Rituxan (Injection, Solution)

dailymed-instance:drugs, http://www4.wiwiss.fu-berlin.de/drugbank/vocab/resource/class/Offer

Relapsed or Refractory, Low-Grade or Follicular, CD20���Positive, B���Cell Non-Hodgkin's Lymphoma: The recommended dose of Rituxan is 375 mg/mIV infusion once weekly for 4 or 8 doses.<br/>Retreatment Therapy: The recommended dose of Rituxan is 375 mg/mIV infusion once weekly for 4 doses in responding patients who develop progressive disease after previous Rituxan therapy. Currently there are limited data concerning more than 2 courses.<br/>Previously Untreated, Follicular, CD20���Positive, B���cell NHL: The recommended dose of Rituxan is 375 mg/mIV infusion, given on Day 1 of each cycle of CVP chemotherapy, for up to 8 doses.<br/>Previously Untreated, Low-Grade, CD20���Positive, B���cell NHL: The recommended dose of Rituxan in patients who have not progressed following 6���8 cycles of CVP chemotherapy is 375 mg/mIV infusion, once weekly for 4 doses every 6 months for up to 16 doses.<br/>Diffuse Large B���Cell NHL: The recommended dose of Rituxan is 375 mg/mIV per infusion given on Day 1 of each cycle of chemotherapy for up to 8 infusions.<br/>Rheumatoid Arthritis: Rituxan is given as two-1000 mg IV infusions separated by 2 weeks. Glucocorticoids administered as methylprednisolone 100 mg IV or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion reactions. Safety and efficacy of retreatment have not been established in controlled trials (see PRECAUTIONS: Retreatment in patients with RA). Rituxan is given in combination with methotrexate.<br/>Rituxan as a Component of Zevalin' (Ibritumomab tiuxetan) Therapeutic Regimen: As a required component of the Zevalin therapeutic regimen, Rituxan 250 mg/mshould be infused within 4 hours prior to the administration of Indium���111���(In���111���) Zevalin and within 4 hours prior to the administration of Yttrium���90���(Y���90���) Zevalin. Administration of Rituxan and In���111���Zevalin should precede Rituxan and Y���90-Zevalin by 7���9 days. Refer to the Zevalin package insert for full prescribing information regarding the Zevalin therapeutic regimen. Rituxan may be administered in an outpatient setting. DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS. (SeeAdministration).<br/>Instructions for Administration:<br/>Preparation for Administration: Use appropriate aseptic technique. 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. Discard any unused portion left in the vial. Parenteraldrug products should be inspected visually for particulate matter and discoloration prior to administration. 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.<br/>Administration: DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS Infusion reactions may occur (see BOXED WARNINGS,WARNINGS, andADVERSE REACTIONS). Premedication consisting of acetaminophen and an antihistamine should be considered before each infusion of Rituxan. Premedication may attenuate infusion reactions. Since transient hypotension may occur during Rituxan infusion, consideration should be given to withholding antihypertensive medications 12 hours prior to Rituxan infusion.<br/>First Infusion: The Rituxan solution for infusion should be administered intravenously at an initial rate of 50 mg/hr. Rituxan should not be mixed or diluted with other drugs. If infusion reactions do not occur, escalate the infusion rate in 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr. If an infusion reaction develops, the infusion should be temporarily slowed or interrupted (seeBOXED WARNINGS and WARNINGS). The infusion can continue at one-half the previous rate upon improvement of patient symptoms.<br/>Subsequent Infusions: If the patient tolerated the first infusion well, subsequent Rituxan infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30���minute intervals, to a maximum of 400 mg/hr as tolerated. If the patient did not tolerate the first infusion well, follow the guidelines under First Infusion.<br/>Stability and Storage: 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. Refer to the "Preparation for Administration" section for information on the stability and storage of solutions of Rituxan diluted for infusion.

General: Rituximab binds specifically to the antigen CD20 (human B���lymphocyte���restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein with a molecular weight of approximately 35 kD located on pre���B and mature B lymphocytes. 1, 2 The antigen is also expressed on>90% of B���cell non���Hodgkin's lymphomas (NHL), 3 but is not found on hematopoietic stem cells, pro���B���cells, normal plasma cells or other normal tissues. 4 CD20 regulates an early step(s) in the activation process for cell cycle initiation and differentiation, 4 and possibly functions as a calcium ion channel. 5 CD20 is not shed from the cell surface and does not internalize upon antibody binding.6 Free CD20 antigen is not found in the circulation. 2 B���cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B���cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T cell activation, and/or pro���inflammatory cytokine production. 7<br/>Preclinical Pharmacology and Toxicology: Mechanism of Action: The Fab domain of Rituximab binds to the CD20 antigen on B lymphocytes, and the Fc domain recruits immune effector functions to mediate B���cell lysis in vitro. Possible mechanisms of cell lysis include complement���dependent cytotoxicity (CDC) 8 and antibody-dependent cell mediated cytotoxicity (ADCC). The antibody has been shown to induce apoptosis in the DHL���4 human B���cell lymphoma line. 9 Normal Tissue Cross-reactivity: Rituximab binding was observed on lymphoid cells in the thymus, the white pulp of the spleen, and a majority of B lymphocytes in peripheral blood and lymph nodes. Little or no binding was observed in the non-lymphoid tissues examined.<br/>Pharmacokinetics: In patients with NHL given single doses at 10, 50, 100, 250 or 500 mg/mas an IV infusion, serum levels and the half-life of Rituximab were proportional to dose. 10 In 14 patients given 375 mg/mas an IV infusion for 4 weekly doses, the mean serum half-life was 76.3 hours (range, 31.5 to 152.6 hours) after the first infusion and 205.8 hours (range, 83.9 to 407.0 hours); after the fourth infusion. 11, 12, 13 The wide range of half-lives may reflect the variable tumor burden among patients and the changes in CD20���positive (normal and malignant) B���cell populations upon repeated administrations. Rituxan at a dose of 375 mg/mwas administered as an IV infusion at weekly intervals for 4 doses to 203 patients with NHL naive to Rituxan. 13, 14 The mean Cfollowing the fourth infusion was 486��g/mL (range, 77.5 to 996.6��g/mL). The peak and trough serum levels of Rituximab were inversely correlated with baseline values for the number of circulating CD20���positive B���cells and measures of disease burden. Median steady-state serum levels were higher for responders compared with nonresponders; however, no difference was found in the rate of elimination as measured by serum half-life. Serum levels were higher in patients with International Working Formulation (IWF) subtypes B, C, and D as compared with those with subtype A. 11, 14 Rituximab was detectable in the serum of patients 3 to 6 months after completion of treatment. Rituxan at a dose of 375 mg/mwas administered as an IV infusion at weekly intervals for 8 doses to 37 patients with NHL. 15 The mean Cafter 8 infusions was 550��g/mL (range, 171���1177��g/mL). The mean Cincreased with each successive infusion through the eighth infusion (Table 1). The pharmacokinetic profile of Rituxan when administered as 6 infusions of 375 mg/min combination with 6 cycles of CHOP chemotherapy was similar to that seen with Rituxan alone. 16 Following the administration of 2 doses of Rituximab in patients with rheumatoid arthritis, the mean Cvalues were 183 mcg/mL (CV=24%) for the 2��500 mg dose and 370 mcg/mL (CV=25%) for the 2��1000 mg dose, respectively. Following 2��1000 mg Rituximab dose, mean volume of distribution at steady state was 4.3 L (CV=28%). Mean systemic serum clearance of Rituximab was 0.01 L/h (CV=38%), and mean terminal elimination half���life after the second dose was 19 days (CV=32%).<br/>Special Populations: Gender: The female patients with RA (n=86) had a 37% lower clearance of Rituximab than male patients with RA (n=25). The gender difference in Rituximab clearance does not necessitate any dose adjustment because safety and efficacy of Rituximab do not appear to be influenced by gender. The pharmacokinetics of Rituximab have not been studied in children and adolescents. No formal studies were conducted to examine the effects of either renal or hepatic impairment on the pharmacokinetics of Rituximab.<br/>Pharmacodynamics: Administration of Rituxan resulted in a rapid and sustained depletion of circulating and tissue���based B���cells. Lymph node biopsies performed 14 days after therapy showed a decrease in the percentage of B���cells in seven of eight patients with NHL who had received single doses of Rituximab���100 mg/m.10 Among the 166 patients in the pivotal NHL study, circulating B���cells (measured as CD19���positive cells) were depleted within the first three doses with sustained depletion for up to 6 to 9 months post-treatment in 83% of patients. 14 Of the responding patients assessed (n = 80), 1% failed to show significant depletion of CD19���positive cells after the third infusion of Rituximab as compared to 19% of the nonresponding patients. B���cell recovery began at approximately 6 months following completion of treatment. Median B���cell levels returned to normal by 12 months following completion of treatment. 14 There were sustained and statistically significant reductions in both IgM and IgG serum levels observed from 5 through 11 months following Rituximab administration. However, only 14% of patients had reductions in IgM and/or IgG serum levels, resulting in values below the normal range.14 In RA patients, treatment with Rituxan induced depletion of peripheral B lymphocytes, with all patients demonstrating near complete depletion within 2 weeks after receiving the first dose of Rituxan. The majority of patients showed peripheral B���cell depletion for at least 6 months, followed by subsequent gradual recovery after that timepoint. A small proportion of patients (4%) had prolonged peripheral B���cell depletion lasting more than 3 years after a single course of treatment. In RA studies, total serum immunoglobulin levels, IgM, IgG, and IgA were reduced at 6 months with the greatest change observed in IgM. However, mean immunoglobulin levels remained within normal levels over the 24���week period. Small proportions of patients experienced decreases in IgM (7%), IgG (2%), and IgA (1%) levels below the lower limit of normal. The clinical consequences of decreases in immunoglobulin levels in RA patients treated with Rituxan are unclear. Treatment with Rituximab in patients with RA was associated with reduction of certain biologic markers of inflammation such as interleukin-6 (IL 6), C���reactive protein (CRP), serum amyloid protein (SAA), S100 A8/S100 A9 heterodimer complex (S100 A8/9), anti���citrullinated peptide (anti���CCP) and RF.

None.

http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00073

dailymed-ingredient:rituximab

diseasome-diseases:1173, diseasome-diseases:1693, diseasome-diseases:1694, diseasome-diseases:1696, diseasome-diseases:181, diseasome-diseases:2789, diseasome-diseases:3004, diseasome-diseases:3020, diseasome-diseases:3365, diseasome-diseases:4136, diseasome-diseases:602, diseasome-diseases:698, diseasome-diseases:701, diseasome-diseases:833

rituximab

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. The following serious adverse reactions, some with fatal outcomes, have been reported in patients treated with Rituxan : severe or fatal infusion reactions, tumor lysis syndrome, severe mucocutaneous reactions, hepatitis B reactivation with fulminant hepatitis, progressive multifocal leukoencephalopathy (PML), other viral infections, cardiac arrhythmias, renal toxicity, bowel obstruction and perforation.

Non���Hodgkin's Lymphoma: Rituxan (Rituximab) is indicated for the treatment of patients with relapsed or refractory, low���grade or follicular, CD20���positive, B���cell, non���Hodgkin's lymphoma. Rituxan (Rituximab) is indicated for the first���line treatment of follicular, CD20���positive, B���cell non���Hodgkin's lymphoma in combination with CVP chemotherapy. Rituxan (Rituximab) is indicated for the treatment of low���grade, CD20���positive, B���cell non���Hodgkin's lymphoma in patients with stable disease or who achieve a partial or complete response following first���line treatment with CVP chemotherapy. Rituxan (Rituximab) is indicated for the first���line treatment of diffuse large B���cell, CD20���positive, non���Hodgkin's lymphoma in combination with CHOP or other anthracycline���based chemotherapy regimens.<br/>Rheumatoid Arthritis: Rituxan (Rituximab) in combination with methotrexate is indicated to reduce signs and symptoms in adult patients with moderately- to severely- active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Rituxan