Infliximab
Identification
- Summary
Infliximab is a monoclonal anti tumor necrosis factor alpha antibody used in the treatment of a wide variety of inflammatory conditions such as rheumatoid arthritis, Crohn's disease, and ankylosing spondylitis.
- Brand Names
- Avsola, Flixabi, Inflectra, Remicade, Renflexis
- Generic Name
- Infliximab
- DrugBank Accession Number
- DB00065
- Background
Infliximab is a tumor necrosis factor (TNF-alpha or TNF-α) blocker and a chimeric monoclonal IgG1 antibody composed of human constant (75%) and murine variable (25%) regions 3. Infliximab is produced by a recombinant cell line cultured by continuous perfusion. Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine involved in chronic inflammatory diseases 3. Its hyperactivity and enhanced signalling pathways can be observed in inflammatory diseases where it activates further pro-inflammatory cascades. By binding to both the soluble subunit and the membrane-bound precursor of TNF-α 1, infliximab disrupts the interaction of TNF-α with its receptors and may also cause lysis of cells that produce TNF-α 1.
Infliximab was first approved by the FDA in 1998 under the market name Remicade as an intravenous injection. It is indicated for the treatment of various inflammatory disorders such as adult or pediatric Chron's disease, adult or pediatric ulcerative colitis, rheumatoid arthritis in combination with methotrexate, ankylosing spondyliti, psoriatic arthritis, and plaque psoriasis Label. In clinical trials, multiple infusions of infliximab displayed in a reduction of signs and symptoms of inflammatory diseases and induction of remission in patients who have had an inadequate response to alternative first-line therapies for that disorder Label.
There are currently two biosilimars of infliximab available in the US market that demonstrate a high degree of similarity to the reference product, Remicade. They are approved for all eligible indications of the reference product. Inflectra, a first biosimilar drug product, was approved in 2016. In December 2017, Ixifi, a second biosimilar that was developed by Pfizer, was granted approval by the FDA.
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6428H9912N1694O1987S46
- Protein Average Weight
- 144190.3 Da
- Sequences
- Not Available
- Synonyms
- Infliximab
- Infliximab (genetical recombination)
- Infliximab-abda
- Infliximab-axxq
- Infliximab-dyyb
- Infliximab-qbtx
- External IDs
- ABP 710
- ABP-710
- BOW-015
- BOW015
- CT-P-13
- CT-P13
- GP 1111
- GP-1111
- PF-06438179
- TA-650
Pharmacology
- Indication
- Indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult or pediatric (≥ 6 years of age) patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy
- Indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.
- Indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult or pediatric (≥ 6 years of age) patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
- Indicated for, in combination with methotrexate, reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis.
- Indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
- Indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis.
- Indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Ankylosing spondylitis (as) •••••••••••• ••••• ••••••••• Management of Chronic plaque psoriasis •••••••••••• ••••• •••••••• •• •••••• ••••••• •••••• ••••••••• ••• ••• •••••••••• ••• •••••••• ••••••• •• ••••••••••••• ••• •••• ••••• •••••••• ••••••••• ••• ••••••••• •••• ••••••••••• ••••••••• Management of Fistulizing crohn's disease •••••••••••• ••••• ••••••••• Management of Moderately to severely active crohn's disease •••••••••••• ••••• •••••••••• •••••••• •• •••••••••••• ••••••• ••••••••• Used in combination to manage Moderately to severely active rheumatoid arthritis Regimen in combination with: Methotrexate (DB00563) •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Infliximab disrupts the activation of pro-inflammaory cascade signalling. Infliximab has shown to reduce infiltration of inflammatory cells into sites of inflammation. It also attenautes the expression of molecules mediating cellular adhesion {including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)}, chemoattraction {[IL-8 and monocyte chemotactic protein (MCP-1)} and tissue degradation {matrix metalloproteinase (MMP) 1 and 3} Label.
- Mechanism of action
Infliximab is a IgG1κ monoclonal antibody that binds to soluble and transmembrane forms of TNF-α with high affinity to disrupt the pro-inflammatory cascade signalling. Binding of the antibody to TNF-α prevents TNF-α from interacting with its receptors. Infliximab does not neutralize TNF-β (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNF-α Label. Blocked actions of TNF-α further leads to downregulation of local and systemic pro-inflammatory cytokines (i.e. IL-1, IL-6), reduction of lymphocyte and leukocyte migration to sites of inflammation, induction of apoptosis of TNF-producing cells (i.e. activated monocytes and T lymphocytes), increased levels of nuclear factor-κB inhibitor, and reduction of reduction of endothelial adhesion molecules and acute phase proteins 3. Its inhibitory actions on TNF-α was demonstrated in human fibroblasts, endothelial cells, neutrophils, B and Tlymphocytes and epithelial cells Label. Infliximab also atteunates the production of tissue degrading enzymes synthesized by synoviocytes and/or chondrocytes. According to a transgenic mice study that developed polyarthritis due to consitutive levels of human TNF-α, infliximab decreased synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal Label.
Target Actions Organism ATumor necrosis factor inhibitorHumans - Absorption
Following a single intravenous infusion, infliximab absorption displays a linear relationship between the dose administered and the maximum serum concentration Label.
In patients with Crohn's disease, the maximum plasma concentration (Cmax) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 75 µg/mL and 181 µg/mL, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Cmax of 120 µg/mL and 189 µg/mL , respectively 3.
In patients with rheumatoid arthritis, the Cmax of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 192±51 µg/mL, 427±106 µg/mL, and 907±183 µg/mL, respectively 3.
- Volume of distribution
Based on a pharmacokinetic study of adult patients, the distribution at steady state was independent of dose and indicated that infliximab was distributed primarily within the vascular compartment Label.
In patients with Crohn's disease, the apparent volume of distribution at steady state (Vss) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 80 mL/kg and 65 mL/kg, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Vss of 70 mL/kg and 81 mL/kg , respectively 3.
In patients with rheumatoid arthritis, the Vss of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 4.3±2.5 L, 3.2±0.7 L, and 3.1±0.6 L, respectively 3.
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Therapeutic monoclonal antibodies including infliximab are predicted to be nonspecifically metabolized to peptides and amino acids that can be re-used in the body for de novo synthesis of proteins or arc excreted by the kidney 4. The reticuloendothelial system (RES) are phagocytic cells of the immune system such as macrophages and monocytes that play a role in the elimination of endogenous IgG antibodies. Although administered infliximab accounts for a small fraction of total endogenous IgG and this route is not likely saturated by therapeutic mAbs, infliximab may be removed by opsonization via RES following binding of the Fc part of the antibody to Fcy-receptors expressed on the RES 4.
- Half-life
The median terminal half-life of infliximab is 7.7 to 9.5 days. The data is based on a pharmacokinetic study in patients with Crohn's disease, plaque psoriasis and rheumatoid arthritis receiving a single dose of infliximab Label.
- Clearance
In patients with Crohn's disease, the total body clearance (CL) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 18.4 mL/h and 14.3 mL/h, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in CL of 15.2 mL/h and 15.2 mL/h, respectively 3.
In patients with rheumatoid arthritis, the CL of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 11±7.5 mL/h, 11.4±5 mL/h, and 11±8.9 mL/h, respectively 3.
Development of antibodies to infliximab increased infliximab clearance Label.
- Adverse Effects
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- Toxicity
In an acute toxicity animal study, the NOAEL of intravenous infliximab in rats was 50 mg/kg. In a repeated dose animal study, the NOAEL values of intravenous infliximab was 50 mg/kg in rats at 2 weeks following 3 doses and 40 mg/kg/day in mice at 6 months MSDS.
The toxicological potential of infliximab in humans has not yet been fully established. According to an analogous antibody study, infliximab is not predicted to induce tumorigenic, clastogenic or mutagenic effects. No impairment of fertility was observed in a fertility and general reproduction toxicity study with the analogous mouse antibody used in the 6-month chronic toxicity study Label.
- 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);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Low affinity immunoglobulin gamma Fc region receptor III-A --- (C;C) CC Allele (homozygous) Effect Directly Studied Patients with this genotype have increased ACR20 response when using infliximab to treat rheumatoid arthritis. Details
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 infection can be increased when Infliximab is combined with Abatacept. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Infliximab. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Infliximab. Abrocitinib The metabolism of Abrocitinib can be increased when combined with Infliximab. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Infliximab. - 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.
- International/Other Brands
- Avsola (Amgen)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Avsola Powder, for solution 100 mg / vial Intravenous Amgen 2020-06-01 Not applicable Canada Avsola Injection, powder, lyophilized, for solution 100 mg/10mL Intravenous AMGEN INC 2019-12-12 Not applicable US Flixabi Injection, powder, for solution 100 mg Intravenous Samsung Bioepis Nl B.V. 2016-09-08 Not applicable EU Flixabi Injection, powder, for solution 100 mg Intravenous Samsung Bioepis Nl B.V. 2016-09-08 Not applicable EU Flixabi Injection, powder, for solution 100 mg Intravenous Samsung Bioepis Nl B.V. 2016-09-08 Not applicable EU
Categories
- ATC Codes
- L04AB02 — Infliximab
- Drug Categories
- Agents Causing Muscle Toxicity
- Agents reducing cytokine levels
- Amino Acids, Peptides, and Proteins
- Anti-Inflammatory Agents
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic and Immunomodulating Agents
- Antirheumatic Agents
- Biological Products
- Biologics for Rheumatoid Arthritis Treatment
- Blood Proteins
- Complex Mixtures
- Dermatologicals
- Disease-modifying Antirheumatic Agents
- Gastrointestinal Agents
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Proteins
- Serum Globulins
- Tumor necrosis factor alpha (TNF-alpha) inhibitors
- Tumor Necrosis Factor Blockers
- Tumor Necrosis Factor Receptor Blocking Activity
- 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
- Humans and other mammals
Chemical Identifiers
- UNII
- B72HH48FLU
- CAS number
- 170277-31-3
References
- General References
- Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ: Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med. 1999 May 6;340(18):1398-405. [Article]
- Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ: Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004 Feb 26;350(9):876-85. [Article]
- Klotz U, Teml A, Schwab M: Clinical pharmacokinetics and use of infliximab. Clin Pharmacokinet. 2007;46(8):645-60. doi: 10.2165/00003088-200746080-00002. [Article]
- Keizer RJ, Huitema AD, Schellens JH, Beijnen JH: Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug;49(8):493-507. doi: 10.2165/11531280-000000000-00000. [Article]
- Link [Link]
- Link [Link]
- FDA Label: INFLECTRA (infliximab-dyyb) for Injection, for Intravenous Use [Link]
- FDA Label: IXIFI (infliximab-qbtx) for injection, for Intravenous Use [Link]
- FDA Approved Drug Products: REMICADE (infliximab) injection [Link]
- External Links
- UniProt
- P01857
- Genbank
- J00228
- PubChem Substance
- 46505602
- 1790539
- ChEMBL
- CHEMBL1201581
- Therapeutic Targets Database
- DAP000107
- PharmGKB
- PA452639
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Infliximab
- FDA label
- Download (1.21 MB)
- MSDS
- Download (39.6 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 4 Active Not Recruiting Treatment Axial Spondyloarthritis (AxSpA) 1 4 Active Not Recruiting Treatment Crohn's Disease (CD) 1 4 Active Not Recruiting Treatment Infliximab / Uveitis 1 4 Completed Diagnostic Ankylosing Spondylitis (AS) 1 4 Completed Other Hepato-splenic T-cell Lymphoma 1
Pharmacoeconomics
- Manufacturers
- J&J and Mitsubisi Tanabe
- Packagers
- Centocor Ortho Biotech Inc.
- Hospira Inc.
- Dosage Forms
Form Route Strength Injection, powder, for solution 100 mg Powder Parenteral 100 MG Injection, powder, for solution Intravenous; Parenteral 100 MG Injection, powder, lyophilized, for solution Intravenous 100 mg/10mL Solution Intravenous 100.000 mg Injection, powder, lyophilized, for solution Intravenous 100 mg Powder 100 mg/1vial Powder Intravenous; Parenteral 100 MG Powder, for solution Intravenous 100 mg / vial Injection, powder, lyophilized, for solution Intravenous Injection, powder, for solution Intravenous 100 mg Injection, powder, for solution Intravenous Injection, solution Parenteral; Subcutaneous 120 MG Injection, solution Subcutaneous 120 mg Injection, solution, concentrate Intravenous 100 mg/1vial Injection Intravenous 100 mg Solution Subcutaneous 120 mg Solution Subcutaneous 12000000 mg Kit; solution Subcutaneous 120 mg / mL Solution Subcutaneous 120.00 mg Injection, solution Subcutaneous 120 mg/ml Injection, powder, lyophilized, for suspension Intravenous 100 mg Injection, powder, lyophilized, for solution Intravenous 100 mg/1 - Prices
Unit description Cost Unit Remicade 100 mg Solution Vial 821.02USD vial Remicade 100 mg vial 789.44USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2106299 No 2001-02-06 2012-03-18 Canada
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 61 °C (FAB fragment), 71 °C (whole mAb) Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000) hydrophobicity -0.441 Not Available isoelectric point 8.25 Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- 25644.15 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Mimura T: [Selection of one of the TNF blockers; infliximab and etanercept]. Nihon Rinsho. 2007 Jul;65(7):1282-6. [Article]
- Braun J, Baraliakos X, Listing J, Sieper J: Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum. 2005 Aug;52(8):2447-51. [Article]
- Danese S, Sans M, Scaldaferri F, Sgambato A, Rutella S, Cittadini A, Pique JM, Panes J, Katz JA, Gasbarrini A, Fiocchi C: TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn's disease. J Immunol. 2006 Feb 15;176(4):2617-24. [Article]
- Magro F, Pereira P, Carneiro F, Veloso FT: Reactive hepatitis in a patient with Crohn's disease successfully treated with infliximab: does tumor necrosis factor alpha play a role in reactive hepatitis? Inflamm Bowel Dis. 2005 Jan;11(1):88-90. [Article]
- Mori S, Imamura F, Kiyofuji C, Ito K, Koga Y, Honda I, Sugimoto M: Pneumocystis jiroveci pneumonia in a patient with rheumatoid arthritis as a complication of treatment with infliximab, anti-tumor necrosis factor alpha neutralizing antibody. Mod Rheumatol. 2006;16(1):58-62. [Article]
- Maini RN, Feldmann M: How does infliximab work in rheumatoid arthritis? Arthritis Res. 2002;4 Suppl 2:S22-8. Epub 2002 Mar 27. [Article]
- Sapienza MS, Cohen S, Dimarino AJ: Treatment of pyoderma gangrenosum with infliximab in Crohn's disease. Dig Dis Sci. 2004 Sep;49(9):1454-7. [Article]
- Tobin AM, Kirby B: TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. BioDrugs. 2005;19(1):47-57. [Article]
- Shen C, Assche GV, Colpaert S, Maerten P, Geboes K, Rutgeerts P, Ceuppens JL: Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept. Aliment Pharmacol Ther. 2005 Feb 1;21(3):251-8. [Article]
- Popa C, Netea MG, Barrera P, Radstake TR, van Riel PL, Kullberg BJ, Van der Meer JW: Cytokine production of stimulated whole blood cultures in rheumatoid arthritis patients receiving short-term infliximab therapy. Cytokine. 2005 Apr 21;30(2):72-7. [Article]
Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:41