Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: Disulfide with human-mouse monoclonal IDEC-C2B8 κ-chain immunoglobulin G 1 (human-mouse monoclonal IDEC-C2B8 γ1-chain anti-human antigen CD20) dimer
CAS Number: 174722-31-7
- Fatal Infusion-related Reactions
Severe, sometimes fatal infusion-related effects reported.1
Death has occurred within 24 hours of administration.1
Approximately 80% of fatal reactions have occurred with the first dose.1
Monitor patients carefully during infusions.1 If grade 3 or 4 infusion reactions occur, discontinue rituximab infusion and institute appropriate treatment.1 (See Infusion-related Effects under Cautions.)
- Severe Mucocutaneous Reactions
Risk of severe, sometimes fatal, mucocutaneous reactions.1 (See Mucocutaneous Reactions under Cautions.)
- HBV Reactivation
- Progressive Multifocal Leukoencephalopathy (PML)
Risk of potentially fatal PML, secondary to JC virus infection.1 (See Progressive Multifocal Leukoencephalopathy under Cautions.)
Antineoplastic agent; a chimeric human-murine anti-human antigen CD20 monoclonal antibody.1
Uses for Rituximab
Used as monotherapy for treatment of nonprogressing (e.g., stable disease), low-grade, antigen CD20-positive, B-cell NHL following first-line treatment with CVP chemotherapy.1
Treatment of previously untreated diffuse large B-cell, antigen CD20-positive, NHL; used in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or other anthracycline-based chemotherapy.1 9 14
Designated an orphan drug by FDA for the treatment of NHL.6
Used as a required component of a therapeutic regimen with ibritumomab tiuxetan (ibritumomab tiuxetan therapeutic regimen) for treatment of relapsed or refractory low-grade or follicular B-cell NHL, including follicular NHL that is refractory to rituximab therapy; also as part of the ibritumomab tiuxetan therapeutic regimen for consolidation treatment of newly diagnosed follicular NHL in patients who have achieved partial or complete response to first-line induction chemotherapy.18 55 Rituximab is used prior to ibritumomab to deplete peripheral B cells and to improve distribution of the radioimmunotherapeutic agent.1 18
Has been used in combination with bendamustine† for treatment of previously untreated† and relapsed/refractory indolent NHL†, including mantle cell lymphoma†;10001 10002 10003 however, use of this regimen for the treatment of previously untreated indolent NHL or mantle cell lymphoma currently is not fully established because of inadequate data/experience.10008
Chronic Lymphocytic Leukemia
Used in combination with fludarabine and cyclophosphamide (FC) for treatment of previously untreated and previously treated antigen CD20-positive chronic lymphocytic leukemia (CLL).1
Designated an orphan drug by FDA for the treatment of CLL.6
Prolonged progression-free survival observed in previously untreated and previously treated patients with CLL.38 39 However, no benefit of adding rituximab to fludarabine/cyclophosphamide observed in previously untreated patients ≥70 years of age or in previously treated patients ≥65 years of age. 1 51
Used in conjunction with methotrexate for treatment of moderately to severely active rheumatoid arthritis (RA) in adults with disease that has shown an inadequate response to ≥1 tumor necrosis factor (TNF; TNF-α) blocking agents.1 Manufacturer states that use in patients who have not demonstrated an inadequate response to ≥1 TNF blocking agents is not recommended.1
Although efficacy has been demonstrated in clinical studies in patients with prior inadequate response to nonbiologic disease-modifying antirheumatic drugs (DMARDs) and in methotrexate-naive patients, manufacturer states that favorable risk-to-benefit ratio has not been established in these populations.1
Idiopathic Thrombocytopenic Purpura
Has been used in adults with idiopathic thrombocytopenic purpura (ITP; also known as immune thrombocytopenic purpura)†.33 However, because efficacy compared with standard treatments cannot be determined (due to lack of controlled randomized studies), avoid indiscriminate use.33
Has been used in children with severe chronic ITP that is refractory to standard therapy†.34 However, because of low response rate (30–60%) and potentially serious adverse effects (including PML, some experts recommend use only in patients who have failed splenectomy.40
Rituximab Dosage and Administration
To minimize the risk of infusion-related events, premedication with acetaminophen and an antihistamine is recommended before each infusion.1 In patients receiving rituximab over 90 minutes, administer glucocorticoid component of the chemotherapy regimen prior to each rituximab infusion.56 64 (See Rate of Administration under Dosage and Administration.) Premedication with methylprednisolone 100 mg IV (or equivalent) is recommended 30 minutes prior to each infusion in patients with rheumatoid arthritis (given in conjunction with antihistamines and acetaminophen in clinical studies). 1 (See Infusion-related Effects under Cautions.)
Monitor patients during infusion; appropriate diagnostic and treatment facilities, including medications for the treatment of severe adverse reactions (e.g., infusion-related reactions, cardiac arrhythmias) must be readily available.56 (See Infusion-related Effects and also Cardiac Effects under Cautions.)
Prophylaxis against Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) and herpes virus infection recommended in patients with CLL during treatment and for up to 12 months after completion of therapy.1
For solution and drug compatibility information, see Compatibility under Stability.
Do not admix with other drugs or administer other drugs in the same IV line with rituximab infusion.1
Use aseptic technique since drug product contains no preservative.1
Withdraw the appropriate dose of rituximab concentrate and dilute in an appropriate volume of 0.9% sodium chloride or 5% dextrose injection to yield a final rituximab concentration of 1–4 mg/mL;1 gently invert infusion bag several times to ensure complete mixing.1
Discard any unused solution remaining in the vial.1
Rate of Administration
Infuse initial dose at an initial rate of 50 mg/hour; if infusion-related events do not occur, infusion rate may be increased in increments of 50 mg/hour every 30 minutes to a maximum infusion rate of 400 mg/hour.1 11
If first infusion is tolerated well, administer subsequent infusions at an initial rate of 100 mg/hour; infusion rate may be increased in increments of 100 mg/hour every 30 minutes as tolerated to a maximum infusion rate of 400 mg/hour.1
Alternatively, an accelerated (90-minute) infusion may be used beginning with the second dose in patients with previously untreated follicular NHL or previously untreated diffuse large B-cell NHL who are receiving rituximab with a glucocorticoid-containing chemotherapy regimen if they tolerated the first dose (administered at the standard rate) without experiencing grade 3 or 4 infusion-related events.56 64 To administer dose over 90 minutes, administer 20% of total dose over 30 minutes and remaining 80% of dose over next 60 minutes.56 64 If infusion is tolerated, the same 90-minute infusion rate may be used for subsequent doses (through cycle 6 or 8).56 64
Do not administer over 90 minutes in patients with clinically important cardiovascular disease (i.e., uncontrolled hypertension, MI, unstable angina, NYHA class II or greater CHF, ventricular arrhythmia requiring medication within the past year, NYHA class II or greater peripheral vascular disease) or those with high circulating lymphocyte count (≥5000/mm3) before cycle 2.56 64 67
Decrease infusion rate or interrupt infusion if infusion-related events occur.1 Employ a slower infusion rate (i.e., at least 50% reduction in rate) when therapy is resumed following complete resolution of symptoms.1
Relapsed or Refractory Low-grade or Follicular, Antigen CD20-positive, B-cell NHLIV
If disease subsequently progresses following response to previous rituximab therapy, administer an additional course of 375 mg/m2 once weekly for 4 weeks.1
Previously Untreated Follicular, Antigen CD20-Positive, B-Cell NHLIV
Nonprogressing, Low-Grade, Antigen CD20-Positive, B-Cell NHLIV
For patients with nonprogressing (including stable disease) who have received first-line therapy with 6–8 cycles of CVP chemotherapy, 375 mg/m2 once weekly for 4 weeks; repeat every 6 months for up to 16 doses.1
Previously Untreated Diffuse Large B-cell, Antigen CD20-positive, NHLIV
375 mg/m2 on day 1 of each chemotherapy cycle for up to 8 doses.1
Radioimmunotherapy with Rituximab and IbritumomabIV
Step 1 (day 1): Administer rituximab 250 mg/m2.18
Previously Untreated Antigen CD20-Positive CLLIV
Previously Treated Antigen CD20-Positive Chronic Lymphocytic LeukemiaIV
Therapy Interruptions or Discontinuance for Toxicity
Depending on the nature and severity of rituximab-related toxicities, slowing of the infusion rate, interruption of the infusion, or discontinuance of the drug may be required; provide appropriate treatment as indicated. 1 (See Cautions and see Rate of Administration under Dosage and Administration.)
Previously Untreated Follicular, Antigen CD20-Positive, B-Cell NHLIV
Maximum 8 infusions.1
Nonprogressing, Low-Grade, Antigen CD20-Positive, B-Cell NHLIV
Maximum 16 infusions.1
Previously Untreated Diffuse Large B-cell, Antigen CD20-positive, NHLIV
Maximum 8 infusions.1
Previously Untreated Antigen CD20-Positive CLLIV
Previously Treated Antigen CD20-Positive CLLIV
Course of rituximab and methotrexate should not be repeated sooner than every 16 weeks.1
No special population dosage recommendations at this time.1
Cautions for Rituximab
No known contraindications.1
Appropriate diagnostic and treatment facilities, including medications for the treatment of severe adverse reactions (e.g., infusion-related reactions, cardiac arrhythmias) must be readily available.54 56
Risk of severe and sometimes fatal infusion-related reactions (e.g., urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, MI, VF, cardiogenic shock, anaphylactoid events).1 13 (See Fatal Infusion-related Reactions in Boxed Warning.)
If signs and symptoms of a severe infusion reaction occur, interrupt infusion and institute appropriate therapy (e.g., epinephrine, oxygen, bronchodilators, corticosteroids).1 Monitor closely until complete resolution occurs.13 When symptoms have completely resolved, consider resuming infusion at a slower infusion rate (i.e., at least 50% reduction in rate), depending on severity of reaction and required interventions.1
Close monitoring required in patients with preexisting cardiac and/or pulmonary conditions, patients with prior adverse cardiopulmonary events, and patients with high numbers of circulating malignant cells (≥25,000/mm3).1
In patients with NHL, infusion reactions consisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension usually resolved with slowing or interruption of the infusion and administration of supportive care (e.g., diphenhydramine, acetaminophen, IV sodium chloride injection).1
Severe and sometimes fatal mucocutaneous reactions, including paraneoplastic pemphigus,1 Stevens-Johnson syndrome,1 47 lichenoid dermatitis,1 vesiculobullous dermatitis,1 and toxic epidermal necrolysis,1 15 have been reported.15 Onset is variable but may occur as early as the first day of rituximab administration.56
Discontinue therapy if a severe mucocutaneous reaction occurs.1 15 Safety of administering additional courses of rituximab in patients who have experienced a mucocutaneous reaction has not been determined.1 15
Reactivation reported in patients with the following serologic markers: hepatitis B surface antigen-positive [HBsAg-positive]; HBsAg-negative and hepatitis B core antibody-positive [anti-HBc-positive]; or HBsAg-negative, anti-HBc-positive, and hepatitis B surface antibody-positive [anti-HBs-positive].56 57
FDA's review of 109 reports of fatal HBV-related acute liver injury in patients receiving rituximab or ofatumumab revealed highly variable onset of HBV reactivation (from 63 days after initiation of therapy to 12 months after last dose) and recent or concomitant use of other immunosuppressive agents in all 32 patients with documented (by seroconversion or serum HBV DNA) HBV reactivation.57 Longer intervals to HBV reactivation (up to 24 months after completion of rituximab therapy) also reported.56 58
Screen all patients for HBV infection prior to initiation of rituximab therapy.56 57 62 63 Consult hepatitis expert regarding monitoring and antiviral prophylaxis for patients with evidence of HBV infection (HBsAg-positive with any antibody status or HBsAg-negative and anti-HBc-positive).56 57 Monitor patients with evidence of current or prior HBV infection for clinical or laboratory manifestations of hepatitis or HBV reactivation during therapy and for several months thereafter.56 57 58
If HBV reactivation occurs, discontinue rituximab and any concomitant chemotherapy immediately and initiate appropriate treatment (e.g., antiviral therapy).56 57 Discontinue concomitant chemotherapy until control or resolution of HBV infection is achieved.56 57 Consult expert in managing HBV infection regarding resumption of rituximab once control of HBV reactivation has been achieved.56 Safety of resuming rituximab not known.56 57
Progressive Multifocal Leukoencephalopathy
PML (sometimes fatal) reported in patients with hematologic malignancies or autoimmune diseases (i.e., RA, systemic lupus erythematosus [SLE]†) receiving rituximab.1 35 42 43 46 Most patients with hematologic malignancies had received rituximab in combination with chemotherapy or as a component of hematopoietic stem cell transplantation.1 35 Patients with autoimmune diseases had received prior or concurrent therapy with immunosuppressive agents or had possible risk factors for PML (e.g., prior chemotherapy and radiation therapy, long-standing lymphopenia); PML also reported in at least one patient with RA who had not received prior therapy with a TNF antagonist.1 41 PML caused by reactivation of JC virus (latent form present in up to 80% of healthy adults);43 may occur up to 12 months following discontinuance of rituximab.1 Usually causes death or severe disability; no known treatment, prevention, or cure.1 41 42 43
Inform patients of risk of PML prior to initiation of rituximab.1 42 43 Consider PML in any patient presenting with new neurologic manifestations.1 41 43 (See Advice to Patients.) Consider brain magnetic resonance imaging (MRI), lumbar puncture, and consultation with a neurologist as clinically indicated.1 41
Tumor Lysis Syndrome
Potentially fatal tumor lysis syndrome (i.e., rapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia) may occur within 12–24 hours of completion of the initial infusion.1
Increased risk in patients with a large tumor burden or a large number of circulating malignant cells (≥25,000/mm3); administer aggressive IV hydration and anti-hyperuricemic therapy in these patients.1
Closely monitor for development of tumor lysis syndrome, including manifestations of renal failure.1 If tumor lysis syndrome develops, institute appropriate medical treatment (e.g., correction of electrolyte abnormalities, monitoring of renal function and fluid balance, any necessary supportive care [e.g., dialysis]). 1
Serious (sometimes fatal) bacterial, fungal, and new or reactivated viral infections reported during and following discontinuance of rituximab therapy.1
Infections in patients with prolonged hypogammaglobulinemia reported.56
New or reactivated viral infections include herpes simplex virus, cytomegalovirus, parvovirus B19, varicella-zoster virus, West Nile virus, HCV, and HBV.1 If serious infections occur, discontinue rituximab and institute appropriate anti-infective therapy.1
Prophylaxis against PCP (i.e., co-trimoxazole) and herpes virus (i.e., acyclovir or valacyclovir) recommended in patients with CLL during treatment and for up to 12 months after completion of therapy.1 39
Use not recommended in patients with severe, active infections.1
Severe and sometimes fatal renal toxicity can occur after rituximab administration in patients with NHL.1 Acute renal failure requiring dialysis, sometimes resulting in death, reported in patients who experience tumor lysis syndrome (see Tumor Lysis Syndrome under Cautions).1
Renal toxicity reported in patients with NHL receiving investigational regimen consisting of rituximab and cisplatin.1
Bowel Obstruction and Perforation
Abdominal pain, bowel obstruction, and perforation, sometimes fatal, reported in patients receiving rituximab in combination with chemotherapy. 1 Mean time to documented GI perforation was 6 days (range: 1–77 days) in patients with NHL.1
If abdominal pain or repeated vomiting develops, evaluate patient for bowel obstruction.56
Adequate Patient Monitoring and Evaluation
NHL and CLL patients receiving rituximab as monotherapy: monitor CBCs and platelet counts prior to each rituximab course.1
NHL and CLL patients receiving rituximab in combination with chemotherapy: monitor CBCs and platelet counts weekly or monthly during therapy; monitor more frequently if cytopenias develop.1
RA patients: monitor CBCs and platelet counts every 2–4 months during treatment.1
Concomitant Therapy for Rheumatoid Arthritis
Anaphylactoid reactions have occurred as severe infusion-related effects. 1 If severe infusion-related reactions occur, interrupt the infusion and provide appropriate medications and supportive care as clinically indicated.1 (See Infusion-related Effects under Cautions.)
Adverse hematologic effects (mainly lymphopenia1 but also neutropenia,1 7 16 17 leukopenia,1 7 16 thrombocytopenia,1 7 and anemia1 7 ) may be severe. 1 Cytopenias may persist for an extended duration (i.e., months) following discontinuance of therapy.1
Delayed pulmonary toxicity (e.g., bronchiolitis obliterans [presenting during and up to 6 months following rituximab infusion], pneumonitis [including interstitial pneumonitis]), sometimes fatal, reported.1 44 45 Most common manifestations include dyspnea, fever, and cough.45 48 If interstitial lung disease is suspected, some clinicians recommend discontinuance of rituximab and initiation of corticosteroid (i.e., glucocorticoid) therapy, along with other clinically appropriate measures (e.g., antibiotics).44 45 48 Manufacturer states safety of continuing or reinitiating rituximab in patients experiencing pneumonitis or bronchiolitis obliterans not established.54 Interstitial pneumonitis reportedly recurred in a limited number of patients following rechallenge with rituximab.48
Assess vaccination status prior to initiating rituximab therapy.1
Manufacturer makes no specific recommendations regarding vaccination in patients with NHL receiving rituximab; consult CDC and US Public Health Service Advisory Committee on Immunization Practices (ACIP) guidelines for recommendations on use of vaccines in individuals with altered immunocompetence.51 53
For patients with RA, follow CDC guidelines for adult immunization and administer non-live (e.g., inactivated) vaccines at least 4 weeks prior to a course of rituximab.1 According to some experts, may administer certain vaccines (e.g., influenza virus vaccine) during rituximab therapy when clinically indicated; however, immune responses are submaximal.50
Manufacturer recommends avoiding administration of live viral vaccines prior to or during rituximab therapy;1 however, according to some experts, may administer such vaccines in patients with RA before initiation of rituximab therapy.50 (See Live Viral Vaccines under Interactions.)
Produces rapid and sustained depletion of B cells from the peripheral blood and tissues.1
In patients with NHL, sustained and clinically important reductions in serum IgM and IgG concentrations observed 5–11 months following rituximab therapy; serum IgG and/or IgM decreased to below normal range in 14% of patients.1 In patients with rheumatoid arthritis, serum immunoglobulin concentrations were reduced at 6 months, with greatest change observed in IgM concentrations.1 Clinical importance of decreased immunoglobulin concentrations in patients receiving rituximab for rheumatoid arthritis is uncertain.1
Positive human antichimeric antibody (HACA) responses detected in about 1% of patients with low-grade or follicular NHL and 11% of patients with RA.1 No increase in infusion reactions in HACA-positive rheumatoid arthritis patients retreated with rituximab.1 Clinical importance of HACA formation in patients receiving rituximab is unclear.1
Women of childbearing potential should use effective contraceptive methods during therapy and for at least 12 months following completion of therapy.1
Distributed into milk in monkeys.1 Not known whether rituximab is distributed into human milk.1 IgG is distributed into human milk; however, antibodies in breast milk do not appear to enter neonatal and infant circulations in substantial amounts.1 Weigh unknown risks to infant against known benefits of breastfeeding.1
Safety and efficacy not established.1
Pharmacokinetics not evaluated in pediatric patients.1
Low-grade or follicular NHL: Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1
Diffuse large B-cell NHL: No substantial differences in efficacy relative to younger adults; however, adverse cardiac events (mainly supraventricular arrhythmias) and serious pulmonary events (e.g., pneumonia, pneumonitis) were more common in geriatric patients than in younger adults.1
CLL: No benefit in progression-free survival from addition of rituximab to chemotherapy (fludarabine and cyclophosphamide) among previously treated patients ≥65 years of age or previously untreated patients ≥70 years of age.1 51 Compared with younger patients, patients ≥70 years of age experienced higher incidence of grade 3 or 4 adverse effects, including neutropenia, febrile neutropenia, anemia, and pancytopenia (among patients with previously untreated CLL) and neutropenia, anemia, thrombocytopenia, pancytopenia, and infections (among patients with previously treated CLL).1
RA: Increased rate of serious adverse events, including severe infections, malignancies, and cardiovascular events, in older patients.1
Effects of hepatic impairment on pharmacokinetic disposition of rituximab not formally studied.1
Effects of renal impairment on pharmacokinetic disposition of rituximab not formally studied.1
Common Adverse Effects
Patients with CLL (incidence ≥25%): infusion reactions, neutropenia.1
Interactions for Rituximab
No formal drug interaction studies to date.1
Live Viral Vaccines
Safety and efficacy of live viral vaccines administered following rituximab therapy have not been established;1 manufacturer states use not recommended prior to or during rituximab therapy.1 However, according to some experts, may administer live viral vaccines in patients with RA before initiation of rituximab therapy.50
Disease Modifying Anti-Rheumatic Drugs (DMARDS)
Limited data available on the safety of concomitant use with DMARDs other than methotrexate.1 (See Concomitant Therapy for Rheumatoid Arthritis under Cautions.)
Limited data available on the safety of concomitant use with biologic agents.1 (See Concomitant Therapy for Rheumatoid Arthritis under Cautions.)
CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
Pharmacokinetic disposition of rituximab not altered with concomitant use1
Increased risk of renal toxicity1 (see Renal Effects under Cautions)
Extreme caution should be used if administered concomitantly; monitor patients closely for signs of renal toxicity1
Pharmacokinetic disposition of rituximab not altered with concomitant use1
Systemic exposure to cyclophosphamide not altered with concomitant use1
Systemic exposure to fludarabine not altered with concomitant use1
Pharmacokinetic disposition of rituximab not altered with concomitant use1
Depletion of circulating B cells lasted for up to 6–9 months in 83% of patients with NHL in one study.1 Following completion of rituximab therapy, recovery of B cells begins at approximately 6 months, and median levels of B cells return to normal by 12 months.1
Serum concentrations detectable for 3–6 months following completion of 4-dose course of therapy for NHL.1
Binding of rituximab observed on lymphoid cells in the thymus, the white pulp of the spleen, and most B cells in peripheral blood and lymph nodes.1 Little or no binding observed on nonlymphoid tissues.1
Terminal half-life is approximately 32 days (range: 14–62 days) in patients with CLL.1
Pharmacokinetics not affected by age or gender in patients with non-Hodgkin's lymphoma.1
Pharmacokinetics not affected by age, weight, and gender in patients with rheumatoid arthritis.1
Pharmacokinetics not evaluated in patients with renal or hepatic impairment.1
Following dilution as recommended, store for up to 24 hours at 2–8°C.1
For information on systemic interactions resulting from concomitant use, see Interactions.
No incompatibilities between rituximab and PVC or polyethylene bags have been observed.1
Dextrose 5% in water
Sodium chloride 0.9%
Binds specifically to antigen CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein located on pre-B and mature B lymphocytes.1 3 11 Antigen CD20 is expressed on >90% of B-cell NHL but is not found on hematopoietic stem cells, early pre-B cells, normal plasma cells, or other normal tissues.1 3 11
Produces a rapid and sustained depletion of B cells from the peripheral blood and tissues.1
Inhibits cellular proliferation and induces apoptosis in some NHL cell lines.1 5 Also increases the in vitro sensitivity of certain chemoresistant human lymphoma cell lines to some cytotoxic agents, including doxorubicin.5
Associated with reductions of certain biologic markers of inflammation (including interleukin-6, C-reactive protein, rheumatoid factor) in patients with RA.1
Advice to Patients
Importance of reading the manufacturer's patient information (medication guide) before each infusion.1
Risk of serious and sometimes fatal adverse effects, including cardiac effects, infusion-related effects, mucocutaneous reactions, tumor lysis syndrome, and progressive multifocal leukoencephalopathy.1 42 43 Importance of immediately informing clinician if hives, swelling, dizziness, blurred vision, drowsiness, weakness, feeling faint, headache, cough, shortness of breath, wheezing, or trouble breathing occurs; if severe skin reactions (painful sores, ulcers, blisters, peeling skin, rash, or pustules) occur; if new or worsening medical problems (confusion, trouble thinking, loss of balance, change in walking or talking, decreased strength or weakness on one side of body, or blurred or loss of vision) occur; or if heart problems (chest pain, irregular heart beats) occur.1 42 43
Risk of other potentially serious infections.1 Importance of promptly reporting flu-like symptoms, persistent cough, fever, chills, congestion, tiredness, body aches, earache, headache, pain during urination, white patches in mouth or throat, or cuts/scrapes/incisions that are red, warm, swollen, or painful.1
Importance of promptly reporting abdominal pain.1
Importance of informing clinicians of existing or contemplated therapy, including prescription (e.g., TNF inhibitor, disease modifying anti-rheumatic drug) and OTC drugs, contemplated vaccinations, as well as any concomitant illnesses (e.g., cardiovascular or respiratory disease, current or recurrent infections).1
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
For injection concentrate, for IV infusion
10 mg/mL (100 and 500 mg)
IDEC, (also promoted by Genentech)
AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions September 15, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Biogen Idec/Genentech. Rituxan (rituximab) prescribing information. San Diego/South San Francisco, CA; 2010 Feb.
2. Maloney DG, Grillo-López AJ, White CA et al. IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood. 1997; 90:2188-95. [IDIS 393616] [PubMed 9310469]
3. Maloney DG, Liles TM, Czerwinski DK et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994; 84:2457-66. [IDIS 337031] [PubMed 7522629]
4. Maloney DG, Grillo-López AJ, Bodkin DJ et al. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin’s lymphoma. J Clin Oncol. 1997; 15:3266-74. [IDIS 395156] [PubMed 9336364]
5. Demidem A, Lam T, Alas S et al. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm. 1997; 12:177-86. [PubMed 10851464]
6. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD. From FDA website .
7. McLaughlin P, Grillo-Lopez 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; 16:2825-33. [IDIS 410706] [PubMed 9704735]
8. Czuczman M, Grillo-López AJ, White CA et al. IDEC-C2B8/CHOP chemoimmunotherapy in patients with low-grade lymphoma: clinical and bcl-2 (PCR) final results. Blood. 1996; 88(Suppl 1):453A.
9. Adult non-Hodgkin’s lymphoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2007 Apr 5.
10. US Department of Health and Human Services (HHS). First monoclonal antibody approved to treat cancer. Rockville, MD. 1997 Nov 26. Press release No. P97-39.
11. Genentech, Inc., South San Francisco, CA: Personal communication.
12. Anon. Rituximab for non-Hodgkins lymphoma. Med Lett Drugs Ther. 1998; 40:65-6. [PubMed 9653426]
13. Hellmann SD, Grillo-Lopez AJ. Dear doctor letter regarding important prescribing information on severe infusion-related events and deaths with Rituxan (rituximab). South San Francisco, CA; 1998 Dec 5.
14. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]
15. Hellmann SD, Grint PC. Dear healthcare provider letter regarding important drug warning and updated safety information on severe mucocutaneous reactions and deaths with Rituxan (rituximab). South San Francisco, CA; 2001 May 8.
16. Piro LD, White CA, Grillo-Lopez 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; 10:655-61. [PubMed 10442187]
17. Davis TA, Grillo-Lopez AJ, White CA et al. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin’s lymphoma: safety and efficacy of re-treatment. J Clin Oncol. 2000; 18:3135-43. [IDIS 452754] [PubMed 10963642]
18. Spectrum Pharmaceuticals, Inc. Zevalin (ibritumomab tiuxetan) injection prescribing information. Irvine, CA; 2011 Nov.
19. Barron H, Soo W. Dear healthcare professional letter regarding important drug warning and updated safety information on hepatitis B reactivation with fulminant hepatitis, hepatic failure, and death with Rituxan (rituximab). South San Francisco, CA; 2004 Jul 12.
20. 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; 105:1417-23. [PubMed 15494430]
21. Habermann TM, Weller EA, Morrison VA et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006; 24:3121-7. [PubMed 16754935]
22. Coiffier B, Lepage E, Briere 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; 346:235-42. [PubMed 11807147]
23. Pfreundschuh M, Trumper L, Osterborg A et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006; 7:379-91. [PubMed 16648042]
24. Cohen SB, Emery P, Greenwald MW et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006; 54:2793-806. [PubMed 16947627]
25. Edwards JC, Szczepanski L, Szechinski J et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004; 350:2572-81. [PubMed 15201414]
26. IDEC Pharmaceuticals/Genentech. Rituxan (rituximab) prescribing information. San Diego/South San Francisco, CA; 2004 Jun.
27. Feugier P, Van Hoof A, Sebban C et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005; 23:4117-26. [PubMed 15867204]
28. Friedberg JW. Rituximab for early-stage diffuse large-B-cell lymphoma. Lancet Oncol. 2006; 7:357-9. [PubMed 16648037]
29. Hochster HS, Weller E, Ryan T et al. Results of E1496: a phase III trial of CVP with or without maintenance rituximab in advanced indolent lymphoma (NHL). Proc ASCO. 2004; Abstract No. 6502.
30. Forstpointner R, Unterhalt M, Dreyling M et al. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006; 108:4003-8. [PubMed 16946304]
31. van Oers MH, Klasa R, Marcus RE et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006; 108:3295-301. [PubMed 16873669]
32. Hairy cell leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2005 Nov 21.
33. Arnold DM, Dentali F, Crowther MA et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007; 146:25-33. [PubMed 17200219]
34. Bennett CM, Rogers ZR, Kinnamon DD et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood. 2006; 107:2639-42. [PubMed 16352811]
35. Barron H, Pickett C. Dear healthcare professional letter regarding important drug warning and updated safety information on progressive multifocal encephalopathy in patients receiving Rituxan (rituximab). South San Francisco, CA; 2006 Dec.
36. Ahmed AR, Spigelman Z, Cavacini LA et al. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006; 355:1772-9. [PubMed 17065638]
37. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007; 146:657-65. [PubMed 17470834]
38. Hallek M, Fingerle-Rowson G, Fink AM et al. First-line treatment with fludarabine, cyclophosphamide, and rituximab (FCR) improves overall survival in previously untreated patients with advanced chronic lymphocytic leukemia CLL: Results of a randomized phase III trial on behalf of an international group of investigators and the German CLL group. Proceedings of the 51st Annual Meeting of ASH, New Orleans, LA, 2009 Dec 5–8. Abstract No. 535.
39. Robak T, Dmoszynska A, Solal-Céligny P et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010; 28:1756-65. [PubMed 20194844]
40. Tamary H, Roganovic J, Chitlur M et al. Consensus Paper-ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia. Ann Hematol. 2010; :.
41. Hagerty D. Dear healthcare professional letter regarding important drug warning and updated safety information on progressive multifocal encephalopathy associated with Rituxan (rituximab). South San Francisco, CA; 2009 Oct.
42. FDA public health advisory: Life-threatening brain infection in patients with systemic lupus erythematosus after Rituxan (rituximab) treatment. Rockville, MD; 2006 Dec 18. From FDA web site .
43. Food and Drug Administration. FDA alert for healthcare professionals on rituximab (marketed as Rituxan). From FDA website . Accessed 2007 May 23.
44. Heresi GA, Farver CF, Stoller JK. Interstitial pneumonitis and alveolar hemorrhage complicating use of rituximab: case report and review of the literature. Respiration. 2008; 76:449-53. [PubMed 17596682]
45. Wagner SA, Mehta AC, Laber DA. Rituximab-induced interstitial lung disease. Am J Hematol. 2007; 82:916-9. [PubMed 17597477]
46. Carson KR, Evens AM, Richey EA et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood. 2009; 113:4834-40. [PubMed 19264918]
47. Lowndes S, Darby A, Mead G et al. Stevens-Johnson syndrome after treatment with rituximab. Ann Oncol. 2002; 13:1948-50. [PubMed 12453865]
48. Liu X, Hong XN, Gu YJ et al. Interstitial pneumonitis during rituximab-containing chemotherapy for non-Hodgkin lymphoma. Leuk Lymphoma. 2008; 49:1778-83. [PubMed 18798110]
49. Bingham CO, Looney RJ, Deodhar A et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010; 62:64-74. [PubMed 20039397]
50. Furst DE, Keystone EC, Fleischmann R et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis. 2010; 69 Suppl 1:i2-29. [PubMed 19995740]
51. Genentech, South San Francisco, CA: Personal Communication.
52. Winkler U, Jensen M, Manzke O et al. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood. 1999; 94:2217-24. [PubMed 10498591]
53. Center for Disease Control and Prevention.Recommendations of the Advisory Committee on Immunization Practices (ACIP); use of vaccines and immune globulins in persons with altered immunocompetence. MMWR Morb Mortal Wkly Rep. 1993; 42(No. RR-4):1-18. From CDC website ().
54. Biogen Idec/Genentech. Rituxan (rituximab) prescribing information. San Diego/South San Francisco, CA; 2007 Feb 21.
55. Morschhauser F, Radford J, Van Hoof A et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008; 26:5156-64. [PubMed 18854568]
56. Biogen Idec/Genentech. Rituxan (rituximab) prescribing information. South San Francisco, CA; 2013 Sept.
57. Food and Drug Administration. Drug safety communication: Boxed warning and new recommendations to decrease risk of hepatitis B reactivation with the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and rituxan (rituximab) [2013 Sep 25]. From FDA website.
58. Chew E, Thursky K, Seymour JF. Very late onset hepatitis-B virus reactivation following rituximab despite lamivudine prophylaxis: the need for continued vigilance. Leuk Lymphoma. 2013; :.
59. Oh MJ, Lee HJ. A study of hepatitis B virus reactivation associated with rituximab therapy in real-world clinical practice: a single-center experience. Clin Mol Hepatol. 2013; 19:51-9. [PubMed 23593610]
60. Yang JD, Girotra M, Vaid A et al. Hepatitis B reactivation in patient with non-Hodgkin's lymphoma receiving rituximab-based chemotherapy: need for education and attention. J Ark Med Soc. 2013; 110:110-2. [PubMed 24367885]
61. Artz AS, Somerfield MR, Feld JJ et al. American Society of Clinical Oncology provisional clinical opinion: chronic hepatitis B virus infection screening in patients receiving cytotoxic chemotherapy for treatment of malignant diseases. J Clin Oncol. 2010; 28:3199-202. [PubMed 20516452]
62. European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012; 57:167-85. [PubMed 22436845]
63. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009; 50:661-2. [PubMed 19714720]
64. Dakhil S, Hermann R, Schreeder MT et al. Phase III safety study of rituximab administered as a 90-minute infusion in patients with previously untreated diffuse large B-cell and follicular lymphoma. Leuk Lymphoma. 2014; :. [PubMed 24471908]
65. Gigi E, Georgiou T, Mougiou D et al. Hepatitis B reactivation in a patient with rheumatoid arthritis with antibodies to hepatitis B surface antigen treated with rituximab.Hippokratia. 2013; 17(1):91–3.
66. Yang SH, Kuo SH. Reactivation of hepatitis B virus during rituximab treatment of a patient with follicular lymphoma. Ann Hematol. 2008; 87:325-7. [PubMed 17932671]
67. A study of rituximab alternative dosing rate in patients with previously untreated diffuse large B-cell or follicular non-Hodgkin's lymphoma (RATE). From National Institutes of Health clinical trials website. Accessed 2014 Apr 28.
10001. Rummel MJ, von Gruenhagen U, Niederle N et al. Bendamustine plus rituximab versus CHOP plus rituximab in the first-line treatment of patients with indolent and mantle cell lymphomas: first interim results of a randomized phase III study of the Study Group Indolent Lymphomas, Germany. Proceedings of the 49th Annual Meeting of ASH, Atlanta, GA, 2007 Dec 8-11. Abstract No. 385.
10002. Rummel MJ, Al-Batran SE, Kim SZ, et al. Bendamustine plus rituximab is effective and has a favorable toxicity in the treatment of mantle cell and low-grade non-Hodgkin’s lymphoma. J Clin Oncol. 2005;23:3383-9.
10003. Robinson KS, Williams ME, van der Jagt RH et al. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26:4473-9.
10008. AHFS Oncology Expert Committee reviewer’s comments (personal observations).
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- Other brands: Rituxan