Dosing and Administration

Dosing

Administration

Established dosing regimens for treatment settings in NHL and CLL

RITUXAN DOSING BY TREATMENT SETTING1

Chart: RITUAN DOSING BY TREATMENT SETTING
  • *R-CHEMO: Approximately 75% of patients in both arms of the PRIMA trial received R-CHOP, 22% received R-CVP, and 3% received R-FCM.1
  • †RITUXAN dosing for post-induction setting.
  • NHL=non-Hodgkin's lymphoma; CLL=chronic lymphocytic leukemia; DLBCL=diffuse large B-cell lymphoma; R=RITUXAN; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone; CVP=cyclophosphamide, vincristine, and prednisone; FC=fludarabine and cyclophosphamide; PRIMA=Primary RItuximab and MAintenance; FCM=fludarabine, cyclophosphamide, and mitoxantrone.

Administration1

  • DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS
  • Premedicate patients with an antihistamine and acetaminophen before each infusion (see DOSAGE AND ADMINISTRATION)
  • Administer only as an intravenous infusion (see DOSAGE AND ADMINISTRATION)
  • Interrupt the infusion or slow the infusion rate for infusion reactions (see BOXED WARNINGS and WARNINGS AND PRECAUTIONS). Continue the infusion at one-half the previous rate upon improvement of symptoms
  • Discontinue RITUXAN infusion and provide medical treatment for Grade 3 and 4 infusion reactions (see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS)
  • First infusion: Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50-mg/hr increments every 30 minutes, to a maximum of 400 mg/hr
  • Subsequent infusions: Initiate infusion at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100-mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr

Infusion reactions

  • RITUXAN can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion, with time to onset of 30 to 120 minutes
  • RITUXAN-induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death
  • Premedicate patients with an antihistamine and acetaminophen prior to dosing. Depending on the severity of the infusion reaction and the required interventions, slow the infusion rate, interrupt the infusion, or permanently discontinue RITUXAN
  • Closely monitor patients with pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm3)

How supplied1

  • RITUXAN is supplied as 100-mg/10-mL (NDC 50242-051-21) and 500-mg/50-mL (NDC 50242-053-06) solution in a single-use vial

Stability and storage1

  • RITUXAN vials are stable at 2°C–8°C (36°F–46°F). Do not use beyond expiration date stamped on carton. RITUXAN vials should be protected from direct sunlight. Do not freeze or shake
  • RITUXAN solutions for infusion may be stored at 2°C–8°C (36°F–46°F) for 24 hours. RITUXAN solutions for infusion have been shown to be stable for an additional 24 hours at room temperature. However, since RITUXAN solutions do not contain a preservative, diluted solutions should be stored refrigerated (2°C–8°C) (36°F–46°F). No incompatibilities between RITUXAN and polyvinylchloride or polyethylene bags have been observed

Reference:
  1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2011.

Indications

RITUXAN® (Rituximab) is indicated for the treatment of patients with:

  • Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
  • •  Weekly ×4  •  Weekly ×8  •  Bulky disease  •  Retreatment
  • Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to RITUXAN 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 CVP chemotherapy
  • Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
  • Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)

RITUXAN is not recommended for use in patients with severe, active infections.

Important Safety Information

WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Infusion Reactions: RITUXAN administration can result in serious, including fatal, infusion reactions. Deaths within 24 hours of RITUXAN infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue RITUXAN infusion and provide medical treatment for Grade 3 or 4 infusion reactions.

Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin's lymphoma (NHL) with RITUXAN monotherapy.

Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving RITUXAN.

Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving RITUXAN.

Warnings and Precautions

RITUXAN has also been associated with other serious and/or fatal adverse reactions. These include

  • hepatitis B reactivation with fulminant hepatitis; hepatic failure resulting in death
  • serious, including fatal, bacterial, fungal, and new or reactivated viral infections
  • cardiovascular events, including serious or life-threatening cardiac arrhythmias
  • severe, including fatal, renal toxicity
  • abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy

Additional Important Safety Information

  • The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. These infusion reactions typically resolved with slowing or interruption of the infusion and with supportive care. The most frequent Grade 3 or 4 adverse reactions observed in NHL were cytopenias, including lymphopenia
  • The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Infusion-related adverse reactions occurring during or within 24 hours of the start of infusion included nausea, pyrexia, chills, hypotension, vomiting, and dyspnea
  • Most CLL patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction. The Grade 3 or 4 adverse reactions observed more frequently with R-FC compared with FC alone were neutropenia, leukopenia, febrile neutropenia, thrombocytopenia, infusion reactions, pancytopenia, hypotension, and hepatitis B
  • In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment

For additional safety information, please see the full prescribing information, including BOXED WARNINGS and Medication Guide.

Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.