Peringatan Keamanan

The most common (incidence 15 %) grade 3 or 4 treatment-related adverse events in dinutuximab compared with standard therapy recipients were neuropathic pain (52 vs. 6 %), fever without neutropenia (39 vs. 6 %), any in-fection (39 vs. 22 %), hypokalaemia (35 vs. 2 %), hypersensitivity reactions (25 vs. 1 %), hyponatraemia (23 vs. 4 %), elevation of alanine transferase levels (23 vs. 3 %) and hypotension (18 vs. 0 %). Based on its mechanism of action, dinutuximab may cause fetal harm when administered to a pregnant woman however, there are no studies in pregnant women and no reproductive studies in animals to inform the drug-associated risk. Non-clinical studies suggest that dinutuximab-induced neuropathic pain is mediated by binding of the antibody to the GD2 antigen located on the surface of peripheral nerve fibers and myelin and subsequent induction of cell- and complement-mediated cytotoxicity. In clinical trials, 114 (85%) patients treated in the dinutuximab/RA group experienced pain despite pre­-treatment with analgesics including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients in the dinutuximab/RA group compared to 5 (5%) patients in the RA group. Pain typically occurred during the dinutuximab infusion and was most commonly reported as abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, and arthralgia.

Dinutuximab

DB09077

biotech approved investigational

Deskripsi

Dinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour. It is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse.

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal half-life is 10 days
Volume Distribusi The mean volume of distribution at steady state (Vdss) is 5.4 L
Klirens (Clearance) The clearance is 0.21 L/day and increases with body size

Absorpsi

Data absorpsi tidak tersedia.

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

1114 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Dinutuximab.
Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Dinutuximab.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Dinutuximab.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Dinutuximab.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Dinutuximab.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Dinutuximab.
Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Dinutuximab.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Dinutuximab.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Dinutuximab.
Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Dinutuximab.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Dinutuximab.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Dinutuximab.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Dinutuximab.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Dinutuximab.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Dinutuximab.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Dinutuximab.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Dinutuximab.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Dinutuximab.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Dinutuximab.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Dinutuximab.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Dinutuximab.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Dinutuximab.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Dinutuximab.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Dinutuximab.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Dinutuximab.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Dinutuximab.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Dinutuximab.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Dinutuximab.
Flunisolide The risk or severity of adverse effects can be increased when Flunisolide is combined with Dinutuximab.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Dinutuximab.
Cladribine Dinutuximab may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Dinutuximab.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Dinutuximab.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Dinutuximab.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Dinutuximab.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Dinutuximab.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Dinutuximab.
Bexarotene The risk or severity of adverse effects can be increased when Bexarotene is combined with Dinutuximab.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Dinutuximab.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Dinutuximab.
Indomethacin The risk or severity of adverse effects can be increased when Indomethacin is combined with Dinutuximab.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Dinutuximab.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Dinutuximab.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Dinutuximab.
Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Dinutuximab.
Sorafenib The risk or severity of adverse effects can be increased when Sorafenib is combined with Dinutuximab.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Dinutuximab.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Dinutuximab.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Dinutuximab.
Betamethasone The risk or severity of adverse effects can be increased when Betamethasone is combined with Dinutuximab.
Teniposide The risk or severity of adverse effects can be increased when Teniposide is combined with Dinutuximab.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Dinutuximab.
Chloramphenicol The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Dinutuximab.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Dinutuximab.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Dinutuximab.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Dinutuximab.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Dinutuximab.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Dinutuximab.
Cyclophosphamide The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Dinutuximab.
Vincristine The risk or severity of adverse effects can be increased when Vincristine is combined with Dinutuximab.
Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Dinutuximab.
Propylthiouracil The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Dinutuximab.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Dinutuximab.
Methotrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Dinutuximab.
Carbamazepine The risk or severity of adverse effects can be increased when Carbamazepine is combined with Dinutuximab.
Vinblastine The risk or severity of adverse effects can be increased when Vinblastine is combined with Dinutuximab.
Fluticasone propionate The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Dinutuximab.
Fluocinolone acetonide The risk or severity of adverse effects can be increased when Fluocinolone acetonide is combined with Dinutuximab.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Dinutuximab.
Imatinib The risk or severity of adverse effects can be increased when Imatinib is combined with Dinutuximab.
Triamcinolone The risk or severity of adverse effects can be increased when Triamcinolone is combined with Dinutuximab.
Clofarabine The risk or severity of adverse effects can be increased when Clofarabine is combined with Dinutuximab.
Prednisone The risk or severity of adverse effects can be increased when Prednisone is combined with Dinutuximab.
Pemetrexed The risk or severity of adverse effects can be increased when Pemetrexed is combined with Dinutuximab.
Fludrocortisone The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Dinutuximab.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Dinutuximab.
Daunorubicin The risk or severity of adverse effects can be increased when Daunorubicin is combined with Dinutuximab.
Irinotecan The risk or severity of adverse effects can be increased when Irinotecan is combined with Dinutuximab.
Methimazole The risk or severity of adverse effects can be increased when Methimazole is combined with Dinutuximab.
Etoposide The risk or severity of adverse effects can be increased when Etoposide is combined with Dinutuximab.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Dinutuximab.
Dacarbazine The risk or severity of adverse effects can be increased when Dacarbazine is combined with Dinutuximab.
Temozolomide The risk or severity of adverse effects can be increased when Temozolomide is combined with Dinutuximab.
Penicillamine The risk or severity of adverse effects can be increased when Penicillamine is combined with Dinutuximab.
Prednisolone The risk or severity of adverse effects can be increased when Prednisolone is combined with Dinutuximab.
Sirolimus The risk or severity of adverse effects can be increased when Sirolimus is combined with Dinutuximab.
Mechlorethamine The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Dinutuximab.
Azacitidine The risk or severity of adverse effects can be increased when Azacitidine is combined with Dinutuximab.
Carboplatin The risk or severity of adverse effects can be increased when Carboplatin is combined with Dinutuximab.
Methylprednisolone The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Dinutuximab.
Dactinomycin The risk or severity of adverse effects can be increased when Dactinomycin is combined with Dinutuximab.
Cytarabine The risk or severity of adverse effects can be increased when Cytarabine is combined with Dinutuximab.
Azathioprine The risk or severity of adverse effects can be increased when Azathioprine is combined with Dinutuximab.
Doxorubicin The risk or severity of adverse effects can be increased when Doxorubicin is combined with Dinutuximab.
Hydroxyurea The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Dinutuximab.
Busulfan The risk or severity of adverse effects can be increased when Busulfan is combined with Dinutuximab.
Mycophenolic acid The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Dinutuximab.
Topotecan The risk or severity of adverse effects can be increased when Topotecan is combined with Dinutuximab.
Mercaptopurine The risk or severity of adverse effects can be increased when Mercaptopurine is combined with Dinutuximab.
Thalidomide The risk or severity of adverse effects can be increased when Thalidomide is combined with Dinutuximab.

Target Protein

GD2 disialoganglioside

Referensi & Sumber

Artikel (PubMed)
  • PMID: 25940913
    Dhillon S: Dinutuximab: first global approval. Drugs. 2015 May;75(8):923-7. doi: 10.1007/s40265-015-0399-5.
  • PMID: 24295643
    Ahmed M, Cheung NK: Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy. FEBS Lett. 2014 Jan 21;588(2):288-97. doi: 10.1016/j.febslet.2013.11.030. Epub 2013 Dec 1.
  • PMID: 1988079
    Barker E, Mueller BM, Handgretinger R, Herter M, Yu AL, Reisfeld RA: Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res. 1991 Jan 1;51(1):144-9.
  • PMID: 15923178
    Aixinjueluo W, Furukawa K, Zhang Q, Hamamura K, Tokuda N, Yoshida S, Ueda R, Furukawa K: Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies: roles of anoikis. J Biol Chem. 2005 Aug 19;280(33):29828-36. Epub 2005 May 26.

Contoh Produk & Brand

Produk: 4 • International brands: 0
Produk
  • Qarziba
    Injection, solution, concentrate • 4.5 mg/ml • Intravenous • EU • Approved
  • Unituxin
    Injection • 3.5 mg/1mL • Intravenous • US • Approved
  • Unituxin
    Solution • 3.5 mg / mL • Intravenous • Canada • Approved
  • Unituxin
    Injection, solution, concentrate • 3.5 mg/ml • Intravenous • EU

Sekuens Gen/Protein (FASTA)

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