Rituxan Rituximab
Driving patient outcomes

NHL Dosing and Administration

Established dosing regimens for a variety of treatment settings in NHL1

Relapsed/refractory: For relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent

  • Retreatment
  • Weekly x4
  • Weeky x8
  • Bulky disease

First-line follicular NHL: For previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy

First-line low-grade NHL after CVP: For non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy

Diffuse large B-cell lymphoma (DLBCL): For previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

RITUXAN dosing by treatment setting

Chart: RITUXAN dosing by indication

Administration

  • DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.
  • Premedicate before each infusion (see DOSAGE AND ADMINISTRATION section of full prescribing information). Administer only as an intravenous infusion (see DOSAGE AND ADMINISTRATION section of full prescribing information). Interrupt the infusion or slow the infusion rate for infusion reactions (see BOXED WARNINGS and WARNINGS AND PRECAUTIONS sections of full prescribing information).

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)

Previously untreated follicular, CD20+, B-cell NHL1

In combination with CVP chemotherapy

  • The recommended dose of RITUXAN is 375 mg/m2 IV infusion, given on Day 1 of each 21-day cycle of CVP chemotherapy for up to 8 doses

Treatment protocol from Marcus: R-CVP x81,2

Chart: Treatment protocol from Marcus: R-CVP x8

Safety summary:

  • Patients in the R-CVP arm had higher incidences of infusional toxicity and of neutropenia as compared with those in the CVP arm. The following adverse reactions occurred more frequently (≥5%) in patients receiving R-CVP compared with CVP alone: rash (17% vs 5%), cough (15% vs 6%), flushing (14% vs 3%), rigors (10% vs 2%), pruritus (10% vs 1%), neutropenia (8% vs 3%), and chest tightness (7% vs 1%)1

Non-progressing, low-grade, CD20+, B-cell NHL1

Following first-line CVP chemotherapy

  • The recommended dose of RITUXAN in patients who have not progressed following 6–8 cycles of CVP chemotherapy is 375 mg/m2 IV infusion once weekly for 4 weeks, every 6 months for up to 16 doses

Treatment protocol from E1496:
16 doses of RITUXAN following CVP1,3

Chart: Treatment protocol from E1496: 16 doses of RITUXAN following CVP

Safety summary:

  • The following common adverse reactions were reported more frequently (≥5%) in patients receiving RITUXAN following CVP compared with those who received no further therapy: fatigue (39% vs 14%), anemia (35% vs 20%), peripheral sensory neuropathy (30% vs 18%), infections (19% vs 9%), pulmonary toxicity (18% vs 10%), hepatobiliary toxicity (17% vs 7%), rash and/or pruritus (17% vs 5%), arthralgia (12% vs 3%), and weight gain (11% vs 4%)1
  • Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the RITUXAN arm compared with those who received no further therapy (4% vs 1%)1

Relapsed or refractory, low-grade or follicular, CD20+, B-cell NHL1

  • The recommended dose of RITUXAN is 375 mg/m2 IV infusion once weekly for 4 or 8 doses

Treatment protocol from McLaughlin
weekly x4 and Piro weekly x81,4,5

Chart: Treatment protocol from McLaughlin weekly x4 and Piro weekly x8

Retreatment therapy

  • The recommended dose of RITUXAN is 375 mg/m2 IV infusion once weekly for 4 doses in responding patients who develop progressive disease after previous RITUXAN therapy

Safety summary:

  • In RITUXAN clinical trials of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL, the most common Grade 3 or 4 adverse reactions that occurred more frequently (>1%) in patients receiving single-agent RITUXAN (N=356) were lymphopenia (40%), neutropenia (6%), leukopenia (4%), infection (4%), anemia (3%), chills (3%), and thrombocytopenia (2%)1

Diffuse large B-cell NHL (DLBCL)1

  • The recommended dose of RITUXAN is 375 mg/m2 IV per infusion given on Day 1 of each cycle of CHOP or other anthracycline-based chemotherapy regimens for up to 8 infusions

Treatment protocol from GELA: R-CHOP x81,6*

Chart: Treatment protocol from GELA: R-CHOP x8

*CHOP is given on Days 1 through 5. A RITUXAN dose of 375 mg/m2 is given on the first day of each CHOP cycle for up to 8 infusions.

Safety summary:

  • Detailed safety data collection in these trials was primarily limited to Grade 3 and 4 adverse reactions and serious reactions. In studies of elderly patients with DLBCL, the following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients ≥60 years of age receiving R CHOP as compared with CHOP alone: pyrexia (56% vs 46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%). In one of the studies of elderly patients, GELA LNH 98-5, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs 1.0% for CHOP)
  • The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs 7%) and lung disorder (6% vs 3%). Other Grade 3 or 4 adverse reactions reported more frequently among patients receiving R CHOP were viral infection (GELA LNH 98-5 study), neutropenia (GELA LNH 98-5 and MInT studies), and anemia (MInT study)

Administration1

  • DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS
  • Premedicate 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 WARNING and WARNINGS AND PRECAUTIONS)
  • Depending on the severity of the infusion reaction and the required interventions, temporarily or permanently discontinue RITUXAN.
  • 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

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). No incompatibilities between RITUXAN and polyvinylchloride or polyethylene bags have been observed

View Indication and Safety Information
Proposed Mechanism of Action

INDICATIONS AND IMPORTANT SAFETY INFORMATION

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

  • Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)
  • 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 CVP chemotherapy
  • 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

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

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 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.

References
  1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010.
  2. Marcus R, Imrie K, Belch A, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005:1417-1423.
  3. Data on file, Genentech, Inc.
  4. McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825-2833.
  5. Piro LD, White CA, Grillo-López AJ, et al. Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol. 1999;10:655-661.
  6. Coiffier B, Lepage E, Brière J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-242.