National Stroke Foundation

Rituxan (rituximab)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved November 1997

Specific Treatments:

Non-hodgkin's lymphoma

Therapeutic Areas

General Information

Rituxan (rituximab) is a CD20-directed cytolytic antibody. 

Rituxan is specifically indicated for the following:

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent;

• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy.

• Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.

• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens. 

Rituxan is supplied as an injection for intravenous administration. The recommended dose of Rituxan for NHL is 375 mg/m2 as an intravenous infusion according to the following schedules:

• Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL Administer once weekly for 4 or 8 doses.

• Retreatment for Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL Administer once weekly for 4 doses.

• Previously Untreated, Follicular, CD20-Positive, B-Cell NHL Administer on Day 1 of each cycle of chemotherapy, for up to 8 doses. In patients with complete or partial response, initiate Rituxan maintenance eight weeks following completion of a rituximab product in combination with chemotherapy. Administer Rituxan as a single-agent every 8 weeks for 12 doses.

• Non-progressing, Low-Grade, CD20-Positive, B-Cell NHL, after first-line CVP chemotherapy Following completion of 68 cycles of CVP chemotherapy, administer once weekly for 4 doses at 6-month intervals to a maximum of 16 doses.

• Diffuse Large B-Cell NHL Administer on Day 1 of each cycle of chemotherapy for up to 8 infusions.

Clinical Results

FDA Approval

The FDA approval of Rituxan for relapsed, refractory CD20+ NHL was demonstrated in 3 single-arm studies enrolling 296 patients.

 Study 1: A multicenter, open-label, single-arm study was conducted in 166 patients with relapsed or refractory, low-grade or follicular, B-cell NHL who received 375 mg/m2 of Rituxan given as an intravenous infusion weekly for 4 doses. The Overall Response Rate was 48%, the Complete Response Rate was 6% and the Median Duration of Response was 11.2 months.

Study 2: A multicenter, single-arm study conducted 37 patients with relapsed or refractory, low-grade NHL who received 375 mg/m2 of Rituxan weekly for 8 doses. The Overall Response Rate was 57%, the Complete Response Rate was 14% and the Median Duration of Response was 13.4 months.

Study 3: A multicenter, single-arm study conducted in 60 patients who received 375 mg/m2 of Rituxan weekly for 4 doses. All patients had relapsed or refractory, low-grade or follicular, B-cell NHL and had achieved an objective clinical response to Rituxan administered 3.8 to 35.6 months (median 14.5 months) prior to retreatment with Rituxan. Of these 60 patients, 5 received more than one additional course of Rituxan. The Overall Response Rate was 38%, the Complete Response Rate was 10% and the Median Duration of Response was 15 months.

 

Side Effects

Adverse effects associated with the use of Rituxan may include, but are not limited to, the following:

infusion-related reactions

fever

lymphopenia

chills

infection

asthenia

The Rituxan drug label comes with the following Black Box Warning:

Infusion-Related Reactions: Rituxan administration can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Monitor patients closely. Discontinue Rituxan infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions. Severe Mucocutaneous Reactions Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan. Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with Rituxan, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with Rituxan. Discontinue Rituxan and concomitant medications in the event of HBV reactivation. Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving Rituxan.

Mechanism of Action

Rituxan (rituximab) is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production.

Additional Information

For additional information regarding Rituxan or non-Hodgkin's lymphoma, please visit https://www.rituxan.com