denileukin diftitox

(redirected from Ontak)

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 ?
The FDA's action, following a priority review, marks the conversion of an accelerated approval indication to full approval and is based on data from a Phase III clinical trial that evaluated the overall efficacy and safety of ONTAK in certain patients with CTCL.
Tokyo, Japan, Sept 8, 2006 - (JCN) - Eisai has announced that it signed a product acquisition agreement with California-based Ligand Pharmaceuticals for exclusive global rights for their four oncology-related products, ONTAK (denileukin diftitox), Targretin (bexarotene) capsules, Targretin (bexarotene) gel 1% and Panretin (alitretinoin) gel 0.
Food and Drug Administration approved ONTAK in the United States in February 1999.
Adina 'ortak' denmesine ragmen neye, kime, nasil, ne kadar ontak oldugunu bilemeden yasamis; muhabbeti, sevdayi hic bilmemistir.
During the fourth quarter of this year, we completed the doubling of our sales force from 20 to 40 representatives in order to support the Targretin launch and accelerate ONTAK growth.
ONTAK is a genetically-engineered cytotoxic fusion protein consisting of the amino acid sequences for the enzymatically-active portion of diphtheria toxin fused to the sequence of human interleukin-2, resulting in a molecule that is cytotoxic for cells bearing the target IL-2 receptor.
Targretin capsules, together with Targretin gel, targeted for a fourth quarter 1999 NDA filing, and ONTAK, recently approved for CTCL, forms a product portfolio that could offer patients and physicians a range of therapeutic options for all clinical stages of CTCL.
These increases are partially offset by lower net product sales of ONTAK due to lower demand.
It promises to be an advance over Ontak, currently marketed for the treatment of cutaneous T cell lymphoma and with reports of efficacy in other cancers as well, including peripheral T cell lymphoma and melanoma.
Overall, given the continuing impact of price increases and the fixed level of amortization of the capitalized license, royalty and technology rights, we expect the overall gross margin percentage to increase as sales of AVINZA and ONTAK increase.
Physicians can have confidence in ONTAK since it is the most extensively studied agent in CTCL.