Rituxan Rituximab
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Dosing and Administration

RITUXAN Dosing Information

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

  • Retreatment
  • Weekly x4
  • Weeky x8
  • Bulky disease

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

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

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

RITUXAN dosing by indication1

Chart: RITUXAN dosing by indication

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 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

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

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

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

Preparation for administration1

  • Use appropriate aseptic technique. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Withdraw the necessary amount of RITUXAN and dilute to a final concentration of 1 to 4 mg/mL into an infusion bag containing either 0.9% Sodium Chloride, USP, or 5% Dextrose in Water, USP. Gently invert the bag to mix the solution. Do not mix or dilute with other drugs. Discard any unused portion left in the vial
  • Provide Medication Guide to patient prior to RITUXAN infusion

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)
  • 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 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.

Attention Healthcare Provider: Provide Medication Guide to patient prior to Rituxan infusions.

References
  1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2008.
  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.