denileukin diftitox


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denileukin diftitox

 [den″ĭ-loo´kin dif´tĭ-toks]
a genetically engineered construct containing amino acid sequences for specific diphtheria toxin fragments linked to sequences for interleukin-2 (IL-2), so that the cytotoxic action of the diphtheria toxin is targeted to cells expressing a specific form of the IL-2 receptor, as in certain leukemias and lymphomas. It is used as an antineoplastic in the treatment of cutaneous T-cell lymphomas, administered intravenously.

denileukin diftitox

Ontak

Pharmacologic class: Biological response modifier

Therapeutic class: Antineoplastic

Pregnancy risk category C

FDA Box Warning

• Give only under supervision of physician experienced in cancer chemotherapy, in facility equipped and staffed for cardiopulmonary resuscitation where patient can be monitored closely.

Action

Recombinant DNA-derived cytotoxic protein. Interacts with interleukin-2 (IL-2) receptors on cell surface and inhibits cellular protein synthesis, causing cell death.

Availability

Frozen solution for injection: 150 mcg/ml

Indications and dosages

Persistent or recurrent cutaneous T-cell lymphoma that expresses CD25 component of IL-2 receptor

Adults: 9 or 18 mcg/kg/day I.V. infused over 15 minutes for 5 consecutive days q 21 days

Contraindications

• Hypersensitivity to drug, its components, diphtheria toxin, or IL-2

Precautions

Use cautiously in:

• cardiovascular disease

• elderly patients

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Follow facility procedures for safe handling, administration, and disposal of chemotherapeutic agents.

Administer by I.V. infusion only. Don't give by I.V. bolus.

• Dilute I.V. dose further with normal saline to concentration of at least 15 mcg/ml. Infuse over at least 15 minutes.

• Premedicate with acetaminophen, nonsteroidal anti-inflammatory drugs, and antihistamines, as ordered, to minimize infusion-related events.

• Gently swirl vial to mix, but avoid vigorous agitation.

• Don't mix with other drugs.

• Don't deliver through in-line filter.

• Infuse over at least 15 minutes.

During infusion, observe closely for signs and symptoms of hypersensitivity reaction.

Adverse reactions

CNS: dizziness, paresthesia, nervousness, confusion, insomnia, syncope, headache

CV: hypotension, hypertension, vasodilation, tachycardia, chest pain, capillary leak syndrome (with extravasation), thrombosis, arrhythmias

EENT: rhinitis, pharyngitis, laryngospasm

GI: nausea, vomiting, diarrhea, constipation, flatulence, dyspepsia, difficulty swallowing, anorexia

GU: hematuria, albuminuria, pyuria

Hematologic: anemia, thrombocytopenia, leukopenia

Musculoskeletal: myalgia, back or joint pain

Metabolic: hypoalbuminemia, hypocalcemia, hypokalemia, dehydration

Respiratory: dyspnea, cough, lung disorder

Skin: rash, pruritus, sweating

Other: weight loss, edema, flulike symptoms, injection site reaction, hypersensitivity reactions including anaphylaxis

Interactions

Drug-drug. Live-virus vaccines: decreased antibody reaction

Drug-diagnostic tests. Albumin, calcium, potassium: decreased levels

Urine creatinine: increased level

Patient monitoring

• Monitor patient closely during first infusion and for 24 hours afterward.

• Evaluate patient for vascular leak syndrome (marked by at least two of the following: edema, hypotension, hypoalbuminemia).

• Monitor CBC, blood chemistry panel, renal and hepatic function, and albumin level. Repeat all tests weekly during therapy.

Patient teaching

Instruct patient to immediately report chest pain, difficulty breathing, chills, burning at infusion site, or throat tightness, redness, swelling, or pain.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Inform patient that drug makes him more susceptible to infection. Advise him to avoid crowds and exposure to illness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

References in periodicals archive ?
Systemic treatments for patients who do not respond to local therapy, or in more advanced disease include methotrexate, interferon-alpha, oral bexarotene, denileukin diftitox, and combination chemotherapy Photopheresis is reserved for erythrodermic disease.
Similarly, the IL-2-diphtheria toxin fusion protein denileukin diftitox was effective in patients with renal cell carcinoma (RCC) [76] but had an adverse effect in metastatic melanoma [77].
Duvic et al., "Toxic epidermal necrolysis associated with denileukin diftitox (DAB389IL-2) administration in a patient with follicular large cell lymphoma," Leukemia & Lymphoma, vol.
Palena, "IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity," Blood, vol.
Therapies for GVHD included steroids, mycophenolate mofetil, tacrolimus, sirolimus, denileukin diftitox, and infliximab.
Denileukin diftitox is a novel recombinant fusion protein consisting of fragments of diphtheria toxin linked to human interleukin-2 and works by targeting the high-affinity interleukin-2 receptors.
Foss, "Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous Tcell lymphoma," Cancer Management and Research, vol.
Olsen et al., "Quality-of-life improvements in cutaneous T-cell lymphoma patients treated with Denileukin Diftitox (ONTAK)," Clinical Lymphoma, vol.
Therefore, comparison of the incidence of antibodies to Elspar with the incidence of antibodies to other products may be misleading' Ontak An immune response to denileukin diftitox was (denileukin difitox) assessed using two enzyme-linked immunoassays (ELISA).
The agreement is designed to enable Eisai to extend its oncology program, increasing the number of indications investigated for the six potential products, including eribulin (E7389), E7080, Ontak (denileukin diftitox), E7820, E6201 and E7050.
This collaboration is a new business model in which Eisai and Quintiles share clinical development risks and work together to increase speed and probability of success in developing Eisai's six oncology candidate compounds, which include eribulin mesylate (E7389), E7080, ONTAK(R)(generic name: denileukin diftitox), E7820, E6201, and E7050.
Foodand Drug Administration (FDA) has approved an efficacy supplemental biologics license application (sBLA) for ONTAK' (denileukin diftitox) solution for intravenous injection for the treatment of patients with persistent or recurrent cutaneous T-celllymphoma (CTCL) whose malignant cells express the CD25 component of the interleukin (IL)-2 receptor (CD25+).