Overview
11 DESCRIPTION Infliximab-dyyb, a tumor necrosis factor (TNF) blocker, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions). It has a molecular weight of approximately 149.1 kilodaltons. Infliximab-dyyb is produced by a recombinant murine myeloma cell line, SP2/0.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Infliximab products neutralize the biological activity of TNFα by binding with high affinity to 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 cytokine that utilizes the same receptors as TNFα. Biological activities attributed to TNFα include: induction of proinflammatory 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...
Indications
- 1 INDICATIONS AND USAGE INFLECTRA is a tumor necrosis factor (TNF) blocker indicated for: Crohn's Disease ( 1.1 ): • 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 ( 1.
Common Doses
- 5 mg
- 10 mg
- 3 mg
- 100 mg
Dosage
2 DOSAGE AND ADMINISTRATION Prior to treatment, ensure appropriate personnel and medication are available to treat reactions (e.g., hypersensitivity) that occur during infusion and shortly after infusion ( 2.11 ) INFLECTRA is administered by intravenous infusion for at least 2 hours with an in-line filter ( 2.11 ) Crohn's Disease ( 2.1 ) • 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) ( 2.
Black Box Warning
WARNING: SERIOUS INFECTIONS and MALIGNANCY WARNING: SERIOUS INFECTIONS and MALIGNANCY See full prescribing information for complete boxed warning • 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. ( 5.1 ) • Discontinue INFLECTRA if a patient develops a serious infection. • Perform test for latent TB; if positive, start treatment for TB prior to starting INFLECTRA.
Contraindications
- 4 CONTRAINDICATIONS The use of INFLECTRA at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure [see Warnings and Precautions (5.5) and Adverse Reactions (6.1) ]. INFLECTRA is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab products or any of the inactive ingredients of INFLECTRA or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness] [see Warnings and Precautions (5.7) and Adverse Reactions (6.1) ].
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions (>10%) – infections (e.g. upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact CELLTRION, Inc. at 1-800-383-7504 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates...
Interactions
- 7 DRUG INTERACTIONS Other Biological Products – increased risk of serious infections ( 7.1 ) 7.1 Other Biological Products The combination of INFLECTRA with other biological products used to treat the same conditions as INFLECTRA is not recommended [see Warnings and Precautions (5.10) ]. 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.