Denileukin diftitox

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Denileukin diftitox
Names
Pronunciationden" i loo' kin dif' ti tox[1]
Trade namesOntak
  • Diphtheria toxin-Interleukin-2 fusion protein
Clinical data
Main usesCutaneous T-cell lymphoma (CTCL).[2]
Side effectsTiredness, fever, nausea, diarrhea, joint pain, headache, rash[1]
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
use		Intravenous
External links
AHFS/Drugs.comMonograph
MedlinePlusa611024
Legal
Legal status
Pharmacokinetics
Elimination half-life70-80 min
Chemical and physical data
FormulaC2560H4042N678O799S17
Molar mass57647.46 g·mol−1

Denileukin diftitox, sold under the brand name Ontak, is a medication used to treat cutaneous T-cell lymphoma (CTCL).[2] It is used for certain cases that have failed other treatments.[1] It is given by injection into a vein.[2]

Common side effects include tiredness, fever, nausea, diarrhea, joint pain, headache, and rash.[1] Other side effects may include capillary leak syndrome, low blood pressure, kidney problems, infections, blood clots, pancreatitis, and pulmonary edema.[1] It is a fusion protein that combines human interleukin-2 (IL-2) with diphtheria toxin fragments.[1]

Denileukin diftitox was approved for medical use in the United States in 1999.[2] When launched it cost about 25,000 to 50,000 USD per person treated.[3] It; however, was discontinued in 2014 due to difficulties with manufacturing.[4]

Medical uses

Dosage

The typical dose is 9 to 18 µg/kg given intravenously once daily for 5 consecutive days every 21 days for up to 8 cycles.[1]

Side effects

There is some evidence tying it to vision loss, and in 2006 the FDA added a black box warning to the drug's label.[5]

Mechanism of action

It is a manufactured protein combining interleukin-2 and diphtheria toxin. Denileukin diftitox could bind to interleukin-2 receptors[6] and introduce the diphtheria toxin into cells that express those receptors, killing the cells. In some leukemias and lymphomas, malignant cells express these receptors, so denileukin diftitox can target these.

History

In 1999, Ontak was approved by the U.S. Food and Drug Administration (FDA) for treatment of cutaneous T-cell lymphoma (CTCL).[7]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Denileukin Diftitox". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. Archived from the original on 8 May 2021. Retrieved 23 December 2021.
  2. ↑ 2.0 2.1 2.2 2.3 "Denileukin Monograph for Professionals". Drugs.com. Archived from the original on 30 November 2021. Retrieved 23 December 2021.
  3. ↑ "FDA approves Ligand's Ontak for cutaneous T cell lymphoma - Pharmaceut". www.thepharmaletter.com. Archived from the original on 11 January 2022. Retrieved 23 December 2021.
  4. ↑ Shafiee, Fatemeh; Aucoin, Marc G.; Jahanian-Najafabadi, Ali (18 October 2019). "Targeted Diphtheria Toxin-Based Therapy: A Review Article". Frontiers in Microbiology. 10: 2340. doi:10.3389/fmicb.2019.02340.
  5. ↑ Lansigan F, Stearns DM, Foss F (February 2010). "Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous T-cell lymphoma". Cancer Management and Research. 2: 53–9. doi:10.2147/cmar.s5009. PMC 3004568. PMID 21188096.
  6. ↑ Turturro F (January 2007). "Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid-derived disorders". Expert Review of Anticancer Therapy. 7 (1): 11–7. doi:10.1586/14737140.7.1.11. PMID 17187516. S2CID 9028829.
  7. ↑ Manoukian G, Hagemeister F (November 2009). "Denileukin diftitox: a novel immunotoxin". Expert Opinion on Biological Therapy. 9 (11): 1445–51. doi:10.1517/14712590903348135. PMID 19817678. S2CID 23956460.

External links

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