GAZYVA 1000.00mg

Indicated for previously untreated, chronic lymphocytic leukemia, in combination with chlorambucil, Follicular Lymphoma, Refractory or relapsed follicular lymphoma Hypersensitivity to this drug including serum sickness. Administration of live viral vaccines.

Anti neoplastic preparations

Obinutuzumab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B lymphocytes. Upon binding to CD20, obinutuzumab mediates B-cell lysisthrough (1) engagement of immune effector cells (2) by directly activating intracellular death signaling pathways (direct cell death), and/or (3) activation of the complement cascade. The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity (ADCC) and antibodydependent cellular phagocytosis.As an antibody with reduced fucose content, obinutuzumab induces greater ADCC activity than rituximab in vitro using human cancer cell lines. Obinutuzumab also demonstrated an increased ability to induce direct cell death when compared to rituximab. Obinutuzumab binds to FcγRIII using purified proteins with a higher affinity than rituximab. Obinutuzumab and rituximab bind with similar affinity to overlapping epitopes on CD20.

Administration: IV Preparation Inspect visually for any particulate matter and discoloration prior to administration Dilute into 0.9% NaCl PVC or non-PVC polyolefin infusion bag Do not use other diluents (eg, dextrose 5%) Dilute under appropriate aseptic conditions 100 mg and 900 mg doses Withdraw 40 mL of solution from the vial Dilute 4 mL (100 mg) into 100 mL 0.9% NaCl infusion bag for immediate administration Dilute the remaining 36 mL (900 mg) into a 250 mL 0.9% sodium chloride infusion bag at the same time for use on Day 2 After allowing the diluted bag to come to room temperature, use immediately Clearly label each infusion bag 1000 mg dose Withdraw 40 mL of solution from the vial Dilute 40 mL (1000 mg) into a 250 mL 0.9% NaCl infusion bag Mix diluted solution by gentle inversion; do not shake For microbiological stability, the diluted infusion solution should be used immediately The product can be administered at a final concentration of 0.4 mg/mL to 4 mg/mL If not used immediately, diluted solution may be refrigerated at 2-8°C (36-46°F) for up to 24 hours prior to use IV Administration Administer as IV infusion only Do not administer as IV push or bolus Do not mix with other drugs Adult Dose: Intravenous Chronic lymphocytic leukaemia Adult: In combination with chlorambucil in 6 28-day cycles: CYCLE 1: Day 1: 100 mg at 25 mg/hour over 4 hours; Day 2: 900 mg at 25-50 mg/hour, increased by 50 mg/hour every 30 minutes to a max rate of 400 mg/hour; Days 8 and 15: 1,000 mg at 50-100 mg/hour, increased by 50-100 mg/hour every 30 minutes to a max rate of 400 mg/hour. CYCLE 2-6: Day 1: 1,000 mg at 50-100 mg/hour, increased by 50-100 mg/hour every 30 minutes to a max rate of 400 mg/hour. In case of toxicity, modify dose according to product literature. Pre-medicate with IV corticosteroid, oral analgesic (e.g. acetaminophen)/antipyretics and antihistamine. Follicular lymphoma Adult: Induction in combination with chemotherapy in either 6 21/28-day cycles or 8 21-day cycles: 1,000 mg on Cycle 1, Days 1, 8 and 15 and on Cycles 2-6/8, Day 1 at 50-100 mg/hour, increased by 50-100 mg/hour to a max rate of 400 mg/hour. Maintenance as monotherapy initiated approx 2 months after last induction dose: 1,000 mg every 2 months for 2 years or until disease progression. In case of toxicity, modify dose according to product literature. Pre-medicate with IV corticosteroid, oral analgesic (e.g. acetaminophen)/antipyretics and antihistamine. Refractory or relapsed follicular lymphoma Adult: Induction in combination with bendamustine in 6 28-day cycles: 1,000 mg on Cycle 1, Days 1, 8 and 15 and on Cycles 2-6, Day 1 at 50-100 mg/hour, increased by 50-100 mg/hour to a max rate of 400 mg/hour. Maintenance as monotherapy initiated approx 2 months after last induction dose: 1,000 mg every 2 months for 2 years or until disease progression. In case of toxicity, modify dose according to product literature. Pre-medicate with IV corticosteroid, oral analgesic (e.g. acetaminophen)/antipyretics and antihistamine.

May increase risk of hypotension with antihypertensive agents. May increase risk of haemorrhage with anticoagulants, platelet inhibitors. Potentially Fatal: May enhance the adverse effects and diminish the therapeutic effects of live vaccines.

Hypersensitivity to this drug including serum sickness. Administration of live viral vaccines.

>10% Infusion related reactions (69%) Neutropenia (33%) Hypocalcemia (32%) Hyperkalemia (31%) Hyponatremia (29%) Creatinine increased (28%) AST/SGOT increased (28%) AST/SGPT increased (25%) Hypoalbuminemia (16%) Alkaline phosphatase increased (16%) Thrombocytopenia (15%) Hypokalemia (13%) Anemia (12%) 1-10% Pyrexia (10%) Cough (10%) Leukopenia (7%) Tumor lysis syndrome (2%)

Pregnancy: Obinutuzumab is likely to cause fetal B-cell depletion based on findings from animal studies and the drug’s mechanism of action. There are no data with Obinutuzumab use in pregnant women to inform a drug-associated risk. Monoclonal antibodies are transferred across the placenta. In animal reproduction studies, weekly intravenous administration of obinutuzumab to pregnant cynomolgus monkeys from day 20 of pregnancy until parturition which includes the period of organogenesis at doses with exposures up to 2.4 times the exposure at the clinical dose of 1000 mg monthly produced opportunistic infections and immune complex mediated hypersensitivity reactions. No embryo-toxic or teratogenic effects were observed in the monkeys. Consider the potential risk to the fetus when prescribing Obinutuzumab to a pregnant woman.The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.Lactation: There is no information regarding the presence of Obinutuzumab in human milk, the effects on the breastfed child, or the effects on milk production. However, low levels of obinutuzumab were present in the milk of lactating cynomolgus monkeys [see Pregnancy]. Human IgG is known to be present in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and child circulations in substantial amounts. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Obinutuzumab and any potential adverse effects on the breastfed child from Obinutuzumab or from the underlying maternal condition.

Precaution: Patient with history or current serious infection especially hepatitis B virus (HBV) infection, risk of tumour lysis syndrome (e.g. high tumour burden, high lymphocyte count), cardiac and respiratory impairment. Renal impairment. Pregnancy and lactation. Lactation Unknown if distributed in human breast milk Excreted in the milk of lactating cynomolgus monkeys and human IgG is known to be excreted in human milk; consider developmental and health benefits along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant

Store vials in a refrigerator at 2°C-8°C. Keep vial in the outer carton in order to protect from light. Do not freeze. Do not shake.

Anti neoplastic preparations

CD20-directed cytolytic antibody; upon binding to CD20, obinutuzumab mediates B-cell lysis through 1) engagement of immune effector cells, 2) by directly activating intracellular death signaling pathways and/or, 3) activation of the complement cascade CD20 antigen is expressed on the surface of pre B- and mature B-lymphocytes; the immune effector cell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis

Pregnancy: Obinutuzumab is likely to cause fetal B-cell depletion based on findings from animal studies and the drug’s mechanism of action. There are no data with Obinutuzumab use in pregnant women to inform a drug-associated risk. Monoclonal antibodies are transferred across the placenta. In animal reproduction studies, weekly intravenous administration of obinutuzumab to pregnant cynomolgus monkeys from day 20 of pregnancy until parturition which includes the period of organogenesis at doses with exposures up to 2.4 times the exposure at the clinical dose of 1000 mg monthly produced opportunistic infections and immune complex mediated hypersensitivity reactions. No embryo-toxic or teratogenic effects were observed in the monkeys. Consider the potential risk to the fetus when prescribing Obinutuzumab to a pregnant woman.The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.Lactation: There is no information regarding the presence of Obinutuzumab in human milk, the effects on the breastfed child, or the effects on milk production. However, low levels of obinutuzumab were present in the milk of lactating cynomolgus monkeys [see Pregnancy]. Human IgG is known to be present in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and child circulations in substantial amounts. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Obinutuzumab and any potential adverse effects on the breastfed child from Obinutuzumab or from the underlying maternal condition.