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Rituximab-Arrx

FDA Drug Information • Also known as: Riabni

Brand Names
Riabni
Dosage Form
INJECTION, SOLUTION
Product Type
DRUG FOR FURTHER PROCESSING

⚠ Boxed Warning (Black Box)

WARNING: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY WARNING: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY See full prescribing information for complete boxed warning. Fatal infusion-related reactions within 24 hours of rituximab infusion; approximately 80% of fatal reactions occurred with first infusion. Monitor patients and discontinue RIABNI infusion for severe reactions ( 5.1 ). Severe mucocutaneous reactions, some with fatal outcomes ( 5.2 ). Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death ( 5.3 ). Progressive multifocal leukoencephalopathy (PML) resulting in death ( 5.4 ). Infusion-Related Reactions Administration of rituximab products can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion-related reactions occurred in association with the first infusion. Monitor patients closely. Discontinue RIABNI infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions [see Warnings and Precautions (5.1) , Adverse Reactions (6.1) ] . Severe Mucocutaneous Reactions Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab products [see Warnings and Precautions (5.2) ] . Hepatitis B Virus (HBV) Reactivation HBV reactivation can occur in patients treated with rituximab products, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation and monitor patients during and after treatment with RIABNI. Discontinue RIABNI and concomitant medications in the event of HBV reactivation [see Warnings and Precautions (5.3) ] . Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving rituximab products [see Warnings and Precautions (5.4) and Adverse Reactions (6.1) ] .

Description

11 DESCRIPTION Rituximab-arrx is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. Rituximab-arrx has an approximate molecular weight of 145 kD. Rituximab-arrx is produced in a mammalian cell (Chinese Hamster Ovary) suspension culture in a nutrient medium. RIABNI (rituximab-arrx) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for intravenous infusion. RIABNI is supplied at a concentration of 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-dose vials. Each mL of solution contains 10 mg rituximab-arrx, polysorbate 80 (0.7 mg), sodium chloride (9 mg), sodium citrate dihydrate (7.35 mg), and Water for Injection, USP. Hydrochloric acid is used to adjust the buffer solution pH. The pH is 6.5.

What Is Rituximab-Arrx Used For?

1 INDICATIONS AND USAGE RIABNI is a CD20-directed cytolytic antibody indicated for the treatment of: Adult patients with Non-Hodgkin's Lymphoma (NHL) ( 1.1 ). 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 first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy. Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other anthracycline-based chemotherapy regimens. Adult patients with Chronic Lymphocytic Leukemia (CLL) ( 1.2 ). Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC). Rheumatoid Arthritis (RA) in combination with methotrexate in adult patients with moderately- to-severely- active RA who have inadequate response to one or more TNF antagonist therapies ( 1.3 ). Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) in adult patients in combination with glucocorticoids ( 1.4 ). Moderate to severe Pemphigus Vulgaris (PV) in adult patients ( 1.5 ). 1.1 Non-Hodgkin's Lymphoma (NHL) RIABNI is indicated for the treatment of adult 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 first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy. Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens. 1.2 Chronic Lymphocytic Leukemia (CLL) RIABNI, in combination with fludarabine and cyclophosphamide (FC), is indicated for the treatment of adult patients with previously untreated and previously treated CD20-positive CLL. 1.3 Rheumatoid Arthritis (RA) RIABNI, in combination with methotrexate, is indicated for the treatment of adult patients with moderately- to-severely- active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies. 1.4 Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) RIABNI, in combination with glucocorticoids, is indicated for the treatment of adult...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Administer only as an intravenous infusion ( 2.1 ). Do not administer as an intravenous push or bolus ( 2.1 ). RIABNI should only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur ( 2.1 ). The dose for adult B-cell NHL is 375 mg/m 2 ( 2.2 ). The dose for CLL is 375 mg/m 2 in the first cycle and 500 mg/m 2 in cycles 2–6, in combination with FC, administered every 28 days ( 2.3 ). The dose as a component of Zevalin ® (ibritumomab tiuxetan) Therapeutic Regimen is 250 mg/m 2 ( 2.4 ). The dose for RA in combination with methotrexate is two-1,000 mg intravenous infusions separated by 2 weeks (one course) every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion ( 2.5 ). The induction dose for adult patients with active GPA and MPA in combination with glucocorticoids is 375 mg/m 2 once weekly for 4 weeks. The follow up dose for adult patients with GPA and MPA who have achieved disease control with induction treatment, in combination with glucocorticoids is two 500 mg intravenous infusions separated by two weeks, followed by a 500 mg intravenous infusion every 6 months thereafter based on clinical evaluation ( 2.6 ). The dose for PV is two-1,000 mg intravenous infusions separated by 2 weeks in combination with a tapering course of glucocorticoids, then a 500 mg intravenous infusion at Month 12 and every 6 months thereafter or based on clinical evaluation. Dose upon relapse is a 1,000 mg intravenous infusion with considerations to resume or increase the glucocorticoid dose based on clinical evaluation. Subsequent infusions may be no sooner than 16 weeks after the previous infusion ( 2.7 ). Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion ( 2.8 ). 2.1 Important Dosing Information Administer only as an intravenous infusion [see Dosage and Administration (2.8) ] . Do not administer as an intravenous push or bolus. RIABNI should only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur [see Warnings and Precautions (5.1) ]. Premedicate before each infusion [see Dosage and Administration (2.8) ] . Prior to First Infusion Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with RIABNI [see Warnings and Precautions (5.3) ] . Obtain complete blood counts (CBC) including platelets prior to the first dose. During RIABNI Therapy In patients with lymphoid malignancies during treatment with RIABNI monotherapy, obtain complete blood counts (CBC) with differential and platelet counts prior to each RIABNI course. During treatment with RIABNI and chemotherapy, obtain CBC with differential and...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Infusion-related reactions [see Warnings and Precautions (5.1) ] Severe mucocutaneous reactions [see Warnings and Precautions (5.2) ] Hepatitis B reactivation with fulminant hepatitis [see Warnings and Precautions (5.3) ] Progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.4) ] Tumor lysis syndrome [see Warnings and Precautions (5.5) ] Infections [see Warnings and Precautions (5.6) ] Cardiovascular adverse reactions [see Warnings and Precautions (5.7) ] Renal toxicity [see Warnings and Precautions (5.8) ] Bowel obstruction and perforation [see Warnings and Precautions (5.9) ] Most common adverse reactions in clinical trials were: NHL (greater than or equal to 25%): infusion-related reactions, fever, lymphopenia, chills, infection, and asthenia ( 6.1 ). CLL (greater than or equal to 25%): infusion-related reactions and neutropenia ( 6.1 ). RA (greater than or equal to 10%): upper respiratory tract infection, nasopharyngitis, urinary tract infection, and bronchitis (other important adverse reactions include infusion-related reactions, serious infections, and cardiovascular events) ( 6.1 ). GPA and MPA (greater than or equal to 15%): infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema, infusion-related reactions ( 6.1 ). PV (greater than or equal to 15%): infusion-related reactions, depression, upper respiratory tract infection/ nasopharyngitis, headache (other important adverse reactions include infections) ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Amgen, Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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 clinical practice. B-Cell Malignancies The data described below reflect exposure to rituximab in 3,092 patients, with exposures ranging from a single infusion up to 2 years. Rituximab was studied in both single-arm and controlled trials (n = 356 and n = 2,427). The population included 1,180 patients with low grade or follicular lymphoma, 927 patients with DLBCL, 676 patients with CLL, and 309 patients with another indication. Most NHL patients received rituximab as an infusion of 375 mg/m 2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses. CLL patients received rituximab 375 mg/m 2 as an initial infusion followed by 500 mg/m 2 for up to 5 doses, in combination with fludarabine and cyclophosphamide. Seventy-one percent of CLL patients received 6 cycles and 90% received at least 3 cycles of rituximab-based therapy. The most common adverse reactions of rituximab (incidence greater than or equal to 25%) observed in clinical trials of patients with NHL were infusion-related reactions, fever, lymphopenia, chills, infection, and asthenia. The most common adverse reactions of rituximab (incidence greater than or equal to 25%) observed in clinical trials of patients with CLL were: infusion-related reactions and neutropenia. Infusion-Related Reactions In the majority of patients with NHL, infusion-related reactions consisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first rituximab infusion. Infusion-related reactions typically occurred within 30 to 120 minutes of beginning the first infusion and resolved with slowing or interruption of the rituximab infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous saline). The incidence of...

Drug Interactions

7 DRUG INTERACTIONS Formal drug interaction studies have not been performed with rituximab products. In patients with CLL, rituximab did not alter systemic exposure to fludarabine or cyclophosphamide. In clinical trials of patients with RA, concomitant administration of methotrexate or cyclophosphamide did not alter the pharmacokinetics of rituximab. Renal toxicity when used in combination with cisplatin ( 5.8 ).

Contraindications

4 CONTRAINDICATIONS None. None ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on human data, rituximab products can cause adverse developmental outcomes including B-cell lymphocytopenia in infants exposed in utero ( see Clinical Considerations ). In animal reproduction studies, intravenous administration of rituximab to pregnant cynomolgus monkeys during the period of organogenesis caused lymphoid B-cell depletion in the newborn offspring at doses resulting in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans. Advise pregnant women of the risk to a fetus. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk of major birth defects and miscarriage for the indicated populations is unknown. The estimated background risk in the U.S. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies. Clinical Considerations Fetal/Neonatal Adverse Reactions Observe newborns and infants for signs of infection and manage accordingly. Data Human Data Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than 6 months can occur in infants exposed to rituximab in utero . Rituximab was detected postnatally in the serum of infants exposed in utero . Animal Data An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received rituximab via the intravenous route during early gestation (organogenesis period; post coitum Days 20 through 50). Rituximab was administered as loading doses on post coitum (PC) Days 20, 21 and 22, at 15, 37.5 or 75 mg/kg/day, and then weekly on PC Days 29, 36, 43 and 50, at 20, 50 or 100 mg/kg/week. The 100 mg/kg/week dose resulted in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans. Rituximab crosses the monkey placenta. Exposed offspring did not exhibit any teratogenic effects but did have decreased lymphoid tissue B cells....

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING RIABNI (rituximab-arrx) injection is a sterile, clear to slightly opalescent, colorless to slightly yellow preservative free solution for intravenous use supplied as a carton containing one 100 mg/10 mL (10 mg/mL) single dose vial (NDC 55513-224-01, 55513-224-21) and a carton containing one 500 mg/50 mL (10 mg/mL) single dose vial (NDC 55513-326-01, 55513-326-21). Store RIABNI vials refrigerated at 2°C to 8°C (36°F to 46°F). Protect RIABNI vials from direct sunlight. Do not freeze or shake.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.