IMPORTANT SAFETY INFORMATION

RISK OF SERIOUS INFECTIONS

Patients treated with ENBREL 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 or were predisposed to infection because of their underlying disease.  ENBREL should not be initiated in the presence of sepsis, active infections or allergy to ENBREL or its components.  ENBREL should be discontinued if a patient develops a serious infection or sepsis.  Reported infections include: 1) 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 ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use. 2) 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, and 3) Bacterial, viral and other infections due to opportunistic pathogens, such as listeriosis.

The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to tuberculosis, 3) who have resided or traveled in areas of endemic tuberculosis or endemic mycoses or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes.  Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis prior to initiating therapy. 

Neurologic Events
TNF inhibitors, including ENBREL, have been associated with rare cases of new onset or exacerbation of CNS demyelinating disorders (some presenting with mental status changes and some associated with permanent disability). Transverse myelitis, optic neuritis, multiple sclerosis, and cases of new onset or exacerbation of seizure disorders have been observed in association with ENBREL therapy. A causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL for patients with these disorders.

Hematologic Events
Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. A causal relationship to ENBREL therapy remains unclear. Exercise caution in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed.

Malignancies
In clinical trials of all TNF inhibitors, more cases of lymphoma were seen compared to control patients.  The risk of lymphoma may be up to several-fold higher in RA and psoriasis patients. The role of TNF inhibitors in the development of malignancies is unknown.

Hepatitis B Reactivation
TNF inhibitors, including ENBREL, have been associated with reactivation of hepatitis B virus (HBV) in chronic carriers of this virus. The majority of these reports occurred in patients on concomitant immunosuppressive agents, which may also contribute to HBV reactivation. Prescribers should exercise caution in prescribing TNF blockers for patients identified as carriers of HBV.

Moderate to Severe Alcoholic Hepatitis
Based on a study of patients treated for alcoholic hepatitis, physicians should use caution when using ENBREL in patients with moderate to severe alcoholic hepatitis.

Adverse Events
The most commonly reported adverse events in RA clinical trials were injection site reaction, infection, and headache. In clinical trials of all other adult indications, adverse events were similar to those reported in RA clinical trials.

In a JIA study, infection, headache, abdominal pain, vomiting, and nausea occurred more frequently than in adult RA patients in placebo-controlled trials. The types of infections reported in JIA patients were generally mild and consistent with those commonly seen in outpatient pediatric populations.

Please see accompanying Prescribing Information and Medication Guide