Tositumomab

Identification

Name
Tositumomab
Accession Number
DB00081
Description

Murine IgG2a lambda monoclonal antibody against CD20 antigen (2 heavy chains of 451 residues, 2 lambda chains of 220 residues). It is produced in an antibiotic-free culture of mammalian cells. It can be covalently linked to Iodine 131 (a radioactive isotope of iodine).

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db00081
Protein Chemical Formula
C6416H9874N1688O1987S44
Protein Average Weight
143859.7 Da
Sequences
>Mouse-Human chimeric Anti-CD20 Heavy Chain 1
QAYLQQSGAELVRPGASVKMSCKASGYTFTSYNMHWVKQTPRQGLEWIGAIYPGNGDTSY
NQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYFCARVVYYSNSYWYFDVWGTGTTVTV
SGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGK
>Mouse-Human chimeric Anti-CD20 Light Chain 1
QIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYAPSNLASGVPAR
FSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGAGTKLELKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNR
>Mouse-Human chimeric Anti-CD20 Heavy Chain 2
QAYLQQSGAELVRPGASVKMSCKASGYTFTSYNMHWVKQTPRQGLEWIGAIYPGNGDTSY
NQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYFCARVVYYSNSYWYFDVWGTGTTVTV
SGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGK
>Mouse-Human chimeric Anti-CD20 Light Chain 2
QIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYAPSNLASGVPAR
FSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGAGTKLELKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNR
Download FASTA Format
Synonyms
Not Available

Pharmacology

Indication

For treatment of non-Hodgkin's lymphoma (CD20 positive, follicular)

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Tositumomab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lympohomas. The antibody leads to selective killing of B-cells.

Mechanism of action

Binds to the CD20 antigen which is found on mature B lymphocytes. The antibody binding appears to induce apoptosis, complement-dependent cytotoxicity and cell death through ionizing radiation.

TargetActionsOrganism
AB-lymphocyte antigen CD20
antibody
Humans
ULow affinity immunoglobulin gamma Fc region receptor II-bNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to B lymphocytes, or by human antimurine antibody production

Route of elimination

Elimination of Iodine-131 occurs by decay and excretion in the urine.

Half-life

0.8 hours (mammalian reticulocytes, in vitro)

Clearance
  • 68.2 mg/hr [patients with NHL]
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirTositumomab may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Tositumomab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Tositumomab.
AcarboseTositumomab may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Tositumomab which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Tositumomab which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Acenocoumarol is combined with Tositumomab.
AcetaminophenTositumomab may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Tositumomab which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Tositumomab.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Tositumomab I-131K1KT5M40JC192391-48-3Not applicable
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Bexxar DosimetricInjection0.61 mCi/1mLIntravenousGlaxosmithkline Inc2009-07-152014-02-13US flag
Bexxar TherapeuticInjection5.6 mCi/1mLIntravenousGlaxosmithkline Inc2009-07-152014-02-20US flag
Bexxar TherapyKit; SolutionIntravenousGlaxosmithkline Inc2006-04-102014-07-31Canada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BexxarTositumomab (14 mg/1mL) + Tositumomab (14 mg/1mL)KitIntravenousGlaxosmithkline Inc2009-07-152014-11-28US flag
BexxarTositumomab (14 mg/1mL) + Tositumomab (14 mg/1mL)KitIntravenousGlaxosmithkline Inc2009-07-152014-11-28US flag

Categories

ATC Codes
V10XA53 — Tositumomab/iodine (131i) tositumomab
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
0343IGH41U
CAS number
208921-02-2

References

General References
Not Available
UniProt
P01857
Genbank
J00228
PubChem Substance
46506662
RxNav
263010
ChEMBL
CHEMBL1201604
Therapeutic Targets Database
DAP000384
PharmGKB
PA164748364
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tositumomab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentLymphoma, B-Cell / Lymphoma, Large-Cell, Immunoblastic / Non-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
3Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
3WithdrawnTreatmentFollicular Lymphoma (FL) / Lymphoma, Large-Cell, Follicular / Lymphoma, Small Cleaved-Cell, Follicular / Non-Hodgkin's Lymphoma (NHL)1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)1
2CompletedNot AvailableNon-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentFollicular Lymphoma (FL)1
2CompletedTreatmentLymphoid Leukemia in Remission / Stage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage III Small Lymphocytic Lymphoma / Stage IV Chronic Lymphocytic Leukemia / Stage IV Small Lymphocytic Lymphoma1
2CompletedTreatmentLymphoma, B-Cell1
2CompletedTreatmentMalignant Lymphomas2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • GlaxoSmithKline Inc.
  • MDS Nordion
Dosage Forms
FormRouteStrength
KitIntravenous
InjectionIntravenous0.61 mCi/1mL
InjectionIntravenous5.6 mCi/1mL
Kit; solutionIntravenous
Prices
Unit descriptionCostUnit
Bexxar 131 iodine dosimetric180.77USD ml
Bexxar 14 mg/ml dosimetric100.43USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.414Not Available
isoelectric point8.68Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Mhc class ii protein complex binding
Specific Function
This protein may be involved in the regulation of B-cell activation and proliferation.
Gene Name
MS4A1
Uniprot ID
P11836
Uniprot Name
B-lymphocyte antigen CD20
Molecular Weight
33076.99 Da
References
  1. Goldenberg DM: The role of radiolabeled antibodies in the treatment of non-Hodgkin's lymphoma: the coming of age of radioimmunotherapy. Crit Rev Oncol Hematol. 2001 Jul-Aug;39(1-2):195-201. [PubMed:11418316]
  2. Dillman RO: Monoclonal antibody therapy for lymphoma: an update. Cancer Pract. 2001 Mar-Apr;9(2):71-80. [PubMed:11879282]
  3. Authors unspecified: Iodine-131 Tositumomab: (131)I-anti-B1 antibody, (131)I-tositumomab, anti-CD20 murine monoclonal antibody-I-131, B1, Bexxar, (131)I-anti-B1 antibody, iodine-131 tositumomab, iodine-131 anti-B1 antibody, tositumomab. BioDrugs. 2003;17(4):290-5. [PubMed:12899647]
  4. Friedberg JW, Fisher RI: Iodine-131 tositumomab (Bexxar): radioimmunoconjugate therapy for indolent and transformed B-cell non-Hodgkin's lymphoma. Expert Rev Anticancer Ther. 2004 Feb;4(1):18-26. [PubMed:14748653]
  5. Silverman DH, Delpassand ES, Torabi F, Goy A, McLaughlin P, Murray JL: Radiolabeled antibody therapy in non-Hodgkins lymphoma: radiation protection, isotope comparisons and quality of life issues. Cancer Treat Rev. 2004 Apr;30(2):165-72. [PubMed:15023434]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Beeson C, Butrynski JE, Hart MJ, Nourigat C, Matthews DC, Press OW, Senter PD, Bernstein ID: Conditionally cleavable radioimmunoconjugates: a novel approach for the release of radioisotopes from radioimmunoconjugates. Bioconjug Chem. 2003 Sep-Oct;14(5):927-33. [PubMed:13129395]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complex...
Gene Name
FCGR2B
Uniprot ID
P31994
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-b
Molecular Weight
34043.355 Da
References
  1. Glennie MJ, French RR, Cragg MS, Taylor RP: Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol. 2007 Sep;44(16):3823-37. [PubMed:17768100]
  2. Vaughan AT, Chan CH, Klein C, Glennie MJ, Beers SA, Cragg MS: Activatory and inhibitory Fcgamma receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain. J Biol Chem. 2015 Feb 27;290(9):5424-37. doi: 10.1074/jbc.M114.593806. Epub 2015 Jan 7. [PubMed:25568316]

Drug created on June 13, 2005 07:24 / Updated on September 03, 2020 19:00

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