Obinutuzumab (1 brand name, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- GAZYVA
Boxed Warning
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. Discontinue GAZYVA and concomitant medications in the event of HBV reactivation [see Warnings and Precautions (5.1)]. Progressive Multifocal Leukoencephalopathy (PML) including fatal PML, can occur in patients receiving GAZYVA [see Warnings and Precautions (5.2)].
Contraindications
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 [see Warnings and Precautions (5.4)].
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatitis B virus reactivation [see Warnings and Precautions (5.1)] Progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.2)] Infusion-related reactions [see Warnings and Precautions (5.3)] Hypersensitivity reactions including serum sickness [see Warnings and Precautions (5.4)] Tumor lysis syndrome [see Warnings and Precautions (5.5)] Infections [see Warnings and Precautions (5.6)] Neutropenia [see Warnings and Precautions (5.7)] Thrombocytopenia [see Warnings and Precautions (5.8)] Disseminated intravascular coagulation [see Warnings and Precautions (5.9) ]
Mechanism of Action
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 (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 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. Obinutuzumab and rituximab bind with similar affinity to overlapping epitopes on CD20.
Overdosage
There has been no experience with overdose in human clinical trials. For patients who experience overdose, treatment should consist of immediate interruption or reduction of GAZYVA and supportive therapy.