of Grade 3 and 4 infections Neoplasia: Disease progression of Kaposi sarcoma Skin: Severe mucocutaneous reactions, pyoderma gangrenosum (including genital presentation) Gastrointestinal: Bowel obstruction and perforation Pulmonary: Fatal bronchiolitis obliterans and fatal interstitial lung disease Nervous system: Posterior reversible encephalopathy syndrome (PRES)/reversible posterior leukoencephalopathy syndrome (RPLS) Black Box Warnings Fatal infusion reaction Can result in serious, including fatal reactions Deaths within 24 hr of infusion have occurred Approximately 80% of fatal infusion reactions occurred in association with the first infusion Carefully monitor patients during infusion In patients with NHL receiving rituximab monotherapy, grade 3 and 4 cytopenias reported; reactions included lymphopenia, neutropenia, leukopenia, anemia, and thrombocytopenia; discontinue infusion and provide medical treatment for grade 3 or 4 reactions Severe mucocutaneous reactions Severe, including fatal, mucocutaneous reactions reported including paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis Progressive multifocal leukoencephalopathy John Cunningham virus infection resulting in progressive multifocal leukoencephalopathy and death has been reported in patients treated with rituximab Hepatitis B virus reactivation Reactivation of hepatitis B virus (HBV) infection reported, including deaths Screen all patients for HBV infection before initiating drug by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) Consult with hepatitis experts regarding monitoring and use of HBV antiviral therapy when screening identifies patients at risk of HBV reactivation due to evidence of prior HBV infection Monitor patients with evidence of prior HBV infection for clinical and laboratory signs of hepatitis B or HBV reactivation during therapy and for several months thereafter, since reactivations have occurred several months following completion of therapy In patients who develop reactivation of HBV, immediately discontinue drug and start appropriate HBV treatment, also discontinue any chemotherapy until the HBV infection is controlled or resolved Because of insufficient data, no recommendation can be made regarding the resumption of the drug in patients who develop HBV reactivation Contraindications None Cautions Severe, including fatal, infusion-related reactions may occur; severe reactions typically occurred during the first infusion with time to onset of 30-120 minutes; premedicate as recommended according to indication; have appropriate medical management available if reaction occurs (eg, glucocorticoids, epinephrine, bronchodilators, oxygen) (see Black Box Warnings and Administration); methylprednisolone 100 mg intravenously or its equivalent recommended 30 min prior to each infusion Risk of potentially fatal mucocutaneous reactions (see Black Box Warnings) Increased risk of potentially fatal hepatitis B virus reactivation (see Black Box Warnings) Potential risk of progressive multifocal leukoencephalopathy (see Black Box Warnings) Risk of potentially fatal tumor lysis syndrome Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of therapy; not recommended for patients with severe, active infections Cardiac adverse reactions (eg, ventricular fibrillation, myocardial infarction, cardiogenic shock) may occur; discontinue infusions for serious or life-threatening cardiac arrhythmias; cardiac monitoring needed during and after all infusions patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina Severe, including fatal, renal toxicity can occur after administration in patients with NHL; renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials; the combination of cisplatin and rituximab is not an approved treatment regimen Abdominal pain, bowel obstruction and perforation reported, including cases leading to death Based on human data, rituximab can cause fetal harm owing to B-cell lymphocytopenia in infants exposed in utero (see Pregnancy) A favorable risk-benefit relationship has not been established in in patients with RA with prior inadequate responses to nonbiologic DMARDs; use in these patients is not recommended Hypogammaglobulinemia has been observed in pediatric patients treated with rituximab Majority of patients with hematologic malignancies diagnosed with PML received rituximab in combination with chemotherapy or as part of a hematopoietic stem cell transplant; patients with autoimmune diseases had prior or concurrent immunosuppressive therapy; most cases of PML were diagnosed within 12 months of their last infusion of rituximab Drug interaction overview Safety of immunization with live viral vaccines following rituximab has not been studied and vaccination with live virus vaccines is not recommended before or during treatment; for patients with RA, follow current immunization guidelines and administer non-live vaccines at least 4 weeks before treatment Limited data are available on the safety of the use of biologic agents or disease modifying antirheumatic drugs (DMARDs) other than methotrexate in RA patients exhibiting peripheral B-cell depletion following treatment; observe closely for signs of infection if biologic agents and/or DMARDs are used concomitantly Pregnancy Verify pregnancy status in females of reproductive potential prior to initiating therapy Based on human data, can cause adverse developmental outcomes including B-cell lymphocytopenia in infants exposed to rituximab in-utero Observe newborns and infants for signs of infection and manage accordingly Animal data IV administration to pregnant cynomolgus monkeys during organogenesis caused lymphoid B-cell depletion in newborn offspring at doses resulting in 80% of exposure (based on AUC) of those achieved following a 2 gram-dose in humans Advise pregnant females of the risk to a fetus Contraception Females of childbearing potential: Use effective contraception during and for 12 months following treatment Lactation Data unavailable on drug presence in human milk, effects on breastfed children, or effects on milk production Detected in the milk of lactating cynomolgus monkeys, and IgG is present in human milk Rituximab reported to be excreted at low concentrations in human breast milk; given that clinical significance of this finding for children is not known, advise women not to breastfeed during treatment and for 6 months after last dose due to potential of serious adverse reactions in breastfed childrenPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against CD20 antigen Absorption Peak plasma concentration (RA): 157 mcg/mL (first infusion); 183 mcg/mL (second infusion); 318 mcg/mL (2 x 500 mg); 381 mcg/mL (2 x 1000 mg) Distribution Vd: 3.1 L (RA); 4.5 L (GPA and MPA) Elimination Clearance: 0.335 L/day (RA); 0.312 L/day (GPA and MPA) Half-life RA: 18 days NHL: 22 days CLL: 32 days GPA and MPA: 23 days IV Compatibilities 0.9% NaCl D5W IV Preparation Withdraw necessary amount of rituximab and dilute to a final concentration of 1-4 mg/mL into an infusion bag containing either 0.9% NaCl or D5W Visually inspect vials, solution should appear clear and colorless, do not use vial if particular is present Gently invert the bag to mix the solution Do not mix with other drugs Discard any unused portion left in the vial Premedication Before each infusion: Premedicate with acetaminophen and an antihistamine; add glucocorticoid as per the following recommendations Rapid 90-min infusion: Administer glucocorticoid component of the chemotherapy regimen before infusion RA, GPA, MPA, PV: Methylprednisolone 100 mg IV (or equivalent) 30 minutes before each infusion PCP and herpes virus prophylaxis Consider antiviral prophylaxis to prevent hepatitis B reactivation for all patients receiving rituximab (oncology and non-oncology indications) with resolved hepatitis B virus infection PCP prophylaxis CLL: During and for up to 12 months following treatment as appropriate GPA and MPA: During and for up to 6 months following final infusion PV: Consider during and following treatment IV Administration Administer IV infusion only; do not give IV push or bolus First infusion Initiate infusion rate at 50 mg/hr; if no infusion reaction, increase infusion rate by 50 mg/hr increments q30min, to a maximum of 400 mg/hr Subsequent infusions Standard infusions Initiate infusion rate at 100 mg/hr; if no infusion reaction, increase rate by 100 mg/hr increments at q30min, to a maximum of 400 mg/hr Pediatric patients with mature B-cell NHL/B-AL Initiate infusion at 0.5 mg/kg/hr (up to 50 mg/hr); if no infusion reaction, increase infusion rate by 0.5 mg/kg/hr q30min, up to 400 mg/hr Patients with previously untreated follicular NHL and DLBCL No Grade 3 or 4 infusion-related events during Cycle 1: Infuse over 90 min during Cycle 2 with a glucocorticoid-containing chemotherapy regimen Do NOT administer 90-min infusions to patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count ≥5,000/mm3 before Cycle 2 Initiate rate of 20% of total dose given in the first 30 min and remaining 80% given over the next 60 min If 90-min infusion tolerated in Cycle 2, administer the same rate for remaining treatment cycles (through Cycle 6 or 8) Interrupt infusion or slow infusion rate for IRR; once symptoms improve, continue infusion at one-half the previous rate Pediatric patients with mature B-cell NHL/B-AL Infuse at 1 mg/kg/hr (up to 50 mg/hr); if no infusion reaction occurs, increase rate by 1 mg/kg/hr q30min, up to 400 mg/hr Interrupt or slow infusion rate for infusion-related reactions; once symptoms improve, continue infusion at one-half the previous rate Storage IV Unused vials: Refrigerate at 2-8°C (36-46°F); protect vials from direct sunlight Diluted solutions: Store at 2-8°C (36-46°F) for 24 hr; shown also be stable for additional 24 hr at room temperature BRAND FORM. UNIT PRICE PILL IMAGE Rituxan intravenous- 10 mg/mL vialRituxan intravenous- 10 mg/mL vialCopyright © 2010 First DataBank, Inc.Print Patient Educationrituximab intravenous RITUXIMAB - INJECTION (ri-TUX-i-mab) COMMON BRAND NAME(S): Riabni, Rituxan, Ruxience, Truxima WARNING: Rituximab may rarely cause serious (sometimes fatal) side effects including severe breathing problems or heart problems (such as heart attack, irregular heartbeat). If these serious side effects occur, they usually happen during the first treatment with rituximab. Your doctor will carefully watch you during treatment and may stop or slow down your treatment if you have any signs of a reaction. Get medical help right away if you have trouble breathing, itching, swelling (especially of the throat/lips), dizziness, fast/slow/irregular heartbeat, or chest pain.Rarely, people using this medication have had serious (sometimes fatal) skin reactions (such as Stevens-Johnson syndrome). Get medical help right away if you develop any rash, blisters, peeling skin, or sores on your skin, lips, or in your mouth.This medication may increase your risk of getting a rare but very serious (possibly fatal) brain infection (progressive multifocal leukoencephalopathy-PML). Get medical help right away if you have any of these side effects: clumsiness, loss of coordination/balance, weakness, sudden change in your thinking (such as confusion, difficulty concentrating, memory loss), difficulty talking/walking, seizure, vision changes.Rituximab may cause serious (possibly fatal) liver disease in people who have a current or past infection with hepatitis B. This may occur during treatment or up to 2 years after treatment is finished. Before starting this medication, tell your doctor if you have ever had hepatitis B. Your doctor should order a test to see if you have the hepatitis B infection before starting treatment. Tell your doctor right away if you have symptoms of liver disease, such as nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, or dark urine. USES: Rituximab is used to treat certain types of cancer (such as non-Hodgkin's lymphoma, chronic lymphocytic leukemia). It works by slowing or stopping the growth of cancer cells.Some brands of rituximab are also used to treat rheumatoid arthritis and can decrease joint pain and swelling. This drug is also used to treat certain types of blood vessel disease (such as granulomatosis with polyangiitis, microscopic polyangiitis) and can decrease the swelling of the blood vessels. Rituximab is also used to treat a certain skin condition (pemphigus vulgaris). It helps to reduce the number of skin lesions.This monograph is about the following rituximab products: rituximab, rituximab-abbs, rituximab-arrx, and rituximab-pvvr. HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using rituximab and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Your doctor should prescribe other medications (such as acetaminophen, an antihistamine, methylprednisolone) for you to take before each treatment to help reduce side effects, such as fever and chills. Carefully follow your doctor's instructions.This medication is given