Rituximab (Rituxan; Genentech, Biogen) is an anti-CD20 monoclonal antibody used in the treatment of non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The drug is administered as an IV infusion. This section discusses the most common adverse reactions reported in clinical trials as well as any warnings, precautions and drug interactions.
Common adverse reactions
Warnings and precautions
Drug interactions and other contraindications
Rituximab common adverse reactions
In clinical trials for patients with NHL receiving rituximab, the most commonly reported adverse reactions were infusion reactions, lymphopenia (low levels of circulating lymphocytes), chills, infection and asthenia (weakness). These reactions were reported by at least 25% of trial participants receiving rituximab.
The most common adverse reaction reported in CLL clinical trials of rituximab were infusion reactions and neutropenia (low levels of neutrophils, a type of white blood cell).
Rituximab warnings and precautions
Infusion reaction is a serious and potentially fatal adverse event associated with rituximab therapy. Most of these reactions occur within 30 minutes to 120 minutes of initiation of the first infusion of rituximab, and 80% of fatal reactions occur during the first infusion. The signs and symptoms of infusion reaction include urticaria (hives), hypotension, angioedema (swelling), hypoxia, bronchospasm, pulmonary infiltrates (fluid in the lungs), acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylaxis and death. Patients receiving an infusion of rituximab should be closely monitored for signs of infusion reaction and should receive prophylactic treatment with an antihistamine and acetaminophen. Infusion reactions are more likely to occur in patients with pre-existing cardiopulmonary conditions and those with a high tumor burden.
Patients with large tumor burdens or high numbers of circulating malignant cells (≥ 25,000) are also at increased risk for tumor lysis syndrome, a syndrome caused by the release of electrolytes and waste products from tumor cells during lysis or destruction (Figure 1). This results in hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia, which may lead to renal insufficiency and failure, arrhythmia, seizure and death. The symptoms often present within 12 hours to 24 hours of the first infusion of rituximab. Management of tumor lysis syndrome includes IV hydration, administration of anti-hyperuricemic agents and the monitoring of renal function.
Figure 1. Tumor lysis syndrome.
Severe reactions involving the skin and mucous membranes (mucocutaneous reactions) have also been reported in association with rituximab therapy; these reactions can be fatal and include the following:
- Paraneoplastic pemphigus: an autoimmune reaction mediated by the effects of tumor cells on the immune system and one that is most often associated with lymphoproliferative malignancies; symptoms include inflammation of the mucous membranes (mucositis) and blistering of the skin as well as potential pulmonary involvement.
- Stevens-Johnson syndrome (SJS): a medication reaction, the symptoms of which include hives, swelling of the face and tongue, painful skin, a red or purple spreading rash, blistering of the skin and mucous membranes, and shedding of the skin usually involving less than 10% of the surface area of the body.
- Toxic epidermal necrolysis (TEN): a more severe form of SJS in which the skin blistering is much more widespread, involving greater than 30% of the body’s surface area.
Another potential complication of rituximab treatment is progressive multifocal leukoencephalopathy (PML), a brain infection caused by the JC virus. This virus generally does not cause infection in healthy people, but can cause PML in the immunocompromised. Symptoms of PML include clumsiness, difficulty speaking, partial blindness and a decline in mental function, and, if untreated, will likely result in death within 9 months of the onset of symptoms. Progressive multifocal leukoencephalopathy is more likely to occur in patients who are receiving rituximab in combination with a chemotherapy regimen or as part of or after a hematopoietic stem cell transplant. Most cases of PML are diagnosed within 12 months of last infusion of rituximab.
Patients should be screened for hepatitis B virus (HBV) infection before initiating treatment with rituximab, as HBV reactivation can occur, resulting in acute hepatitis, hepatic failure and death.
Rituximab drug interactions and other contraindications
Regarding drug interactions, contraindications and limitations of use of rituximab, it is important to note the following:
- Rituximab is associated with renal toxicity when used in combination with a cisplatin-containing chemotherapy regimen.
- It should not be used in patients with severe, active infections; if a patient develops an infection during treatment, then rituximab should be withheld until the infection resolves.
- Patients beginning treatment with rituximab should not receive any live virus vaccines either before or during treatment.
- Blood counts should be monitored at regular intervals to evaluate patients for cytopenia (low levels of one or more blood cell types).
- Rituximab should be discontinued in the event of a serious infusion reaction.
- There are no specific contraindications listed in the Rituxan prescribing information.