Label Changes for:
Changes have been made to the BOXED WARNING and WARNINGS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
BOXED WARNING (edited)
WARNING: SERIOUS INFECTIONS and MALIGNANCY
- Patients treated with Remicade are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
- Remicade should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: • Active tuberculosis, including reactivation of latent tuberculosis.
- Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before Remicade use and during therapy. Treatment for latent infection should be initiated prior to Remicade use.
- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
- Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria. The risks and benefits of treatment with Remicade should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with Remicade, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
- Lymphoma and other malignancies, some fatal, have been reported inchildren and adolescent patients treated with TNF blockers, including Remicade.
- Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including Remicade. These cases have had a very aggressive disease course and have been fatal. Almost all patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. The majority of reported Remicade cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were in adolescent and young adult males.
- Tuberculosis - Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving REMICADE, including patients who have previously received treatment for latent or active tuberculosis. Cases of active tuberculosis have also occurred in patients being treated with REMICADE during treatment for latent tuberculosis.
- Malignancies – the incidence of malignancies including lymphoma was greater in REMICADE treated patients than in controls. Due to the risk of HSTCL carefully assess the risk/benefit especially if the patient has Crohn’s disease or ulcerative colitis, is male, and is receiving azathioprine or 6-mercaptopurine treatment.
- Hepatosplenic T-cell lymphoma (HSTCL)- Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including REMICADE. These cases have had a very aggressive disease course and have been fatal. Almost all patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. The majority of reported REMICADE cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were in adolescent and young adult males. It is uncertain whether the occurrence of HSTCL is related to TNF-blockers or TNF-blockers in combination with these other immunosuppressants.
- When treating patients, consideration of whether to use REMICADE alone or in combination with other immunosuppressants such as azathioprine or 6-mercaptopurine should take into account a possibility that there is a higher risk of HSTCL with combination therapy versus an observed increased risk of immunogenicity and hypersensitivity reactions with REMICADE monotherapy from the clinical trial data
WARNINGS AND PRECAUTIONS
- Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including REMICADE [see Adverse Reactions (6.2)]. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
Concurrent Administration with other Biological Therapeutics
- There is insufficient information regarding the concomitant use of REMICADE with other biological therapeutics used to treat the same conditions as REMICADE. The concomitant use of REMICADE with these biologics is not recommended because of the possibility of an increased risk of infection
- serious infections and malignancies, including melanoma and Merkel cell carcinoma
WARNINGS AND PRECAUTIONS
Use with Abatacept
- In clinical studies, concurrent administration of TNF-blocking agents and abatacept have been associated with an increased risk of infections including serious infections compared with TNF-blocking agents alone, without increased clinical benefit. Therefore, the combination of Remicade and abatacept is not recommended.
Switching between Biological Disease-Modifying Antirheumatic Drugs (DMARDs)
- Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.
What should I avoid while receiving Remicade?