Gemtuzumab Ozogamicin
- Atc Codes:L01XC05
- CAS Codes:220578-59-6
- PHARMGKB ID:220578-59-6
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Unlabeled Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Toxicological Effects
- Genes that may be involved
- Drug Interactions
- Nutrition/Nutraceutical Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
North America (d)
Canada: Mylotarg; USA: Mylotarg.
Latin America (d)
Argentina: Mylotarg.
Asia (d)
Japan: Mylotarg.
Drug combinations
Chemistry
Gemtuzumab Ozogamicin: Mw: approx. 153000.01. (1) Immunoglobulin G~4~, anti-(human CD33 (antigen))(human-mouse monoclonal hP67.6γ4-chain), disulfide with human-mouse monoclonal hP67.6κ-chain, dimer, methyl [(1R,4Z,8S,13E)-[8-[[2-O-[4-(acetylethylamino)-2,4-dideoxy-3-O-methyl-α-L-threo-pentopyranosyl]-4,6-dideoxy-4-[[[2,6-dideoxy-4-S-[4-[(6-deoxy-3-O-methyl-α-L-mannopyranosyl)oxy]-3-iodo-5,6-dimethoxy-2-methylbenzoyl]-4-thio-β-D-ribo-hexopyranosyl]oxy]amino]-β-D-glucopyranosyl]oxy]-13-[2-[[3-[[1-[4-(4-amino-4-oxobutoxy)phenyl]ethylidene]hydrazino]-1,1-dimethyl-3-oxopropyl]dithio]ethylidene]-1-hydroxy-11-oxobicyclo[7.3.1]trideca-4,9-diene-2,6-diyn-10-yl]carbamate conjugate; (2) Immunoglobulin G~4~ (human-mouse monoclonal hP67.6γ4-chain anti-human antigen CD33), disulfide with human-mouse monoclonal hP67.6κ-chain, dimer, conjugate with methyl(1R,4Z,8S,13E)-13-[2-[[2-[[[p-(3-carbamoylpropoxy)-α-methylbenzylidene]hydrazino]carbonyl]-1,1-dimethylethyl]dithio]ethylidene]-8-[[4,6-dideoxy-4-[[[2,6-dideoxy-4-S-[4-[(6-deoxy-3-O-methyl-a-L-mannopyranosyl)oxy]-3-iodo-5,6-dimethoxy-o-toluoyl]-4-thio-β-D-ribo-hexopyranosyl]oxy]amino]-2-O-[2,4-dideoxy-4-(N-ethylacetamido)-3-O-methyl-α-L-threo-pentopyranosyl]-β-D-glucopyranosyl]oxy]-1-hydroxy-11-oxobicyclo[7.3.1]trideca-4,9-diene-2,6-diyne-10-carbamate. CAS-220578-59-6 (2000).
Pharmacologic Category
Other Antineoplastic Agents; Monoclonal Antibodies. (ATC-Code: L01XC05).
Mechanism of action
Antibody component is an IgG~4κ~-immunoglobulin conjugated with cytotoxic antitumor antibiotic calicheamicin. Binds to CD33 antigen, expressed on leukemic blasts in 80% of acute myelocytic leukemia (AML) patients, resulting in internalization of antibody-antigen complex. Following internalization, calicheamicin derivative is released inside myeloid cell, and binds to DNA resulting in double strand breaks and cell death. Pluripotent stem cells and nonhematopoietic cells not affected.
Therapeutic use
Treatment of CD33-positive AML in first relapse in patients who are ≥60 years of age and not considered candidates for cytotoxic chemotherapy (designated orphan drug by US FDA for this use).
Pregnancy and lactiation implications
Animal studies demonstrated teratogenic effects, fetal loss, and maternal toxicity. May cause fetal harm when administered to a pregnant woman. Not recommended during lactation.
Unlabeled use
Salvage therapy for acute promyelocytic leukemia (APL), relapsed/ refractory CD33 positive acute myeloid leukemia in children and adults <60 years.
Contraindications
Hypersensitivity to gemtuzumab ozogamicin, calicheamicin derivatives, or any component of the formulation. Patients with anti-CD33 antibody. Pregnancy.
Warnings and precautions
Hazardous agent. Severe myelosuppression occurs in all patients at recommended dosages. Risk of severe adverse pulmonary events, including dyspnea, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, and acute respiratory distress syndrome. Risk of severe hepatotoxicity including severe hepatic veno-occlusive disease. Possible fetal harm. Severe hypersensitivity reactions (including anaphylaxis) and other infusion-related reactions may occur. Possible thrombocytopenia, anemia, or bleeding (e.g. epistaxis, cerebral hemorrhage, disseminated intravascular coagulation, intracranial hemorrhage, hematuria). Risk of infections (e.g. sepsis, pneumonia), including opportunistic infections, during and immediately after treatment. Possible oral mucositis or stomatitis. Tumor lysis syndrome might occur. Use with caution in hepatic or renal impairment (not studied). Not FDA-approved for use in children.