Drug/Small Molecule:
denileukin diftitox

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

PharmGKB annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency, Japan (PMDA). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.

Sources:

  • FDA Information is gathered from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" and from FDA-approved labels brought to our attention. Please note that drugs may be removed from or added to the FDA's Table without our knowledge. We periodically check the Table for changes and update PharmGKB accordingly. Drugs listed on the Table to our knowledge are tagged with the Biomarker icon. A drug label that has been removed from the Table will not have the Biomarker icon but will continue to have an annotation on PharmGKB stating the label has been removed from the FDA's Table. We acquire label PDF files from DailyMed.
  • EMA European Public Assessment Reports (EPARs) that contain PGx information were identified from [Article:24433361] and also by searching for drugs for which we have PGx-containing FDA drug labels.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA, PMDA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for denileukin diftitox and IL2RA

Genetic testing required

Summary

The FDA-approved drug label for denileukin diftitox (Ontak) notes that it is indicated for patients with persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor. Confirmation of malignant cells expressing CD25 is necessary prior to administration of the drug.

Annotation

Denileukin diftitox (Ontak) is indicated for patients with persistent or recurrent cutaneous T-cell lymphoma. The FDA-approved drug label for denileukin diftitox states that confirmation that a patient's malignant cells express CD25 is necessary prior to beginning treatment with the drug.

Excerpts from the denileukin diftitox (Ontak) label:

Ontak is a CD25-directed cytotoxin indicated for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor.

CD25 Tumor Expression and Evaluation...Confirm that the patient's malignant cells express CD25 prior to administration of Ontak. A testing service for the assay of CD25 expression in tumor biopsy samples is available.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the denileukin diftitox 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

  • IL2RA
    • Indications & usage section, Description section, Clinical pharmacology section, Warnings and precautions section, efficacy
    • source: FDA Label

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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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

Overview

Generic Names
  • DT
  • Diphtheria toxin precursor
  • NAD(+--diphthamide ADP- ribosyltransferase)
  • denileukin diftitox
Trade Names
  • Ontak
  • Ontak (Seragen Inc)
Brand Mixture Names

PharmGKB Accession Id:
PA164750594

Description

A recombinant DNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met 1-Thr 387)-His followed by the sequences for interleukin-2 (IL-2; Ala 1-Thr 133). It is produced in an E. coli expression system.

Source: Drug Bank

Indication

For treatment of cutaneous T-cell lymphoma

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Denileukin diftitox binds to the high-affinity IL-2 receptor complex. The IL-2 receptor (Tac) subunit is expressed on activated but not resting lymphocytes. The diphtheria toxin associated with Ontak then selectively kills the IL-2 bearing cells.

Source: Drug Bank

Pharmacology

Denileukin diftitox (Ontak) directs the cytocidal action of diphtheria toxin to cells which express the IL-2 receptor. The human IL-2 receptor exists in three forms, low (CD25), intermediate (CD122/CD132) and high (CD25/CD122/CD132) affinity. Malignant cells expressing one or more of the subunits of the IL-2 receptor are found in certain leukemias and lymphomas including cutaneous T-cell lymphoma (CTCL). Ontak interacts with the high affinity IL-2 receptor on the cell surface and inhibits cellular protein synthesis, resulting in cell death within hours.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Half-Life

70-80 min

Source: Drug Bank

Clearance

Source: Drug Bank

Volume of Distribution

  • 0.06 to 0.09 L/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C2560H4042N678O799S17

Source: Drug Bank

Canonical SMILES

Not Available

Source: Drug Bank

Average Molecular Weight

57647.3000

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
IL2RA

Drug Targets

Gene Description
IL2RA (source: Drug Bank)
IL2RB (source: Drug Bank)
IL2RG (source: Drug Bank)
No related drugs are available.
No related diseases are available

LinkOuts

GenBank:
V01536
Web Resource:
Wikipedia
UniProtKB:
P00587
National Drug Code Directory:
62856-603-01
DrugBank:
DB00004
Therapeutic Targets Database:
DAP001098
FDA Drug Label at DailyMed:
42dfffb1-d0f3-42d5-944c-64f092fc436e

Clinical Trials

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

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.