RUXIENCE (rituximab-pvvr) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale brownish-yellow solution for intravenous infusion supplied as a carton containing one 100 mg/10 mL (10 mg/mL) single-dose vial (NDC 0069-0238-01) or a carton containing one 500 mg/50 mL (10 mg/mL) single-dose vial (NDC 0069-0249-01). Store RUXIENCE vials refrigerated at 2�C to 8�C (36�F to 46�F) in the original carton. RUXIENCE vials should be protected from direct sunlight. Do not freeze or shake. HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use RUXIENCE safely and effectively. See full prescribing information for RUXIENCE. RUXIENCETM (rituximab-pvvr) injection, for intravenous use Initial U.S. Approval: 2019 RUXIENCE (rituximab-pvvr) is biosimilar* to RITUXAN (rituximab). WARNING: FATAL INFUSION-RELATED REACTIONS, SEVEREMUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHYSee 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 RUXIENCE infusion for severe reactions (5.1, 6.1). ?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, 6.2). --------------------------- INDICATIONS AND USAGE---------------------------- RUXIENCE (rituximab-pvvr) 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. ?Chronic Lymphocytic Leukemia (CLL) (1.2). ?Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC). ?Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) in adult patients in combination with glucocorticoids (1.3). ----------------------- DOSAGE AND ADMINISTRATION ----------------------- ?Administer only as an intravenous infusion (2.1). ?Do not administer as an intravenous push or bolus (2.1). ?RUXIENCE 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 NHL is 375 mg/m2 (2.2). ?The dose for CLL is 375 mg/m2 in the first cycle and 500 mg/m2 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/m2 (2.4). ?The induction dose for patients with active GPA and MPA in combination with glucocorticoids is 375 mg/m2 once weekly for 4 weeks. The follow up dose for 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 (2.5). --------------------- DOSAGE FORMS AND STRENGTHS --------------------- ?Injection: 100 mg/10 mL (10 mg/mL) and 500 mg/50 mL (10 mg/mL) solution in single-dose vials (3). ------------------------------ CONTRAINDICATIONS ------------------------------ None (4). ----------------------- WARNINGS AND PRECAUTIONS ----------------------- ?Tumor lysis syndrome: Administer aggressive intravenous hydration, anti-hyperuricemic agents, monitor renal function (5.5). ?Infections: Withhold RUXIENCE and institute appropriate anti-infective therapy (5.6). ?Cardiac adverse reactions: Discontinue infusions in case of serious or life- threatening events (5.7). ?Renal toxicity: Discontinue in patients with rising serum creatinine or oliguria (5.8). ?Bowel obstruction and perforation: Consider and evaluate for abdominal pain, vomiting, or related symptoms (5.9). ?Immunizations: Live virus vaccinations prior to or during RUXIENCE treatment not recommended (5.10). ?Embryo-Fetal toxicity: Can cause neonatal harm. Advise of potential risk to neonates and use of effective contraception (5.11). ------------------------------ ADVERSE REACTIONS ------------------------------ Most common adverse reactions in clinical trials were: ?NHL (?25%): infusion-related reactions, fever, lymphopenia, chills, infection and asthenia (6.1). ?CLL (?25%): infusion-related reactions and neutropenia (6.1). ?GPA and MPA (?15%): infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema (other important adverse reactions include infusion-related reactions) (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. ------------------------------ DRUG INTERACTIONS------------------------------- Renal toxicity when used in combination with cisplatin (5.8). ----------------------- USE IN SPECIFIC POPULATIONS ----------------------- ?Lactation: Advise not to breastfeed (8.2). ?Geriatric Use: In CLL patients older than 70 years of age, exploratory analyses suggest no benefit with the addition of rituximab to FC (8.5). See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of RUXIENCE has been demonstrated for the condition(s) of use (e.g. indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information. Revised: 7/2019
