Understanding Rituximab and Its Mechanism
Rituximab is a chimeric murine/human monoclonal antibody used to treat certain types of cancers, such as non-Hodgkin lymphoma and chronic lymphocytic leukemia, as well as autoimmune diseases like rheumatoid arthritis. It works by targeting a specific protein called CD20, which is found on the surface of B-cells, a type of white blood cell. By binding to CD20, rituximab triggers the destruction of these B-cells through several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and by directly inducing programmed cell death (apoptosis). This depletion of B-cells helps to control the growth of cancerous cells and reduce the autoimmune response.
Common Adverse Effects of Rituximab
While effective, rituximab treatment is associated with a range of adverse effects. These can vary in severity from mild and manageable to severe and life-threatening.
Infusion-Related Reactions (IRRs)
Infusion-related reactions are the most common side effect of rituximab treatment. These reactions typically occur during or within 24 hours of the infusion, and are most frequent and severe during the first dose. The incidence of IRRs can be high. Symptoms are often flu-like and can include:
- Fever and chills
- Itching, rash, or hives
- Throat irritation and cough
- Weakness and dizziness
- Headache
To mitigate these reactions, healthcare providers typically administer premedications such as an antihistamine (like diphenhydramine) and acetaminophen before the infusion. The infusion may be slowed or stopped temporarily for more severe reactions.
Infections
Rituximab increases the risk of bacterial, fungal, and viral infections by depleting B-cells. These can occur during and after treatment. Common infections include upper respiratory tract infections, nasopharyngitis, urinary tract infections, and bronchitis. Patients should watch for signs of infection and report them to their healthcare provider. Prolonged low antibody levels can also increase infection risk after treatment.
Serious and Potentially Fatal Adverse Effects
Rituximab carries boxed warnings from the FDA for several severe, potentially fatal adverse effects.
Hepatitis B Virus (HBV) Reactivation
Rituximab can reactivate the hepatitis B virus in carriers or those with a history of the virus, potentially leading to serious liver problems, including liver failure. Patients are screened for HBV before starting treatment.
Progressive Multifocal Leukoencephalopathy (PML)
PML is a rare, serious brain infection caused by the JC virus that can occur in patients with weakened immune systems, such as those receiving rituximab. PML can be fatal or cause severe disability, with no known cure. Symptoms include new or worsening confusion, dizziness, difficulty walking or talking, and vision problems.
Severe Mucocutaneous Reactions
Rarely, rituximab can cause severe and fatal skin and mouth reactions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Patients should seek immediate medical help for symptoms such as painful sores, blistering, and peeling skin.
Tumor Lysis Syndrome (TLS)
TLS can occur rapidly after the first rituximab infusion due to the breakdown of cancer cells, potentially causing kidney failure and abnormal heart rhythms. It is more common in patients with a high tumor burden.
Other Serious Effects
- Heart Problems: Chest pain, irregular heartbeats, and heart attacks may occur.
- Kidney Problems: Severe kidney toxicity, sometimes fatal, can occur, especially in patients with Non-Hodgkin's Lymphoma.
- Stomach and Bowel Problems: Blockage or tears in the bowel, sometimes fatal, can occur, particularly when combined with chemotherapy.
Comparison of Adverse Effects
| Common Adverse Effects | Serious (Less Common) Adverse Effects |
|---|---|
| Infusion-related reactions (fever, chills, rash) | Progressive Multifocal Leukoencephalopathy (PML) |
| Infections (upper respiratory, UTI) | Hepatitis B Virus (HBV) Reactivation |
| Body aches and tiredness | Severe Skin/Mouth Reactions (SJS, TEN) |
| Nausea and headache | Tumor Lysis Syndrome (TLS) |
| Night sweats | Severe Heart Problems (heart attack, arrhythmia) |
| Low white blood cell counts | Severe Kidney Problems / Renal Toxicity |
| Joint pain | Bowel Obstruction and Perforation |
Conclusion
The most common adverse effects of rituximab are infusion-related reactions and an increased susceptibility to infections. However, there are also rare but very serious risks, including hepatitis B reactivation, PML, and severe skin reactions, which have FDA boxed warnings. Patients should discuss potential benefits and risks with their doctor and report any new or worsening symptoms. Monitoring and premedication strategies are important for managing adverse effects safely.
For more information from the manufacturer, visit: Rituxan® (rituximab)
