Denileukin diftitox Drugbank ID : DB00004 Chemical formula : C2560H4042N678O799S17 Average wt. : 57647.3 Half life : 70-80 min Image source : Drug bank

For treatment of cutaneous T-cell lymphoma Pharmacodynamics : Description : Ontak (denileukin diftitox), is a recombinant DNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met1-Thr387)-His and the sequences for human interleukin-2 (IL-2; Ala1-Thr133) Indication : For treatment of cutaneous T-cell lymphoma Pharmacodynamics : Denileukin diftitox (Ontak) directs the cytocidal action of diphtheria toxin to cells which 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). Ontak interacts with the high affinity IL-2 receptor on the cell surface and inhibits cellular protein synthesis, resulting in cell death within hours.

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. Volume of distribution : 0.06 to 0.09 L/kg Clearance : * 0.6 - 2.0 mL/min/kg [Lymphoma]

Drug Interaction: Affected organisms : total of 107 drugs (306 brand and generic names) are known to interact. Targets : Interleukin-2 receptor subunit alpha,Interleukin-2 receptor subunit beta,Cytokine receptor common subunit gamma Affected organisms : Humans and other mammals

Categories : Sequence : Antineoplastic Agents MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTHAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT

Brands : Ontak Company : Seragen Inc Description : Ontak (denileukin diftitox), is a recombinant DNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met1-Thr387)-His and the sequences for human interleukin-2 (IL-2; Ala1-Thr133) Used for/Prescribed for : used to treat leukemia and lymphomas, including cutaneous (of the skin) T-cell lymphoma. Formulation : Ontak contains 300 mcg of recombinant denileukin diftitox in a sterile solution of citric acid (20 mM), EDTA (0.05 mM) and polysorbate 20 ( < 1%) in Water for Injection, USP. The solution has a pH range of 6.9 to 7.2. Form : sterile, white, preservative-free, lyophilized powder. Route of administration : intravenous (IV) administration

Dosage : Administer at 9 or 18 mcg/kg/day by intravenous infusion over 30-60 minutes for 5 consecutive days every 21 days for 8 cycles Contraindication : allergic Side effects : common side effects include , headache, dizziness, or nervousness; numbness or tingling, skin itching or rash; runny or stuffy nose; weight gain or loss; mild diarrhea or constipation; Drug interaction : total of 107 drugs (306 brand and generic names) are known to interact in which 29 major drug interactions (72 brand and generic names) 78 moderate drug interactions (234 brand and generic names) .

General references : 1)Turturro F: Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid-derived disorders. Expert Rev Anticancer Ther. 2007 Jan;7(1):11-7. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17187516 2)Park M, Liu GT, Piltz-Seymour J, Wisda CL, Rook AH, Junkins-Hopkins JM, Nasta SD, Kim EJ: Vision loss following denileukin diftitox treatment: a case report of possible posterior ischemic optic neuropathy. Leuk Lymphoma. 2007 Apr;48(4):808-11. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17454642.

References : http://www.drugs.com/mtm/ontak.html http://www.drugs.com/dosage/ontak.html http://www.rxlist.com/ontak-drug.htm