Certolizumab Pegol - Drugbank

Home , Afelimomab

9/19/2018 Certolizumab pegol - DrugBank

Certolizumab pegol

Targets (1) Biointeractions (1)

IDENTIFICATION

Name Certolizumab pegol

Accession Number DB08904

Type Biotech

Groups Approved

Biologic Classiﬁcation Protein Based Therapies Monoclonal antibody (mAb) / Fusion proteins

Description Certolizumab pegol is a recombinant Fab' antibody fragment against tumor necrosis factor alpha which is conjugated to an approximately 40kDa polyethylene glycol (PEG2MAL40K). Polyethylene glycol helps to delay the metabolism and elimination of the drugs. Chemically, the light chain is made up of 214 amino acid residues while the heavy chain is composed of 229 amino acid residues. The molecular mass of the Fab' antibody fragment itself is 47.8 kDa. It is used for the treatment of rheumatoid arthritis and Crohn’s disease. FDA approved on April 22, 2008

Protein chemical formula

C2115H3252N556O673S16

Protein average weight 91000 0 Da https://www.drugbank.ca/drugs/DB08904 1/13 9/19/2018 Certolizumab pegol - DrugBank 91000.0 Da

Sequences

>Amino acid sequence of the light chain DIQMTQSPSSLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASFLYSGVPY RFSGSGSGTDFTLTISSLQPEDFATYYCQQYNIYPLTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>Amino acid sequence of the heavy chain EVQLVESGGGLVQPGGSLRLSCAASGYVFTDYGMNWVRQAPGKGLEWMGWINTYIGEPIY ADSVKGRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCARGYRSYAMDYWGQGTLVTVSSAS TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA

Download FASTA Format

Synonyms Not Available

External IDs

CDP 870 / CDP-870 / CDP870 / PHA-738144

Prescription Products

MARKETING MARKETING NAME ↑↓ DOSAGE ↑↓ STRENGTH ↑↓ ROUTE ↑↓ LABELLER ↑↓ START ↑↓ END ↑↓ ↑↓ ↑↓

Cimzia Injection, 200 mg Subcutaneous Ucb Pharma 2009-10-01 Not applicable solution Sa

Cimzia Solution 200 mg Subcutaneous Ucb Inc 2017-08-04 Not applicable

Cimzia Injection, 200 mg Subcutaneous Ucb Pharma 2009-10-01 Not applicable solution Sa

Cimzia Injection, 200 mg/1mL Subcutaneous Ucb Inc 2009-05-14 Not applicable solution

Cimzia Solution 200 mg Subcutaneous Ucb Inc 2009-08-31 Not applicable

Cimzia Injection, 200 mg Subcutaneous Ucb Pharma 2009-10-01 Not applicable solution Sa

https://www.drugbank.ca/drugs/DB08904 2/13 9/19/2018 Certolizumab pegol - DrugBank

MARKETING MARKETING Cimzia Kit 200 mg/1mL Ucb Inc 2008-04-20 Not applicable NAME ↑↓ DOSAGE ↑↓ STRENGTH ↑↓ ROUTE ↑↓ LABELLER ↑↓ START ↑↓ END ↑↓ ↑↓ ↑↓

Showing 1 to 8 of 8 entries ‹ ›

Categories

Alcohols

Amino Acids, Peptides, and Proteins

Antibodies

Antibodies, Monoclonal

Antibodies, Monoclonal, Humanized

Antineoplastic and Immunomodulating Agents

Biologics for Rheumatoid Arthritis Treatment

Biomedical and Dental Materials

Blood Proteins

Disease-modifying Antirheumatic Agents

Ethylene Glycols

Globulins

Glycols

Immunoglobulin Fab Fragments

Immunoglobulin Fragments

Immunoglobulins

Immunologic Factors

Immunoproteins

Immunosuppressive Agents

Macromolecular Substances

Miscellaneous GI Drugs

Peptide Fragments

Peptides

Polyethylene Glycols

Polymers

Proteins https://www.drugbank.ca/drugs/DB08904 3/13 9/19/2018 Certolizumab pegol - DrugBank Proteins

Serum Globulins

Tumor Necrosis Factor Alpha (TNF-α) Inhibitors

Tumor Necrosis Factor Blocker

Tumor Necrosis Factor Receptor Blocking Activity

UNII G6ADW90R16

CAS number 428863-50-7

PHARMACOLOGY

Indication Reducing signs and symptoms of Crohn's disease and treatment of moderately to severely active rheumatoid arthritis (RA).

Associated Conditions

Ankylosing Spondylitis (AS)

Psoriatic arthritis aggravated

Severe Crohn's Disease

Moderate Crohn's disease

Moderate Rheumatoid arthritis

Severe Rheumatoid arthritis

Pharmacodynamics

TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Biological activity associated to TNFα include the upregulation of cellular adhesion molecules and chemokines, upregulation of major histocompatibility complex (MHC) class I and class II molecules, and direct leukocyte activation. TNFα stimulates the production of downstream inflammatory mediators, including interleukin-1, prostaglandins, platelet activating factor, and nitric oxide. Aer treatment with certolizumab pegol, patients with Crohn's disease demonstrated a decrease in the levels of C-reactive protein (CRP).

Mechanism of action

Certolizumab pegol binds to free and membrane-bound human TNFα with a KD of 90pM and https://www.drugbank.ca/drugs/DB08904 4/13 9/19/2018 p g Certolizumab pegol - DrugBank p neutralizes its activity. Extent of neutralization is also dose-dependent. It also inhibited the release of lipopolysaccharide-induced IL-1β from monocytes. TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes in which elevated levels have been observed in patients with RA and Crohn's. Certolizumab pegol selectively neutralizes TNFα (IC90 of 4 ng/mL for inhibition of human TNFα in the in vitro L929 murine fibrosarcoma cytotoxicity assay). It does not bind to TNF-β. As certolizumab is only a Fab' fragment and thus missing the Fc region, it does not fix complement or cause antibody-dependent cell-mediated cytotoxicity. Furthermore, apoptosis of monocytes or lymphocytes, or neutrophil degranulation have not been observed in vitro.

A Tumor necrosis factor

neutralizer

Human

Absorption There is a linear relationship between dose administered and Cmax and AUC. A mean Cmax of approximately 43 to 49 mcg/mL occurred at Week 5 during the initial loading dose period using the recommended dose regimen for the treatment of patients with rheumatoid arthritis (400 mg sc at Weeks 0, 2 and 4 followed by 200 mg every other week). Tmax, SubQ dose = 54 - 171 hours; Bioavailability, SubQ dose = 80% (range of 76% - 88%)

Volume of distribution Vd, steady state, Crohn's and RA patients = 6 - 8 L

Protein binding Not Available

Metabolism

Metabolism has not been studied in humans.

Route of elimination

The route of elimination of certolizumab pegol has not been studied in human subjects. Studies in animals indicate that the major route of elimination of the PEG component is via urinary excretion.

Half life Terminal plasma elimation half-life = 14 days (for all doses);

Clearance https://www.drugbank.ca/drugs/DB08904 5/13 9/19/2018 Certolizumab pegol - DrugBank Clearance IV dose, healthy subjects = 9.21 mL/h to 14.38 mL/h; SC dose, Crohn's disease patients = 17 mL/h; SC dose, RA patients = 21.0 mL/h;

Toxicity The most common adverse reactions (incidence ≥7% and higher than placebo): upper respiratory tract infection, rash, and urinary tract infection.

Aﬀected organisms

Humans and other mammals

Pathways Not Available

Pharmacogenomic Eﬀects/ADRs

Not Available

INTERACTIONS

Drug Interactions

ALL DRUGS APPROVED VET APPROVED NUTRACEUTICAL ILLICIT WITHDRAWN

INVESTIGATIONAL EXPERIMENTAL

DRUG ↑↓ INTERACTION ↑↓ Abatacept The risk or severity of infection can be increased when Certolizumab pegol is combined with Abatacept.

Abciximab The risk or severity of adverse eﬀects can be increased when Abciximab is combined with Certolizumab pegol.

Adalimumab The risk or severity of infection can be increased when Adalimumab is combined with Certolizumab pegol.

Afelimomab The risk or severity of infection can be increased when Afelimomab is combined with Certolizumab pegol.

Alclometasone The risk or severity of adverse eﬀects can be increased when Certolizumab pegol is combined with Alclometasone.

https://www.drugbank.ca/drugs/DB08904 6/13 9/19/2018 Certolizumab pegol - DrugBank

DRUG ↑↓ INTERACTION ↑↓ Aldesleukin The risk or severity of adverse eﬀects can be increased when Certolizumab pegol is combined with Aldesleukin.

Alemtuzumab The risk or severity of adverse eﬀects can be increased when Certolizumab pegol is combined with Alemtuzumab.

Amcinonide The risk or severity of adverse eﬀects can be increased when Certolizumab pegol is combined with Amcinonide.

Amsacrine The risk or severity of adverse eﬀects can be increased when Certolizumab pegol is combined with Amsacrine.

Anakinra The risk or severity of adverse eﬀects can be increased when Certolizumab pegol is combined with Anakinra.

Showing 1 to 10 of 122 entries ‹ ›

Food Interactions Not Available

REFERENCES

General References

1. Chimenti MS, Saraceno R, Chiricozzi A, Giunta A, Chimenti S, Perricone R: Proﬁle of certolizumab and its potential in the treatment of psoriatic arthritis. Drug Des Devel Ther. 2013 Apr 15;7:339-48. doi: 10.2147/DDDT.S31658. Print 2013. [PubMed:23620660] 2. Ferrante M, Vermeire S, Rutgeerts P: Certolizumab pegol in the treatment of Crohn's disease. Expert Opin Biol Ther. 2013 Apr;13(4):595-605. doi: 10.1517/14712598.2013.777039. Epub 2013 Mar 4. [PubMed:23451881] 3. Link [Link]

External Links

KEGG Drug

D03441

PubChem Substance

347910385

ChEMBL

CHEMBL1201831

PharmGKB

PA165107055

RxList

RxList Drug Page https://www.drugbank.ca/drugs/DB08904 7/13 9/19/2018 Certolizumab pegol - DrugBank RxList Drug Page

Drugs.com Drugs.com Drug Page

Wikipedia Certolizumab_pegol

ATC Codes L04AB05 — Certolizumab pegol L04AB — Tumor necrosis factor alpha (TNF-α) inhibitors L04A — IMMUNOSUPPRESSANTS L04 — IMMUNOSUPPRESSANTS L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

AHFS Codes

92:36.00 — Disease-modifying Antirheumatic Agents

56:92.00 — Miscellaneous GI Drugs

FDA label Download (595 KB)

MSDS Download (479 KB)

CLINICAL TRIALS

Clinical Trials

PHASE ↑↓ STATUS ↑↓ PURPOSE ↑↓ CONDITIONS ↑↓ COUNT ↑↓ 1 Active Not Treatment Adenocarcinoma of Lung Stage IV 1 Recruiting

1 Completed Not Available Sperm Quality 1

1 Completed Basic Science Bioavailability Study on Healthy Volunteers 1

1 Completed Other Ankylosing Spondylitis (AS) / Axial Spondyloarthritis 2 (AxSpA) / Crohn's Disease (CD) / Non-radiographic Evidence-AxSpA / Psoriatic Arthritis / Rheumatoid Arthritis

1 Completed Treatment Healthy Volunteers 2 https://www.drugbank.ca/drugs/DB08904 8/13 9/19/2018 Certolizumab pegol - DrugBank

PHASE ↑↓ STATUS ↑↓ PURPOSE ↑↓ CONDITIONS ↑↓ COUNT ↑↓

2 Active Not Treatment Ulcerative Colitis (UC) 1 Recruiting

2 Completed Treatment Chronic Plaque Psoriasis 1

2 Completed Treatment Crohn's Disease (CD) 4

2 Completed Treatment Psoriasis 1

2 Completed Treatment Rheumatoid Arthritis 2

Showing 1 to 10 of 54 entries ‹ ›

PHARMACOECONOMICS

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

FORM ↑↓ ROUTE ↑↓ STRENGTH ↑↓ Injection, solution Subcutaneous 200 mg

Injection, solution Subcutaneous 200 mg/1mL

Kit 200 mg/1mL

Solution Subcutaneous 200 mg

Showing 1 to 4 of 4 entries ‹ ›

Prices

Not Available

Patents

https://www.drugbank.ca/drugs/DB08904 9/13 9/19/2018 Certolizumab pegol - DrugBank

PATENT NUMBER ↑↓ PEDIATRIC EXTENSION ↑↓ APPROVED ↑↓ EXPIRES (ESTIMATED) ↑↓ ↑↓ CA2380298 No 2010-09-28 2021-06-05

Showing 1 to 1 of 1 entries ‹ ›

PROPERTIES

State Solid

Experimental Properties Not Available

TAXONOMY

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 https://www.drugbank.ca/drugs/DB08904 10/13 9/19/2018 Certolizumab pegol - DrugBank Not Available

Molecular Framework Not Available

External Descriptors Not Available

TARGETS

1. Tumor necrosis factor

Kind Protein

Organism Human

Pharmacological action

Yes

Actions

Neutralizer General Function Tumor necrosis factor receptor binding

Speciﬁc Function

Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...

Gene Name

TNF

Uniprot ID

P01375

Uniprot Name

Tumor necrosis factor

Molecular Weight

https://www.drugbank.ca/drugs/DB08904 11/13 9/19/2018 Certolizumab pegol - DrugBank 25644.15 Da

References

Drug created on June 11, 2013 00:11 / Updated on September 18, 2018 23:02

About About DrugBank

DrugBank Blog Wishart Research Group

Support FAQ

Help Email Support

Commercial Products API Pricing

API Docs Data Licenses

Support

This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-proﬁt organization that is leading Canada's national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc.

https://www.drugbank.ca/drugs/DB08904 12/13 9/19/2018 Certolizumab pegol - DrugBank

https://www.drugbank.ca/drugs/DB08904 13/13