Chemical: Drug
tositumomab

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last updated 10/25/2013

1. FDA Label for tositumomab and MS4A1

Informative PGx

Summary

Tositumomab is used to treat patients with CD20-positive non-Hodgkin's lymphoma. The drug is a monoclonal antibody that targets the CD20 antigen, but there is no association with genetic variation within the coding gene, MS4A1, and therefore no mention of genetic testing in the drug label.

Annotation

Tositumomab is an anti-neoplastic radiotherapeutic monoclonal antibody-based regimen targeted against the CD20 antigen. CD20 is coded for by the gene MS4A1 and found on the surface of normal and malignant B lymphocytes. Tositumomab is used to treat CD-20 positive non-Hodgkins' lymphoma during or after rituximab therapy.

Excerpt from the Tositumomab (Bexxar) drug label:

Tositumomab binds specifically to the CD20 (human B-lymphocyte-restricted differentiation antigen, Bp 35 or B1) antigen. This antigen is a transmembrane phosphoprotein expressed on pre-B lymphocytes and at higher density on mature B lymphocytes. The antigen is also expressed on >90% of B-cell non-Hodgkins lymphomas (NHL). The recognition epitope for Tositumomab is found within the extracellular domain of the CD20 antigen. CD20 does not shed from the cell surface and does not internalize following antibody binding.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Tositumomab (Bexxar) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • MS4A1
    • other, Indications & usage section, Clinical pharmacology section
    • source: U.S. Food and Drug Administration

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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Overview

Generic Names
  • Ig gamma-1 chain C region
Trade Names
  • Bexxar (Corixa Corp)
Brand Mixture Names

PharmGKB Accession Id

PA164748364

Type(s):

Drug

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).

Source: Drug Bank

Indication

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

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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.

Source: Drug Bank

Pharmacology

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.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

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

Source: Drug Bank

Half-Life

0.8 hours (mammalian reticulocytes, in vitro)

Source: Drug Bank

Clearance

Source: Drug Bank

Route of Elimination

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

Source: Drug Bank

Chemical Properties

Chemical Formula

C6416H9874N1688O1987S44

Source: Drug Bank

Canonical SMILES

Not Available

Source: Drug Bank

Average Molecular Weight

143859.7000

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
MS4A1

Drug Targets

Gene Description
C1QA (source: Drug Bank)
C1QB (source: Drug Bank)
C1QC (source: Drug Bank)
C1R (source: Drug Bank)
FCGR1A (source: Drug Bank)
FCGR2A (source: Drug Bank)
FCGR2B (source: Drug Bank)
FCGR2C (source: Drug Bank)
FCGR3A (source: Drug Bank)
FCGR3B (source: Drug Bank)
MS4A1 (source: Drug Bank)

Drug Interactions

Interaction Description
tositumomab - natalizumab The immunosuppressant, Tositumomab, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided. (source: Drug Bank)
trastuzumab - tositumomab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)
No related diseases are available

LinkOuts

GenBank:
J00228
Web Resource:
Wikipedia
UniProtKB:
P01857
National Drug Code Directory:
0007-3260-31
DrugBank:
DB00081
Drugs Product Database (DPD):
2270471
Therapeutic Targets Database:
DAP000384
FDA Drug Label at DailyMed:
0d706611-abab-42f1-ae8a-2097eb1be38d

Clinical Trials

These are trials that mention tositumomab and are related to either pharmacogenetics or pharmacogenomics.

No trials found.

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Sources for PharmGKB drug information: DrugBank, PubChem.