Siltuximab
Identification
- Summary
Siltuximab is an interleukin antagonist used to treat multicentric Castleman's disease (MCD) in patients who are HIV and HHV-8 negative.
- Brand Names
- Sylvant
- Generic Name
- Siltuximab
- DrugBank Accession Number
- DB09036
- Background
Siltuximab 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.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6450H9932N1688O2016S50
- Protein Average Weight
- 145000.0 Da
- Sequences
>Heavy Chain Sequence EVQLVESGGKLLKPGGSLKLSCAASGFTFSSFAMSWFRQSPEKRLEWVAEISSGGSYTYY PDTVTGRFTISRDNAKNTLYLEMSSLRSEDTAMYYCARGLWGYYALDYWGQGTSVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light Chain Sequence QIVLIQSPAIMSASPGEKVTMTCSASSSVSYMYWYQQKPGSSPRLLIYDTSNLASGVPVR FSGSGSGTSYSLTISRMEAEDAATYYCQQWSGYPYTFGGGTKLEIKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format- Synonyms
- Siltuximab
- External IDs
- CLLB8
- CNTO 328
- CNTO-328
- CNTO328
Pharmacology
- Indication
Siltuximab 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Castleman's disease •••••••••••• ••••• ••••••••••••• ••••••••• ••• •••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Siltuximab-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 action
Siltuximab complexes with human IL-6 and prevents binding to soluble and membrane-bound IL-6 receptors, thereby inhibiting the proliferation of lymphocytes.
Target Actions Organism AInterleukin-6 antagonistantibodyHumans - Absorption
Not Available
- Volume of distribution
Based on population pharmacokinetic analysis, the central volume of distribution in a male subject with body weight of 70 kg is 4.5 L.
- Protein binding
Not Available
- Metabolism
As siltuximab is an antibody, the expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance.
- Route of elimination
Not Available
- Half-life
The mean terminal half life after the first intravenous infusion of 11 mg/kg is 20.6 days.
- Clearance
Body 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.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The 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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Siltuximab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Siltuximab. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Siltuximab. Abrocitinib The metabolism of Abrocitinib can be increased when combined with Siltuximab. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Siltuximab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Sylvant Injection, powder, for solution 100 mg Intravenous Recordati Netherlands B.V. 2020-12-23 Not applicable EU Sylvant Injection, powder, for solution 400 mg/1 Intravenous EUSA Pharma (UK) Ltd 2014-04-23 Not applicable US Sylvant Injection, powder, lyophilized, for solution 400 mg/1 Intravenous Janssen Biotech, Inc. 2014-04-01 2021-01-31 US Sylvant Powder, for solution 100 mg / vial Intravenous Eusa Pharma (Uk) Limited 2015-03-03 Not applicable Canada Sylvant Injection, powder, for solution 400 mg Intravenous Recordati Netherlands B.V. 2020-12-23 Not applicable EU
Categories
- ATC Codes
- L04AC11 — Siltuximab
- Drug Categories
- Agents reducing cytokine levels
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Immunotherapy
- Interleukin Inhibitors
- Interleukin-6 Antagonist
- Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- T4H8FMA7IM
- CAS number
- 541502-14-1
References
- General References
- Puchalski T, Prabhakar U, Jiao Q, Berns B, Davis HM: Pharmacokinetic and pharmacodynamic modeling of an anti-interleukin-6 chimeric monoclonal antibody (siltuximab) in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2010 Mar 1;16(5):1652-61. doi: 10.1158/1078-0432.CCR-09-2581. Epub 2010 Feb 23. [Article]
- Deisseroth A, Ko CW, Nie L, Zirkelbach JF, Zhao L, Bullock J, Mehrotra N, Del Valle P, Saber H, Sheth C, Gehrke B, Justice R, Farrell A, Pazdur R: FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. Clin Cancer Res. 2015 Mar 1;21(5):950-4. doi: 10.1158/1078-0432.CCR-14-1678. Epub 2015 Jan 19. [Article]
- Liu YC, Stone K, van Rhee F: Siltuximab for multicentric Castleman disease. Expert Rev Hematol. 2014 Oct;7(5):545-57. doi: 10.1586/17474086.2014.946402. Epub 2014 Aug 9. [Article]
- External Links
- KEGG Drug
- D09669
- PubChem Substance
- 347910394
- 1535218
- ChEMBL
- CHEMBL1743070
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Siltuximab
- FDA label
- Download (326 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1 3 Terminated Treatment Acute Respiratory Distress Syndrome (ARDS) / Coronavirus Disease 2019 (COVID‑19) / Lung Disorder / Pneumonia / Respiratory Tract Diseases / Respiratory Tract Infections (RTI) 1 3 Withdrawn Treatment Multiple Myeloma (MM) 1 2 Active Not Recruiting Treatment Multiple Myeloma (MM) / Primary Amyloidosis 1 2 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 100 mg/1 Injection, powder, for solution Intravenous 400 mg/1 Injection, powder, for solution Intravenous; Parenteral 100 MG Injection, powder, for solution Intravenous; Parenteral 400 MG Injection, powder, lyophilized, for solution Intravenous 100 mg/1 Injection, powder, lyophilized, for solution Intravenous 400 mg/1 Powder, for solution Intravenous 100 mg / vial Powder, for solution Intravenous 400 mg / vial Injection Parenteral Injection Parenteral 100 mg Injection, powder, for solution Intravenous 100 mg Injection Parenteral 400 mg Injection, powder, for solution Intravenous 400 mg Injection, powder, lyophilized, for solution Intravenous 100 mg Injection, powder, lyophilized, for solution Intravenous 400 mg Injection, solution, concentrate Intravenous 100 mg/1vial - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7612182 No 2009-11-03 2027-08-01 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAntibody
- General Function
- Interleukin-6 receptor binding
- Specific Function
- Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Inv...
- Gene Name
- IL6
- Uniprot ID
- P05231
- Uniprot Name
- Interleukin-6
- Molecular Weight
- 23717.965 Da
References
- van Zaanen HC, Koopmans RP, Aarden LA, Rensink HJ, Stouthard JM, Warnaar SO, Lokhorst HM, van Oers MH: Endogenous interleukin 6 production in multiple myeloma patients treated with chimeric monoclonal anti-IL6 antibodies indicates the existence of a positive feed-back loop. J Clin Invest. 1996 Sep 15;98(6):1441-8. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
Drug created at March 16, 2015 19:35 / Updated at June 03, 2022 07:24