What is the mechanism of action of Rituxan (Rituximab) and its associated side effects?

From the Guidelines

Rituxan (rituximab) is a monoclonal antibody medication that works by targeting and destroying B cells in the body through binding to the CD20 protein, causing cell death via antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and direct induction of cell death, as supported by the most recent evidence from 2020 1. The mechanism of action of Rituxan involves the depletion of B cells, which makes it effective for treating conditions where B cells are problematic, such as certain cancers (non-Hodgkin's lymphoma, chronic lymphocytic leukemia) and autoimmune disorders. Some key points about Rituxan include:

• It is used to treat non-Hodgkin lymphoma and chronic lymphocytic leukemia by exerting immunosuppressive effects through B-cell destruction 1
• The standard dose is 375 mg/m2 once per week for 4 to 8 infusions, although other schedules have been used, such as 50 mg/m2 per week for 4 weeks 1
• Common side effects include infusion reactions, infectious complications, and potential severe infections due to compromised immune function
• More serious potential side effects include reactivation of hepatitis B in carriers, progressive multifocal leukoencephalopathy, tumor lysis syndrome in cancer patients, severe skin reactions, and cardiac problems
• Blood disorders like neutropenia, thrombocytopenia, and anemia may also occur, with late-onset neutropenia being a concern, particularly when rituximab is combined with chemotherapy 1 The most common adverse events associated with Rituxan are related to infusion reactions or infectious complications, highlighting the need for careful monitoring during and after treatment, as emphasized in the 2020 guidelines 1.

From the FDA Drug Label

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)

The mechanism of action of Rituxan (Rituximab) is through targeting the CD20 antigen on pre-B and mature B-lymphocytes, leading to B-cell lysis. The possible mechanisms of cell lysis include:

• Complement dependent cytotoxicity (CDC)
• Antibody dependent cell mediated cytotoxicity (ADCC) The associated side effects of Rituxan include:
• Serious infections: RITUXAN can increase the risk of getting infections and can lower the ability of the immune system to fight infections
• Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of cancer cells and can cause kidney failure and abnormal heart rhythm
• Heart problems: RITUXAN may cause chest pain, irregular heartbeats, and heart attack
• Kidney problems: RITUXAN can cause severe kidney problems that lead to death
• Stomach and bowel problems: RITUXAN can cause severe stomach-area pain, repeated vomiting, and bowel problems that can sometimes lead to death
• Infusion-related reactions: RITUXAN can cause infusion-related reactions, including fever, chills, and body aches
• Low white and red blood cells: RITUXAN can cause low white and red blood cells, which can increase the risk of infection and anemia
• Other side effects: RITUXAN can also cause other side effects, including nausea, tiredness, diarrhea, muscle spasms, and changes in liver function 2, 2, 2

From the Research

Mechanism of Action of Rituxan (Rituximab)

• Rituximab is a human-mouse chimeric monoclonal antibody that targets the B-cell CD20 antigen and causes rapid and specific B-cell depletion 3, 4.
• The cytotoxic effects of rituximab on CD20-positive malignant B cells appear to involve complement-dependent cytotoxicity, complement-dependent cellular cytotoxicity, antibody-dependent cellular cytotoxicity, and induction of apoptosis 4.
• Rituximab also sensitizes tumor cells to the effects of conventional chemotherapeutic drugs 4.

Associated Side Effects of Rituxan (Rituximab)

• Infusion-related reactions occur in the majority of patients treated with rituximab, usually mild to moderate flu-like symptoms that decrease in frequency with subsequent infusions 4, 5.
• Severe infusion-related reactions develop in approximately 10% of patients, including bronchospasm and hypotension, which are usually reversible with appropriate interventions and supportive care 4, 5.
• Rituximab is associated with a low incidence of serious adverse events, including serious infections, and has a reasonable safety profile 6, 7.
• Opportunistic infections are rare, but reactivation of hepatitis B remains a concern, and the possible association of rituximab and progressive multifocal leukoencephalopathy may still require vigilance 7.
• Malignancies and cardiovascular events do not appear to be increased, and infusion reactions are more likely with the initial infusion, and are usually mild 7.
• Rituximab may cause hypogammaglobulinemia, but any risk of subsequent risk of increased infectious events is not yet well established 7.