increase by 50 mg/hr increments every 30 minutes to maximum 400 mg/hr
- Subsequent infusions may begin at 100 mg/hr, increasing by 100 mg/hr increments every 30 minutes
- Monitor closely during and for at least 1 hour post-infusion
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No specific recommendations; use with caution
- Elderly: No dosage adjustment required
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Administered intravenously only; complete bioavailability Distribution: Volume of distribution approximately 3.1 L; binds specifically to CD20-positive cells Metabolism: Eliminated via antibody-mediated opsonization and phagocytosis by the reticuloendothelial system Elimination: Half-life approximately 22 days (range 6-52 days) in patients with NHL; clearance decreases with repeated dosing due to depletion of CD20-positive B cells Steady State: Achieved after approximately 6 doses in weekly dosing regimensContraindications
- Known hypersensitivity to rituximab, murine proteins, or any component of the formulation
- Active, severe infections
- Hepatitis B virus (HBV) infection (unless appropriate antiviral prophylaxis initiated)
- Severe, uncontrolled heart failure (NYHA Class IV)
Warnings and Precautions
Infusion Reactions: Severe (including fatal) reactions may occur, typically within 30 minutes to 2 hours of initiation Tumor Lysis Syndrome: May occur within 12-24 hours of first infusion in patients with high tumor burden Severe Mucocutaneous Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, and other severe reactions reported Hepatitis B Reactivation: May result in fulminant hepatitis, hepatic failure, and death Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML, which is usually fatal Cardiovascular Events: Arrhythmias, angina, and cardiac arrest have occurred Hypogammaglobulinemia: May develop, particularly with prolonged treatmentDrug Interactions
- Live vaccines: Avoid concurrent administration; may have diminished immune response
- Cisplatin: Increased risk of nephrotoxicity; monitor renal function closely
- Immunosuppressants: Enhanced immunosuppressive effects; increased infection risk
- Antihypertensive medications: Infusion reactions may cause hypotension
Adverse Effects
Very Common (>10%):- Infusion-related reactions (fever, chills, rigors)
- Infections
- Hematologic toxicity (neutropenia, leukopenia, lymphopenia)
- Asthenia
- Nausea
- Thrombocytopenia
- Anemia
- Hypersensitivity reactions
- Angioedema
- Headache
- Hypertension/hypotension
- Cardiac arrhythmias
- Bronchospasm
- Rash
- Arthralgia
- Myalgia
- Severe infusion reactions
- Tumor lysis syndrome
- Hepatitis B reactivation
- Progressive multifocal leukoencephalopathy
- Severe mucocutaneous reactions
- Bowel obstruction and perforation
- Renal toxicity
Monitoring Parameters
Prior to Treatment:- Complete blood count with differential
- Hepatitis B serology (HBsAg, anti-HBc, anti-HBs)
- Renal and hepatic function tests
- Cardiac assessment in patients with cardiac risk factors
- Vital signs every 30 minutes during infusion
- Monitor for infusion reactions
- Weekly CBC during and after treatment
- Regular assessment for infections
- Monitor for delayed neutropenia (may occur months after treatment)
- Regular assessment of immunoglobulin levels
- Continued monitoring for HBV reactivation for several months after treatment
- Monitor for late-onset neutropenia and infections
Patient Education
- Report any signs of infection (fever, chills, cough, sore throat) immediately
- Understand the importance of premedication before infusions
- Be aware of potential infusion reactions and report any symptoms during or after treatment
- Avoid live vaccines during and after treatment; consult healthcare provider before any vaccinations
- Use effective contraception during and for 12 months after treatment
- Understand the need for regular monitoring and follow-up appointments
- Report any unusual skin reactions, neurological symptoms, or signs of hepatitis
- Inform all healthcare providers about Rituxan treatment before any procedures
References
1. FDA Prescribing Information: Rituxan (rituximab). Genentech, Inc. 2022. 2. Salles G, et al. Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience. Adv Ther. 2017;34(10):2232-2273. 3. McLaughlin P, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16(8):2825-2833. 4. Edwards JC, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350(25):2572-2581. 5. Stone JH, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232. 6. van Vollenhoven RF, et al. Long-term safety of rituximab: final report of the rheumatoid arthritis global clinical trial program over 11 years. Lancet. 2021;398(10300):1015-1026. 7. American Society of Clinical Oncology Guidelines for Prevention and Treatment of HBV Reactivation. J Clin Oncol. 2020;38(31):3698-3715.