Obinutuzumab

GAZYVA is a CD20-directed cytolytic antibody indicated: in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). in combination with bendamustine followed by GAZYVA monotherapy, for the treatment of patients with follicular lymphoma (FL)who relapsed after, or are refractory to, a rituximab-containing regimen. in combination with chemotherapy followed by GAZYVA monotherapy in patients achieving at least a partial remission, for the treatment of adult patients with previously untreated stage II bulky, III or IV follicular lymphoma. for the treatment of adult patients with active lupus nephritis (LN) who are receiving standard therapy to reduce the risk of relapse in adult and pediatric patients 2 years of age and older with frequently relapsing or steroid dependent childhood-onset idiopathic nephrotic syndrome who are in…

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 lysis through engagement of immune effector cells, by directly activating intracellular death signaling pathways (direct cell death), and/or activation of the complement cascade. The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent 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.

Premedicate for infusion-related reactions and tumor lysis syndrome. Administer only as intravenous infusion. Do not administer as an intravenous push or bolus. The recommended dosage for chronic lymphocytic leukemia is 100 mg on day 1 and 900 mg on day 2 of Cycle 1, 1,000 mg on day 8 and 15 of Cycle 1, and 1,000 mg on day 1 of Cycles 2–6. The recommended dosage for follicular lymphoma is 1,000 mg on day 1, 8 and 15 of Cycle 1, 1,000 mg on day 1 of Cycles 2-6 or Cycles 2-8, and then 1,000 mg every 2 months for up to 2 years. The recommended dosage for active lupus nephritis is 1,000 mg at the initial infusion, on Week 2, 24, 26, and every 6 months thereafter. The recommended dosage for childhood-onset idiopathic nephrotic syndrome for patients weighing 45 kg or more who are in complete remission is 1,000 mg at the initial infusion, on Week 2, 24 and 26.

GAZYVA is contraindicated in patients with known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or to any of the excipients, or serum sickness with prior obinutuzumab use. GAZYVA is contraindicated in patients with known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or any of the excipients, including serum sickness with prior obinutuzumab use.

Boxed warning (hepatitis b virus reactivation and progressive multifocal leukoencephalopathy): Hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients receiving CD20-directed cytolytic antibodies, including GAZYVA. Screen all patients for HBV infection before treatment initiation. Monitor HBV-positive patients during and after treatment with GAZYVA. Infusion-Related Reactions: Premedicate patients with glucocorticoid, acetaminophen, and anti-histamine. Monitor patients closely during infusions. Interrupt, reduce rate, or discontinue for infusion-related reactions based on severity. Hypersensitivity Reactions Including Serum Sickness: Discontinue GAZYVA permanently.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatitis B virus reactivation Progressive multifocal leukoencephalopathy Infusion-related reactions Hypersensitivity reactions including serum sickness Tumor lysis syndrome Infections Neutropenia Thrombocytopenia Disseminated intravascular coagulation The most common adverse reactions (incidence ≥ 20% and ≥ 2% greater in the GAZYVA treated arm in CLL and NHL, incidence ≥ 5% in the GAZYVA treated arm in LN and incidence ≥ 10% in the GAZYVA treated arm in childhood-onset INS) were: Previously untreated CLL: infusion-related reactions and neutropenia. Relapsed or refractory non-Hodgkin lymphoma (NHL): infusion-related reactions, fatigue, neutropenia, cough, upper respiratory tract infections, and musculoskeletal pain.

Store at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE. Protect from light. DO NOT SHAKE.