Introduction
Obinutuzumab is a humanized monoclonal antibody used in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia. It carries important safety warnings, including the risk of hepatitis B virus (HBV) reactivation and progressive multifocal leukoencephalopathy (PML).
Uses
Obinutuzumab is an antineoplastic CD20 antibody used to treat untreated chronic lymphocytic leukemia in combination with chlorambucil.
Obinutuzumab is used as a combination treatment with chlorambucil to treat patients with untreated chronic lymphocytic leukemia.
Associated Conditions
Pharmacodynamics
Obinutuzumab is more potent than rituximab in depleting B-cells, antitumor activity, and tumor regression.
Mechanism of Action
In contrast to rituximab, which is a classic type I CD20 antibody, obinutuzumab binds to type II CD20 antibodies. This allows obinutuzumab to have a much higher induction of antibody-dependant cytotoxicity and a higher direct cytotoxic effect than the classic CD20 antibodies.
Absorption
Obinutuzumab is administered intravenously, so its absorption is 100%.
Volume of Distribution
Obinutuzumab has a volume of distribution of about 3.8 L.
Protein Binding
Obinutuzumab does not bind to plasma proteins.
Route of Elimination
The route of elimination of obinutuzumab was not indicated (FDA label).
Half Life
The half life of obinutuzumab is 28.4 days.
Clearance
The clearance of obinutuzumab is 0.09L/day.
Toxicity
The most serious toxicities observed with obinutuzumab are Hepatitis B virus (HBV) reactivation and progressive multifocal leukoencephalopathy (PML). HBV reactivation can occur with all anti-CD20 antibodies and can result in hepatic failure, fulminant hepatitis, and death. PML occurs as a result of JC virus infection and can be fatal as well. Other common but less serious adverse reactions include infusion reactions (pre-treat with glucocorticoids, acetaminophen, and anti-histamine to prevent this), neutropenia, thrombocytopenia, and Tumor Lysis Syndrome (TLS) (pre-treat patients, especially with a high lymphocyte count and/or a high tumor burden, with anti-hyperuricemics and hydration). It is also recommended to NOT administer live virus vaccinations prior to or during obinutuzumab treatment.
Food Interactions
- Avoid echinacea. Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.