Infliximab

Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop.

Cerebrovascular accidents, MI (some fatal), hypotension, hypertension, and arrhythmias have been reported within 24 hours of infusion. Transient vision loss has also been reported during or within 2 hours of infusion. Discontinue therapy if serious reaction occurs.

Hematologic toxicities (eg, leukopenia, neutropenia, thrombocytopenia, pancytopenia) have been reported (may be fatal). Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias (eg, persistent fevers); discontinue if significant hematologic abnormalities are confirmed. Use with caution in patients with history of hematologic abnormalities.

Severe hepatic reactions (including hepatitis, jaundice, acute hepatic failure, and cholestasis) have been reported during treatment; reactions occurred between 2 weeks to >1 year after initiation of therapy and some cases were fatal or necessitated liver transplantation; discontinue with jaundice and/or marked increase in liver enzymes (≥5 times ULN).

Reactivation of hepatitis B virus (HBV) has occurred in chronic carriers of the virus, usually in patients receiving concomitant immunosuppressants (may be fatal); evaluate for HBV prior to initiation in all patients. Monitor during and for several months following discontinuation of treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.

Acute infusion reactions may occur. Hypersensitivity reactions, including anaphylaxis, may occur within 2 hours of infusion. Medication and equipment for management of hypersensitivity reaction should be available for immediate use. Interruptions and/or reinstitution at a slower rate may be required (consult protocols). Pretreatment may be considered, and may be warranted in all patients with prior infusion reactions. Serum sickness-like reactions have occurred; may be associated with a decreased response to treatment. The development of antibodies to infliximab may increase the risk of hypersensitivity and/or infusion reactions; concomitant use of immunosuppressants may lessen the development of anti-infliximab antibodies. The risk of infusion reactions may be increased with re-treatment after an interruption or discontinuation of prior maintenance therapy. Re-treatment in psoriasis patients should be resumed as a scheduled maintenance regimen without any induction doses; use of an induction regimen should be used cautiously for re-treatment of all other patients.

Patients receiving infliximab are at increased risk for serious infections which may result in hospitalization and/or fatality; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate or corticosteroids) and may present as disseminated (rather than local) disease. Active tuberculosis (or reactivation of latent tuberculosis), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral or other opportunistic infections (including legionellosis and listeriosis) have been reported. Monitor closely for signs/symptoms of infection. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to use in patients with a history of chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infection and develop severe systemic illness. Caution should be exercised when considering use in the elderly or in patients with conditions that predispose them to infections (eg, diabetes) or residence/travel from areas of endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis), or with latent or localized infections. Do not initiate infliximab therapy in patients with an active infection, including clinically important localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely.

Lymphoma and other malignancies (may be fatal) have been reported in children and adolescent patients receiving TNF-blocking agents including infliximab. Half the cases are lymphomas (Hodgkin's and non-Hodgkin's) and the other cases are varied but include malignancies not typically observed in this population. [US Boxed Warning]: Postmarketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with infliximab. Almost all patients had received concurrent or prior treatment with azathioprine or mercaptopurine at or prior to diagnosis and the majority of reported cases occurred in adolescent and young adult males with Crohn disease or ulcerative colitis. Malignancies occurred after a median of 30 months (range: 1 to 84 months) after the first dose of TNF blocker therapy; most patients were receiving concomitant immunosuppressants. The impact of infliximab on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis alone has been previously associated with an increased rate of lymphoma. Use caution in patients with a history of COPD, higher rates of malignancy were reported in COPD patients treated with infliximab. Psoriasis patients with a history of phototherapy had a higher incidence of nonmelanoma skin cancers. Melanoma and Merkel cell carcinoma have been reported in patients receiving TNF-blocking agents incl

Infliximab treatment has been associated with active tuberculosis (may be disseminated or extrapulmonary) or reactivation of latent infections. Evaluate patients for tuberculosis risk factors and latent tuberculosis infection (with a tuberculin skin test) prior to and during therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment. Most cases of reactivation have been reported within the first couple months of treatment. Caution should be exercised when considering the use in patients who have been exposed to tuberculosis. Disease-related concerns:

Use with caution in patients with preexisting or recent onset CNS demyelinating disorders; rare cases of optic neuritis and demyelinating disease (including multiple sclerosis, systemic vasculitis, and Guillain-Barré syndrome) have been reported; consider discontinuation of therapy if patient develops significant CNS reactions.

Use with caution in patients with mild HF (NYHA Class I, II) or decreased left ventricular function; worsening and new-onset HF has been reported; doses >5 mg/kg should not be administered in patients with moderate to severe HF (NYHA Class III/IV); discontinue therapy with onset of new or worsening symptoms. In a scientific statement from the American Heart Association, TNF blockers have been determined to be agents that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

Use with caution in patients with a history of seizures; discontinue if significant CNS adverse reactions develop. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Malignancies have been reported among children and adolescents receiving TNF-blocking agents. Efficacy was not established in a study to evaluate infliximab use in juvenile idiopathic arthritis (JIA). Dosage form specific issues:

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling. Other warnings/precautions:

Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy. A fatal outcome has been reported in an infant who received a live vaccine (BCG) after in utero exposure to infliximab; infliximab crosses the placenta and has been detected in infants’ serum for up to 6 months. It is recommended to wait ≥6 months following birth before administering any live vaccine to infants exposed to infliximab in utero.