Chemical: Drug
ibritumomab

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


Annotated Labels

  1. FDA Label for ibritumomab and MS4A1
  2. EMA Label for ibritumomab and MS4A1

last updated 12/17/2013

1. FDA Label for ibritumomab and MS4A1

Informative PGx

Summary

Ibritumomab tiuxetan (Zevalin) is used to treat patients with B-cell non-Hodgkin's lymphoma. The drug is a CD20-directed radiotherapeutic antibody, 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

Ibritumomab tiuxetan (Zevalin) binds to the CD20 antigen, which is expressed on pre-B and mature B lymphocytes, and on greater than 90% of B-cell non-Hodgkin's lymphomas. CD20 is coded for by the MS4A1 gene.

Excerpts from the ibritumomab tiuxetan (Zevalin) drug label:

Zevalin is a CD20-directed radiotherapeutic antibody administered as part of the Zevalin therapeutic regimen indicated for the treatment of patients with: relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL)...previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy.

Ibritumomab tiuxetan binds specifically to the CD20 antigen (human B-lymphocyte-restricted differentiation antigen, Bp35)...The CD20 antigen is expressed on pre-B and mature B lymphocytes and on >90% of B-cell non-Hodgkin's lymphomas (NHL).

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the ibritumomab tiuxetan drug label.

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

Former FDA Biomarker

This label used to be included on the FDA biomarker list and has since been removed. The PharmGKB curation staff monitors the FDA biomarker list on a regular basis and notes removals. There is no official list of removals supplied by the FDA.

Full label available at DailyMed

last updated 05/29/2014

2. EMA Label for ibritumomab and MS4A1

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) for ibritumomab (Zevalin) contains information regarding the indication of the drug for the treatment of CD20+ (MS4A1) follicular B-cell non-Hodgkin's lymphoma due to its mechanism of action.

Annotation

Excerpts from the ibritumomab (Zevalin) EPAR:

radiolabelled Zevalin is indicated for the treatment of adult patients with rituximab relapsed or refractory CD20+ follicular B-cell non-Hodgkin's lymphoma (NHL).


Ibritumomab tiuxetan is a recombinant murine IgG1 kappa monoclonal antibody specific for the B cell antigen CD20. Ibritumomab tiuxetan targets the antigen CD20 which is located on the surface of malignant and normal B-lymphocytes. During B-cell maturation, CD20 is first expressed in the midstage of B-lymphoblast (pre-B-cell), and is lost during the final stage of B-cell maturation to plasma cells. It is not shed from the cell surface and does not internalise on antibody binding.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the ibritumomab (Zevalin) EMA drug label.

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


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-2A chain C region, membrane-bound form
  • radiolabeled murine anti-CD20
Trade Names
  • Zevalin (IDEC Pharmaceuticals)
Brand Mixture Names

PharmGKB Accession Id

PA164781375

Type(s):

Drug

Description

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.

Source: Drug Bank

Indication

For treatment of non-Hodgkin's lymphoma

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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.

Source: Drug Bank

Pharmacology

Ibritumomab is a murine monoclonal antibody against CD20 that has been radiolabeled with yttrium-90.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

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

Source: Drug Bank

Half-Life

0.8 hours (mammalian reticulocytes, in vitro)

Source: Drug Bank

Chemical Properties

Chemical Formula

C6382H9830N1672O1979S54

Source: Drug Bank

Canonical SMILES

Not Available

Source: Drug Bank

Average Molecular Weight

143375.5000

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)
C1S (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
trastuzumab - ibritumomab 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:
J00470
Web Resource:
Wikipedia
UniProtKB:
P01865
DrugBank:
DB00078
Therapeutic Targets Database:
DAP000383

Clinical Trials

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

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.