1. Infliximab (DB00065) Approved Drug
Chemical Formula: C6428H9912N1694O1987S46
Molecular Weight:
Tumor necrosis factor (TNF-alpha) binding antibody (chimeric IgG1). It is composed of human constant and murine variable regions. Infliximab is produced by a recombinant cell line cultured by continuous perfusion
Indication/Usage
To manage the signs and symptoms, as well as to induce and maintain clinical remission in adults with moderate to severe active Crohn's disease or ulcerative colitis. Also used to manage signs and symptoms of rheumatoid arthritis (in conjunction with methotrexate), ankylosing spondylitis, psoriatic arthritis, and juvenile arthritis.
Pharmacodynamics
Infliximab is a chimeric human-murine anti-human tumor necrosis factor (TNF) monoclonal antibody. It binds to tumor necrosis factor alpha (TNFa) and inhibits binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as interleukins (IL) 1 and 6. This also limits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Infliximab decreases synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal..

2. Mechanism Of Action Metabolism Half-life Category Affected Organisms
Infliximab neutralizes the biological activity of TNFa by binding with high affinity to the soluble and transmembrane forms of TNFa and inhibits binding of TNFa with its receptors. Infliximab does not neutralize TNFb (lymphotoxin a), a related cytokine that utilizes the same receptors as TNFa. Neutralization of the biological activity of TNFa leads to an overall reduction in inflammation.
Metabolism
Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production
Half-life
9.5 days
Category
Anti-rheumatic Agents and Anti-Inflammatory Agents, Non-Steroidal and Dermatologic Agents and Gastrointestinal Agents and Immunosuppressive Agents
Affected Organisms
Humans and other mammals
Patents
Patent no , Canada, approved: expired:
Drug Interactions
DB06674 (golimumab): Avoid combination with infliximab due to the potential increased immunosuppression of infliximab
DB06372 (Rilonacept): results in increased immunosuppressive effects; increases the risk of infection.
DB08895 (Tofacitinib): Avoid combination with infliximab and other anti-TNF drugs due to the potential enhancement of tofacitinib related adverse effects
DB00072 (Trastuzumab): Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

3. Experimental Properties
Melting Point- 61 °C for FAB Fragment; 71 °C for whole mAb
Hydrophobicity: 0.441
Isoelectric Point: 8.25
Targets
Tumor necrosis factor
General References
Knight DM, Trinh H, Le J, Siegel S, Shealy D, McDonough M, Scallon B, Moore MA, Vilcek J, Daddona P, et al.: Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol Nov;30(16): "Pubmed":
Dubinsky MC, Fleshner PP: Treatment of Crohn's Disease of Inflammatory, Stenotic, and Fistulizing Phenotypes. Curr Treat Options Gastroenterol Jun;6(3): "Pubmed":
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 May 6;340(18): "Pubmed":
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 Feb 26;350(9): "Pubmed":
Hanauer SB: Crohn's disease: step up or top down therapy. Best Pract Res Clin Gastroenterol Feb;17(1):131-7."Pubmed":
Brands
REMICADE - Centocor Inc

4. REMICADE Formulation Used/Prescribed for Dosage Contraindications
REMICADE, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions) specific for human tumor necrosis factor-alpha (TNFα). Infliximab is produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses. REMICADE is supplied as a sterile, white, lyophilized powder, Following reconstitution with 10 mL of Sterile Water for Injection, USP, the resulting pH is approximately 7.2. It is administered as a intavenous infusion
Formulation
Each single-use vial contains 100 mg infliximab, 500 mg sucrose, 0.5 mg polysorbate 80, 2.2 mg monobasic sodium phosphate, monohydrate, and 6.1 mg dibasic sodium phosphate, dihydrate. No preservatives are present.
Used/Prescribed for
used in crohn disease, Ankylosing pondylitis, Psoriatic Arthritis, Plaque Psoriasis and ulcerative colitis
Dosage
for crohn disease, Ankylosing pondylitis, Psoriatic Arthritis, Plaque Psoriasis and ulcerative colitis : The recommended dose of REMICADE is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks and for rhematoid arthritis: The recommended dose of REMICADE is 3 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks
Contraindications
REMICADE at doses > 5 mg/kg should not be administered to patients with moderate to severe heart failure.; REMICADE should not be re-administered to patients who have experienced a severe hypersensitivity reaction to REMICADE
Side-effects
Hepatotoxicity, Immunogenicity, Nausea, Diarrhea, Dysepsia, Sinusitis, Bronchitis, Phrayngitis, Rash, Fatigue, Fever, urinary tract infections.

5. Drug Interactions
Tocilizumab, Similar biotheraupatics as Remicade, Methotrexerate and other antibiotics, Cytochrome P450 Substrates, immunosupressants
References
American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-S247.