| Primary information |
|---|
| ID | 1636 |
| ThPP ID | Th1142 |
| Therapeutic Peptide/Protein Name | Obinutuzumab |
| Sequence | N.A. view full sequnce in fasta |
| Functional Classification | IIb |
| Molecular Weight | 146100 |
| Chemical Formula | C6512H10060N1712O2020S44 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | 28.4 days |
| Description | Humanized monoclonal antibody used along with chlorambucil for the treatment of chronic lymphocytic leukemia. It was approved by the FDA in November 2013 and is marketed under the brand name Gazyva. It carries a black box warning of fatal Hepatitis B Virus (HBV) reactivation and fatal Progressive Multifocal Leukoencephalopathy (PML). |
| Indication/Disease | Obinutuzumab is used as a combination treatment with chlorambucil to treat patients with untreated chronic lymphocytic leukemia. |
| 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. |
| 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. |
| Metabolism | Obinutuzumab is not metabolized by the liver. |
| Absorption | Obinutuzumab is administered intravenously, so its absorption is 100%. |
| Volume of Distribution | Obinutuzumab has a volume of distribution of about 3.8 L. |
| Clearance | The clearance of obinutuzumab is 0.09L/day. |
| Categories | Antineoplastic Agents |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | B-lymphocyte antigen CD20 |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Gazyva |
| Company | Genentech |
| Brand Discription | GAZYVA (obinutuzumab) is a humanized anti-CD20 monoclonal antibody of the IgG1 subclass. It recognizes a specific epitope of the CD20 molecule found on B-cells. The molecular mass of the antibody is approximately 150 kDa. |
| Prescribed for | chronic lymphocytic leukemia (CLL) |
| Chemical Name | N.A. |
| Formulation | GAZYVA is supplied at a concentration of 25 mg/mL in 1000 mg single use vials. The product is formulated in 20 mM L-histidine/L-histidine hydrochloride, 240 mM trehalose, 0.02% poloxamer 188. The pH is 6.0. |
| Physcial Appearance | GAZYVA is produced by mammalian cell (CHO) suspension culture. GAZYVA is a sterile, clear, colorless to slightly brown, preservative free liquid concentrate for intravenousadministration. |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | Each dose of GAZYVA is 1000 mg, administered intravenously, with the exception of the first infusions in cycle 1, which are administered on day 1 (100 mg) and day 2 (900 mg). |
| Contraindication | N.A. |
| Side Effects | Hepatitis B reactivation, Progressive multifocal leukoencephalopathy, Infusion reactions, Tumor lysis syndrome, Infections, Neutropenia, Thrombocytopenia. |
| Useful Link | http://www.rxlist.com/gazyva-drug.htm http://www.gazyva.com/ http://www.roche.com/media/store/releases/med-cor-2013-11-01.htm |
| PubMed ID | 25634683, 25586272, 25538980, 25355689, 25353187 |
| 3-D Structure | N.A. |