1. Ibritumomab(DB00078) Approved Drug
Chemical Formula: C6382H9830N1672O1979S54
Molecular Weight:
Indium conjugated murine IgG1 kappa monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Ibritumomab is produced in Chinese hamster ovary cells and is composed of two murine gamma 1 heavy chains of 445 amino acids each and two kappa light chains of 213 amino acids each.
Indication/Usage
For treatment of non-Hodgkin's lymphoma.
Pharmacodynamics
Ibritumomab is a murine monoclonal antibody against CD20 that has been radiolabeled with yttrium-90.
Mechanism Of Action
The Fab segment of the antibody targets the CD20 epitope on B-cells, allowing the radioactive yttrium to destroy the cell via production of beta particles.
Metabolism
Most likely removed by opsonization via the reticuloendothelial system when bound to B cells, or by human antimurine antibody production

2. Experimental Properties
Half Life
0.8 hours (mammalian reticulocytes, in vitro).
Affected Organisms
Human and other Mammals
Patents
Patent no , Canada, approved: expired:
Drug Interactions
DB00072 (Trastuzumab): Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Sequence
Heavy chain:
QAYLQQSGAELVRPGASVKMSCKASGYTFTSYNMHWVKQTPRQGLEWIGAIYPGNGDTSYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYFCARVVYYSNSYWYFDVWGTGTTVTVSAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRGPTIKPCPPCKCPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISKPKGSVRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNYKNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSR
Light chain:
chainQIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYAPSNLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGAGTKLELKRADAAPTVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
Experimental Properties
Melting Point- 61 °C for FAB Fragment; 71 °C for whole mAb
Hydrophobicity: 0.359
Isoelectric Point: 7.91

3. Targets
B-lymphocyte antigen CD20, Low affinity immunoglobulin gamma Fc region receptor III-B, Complement C1r subcomponent, Complement C1q subcomponent subunit A, Complement C1q subcomponent subunit B, Complement C1q subcomponent subunit C, Low affinity immunoglobulin gamma Fc region receptor III-A, Complement C1s subcomponent, High affinity immunoglobulin gamma Fc receptor I, Low affinity immunoglobulin gamma Fc region receptor II-a, Low affinity immunoglobulin gamma Fc region receptor II-b, Low affinity immunoglobulin gamma Fc region receptor II-c.
Brands
Zevalin - Spectrum Pharmaceuticals

4. Zevalin Formulation Used/Prescribed for Dosage Contraindications
Zevalin (ibritumomab tiuxetan) is the immunoconjugate resulting from a stable thiourea covalent bond between the monoclonal antibody ibritumomab and the linker-chelator tiuxetan [N-[2-bis(carboxymethyl)amino]-3-(p-isothiocyanatophenyl)-propyl]-[N-[2-bis(carboxymethyl)amino]-2-(methyl)-ethyl]glycine. This linker-chelator provides a high affinity, conformationally restricted chelation site for Yttrium-90. The approximate molecular weight of ibritumomab tiuxetan is 148 kD. The antibody moiety of Zevalin is ibritumomab, a murine IgGi kappa monoclonal antibody directed against the CD20 antigen. Ibritumomab tiuxetan is a clear, colorless, sterile, pyrogen-free, preservative-free solution that may contain translucent particles for intravenous infusion.
Formulation
 Each single-use vial includes 3.2 mg of ibritumomab tiuxetan in 2 mL of 0.9% Sodium Chloride.
Used/Prescribed for
Zevalin is indicated for the treatment of relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). Zevalin is indicated for the treatment of previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy.
Dosage
Day 1: Administer rituximab 250 mg/m2 intravenous ; Day 7,8, or 9: Administer rituximab 250 mg/m2 intravenous infusion If platelets ≥ 150,000/mm3: Within 4 hours after rituximab infusion, administer 0.4 mCi/kg (14.8 MBq per kg) Y-90 Zevalin intravenous. If platelets ≥ 100,000 but ≤ 149,000/mm3 in relapsed or refractory patients: Within 4 hours after rituximab infusion, administer 0.3 mCi/kg (11.1 MBq per kg) Y-90 Zevalin intravenous.  
Contraindications
None.

5. Side- effects Drug Interactions References
Serious Infusion Reactions, prolonged and Severe Cytopenias, Severe Cutaneous and Mucocutaneous Reactions, Leukemia and Myelodysplastic Syndrome, Cytopenias, fatigue, nasopharyngitis, nausea, abdominal pain, asthenia, cough, diarrhea, and pyrexia.
Drug Interactions
No formal drug interaction studies have been performed with Zevalin. Patients receiving medications that interfere with platelet function orcoagulation should have more frequent laboratory monitoring for thrombocytopenia.
References