Rituximab

4 CONTRAINDICATIONS None. None 5 WARNINGS AND PRECAUTIONS Tumor lysis syndrome: Administer aggressive intravenous hydration, anti-hyperuricemic agents, monitor renal function. Infections: Withhold TRUXIMA and institute appropriate anti-infective therapy. Cardiac adverse reactions: Discontinue infusions in case of serious or life-threatening events.

Renal toxicity: Discontinue in patients with rising serum creatinine or oliguria. Bowel obstruction and perforation: Consider and evaluate for abdominal pain, vomiting, or related symptoms. Immunizations: Live virus vaccinations prior to or during TRUXIMA treatment not recommended. Embryo-Fetal toxicity: Can cause fetal harm.

Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue TRUXIMA and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. 5.5 Tumor Lysis Syndrome (TLS) Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, sometimes fatal, can occur within 12-24 hours after the first infusion of rituximab products in patients with NHL.

A high number of circulating malignant cells ( ≥25,000/mm3) or high tumor burden, confers a greater risk of TLS. Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated [ see Warnings and Precautions ]. 5.6 Infections Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of rituximab product-based therapy.

Perform cardiac monitoring during and after all infusions of TRUXIMA for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina [see Adverse Reactions ] . 5.8 Renal Toxicity Severe, including fatal, renal toxicity can occur after rituximab product 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 TRUXIMA is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue TRUXIMA in patients with a rising serum creatinine or oliguria. [ see Warnings and Precautions ]. 5.9 Bowel Obstruction and Perforation Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving rituximab products in combination with chemotherapy.

Important Dosing Information Administer only as an Intravenous Infusion [ see Dosage and Administration ]. Do not administer as an intravenous push or bolus. TRUXIMA 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 ] .

Premedicate before each infusion [ see Dosage and Administration ]. Prior to First Infusion: Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with TRUXIMA [see Warnings and Precautions ] . Obtain complete blood counts (CBC) including platelets prior to the first dose. During TRUXIMA Therapy: In patients with lymphoid malignancies, during treatment with TRUXIMA monotherapy, obtain complete blood counts (CBC) with differential and platelet counts prior to each TRUXIMA course.

During treatment with TRUXIMA and chemotherapy, obtain CBC with differential and platelet counts at weekly to monthly intervals and more frequently in patients who develop cytopenias [ see Adverse Reactions ] . In patients with RA, GPA or MPA, obtain CBC with differential and platelet counts at two to four month intervals during TRUXIMA therapy.

Continue to monitor for cytopenias after final dose and until resolution. First Infusion : Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr. Subsequent Infusions : Standard Infusion: Initiate infusion at a rate of 100 mg/hr.

In the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr. For previously untreated follicular NHL and DLBCL patients : If patients did not experience a Grade 3 or 4 infusion related adverse event during Cycle 1, a 90-minute infusion can be administered in Cycle 2 with a glucocorticoid-containing chemotherapy regimen.

Initiate at a rate of 20% of the total dose given in the first 30 minutes and the remaining 80% of the total dose given over the next 60 minutes. If the 90-minute infusion is tolerated in Cycle 2, the same rate can be used when administering the remainder of the treatment regimen (through Cycle 6 or 8). Patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count ≥5000/mm 3 before Cycle 2 should not be administered the 90-minute infusion [ see Clinical Studies ].

Interrupt the infusion or slow the infusion rate for infusion-related reactions [ see Boxed Warning , Warnings and Precautions ] . Continue the infusion at one-half the previous rate upon improvement of symptoms.

Recommended Dose for Rheumatoid Arthritis (RA) Administer TRUXIMA as two-1000 mg intravenous infusions separated by 2 weeks. Glucocorticoids administered as methylprednisolone 100 mg intravenous or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion-related reactions.

Subsequent courses should be administered every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. TRUXIMA is given in combination with methotrexate.

Recommended Dose for Pemphigus Vulgaris (PV) Administer TRUXIMA as two-1,000 mg intravenous infusions separated by 2 weeks in combination with a tapering course of glucocorticoids. Maintenance treatment Administer TRUXIMA as a 500 mg intravenous infusion at Month 12 and every 6 months thereafter or based on clinical evaluation.

Treatment of relapse Administer TRUXIMA as a 1,000 mg intravenous infusion on relapse, and consider resuming or increasing the glucocorticoid dose based on clinical evaluation. Subsequent infusions of TRUXIMA may be administered no sooner than 16 weeks following the previous infusion.

Administration and Storage Use appropriate aseptic technique. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. TRUXIMA should be a clear to opalescent, colorless to pale yellow solution. Do not use vial if particulates or discoloration is present. Administration Use a sterile needle and syringe to prepare TRUXIMA.

Withdraw the necessary amount of TRUXIMA and dilute to a final concentration of 1 mg/mL to 4 mg/mL in an infusion bag containing either 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP. Gently invert the bag to mix the solution. Do not mix or dilute with other drugs. Discard any unused portion left in the vial Storage Diluted TRUXIMA solutions for infusion may be stored at 2°C to 8°C (36°F to 46°F) for 24 hours.

Diluted TRUXIMA solutions for infusion have been shown to be stable for an additional 24 hours at room temperature. However, since TRUXIMA solutions do not contain a preservative, diluted solutions should be stored refrigerated (2°C to 8°C). No incompatibilities between TRUXIMA and polyvinylchloride or polyethylene bags have been observed.