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.

denileukin diftitox

/den·i·leu·kin dif·ti·tox/ (den″ĭ-loo´kin dif´tĭ-toks) a genetically engineered construct combining amino acid sequences for specific diphtheria toxin fragments linked to sequences for interleukin-2 (IL-2); used as an antineoplastic.

denileukin diftitox

a miscellaneous antineoplastic.
indications It is used to treat cutaneous T cell lymphoma that expresses the CD25 component of the IL-2 receptor.
contraindications Hypersensitivity to denileukin, diphtheria toxin, or interleukin-2 prohibits its use.
adverse effects Life-threatening effects are thrombocytopenia and leukopenia. Other serious side effects include hematuria, albuminuria, pyuria, creatinine increase, anemia, hypoalbuminemia, edema, hypocalcemia, dehydration, hypokalemia, infection, chest pain, and flu-like symptoms. Common side effects include dizziness, paresthesia, nervousness, confusion, insomnia, hypotension, vasodilation, tachycardia, thrombosis, hypertension, dysrhythmias, nausea, anorexia, vomiting, diarrhea, constipation, dyspepsia, and dysphagia.
References in periodicals archive ?
Denileukin diftitox has been very effective in treating cutaneous lymphoma; it causes rapid tumor lysis by inhibiting protein synthesis in cells that express the interleukin-2 receptor.
The patient in Figure 2 had stage IIB disease and has been treated with denileukin diftitox, bexarotene capsules, interferon alfa-2a, and, most currently, combination chemotherapy.
In the upcoming trial, patients will be pretreated with a single dose of denileukin diftitox, which can heighten immune responses to vaccine.
Goy tested the efficacy and safety of denileukin diftitox, a genetically engineered fusion protein that targets cancers that express the interleukin-2 receptor.
today announced that they had concluded a license and joint development agreement for the development of denileukin diftitox (generic name) in Japan.
Denileukin diftitox is a solution for intravenous injection for the treatment of patients with cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the interleukin (IL)-2 receptor (CD25+).
Patients treated with denileukin diftitox must be managed in a facility equipped and staffed for cardiopulmonary resuscitation and where the patient can be closely monitored for an appropriate period based on his or her health status.
ONTAK is contraindicated for use in patients with a known sensitivity to denileukin diftitox or any of its components: diphtheria toxin, IL-2, or excipients.
The safety and efficacy of denileukin diftitox in patients with CTCL whose malignant cells do not express the CD25 component of the IL-2 receptor have not been examined.
The investigators concluded that the novel combination of denileukin diftitox and rituximab has significant clinical activity in this heavily pretreated population, with toxicities that can be managed with premedications and close monitoring.