RUXIENCE is a CD20-directed cytolytic antibody indicated for the treatment of:

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Adult patients with Non-Hodgkin's Lymphoma (NHL) (1.1).

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Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent.

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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.

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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.

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Previously untreated diffuse large B-cell, CD20-positive NHL in combination with (cyclophosphamide, doxorubicin, vincristine, and prednisone) (CHOP) or other anthracycline-based chemotherapy regimens.

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Adult patients with Chronic Lymphocytic Leukemia (CLL) (1.2).

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Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC).

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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).

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Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) in adult patients in combination with glucocorticoids (1.4).

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Moderate to severe Pemphigus Vulgaris (PV) in adult patients (1.5).

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Administer only as an intravenous infusion (2.1).

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Do not administer as an intravenous push or bolus (2.1).

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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).

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The dose for adult B-cell NHL is 375 mg/m2 (2.2).

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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).

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The dose as a component of Zevalin® (ibritumomab tiuxetan) Therapeutic Regimen is 250 mg/m2 (2.4).

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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).

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The induction dose for adult patients with active GPA and MPA in combination with glucocorticoids is 375 mg/m2 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).

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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).

Injection: 100 mg/10 mL (10 mg/mL) and 500 mg/50 mL (10 mg/mL) solution in single-dose vials (3).

None (4).

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Tumor lysis syndrome: Administer aggressive intravenous hydration, anti-hyperuricemic agents, monitor renal function (5.5).

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Infections: Withhold RUXIENCE and institute appropriate anti-infective therapy (5.6).

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Cardiac adverse reactions: Discontinue infusions in case of serious or life-threatening events (5.7).

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Renal toxicity: Discontinue in patients with rising serum creatinine or oliguria (5.8).

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Bowel obstruction and perforation: Consider and evaluate for abdominal pain, vomiting, or related symptoms (5.9).

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Immunizations: Live virus vaccinations prior to or during RUXIENCE treatment are not recommended (5.10).

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Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception (5.11).

Most common adverse reactions in clinical trials were:

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NHL (greater than or equal to 25%): infusion-related reactions, fever, lymphopenia, chills, infection and asthenia (6.1).

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CLL (greater than or equal to 25%): infusion-related reactions and neutropenia (6.1).

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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).

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GPA and MPA (greater than or equal to 15%): infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema, infusion-related reactions (6.1).

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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 Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Renal toxicity when used in combination with cisplatin (5.8).

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Lactation: Advise not to breastfeed (8.2).

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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).