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1802 details
Primary information
ThPP IDTh1196
Therapeutic Peptide/Protein NameSiltuximab
SequenceNA view full sequnce in fasta
Functional ClassificationIia
Molecular Weight145000
Chemical FormulaC6450H9932N1688O2016S50
Isoelectric PointNA
HydrophobicityNA
Melting Point (℃)NA
Half LifeThe mean terminal half life after the first intravenous infusion of 11 mg/kg is 20.6 days.
DescriptionSiltuximab is a chimeric (human-mouse) monoclonal immunoglobulin G1-kappa antibody produced in a Chinese hamster ovary (CHO) cell line by recombinant DNA technology. Siltuximab prevents the binding of IL-6 to soluble and membrane-bound IL-6 receptors by forming high affinity complexes with human interleukin-6 (IL-6). Its use is indicated for the treatment of adult patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. MCD is a rare blood disorder caused by dysregulated IL-6 production, proliferation of lymphocytes, and subsequent enlargement of the lymph nodes. It is administered as a 1 hour intravenous infusion every 3 weeks.
Indication/DiseaseIt is indicated for the treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. Siltuximab did not bind to virally produced IL-6 in a nonclinical study and was therefore not studied in patients with MCD who are HIV or HHV-8 positive.
PharmacodynamicsSiltuximab-neutralized antibody-IL-6 complexes interfere with current immunological-based IL-6 quantification methods, therefore measurement of serum or plasma IL-6 concentrations should not be used as a pharmacodynamic marker during treatment. As well, cytochrome P450 enzymes in the liver are down regulated by infection and inflammation stimuli, which includes cytokines such as IL-6. By preventing IL-6 signalling through treatment with siltuximab, CYP450 activity may be increased leading to faster metabolism of drugs that are CYP450 substrates.
Mechanism of ActionSiltuximab complexes with human IL-6 and prevents binding to soluble and membrane-bound IL-6 receptors, thereby inhibiting the proliferation of lymphocytes.
ToxicityThe most common side effects that occurred during siltuximab treatment were pruritis, increased weight, rash, hyperuricemia, and upper respiratory tract infection. Siltuximab should not be administered to patients with severe infections as it may mask signs and symptoms of acute inflammation including suppression of fever and acute phase reactants such as C-reactive protein (CRP). Gastrointestinal perforation has been reported in clinical trials, therefore use with caution in patients who may be at increased risk for GI perforation.
MetabolismAs siltuximab is an antibody, the expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance.
AbsorptionNA
Volume of DistributionBased on population pharmacokinetic analysis, the central volume of distribution in a male subject with body weight of 70 kg is 4.5 L.
ClearanceBody weight was identified as the only statistically significant covariate of siltuximab clearance, therefore body weight based dosing is appropriate. Based on population pharmacokinetic analysis, the clearance of situximab in patients is 0.23 L/day.
CategoriesAntineoplastic and Immunomodulating Agents, Immunosuppressive Agents
Patents NumberUS7612182
Date of Issue39295
Date of Expiry46600
Drug InteractionAbiraterone, Alfuzosin, Alprazolam, Aminophylline, Amiodarone, Amlodipine, Apixaban, Apremilast, Aprepitant, Aripiprazole, Armodafinil, Atazanavir, Atorvastatin, Avanafil, Axitinib, Bedaquiline, Belimumab, Benzphetamine, Bisoprolol, Boceprevir, Bortezomib, Bosutinib, Brexpiprazole, Buprenorphine, Buspirone, Cabazitaxel, Cabozantinib, Calcitriol, Carbamazepine, Ceritinib, Chlordiazepoxide, Chloroquine, Cilostazol, Citalopram, Clarithromycin, Clonazepam, Clorazepate, Cobicistat, Cobimetinib, Conivaptan, Crizotinib, Cyclosporine, Cyproterone acetate, Daclatasvir, Dantrolene, Dapsone, Darifenacin, Darunavir, Dasatinib, Delavirdine, Denosumab, Dexamethasone, Diazepam, Dienogest, Diltiazem, Disopyramide, Docetaxel, Doxazosin, Doxorubicin, Dronedarone, Efavirenz, Eliglustat, Elvitegravir, Enzalutamide, Eplerenone, Erlotinib, Erythromycin, Escitalopram, Estradiol, Estrone sulfate, Eszopiclone, Ethosuximide, Etoposide, Etravirine, Everolimus, Exemestane, Felbamate, Felodipine, Fesoterodine, Flibanserin, Flunisolide, Flurazepam, Flutamide, Fosamprenavir, Fosaprepitant, Gefitinib, Guanfacine, Haloperidol, Hydrocodone, Hydroxyprogesterone caproate, Ibrutinib, Idelalisib, Imatinib, Indinavir, Irinotecan, Isavuconazonium, Isosorbide, Isosorbide Dinitrate, Isosorbide Mononitrate, Isradipine, Itraconazole, Ivabradine, Ivacaftor, Ixabepilone, Ixazomib, Ketoconazole, Lansoprazole, Lapatinib, Leflunomide, Levonorgestrel, Lidocaine, Lomitapide, Losartan, Lovastatin, Lurasidone, Macitentan, Maraviroc, Medroxyprogesterone acetate, Mefloquine, Methadone, Midazolam, Mifepristone, Mirtazapine, Modafinil, Naloxegol, Natalizumab, Nateglinide, Nefazodone, Nelfinavir, Nevirapine, Nicardipine, Nifedipine, Nilotinib, Nimodipine, Nisoldipine, Norethisterone, Olaparib, Ondansetron, Ospemifene, Oxycodone, Paclitaxel, Palbociclib, Panobinostat, Pazopanib, Perampanel, Pimecrolimus, Pimozide, Pipotiazine, Praziquantel, Primaquine, Progesterone, Quetiapine, Quinidine, Quinine, Rabeprazole, Ranolazine, Regorafenib, Repaglinide, Rifabutin, Rilpivirine, Riociguat, Ritonavir, Rivaroxaban, Roflumilast, Rolapitant, Ruxolitinib, Saquinavir, Sildenafil, Silodosin, Simeprevir, Simvastatin, Sipuleucel-T, Sirolimus, Solifenacin, Sonidegib, Spiramycin, Stiripentol, Sunitinib, Suvorexant, Tacrolimus, Tamoxifen, Tamsulosin, Tasimelteon, Telaprevir, Telithromycin, Temsirolimus, Teniposide, Tetracycline, Theophylline, Tiagabine, Ticagrelor, Ticlopidine, Tipranavir, Tofacitinib, Tolterodine, Tolvaptan, Toremifene, Trabectedin, Tramadol, Trastuzumab, Trazodone, Triazolam, Trimethoprim, Trimipramine, Ulipristal, Vandetanib, Vemurafenib, Venlafaxine, Verapamil, Vilazodone, Vinblastine, Vincristine, Vinorelbine, Vortioxetine, Zolpidem, Zonisamide, Zopiclone
TargetInterleukin-6
Information of corresponding available drug in the market
Brand NameSylvant
CompanyJanssen Inc
Brand DiscriptionSYLVANT (siltuximab) is a human-mouse chimeric monoclonal antibody that binds human interleukin-6 (IL-6). SYLVANT is produced by Chinese hamster ovary cells.
Prescribed forNA
Chemical NameNA
Formulation100 mg
Physcial AppearnceLyophilized powder
Route of AdministrationIntravenous infusion
Recommended DosageSYLVANT 11 mg/kg is given over 1 hour as an intravenous infusion administered every 3 weeks until treatment failure.
ContraindicationSevere hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.
Side EffectsConcurrent active severe infections; Infusion-related reactions and hypersensitivity
Useful Linkhttp://www.rxlist.com/sylvant-drug.htm
PubMed ID27195659, 25484055, 24846335, 24284914, 21225019, 28315704, 28241173, 28140696, 28100459
3-D StructureTh1196 Heavy chianor (Download)Th1196 Light chian (View) or (Download)