Drug information of Infliximab

Mechanism of effect

Neutralizes the biological activity of tumor necrosis factor (TNF)–alpha by binding to its soluble and transmembrane forms, and inhibits TNF-alpha receptor binding.

Pharmacodynamic

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

Pharmacokinetics

Single IV infusions show a linear relationship between the dose administered and the C max Distributed primarily within the vascular compartment The half-life is 7.7 to 9.5 days

Dosage

Ankylosing Spondylitis Adults IV 5 mg/kg as an induction regimen at 0, 2, and 6 wk, followed by a maintenance regimen of 5 mg/kg every 6 wk. Crohn Disease Adults IV 5 mg/kg as an induction regimen at 0, 2, and 6 wk, followed by a maintenance regimen of 5 mg/kg every 8 wk. In patients who respond and then lose response, consider treatment with 10 mg/kg. Consider discontinuation of therapy in patients who do not respond by wk 14. Children 6 y and older IV 5 mg/kg as an induction regimen at 0, 2, and 6 wk, followed by a maintenance regimen of 5 mg/kg every 8 wk. Psoriatic Arthritis, Plaque Psoriasis Adults IV 5 mg/kg as an induction regimen at 0, 2, and 6 wk, followed by a maintenance regimen of 5 mg/kg every 8 wk. Can be used in combination with methotrexate in the treatment of psoriatic arthritis. Rheumatoid Arthritis Adults IV 3 mg/kg as an induction regimen at 0, 2, and 6 wk, followed by a maintenance regimen of 3 mg/kg every 8 wk in combination with methotrexate. For patients with incomplete response, may administer up to 10 mg/kg or treat as often as every 4 wk. Ulcerative Colitis Adults IV 5 mg/kg as an induction regimen at 0, 2, and 6 wk followed by a maintenance regimen of 5 mg/kg every 8 wk thereafter.

Alerts

Infections Serious, life-threatening infections leading to hospitalization and death may occur. Infections include active tuberculosis (TB), including disseminated or extrapulmonary disease or reactivation of latent TB. Test patients for latent TB before and during treatment. Start treatment for latent infection before infliximab use. Other infections include invasive fungal infections (eg, histoplasmosis, aspergillosis, pneumocystosis), which may be disseminated rather than localized diseases. Consider empiric antifungal therapy in patients at risk of invasive fungal infections who develop severe systemic illness. In addition, bacterial, viral, and other infections caused by opportunistic pathogens, including Legionella and Listeria , may occur. Discontinue infliximab in patients developing a serious infection or sepsis. Most patients who develop these infections are taking concurrent immunosuppressants, such as corticosteroids or methotrexate. Malignancies Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with TNF blockers, including infliximab. Rare cases of hepatosplenic T-cell lymphoma have been reported in adolescent and young adult patients with Crohn disease or ulcerative colitis treated with infliximab. All the hepatosplenic T-cell lymphomas with infliximab have occurred in patients on concomitant treatment with azathioprine or 6-mercaptopurine. Monitor Closely monitor patients for signs and symptoms of infection during or after infliximab treatment. Monitor long-term carriers of hepatitis B. Test patients for latent TB before and during treatment. If patients with heart failure are treated, closely monitor during treatment and discontinue infliximab if new or worsening symptoms of heart failure occur. Monitor patients with psoriasis for nonmelanoma skin cancers, especially those who have had prolonged phototherapy treatment. Evaluate patients with signs and symptoms of liver dysfunction for evidence of liver injury.

Points of recommendation

For administration by IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration. Reconstitute each vial with 10 mL of sterile water for injection with a syringe equipped with a 21-gauge or smaller needle. Gently swirl by rotating the vial to dissolve the lyophilized powder. Avoid prolonged or vigorous agitation; do not shake. Foaming of the solution on reconstitution is not unusual; allow to stand for 5 min. Further dilute the total volume of reconstituted solution to 250 mL with sodium chloride 0.9% injection. The infusion solution concentration should be between 0.4 and 4 mg/mL. Administer by IV infusion over a period of no less than 2 h through an infusion set with an in-line, sterile, nonpyrogenic, low–protein-binding filter with a pore size of 1.2 micrometers or less. Do not infuse infliximab concomitantly in the same IV line with any other agent. Premedication may be administered at the health care provider's discretion. Premedication could include antihistamines, acetaminophen, and/or corticosteroids. Slow or suspend infusion for mild to moderate infusion reactions; upon resolution of the reaction, reinitiate at a lower infusion rate and/or administer acetaminophen, antihistamines, and/or corticosteroids. Discontinue infliximab in patients who do not tolerate the infusion after these interventions. Discontinue further infliximab treatment in patients who experience severe infusion-related hypersensitivity reactions

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