RITUXAN Indications

*RITUXAN Approvals: November 1997, relapsed/refractory, low-grade/follicular NHL; April 2001, weekly dosing x8, bulky disease, retreatment; February 2006, diffuse large B-cell NHL; September 2006, first-line follicular NHL and previously untreated low-grade NHL.
† For relapsed or refractory, low-grade or follicular, CD20-positive B-cell NHL as a single agent.
‡ For previously untreated follicular, CD20-positive B-cell NHL in combination with CVP chemotherapy.
§ For non-progressing (including stable disease), low-grade, CD20-positive B-cell NHL, as a single agent, after first-line CVP chemotherapy.
|| For previously untreated diffuse large B-cell, CD20-positive NHL (DLBCL) in combination with CHOP or other anthracycline-based chemotherapy regimens.

Learn more about RITUXAN's redefining outcomes in NHL therapy.

Indications for Low-grade or Follicular Non-Hodgkin's Lymphoma

RITUXAN is indicated for the treatment of patients with non-progressing (including stable disease), low-grade, CD20-positive B-cell NHL, as a single agent, after first-line CVP chemotherapy.

Learn more about RITUXAN's use in non-progressing low-grade NHL after CVP.

RITUXAN is indicated for the treatment of patients with previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy.

Learn more about RITUXAN's use in previously untreated follicular NHL in combination with CVP.

RITUXAN is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent.

Learn more about RITUXAN's use in relapsed or refractory, low-grade or follicular NHL.

Indication for Diffuse Large B-Cell, CD20+, Non-Hodgkin's Lymphoma (DLBCL)

RITUXAN is indicated for the treatment of patients with previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens.

Learn more about RITUXAN's use in previously untreated DLBCL with CHOP.

*CHOP is a 4-drug chemotherapy regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone.

Redefining Outcomes in NHL Therapy

INDICATIONS AND USAGE

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
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

BOXED WARNINGS and Additional 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) patients with Rituxan.

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.

Rituxan has also been associated with fatal hepatitis B reactivation with fulminant hepatitis, other serious viral infections, cardiovascular events, renal toxicity, and bowel obstruction and perforation.

The most common adverse reactions of Rituxan (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. These infusion reactions generally have resolved with slowing or interruption of the infusion and with supportive care.

Indication-Specific Safety

Single Agent Rituxan for Relapsed or Refractory, Low-Grade or Follicular NHL
The most common adverse reactions of Rituxan (incidence ≥ 25%) observed in patients with relapsed or refractory, low-grade or follicular NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. Respiratory system events were reported in 38% of patients, and 31% reported infectious events. Grade 3 and 4 cytopenias were reported in 48% of patients and included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%).

Rituxan in Combination with CVP for Previously Untreated, Follicular NHL
Patients in the R-CVP arm had higher incidences of infusional toxicity and of neutropenia as compared to those in the CVP arm. The following adverse reactions occurred more frequently (≥5%) in patients receiving R-CVP compared to 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%).

Single Agent Rituxan for Low-Grade NHL, after First-Line CVP Chemotherapy
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%). 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%).

Rituxan in Combination with CHOP Chemotherapy for DLBCL
The following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients age ≥60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs 46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%). In the GELA LNH 98-5 study, 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).

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

References

1. Data on file, F. Hoffman-La Roche Ltd.

2. US National Institutes of Health. Clinicaltrials.gov Web site. Available at: http://www.clinicaltrials.gov/ct/actions/GetStudy. Accessed August 3, 2007.