Denileukin diftitox – Uses, Dosage, Side Effects, Interaction

Denileukin diftitox is a recombinant cytotoxic protein based on a combination of diphtheria toxin fragments and interleukin-2 used to treat cutaneous T-cell lymphoma by targeting the interleukin-2 receptor. 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.

Denileukin diftitox is a recombinant fusion protein of human interleukin-2 (IL-2) attached to diphtheria toxin fragments A and B that is used as an antineoplastic agent to treat cutaneous T cell lymphomas that express IL-2 receptors. High doses of denileukin diftitox can cause mild-to-moderate elevations in serum enzymes and bilirubin but rarely result in clinically significant acute liver injury.

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.

Denileukin diftitox directs the cytocidal action of diphtheria toxin to cells that 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). Denileukin diftitox interacts with the high-affinity IL-2 receptor on the cell surface and inhibits cellular protein synthesis, resulting in cell death within hours.

Denileukin diftitox is a fusion protein designed to direct the cytocidal action of diphtheria toxin to cells that express the IL-2 receptor. Ex vivo studies report that after binding to the IL-2 receptor on the cell surface, denileukin diftitox is internalized by receptor-mediated endocytosis. The fusion protein is subsequently cleaved, releasing diphtheria toxin enzymatic and translocation domains from the IL fragment, resulting

Pharmacokinetic parameters associated with denileukin diftitox were determined over a range of doses (3 to 31 mcg/kg/day) in patients with lymphoma. Denileukin diftitox was administered as an IV infusion following the schedule used in the clinical trials. Following the first dose, denileukin diftitox displayed 2- compartment behavior with a distribution phase (half-life of approximately 2 to 5 minutes) and a terminal phase (half-life of approximately 70 to 80 minutes). Systemic exposure was variable but proportional to dose. Mean clearance was approximately 0.6 to 2.0 mL/min/kg and the mean volume of distribution was similar to that of circulating blood (0.06 to 0.09 L/kg). The mean clearance increased approximately 2- to 8-fold from course 1 to course 3 corresponding to a decrease in exposure of approximately 75%. No accumulation was evident between the first and fifth doses. Gender and age have no effect on the pharmacokinetics of denileukin diftitox.


  • For treatment of cutaneous T-cell lymphoma
  • Cutaneous T Cell Lymphomas (CTCL)
  • 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

Use in Cancer

Denileukin diftitox is approved to treat:

Denileukin diftitox is also being studied in the treatment of other types of cancer.


  • Known hypersensitivity to denileukin diftitox, diphtheria toxin, aldesleukin (interleukin-2), or any other ingredient in the formulation.
  • low amount of albumin proteins in the blood
  • a decrease in sharpness of vision called reduced visual acuity
  • capillary leak syndrome, a condition where fluid leaks out of small blood vessels
  • orthostatic hypotension, a form of low blood pressure
  • low blood pressure
  • visible water retention
  • pregnancy
  • a patient who is producing milk and breastfeeding


Strengths: 150 mcg/mL


  • 9 mcg/kg/day or 18 mcg/kg/day by IV infusion over 30 to 60 minutes for 5 consecutive days every 21 days for 8 cycles.
  • Pre-medicate with an antihistamine and acetaminophen prior to each infusion.
  • Withhold treatment if serum albumin levels are less than 3.0 g/dL.
  • Discontinue for adverse infusion reactions.
  • Do not administer as a bolus injection.

Administration advice:

  • Do not mix this drug with other medications.
  • Do not administer this drug through an in-line filter.
  • Administer prepared solutions within 6 hours, using a syringe pump or IV infusion bag.

Side Effects

The Most Common

  • nausea
  • vomiting
  • diarrhea
  • loss of appetite
  • change in ability to taste
  • feeling tired
  • pain, including back, muscle, or joint pain
  • cough
  • headache
  • weakness
  • rash
  • itching

More Common

  • Hypoalbuminemia,
  • chills/fever,
  • asthenia,
  • infection,
  • chest pain,
  • hypotension,
  • vasodilation,
  • edema,
  • dyspnea,
  • nausea/vomiting,
  • anorexia,
  • diarrhea,
  • anemia,
  • increase in serum aminotransferase concentrations,
  • dizziness,
  • pain,
  • headache,
  • cough,
  • rash, and pruritus.

Drug Interaction

Pregnancy and Lactation

US FDA pregnancy category Not Assigned


It is not known whether Ontak can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Animal reproduction studies have not been conducted with Ontak. Ontak should be given to a pregnant woman only if clearly needed.


It is not known whether Ontak is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Ontak, a decision should be made whether to discontinue nursing or to discontinue Ontak, taking into account the importance of the drug to the mother.

How should this medicine be used?

Denileukin diftitox comes as a solution (liquid) to be injected over 30 to 60 minutes intravenously (into a vein). Denileukin diftitox is administered by a doctor or nurse in a medical office or infusion center. It is usually given once a day for 5 days in a row. This cycle may be repeated every 21 days for up to eight cycles.

What special precautions should I follow?

Before taking denileukin diftitox,

  • tell your doctor and pharmacist if you are allergic to denileukin diftitox or any of the ingredients in denileukin diftitox. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding.