erapy with appropriate supportive treatment should be initiated.
Hepatobiliary events
Very rare cases of jaundice and non-infectious hepatitis, some with features of autoimmune hepatitis, have been observed in the post-marketing experience of Remicade. Isolated cases of liver failure resulting in liver transplantation or death have occurred. Patients with symptoms or signs of liver dysfunction should be eva luated for evidence of liver injury. If jaundice and/or ALT elevations 5 times the upper limit of normal develop(s), Remicade should be discontinued, and a thorough investigation of the abnormality should be undertaken.
Concurrent administration of TNF-alpha inhibitor and anakinra
Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNFα-blocking agent, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse events seen with combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNFα-blocking agents. Therefore, the combination of Remicade and anakinra is not recommended.
Concurrent administration of TNF-alpha inhibitor and abatacept
In clinical studies concurrent administration of TNF-antagonists and abatacept has been associated with an increased risk of infections including serious infections compared to TNF-antagonists alone, without increased clinical benefit. The combination of Remicade and abatacept is not recommended.
Switching between biological DMARDS
When switching from one biologic to another, patients should continue to be monitored for signs of infection.
Vaccinations
No data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines in patients receiving anti-TNF therapy. It is recommended that live vaccines not be given concurrently.
Autoimmune processes
The relative deficiency of TNFα caused by anti-TNF therapy may result in the initiation of an autoimmune process. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with Remicade and is positive for antibodies against double-stranded DNA, further treatment with Remicade must not be given (see section 4.8).
Neurological events
Use of TNF-blocking agents, including infliximab, has been associated with cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. In patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of anti-TNF treatment should be carefully considered before initiation of Remicade therapy. Discontinuation of Remicade should be considered if these disorders develop.
Malignancies and lymphoproliferative disorders
In the controlled portions of clinical studies of TNF-blocking agents, more cases of malignancies including lymphoma have been observed among patients receiving a TNF blocker compared with control patients. During clinical studies of Remicade across all approved indications the incidence of lymphoma in Remicade-treated patients was higher than expected in the general population, but the occurrence of lymphoma was rare. In the post-marketing setting, cases o |
