ed in effectiveness or safety in 181 patients with rheumatoid arthritis and 75 patientswith plaque psoriasis, aged 65 or older who received infliximab, compared to youngerpatients -although the incidence of serious adverse reactions in patients aged 65 or older washigher in both infliximab and control groups compared to younger patients. In Crohn’sdisease, ulcerative colitis, ankylosing spondylitis and psoriatic arthritis studies, there wereinsufficient numbers of patients aged 65 and over to determine whether they responddifferently from patients aged 18 to 65. There is a greater incidence of infections in theelderly population in general. The incidence of serious infections in infliximab-treatedpatients 65 years and older was greater than in those under 65 years of age; therefore cautionshould be used in treating the elderly [see Adverse Reactions (6.1)].
10 OVERDOSAGE
Single doses up to 20 mg/kg of infliximab have been administered without any direct toxiceffect. In case of overdosage, it is recommended that the patient be monitored for any signs orsymptoms of adverse reactions or effects and appropriate symptomatic treatment institutedimmediately.
11 DESCRIPTION
Infliximab-abda, the active ingredient in RENFLEXIS, is a chimeric IgG1κ monoclonalantibody (composed of human constant and murine variable regions) specific for humantumor necrosis factor-alpha (TNFα). It has a molecular weight of approximately 149.1kilodaltons. Infliximab-abda is produced by a recombinant cell line cultured and is purifiedby a series of steps that includes measures to inactivate and remove viruses.
RENFLEXIS (infliximab-abda) for Injection is supplied as a sterile, white, lyophilizedpowder for intravenous infusion. Following reconstitution with 10 mL of Sterile Water forInjection, USP, the resulting pH is approximately 6. Each mL contains 10 mg infliximab-abda,dibasic sodium phosphate heptahydrate (0.12 mg), monobasic sodium phosphatemonohydrate (0.63 mg), polysorbate 80 (0.05 mg), and sucrose (50 mg). No preservatives are
present.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Infliximab products neutralize the biological activity of TNFα by binding with high affinityto the soluble and transmembrane forms of TNFα and inhibit binding of TNFα with its receptors. Infliximab products do not neutralize TNFβ (lymphotoxin-α), a related cytokinethat utilizes the same receptors as TNFα. Biological activities attributed to TNFα include:
induction of pro-inflammatory cytokines such as interleukins (IL) 1 and 6, enhancement ofleukocyte migration by increasing endothelial layer permeability and expression of adhesionmolecules by endothelial cells and leukocytes, activation of neutrophil and eosinophilfunctional activity, induction of acute phase reactants and other liver proteins, as well astissue degrading enzymes produced by synoviocytes and/or chondrocytes. Cells expressingtransmembrane TNFα bound by infliximab products can be lysed in vitro or in vivo.
Infliximab products inhibit the functional activity of TNFα in a wide variety of in vitrobioassays utilizing human fibroblasts, endothelial cells, neutrophils, B and T-lymphocytesand epithelial cells. The relationship of these biological response markers to the mechanism(s)by which infliximab products exert their clinical effects is unknown. Anti-TNFα antibodiesreduce disea |
