No formal drug interaction studies have been performed with Rituximab. Rituximab in combination with cisplatin has been associated with renal toxicity. Patients should be closely monitored when receiving Rituximab with other nephrotoxic agents. The formation of human antichimeric antibodies has been observed rarely and may affect clinical response. The safety of immunization with live vaccines following Rituximab therapy has not been established, and vaccination responses may be impaired.

For Non-Hodgkin’s Lymphoma, the recommended dose is 375 mg/m² as an intravenous infusion. For relapsed or refractory, low-grade or follicular CD20-positive B-cell NHL, administer once weekly for 4 or 8 doses. For retreatment, administer once weekly for 4 doses. For previously untreated follicular NHL, administer on Day 1 of each chemotherapy cycle for up to 8 doses, followed by maintenance therapy every 8 weeks for 12 doses in responders. For diffuse large B-cell NHL, administer on Day 1 of each cycle of chemotherapy for up to 8 infusions. For CLL, administer 375 mg/m² the day prior to chemotherapy, followed by 500 mg/m² on Day 1 of cycles 2–6. In rheumatoid arthritis, Rituximab is given as two 1000 mg infusions separated by 2 weeks every 24 weeks, with methylprednisolone premedication. For Wegener’s Granulomatosis and Microscopic Polyangiitis, Rituximab is administered at 375 mg/m² once weekly for 4 weeks. Rituximab should be diluted to a final concentration of 1–4 mg/mL in sodium chloride or dextrose before infusion, beginning at 50 mg/hr and increasing gradually if tolerated. Premedication with acetaminophen and antihistamines is recommended.

Rituximab is contraindicated in patients with known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any component of the product.

The most serious adverse reactions include infusion reactions, tumor lysis syndrome, mucocutaneous reactions, hypersensitivity, cardiac arrhythmias, angina, and renal failure. Infusion reactions and lymphopenia are the most commonly occurring side effects. Mild to moderate infusion reactions such as fever, chills, nausea, pruritus, angioedema, hypotension, rash, bronchospasm, throat irritation, urticaria, dizziness, and hypertension commonly occur during the first infusion. Infectious complications, including bacterial, viral, and fungal infections, may occur due to B-cell depletion. Hematologic events such as neutropenia, anemia, and thrombocytopenia have been reported, along with rare cases of aplastic anemia and late-onset neutropenia. Other less common side effects include abdominal pain, dyspnea, hypotension, and edema.

Rituximab is classified as Pregnancy Category C. Animal reproduction studies have not been conducted, and it is not known whether Rituximab can cause fetal harm when administered to a pregnant woman. Human IgG is known to cross the placental barrier and may potentially cause fetal B-cell depletion. Rituximab should be used during pregnancy only if clearly needed. It is not known whether Rituximab is excreted in human milk, but because human IgG is excreted in milk and the potential for absorption and immunosuppression in the infant exists, women should be advised to discontinue nursing until circulating drug levels are no longer detectable.

Because Rituximab targets all CD20-positive B lymphocytes, complete blood counts and platelet counts should be obtained at regular intervals during therapy and more frequently in patients who develop cytopenias. The safety of immunization with live viral vaccines following Rituximab therapy has not been established. Severe infusion reactions may occur, sometimes fatal, typically during the first infusion. Renal toxicity including acute renal failure has been reported, especially in patients with high tumor burden or those receiving concomitant nephrotoxic agents. Severe mucocutaneous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Patients experiencing such reactions should discontinue therapy.

There has been no experience with Rituximab overdose in clinical trials. Single doses of up to 500 mg/m² have been given without unexpected toxicity.

Rituximab vials should be stored in the original carton at 2–8°C and protected from light.