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| Primary information |
|---|
| ID | 10699 |
| Therapeutic ID | Th1159 |
| Protein Name | Gemtuzumab ozogamicin |
| Sequence | >Th1159_Gemtuzumab_ozogamicin
EVQLVQSGAEVKKPGSSVKVSCKASGYTITDSNIHWVRQAPGQSLEWIGYIYPYNGGTDYNQKFKNRATLTVDNPTNTAYMELSSLRSEDTAFYYCVNGNPWLAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
|
| Molecular Weight | 151000 to 153000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | 61 (FAB fr |
| Half-life | 64±44 h |
| Description | Recombinant humanized IgG4, kappa antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin, isolated from fermentation of a bacterium, Micromonospora echinospora ssp. calichensis. The antibody portion of Mylotarg binds specifically to the CD33 antigen, The anti-CD33 hP67.6 antibody is produced by mammalian cell suspension culture using a myeloma NS0 cell line. |
| Indication/Disease | For treatment of CD33-positive acute myeloid leukemia in patients 60 and over who are not candidates for other chemotherapy. |
| Pharmacodynamics | Used for the treatment of acute myeloid leukemia (AML), mylotarg binds to the CD33 antigen, which is expressed on the surface of leukemic cells in more than 80% of patients with AML. The CD33 antigen is not expressed on pluripotent hematopoietic stem cells or nonhematopoietic cells. This gives mylotarg the selectivity needed to target leukemic cells. |
| Mechanism of Action | Mylotarg is directed against the CD33 antigen expressed by hematopoietic cells. Binding of the anti-CD33 antibody portion of Mylotarg with the CD33 antigen results in the formation of a complex that is internalized. Upon internalization, the calicheamicin derivative is released inside the lysosomes of the myeloid cell. The released calicheamicin derivative binds to DNA in the minor groove resulting in DNA double strand breaks and cell death. |
| Toxicity | The most frequently reported toxicities are myelosuppression and hepatic veno-occlusive disorder. |
| Metabolism | Metabolic studies indicate hydrolytic release of the calicheamicin derivative from gemtuzumab ozogamicin. The drug is most likely removed by opsonization via the reticuloendothelial system. |
| Absorption | In pediatric patients receiving a dose level of 9mg/m^2, the peak plasma concentration (Cmax) was approximately 3.47±1.04 mg/L with the AUC of 136 ±107 mg * h/L [A20377]. |
| The volume of distribution at steady state (Vss) was approximately 6.5 ± 5.5 L in pediatric patients receiving a dose level of 9mg/m^2 [A20377]. |
| Clearance | The mean clearance rate was approximately 0.12±0.15 L/h/m^2 in pediatric patients receiving a dose level of 9mg/m^2 [A20377]. |
| Categories | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Antineoplastic Agents,Antineoplastic Agents, Immunological,Antineoplastic and Immunomodulating Agents,Blood Proteins,Cancer immunotherapy,Carbohydrates,CD33-directed Antibody Interactions,CD33-directed Cytotoxin,Globulins,Glycosides,Hepatotoxic Agents,Immunoconjugates,Immunoglobulins,Immunoproteins,Immunosuppressive Agents,Immunotherapy,Immunotoxins,Myelosuppressive Agents,Narrow Therapeutic Index Drugs,Noxae,Proteins,Serum Globulins,Toxic Actions |
| Patents Number | US5585089 |
| Date of Issue | 17-12-1996 |
| Date of Expiry | 17-12-2013 |
| Drug Interaction | Belizumab, Clozapine, Denosumab, Leflunomide, Natalizumab due to adverse effects of these drugs with Gemtuzumab; Pimecrolimus, Roflumilast, Sipuleucel-T, Tacrolimus, Tofacitinib, Trastuzumab due to adverse effects of above immmunosupressants |
| Target | Myeloid cell surface antigen CD33,Low affinity immunoglobulin gamma Fc region receptor III-B,Low affinity immunoglobulin gamma Fc region receptor III-A,High affinity immunoglobulin gamma Fc receptor I |
| Brand Name | Mylotarg |
| Company | Wyeth pharmaceuticals inc |
| Brand Description | Wyeth pharmaceuticals inc |
| Prescribed For | Mylotarg (gemtuzumab ozogamicin for injection) is indicated for the treatment of patients with CD33 positive acute myeloid leukemia |
| Chemical Name | NA |
| Formulation | 5 mg of drug conjugate (protein equivalent) in an amber vial. The inactive ingredients are: dextran 40; sucrose; sodium chloride; monobasic and dibasic sodium phosphate. |
| Physical Appearance | Mylotarg (gemtuzumab ozogamicin for injection) is a sterile, white, preservative-free lyophilized powder |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | The recommended dose of Mylotarg (gemtuzumab ozogamicin for injection) is 9 mg/m² , infused over a 2-hour period. |
| Contraindication | Mylotarg (gemtuzumab ozogamicin for injection) is contraindicated in patients with a known hypersensitivity to gemtuzumab ozogamicin or any of its components: anti-CD33 antibody (hP67.6), calicheamicin derivatives, or inactive ingredients. Mylotarg is contraindicated in lactating mothers. |
| Side Effects | Fever, Nausea, Chills, Vomiting, Headache,Dyspnea, Hypotension, Hypertension, Hypoxia |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |