Inotuzumab Ozogamicin
Inotuzumab Ozogamicin Uses, Dosage, Side Effects, Food Interaction and all others data.
Inotuzumab Ozogamicin is an antibody-drug conjugate using linker and cytotoxic drug technology similar to that developed for the ground-breaking treatment Mylotarg (Gemtuzumab ozogamicin), which was approved by the US FDA in 2000 for the treatment of acute myeloid leukaemia. Inotuzumab Ozogamicin consists of a recombinant humanised IgG4 kappa CD22-targeting monoclonal antibody covalently attached to calicheamicin derivative, N-acetyl-gamma-calicheamicin dimethylhydrazide, which is a potent DNA-binding cytotoxic agent . Developed by Pfizer and UCB, inotuzumab ozogamicin was granted approval by EU in June 2017 followed by FDA on August 17th, 2017 for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). ALL is a rapidly progressing cancer of the bone marrow that is associated with high mortality rates and low therapeutic response from standard chemotherapies in relasping conditions. In a randomized trial, inotuzumab ozogamicin displayed higher percentages of patients undergoing longer periods of complete remission with no evidence of disease in comparison to patients receiving alternative chemotherapy .
Inotuzumab Ozogamicin is an antineoplastic agent that targets CD22 antigen expressed on immature B-cell lymphocytes and blocks further growth of tumor cells. The drug aims to restore normal blood counts and achieve complete remission from the disease. QT interval prolongation was observed in patients receiving inotuzumab ozogamicin.
| Trade Name | Inotuzumab Ozogamicin |
| Generic | Inotuzumab ozogamicin |
| Inotuzumab ozogamicin Other Names | Inotuzumab ozogamicin |
| Weight | 0.9mg, |
| Type | Intravenous Powder For Injection, Intravenous |
| Protein binding | In vitro studies show the binding of the N-acetyl-gamma-calicheamicin dimethylhydrazide to human plasma proteins to be approximately 97% . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Inotuzumab Ozogamicin is an antibody-drug conjugate used to treat B-cell precursor acute lymphoblastic leukemia (ALL).
Indicated as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL).
Inotuzumab Ozogamicin is also used to associated treatment for these conditions: Refractory B-cell precursor acute lymphoblastic leukemia, Relapsed B cell precursor Acute lymphoblastic leukemia
How Inotuzumab Ozogamicin works
Inotuzumab Ozogamicin is comprised of cytotoxic antibiotic N-acetyl-gamma-calicheamicin dimethylhydrazide attached to a humanized monoclonal IgG4 antibody via 4-(4 acetylphenoxy) butanoic acid (acetyl butyrate) linker. The drug exerts a potent cytotoxic effect against CD22+ B-cell lymphoma when the antibody binds to the CD22 receptor on the surface of B cells . The drug-CD22 complex is rapidly internalized into the cell, forming an endosome which subsequently fuses with lysosomes. N-acetyl-gamma-calicheamicin dimethylhydrazide is then intracellularly released into the acidic environment. N-acetyl-gamma-calicheamicin dimethylhydrazide is a calicheamicin derivative, which is naturally produced by the bacterium Micromonospora echinospora, and is toxic to the body when not bound to the antibody. It mediates apoptosis of the cell by binding to the minor groove of DNA in a sequence-specific manner and undergoing a structural change to generate diradicals [A20354]. These changes abstract hydrogen ions from the phosphodiester bonds of double-stranded DNA, resulting in breaks and cell apoptosis .
Toxicity
Inotuzumab Ozogamicin was shown to be clastogenic in vivo in the bone marrow of male mice but was not mutagenic in an* in vitro* bacterial reverse mutation (Ames) assay. In rat toxicity studies, rats developed oval cell hyperplasia, altered hepatocellular foci, and hepatocellular adenomas however the carcinogenic potential of inotuzumab ozogamicin on humans is undetermined. Based on reproductive toxicity studies involving female rats and non-clinical studies, inotuzumab ozogamicin has the potential to impair reproductive function and fertility in men and women .
Food Interaction
No interactions found.Volume of Distribution
The total volume of distribution of inotuzumab ozogamicin is approximately 12L .
Elimination Route
Inotuzumab Ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks. The steady state exposure of the drug is reached by Cycle 4. The mean (SD) maximum serum concentration (Cmax) of inotuzumab ozogamicin was 308 ng/mL (362) with patients receving the recommended dose of 1.8 mg/m^2/cycle .
Half Life
The elimination half life at the end of Cycle 4 of administration is approximately 12.3 days in a 2-compartment model .
Clearance
The clearance of inotuzumab ozogamicin at steady state is 0.0333 L/h .
Elimination Route
The drug is disposited in the body after administration.
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