Infliximab

Infliximab is a tumor necrosis factor (TNF) blocker indicated for: Crohn's Disease: reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing disease. Pediatric Crohn's Disease: reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active disease who have had an inadequate response to conventional therapy.

Infliximab neutralizes the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibits binding of TNFα with its receptors. Infliximab does not neutralize TNFβ (lymphotoxin-α), a related cytokine that 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 of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Cells expressing transmembrane TNFα bound by infliximab can be lysed in vitro or in vivo.

Prior to treatment, ensure appropriate personnel and medication are available to treat reactions (e.g., hypersensitivity) that occur during infusion and shortly after infusion. Infliximab is administered by intravenous infusion for at least 2 hours with an in-line filter. Crohn's Disease: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Some adult patients who initially respond to treatment may benefit from increasing the dose to 10 mg/kg every 8 weeks if they later lose their response. Pediatric Crohn's Disease (≥ 6 years old): 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Ulcerative Colitis: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Pediatric Ulcerative Colitis (≥ 6 years old): 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Rheumatoid Arthritis: In conjunction with methotrexate, 3 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.

The use of Infliximab at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure. Infliximab is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of Infliximab or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness]. Infliximab doses >5 mg/kg in moderate or severe heart failure. Previous severe hypersensitivity reaction to infliximab or any inactive ingredients of Infliximab or to any murine proteins.

Boxed warning (serious infections and malignancy warning: serious infections and malignancy): Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis) and infections due to other opportunistic pathogens. Discontinue Infliximab if a patient develops a serious infection. Serious infections – do not give Infliximab during an active infection. If an infection develops, monitor carefully and stop Infliximab if infection becomes serious. Invasive fungal infections – for patients who develop a systemic illness on Infliximab, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic. Malignancies – the incidence of malignancies, including invasive cervical cancer and lymphoma, was greater in Infliximab treated patients than in controls.

Most common adverse reactions (>10%) – infections (e.g. upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

Other Biological Products – increased risk of serious infections. Other Biological Products The combination of Infliximab with other biological products used to treat the same conditions as Infliximab is not recommended. An increased risk of serious infections was seen in clinical studies of other TNF blockers used in combination with anakinra or abatacept, with no added clinical benefit. Because of the nature of the adverse reactions seen with these combinations with TNF blocker therapy, similar toxicities may also result from the combination of anakinra or abatacept with other TNF blockers. Therefore, the combination of Infliximab and anakinra or abatacept is not recommended. The concomitant use of tocilizumab with biological DMARDs such as TNF antagonists, including Infliximab, should be avoided because of the possibility of increased immunosuppression and increased risk of infection.

Store unopened Infliximab vials in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F). If needed, unopened Infliximab vials may be stored at room temperatures up to a maximum of 30 °C (86 °F) for a single period of up to 6 months but not exceeding the original expiration date. Once removed from the refrigerator, Infliximab cannot be returned to the refrigerator. For storage conditions of the reconstituted and diluted product for administration, see Dosage and Administration.