IMPORTANT SAFETY INFORMATION AND INDICATIONS
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 (TB), including reactivation of latent TB. Patients with TB have
frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB 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
antifungal 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, including Legionella and Listeria.
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 TB, 3) who have resided or traveled in areas of
endemic TB 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 TB in patients who tested negative for latent TB prior to
initiating therapy.
MALIGNANCIES
Lymphoma and other malignancies, some fatal, have been reported in children and
adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.
In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk
of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of
malignancies is unknown.
Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and
other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general
population.
Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including
ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.
Pediatric Patients
In patients who initiated therapy at ≤18 years of age, approximately half of the reported malignancies were
lymphomas (Hodgkin's and non-Hodgkin's lymphoma). Other cases included rare malignancies usually associated with
immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients
were receiving concomitant immunosuppressants.
NEUROLOGIC REACTIONS
Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (<0.1%) cases of new onset or
exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some
associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse
myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies,
and new onset or exacerbation of seizure disorders have been reported in postmarketing experience with ENBREL therapy.
Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset
central or peripheral nervous system demyelinating disorders.
CONGESTIVE HEART FAILURE
Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking
ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored.
HEMATOLOGIC REACTIONS
Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to
ENBREL therapy remains unclear. Exercise caution when considering ENBREL 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.
HEPATITIS B REACTIVATION
Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV)
and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking
immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL
in these patients.
ALLERGIC REACTIONS
Allergic reactions associated with administration of ENBREL during clinical trials have been reported in <2% of
patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be
discontinued immediately and appropriate therapy initiated.
IMMUNIZATIONS
Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up
to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily
discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin.
AUTOIMMUNITY
Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may
resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops.
USE IN GRANULOMATOSIS WITH POLYANGIITIS PATIENTS
The use of ENBREL in patients with granulomatosis with polyangiitis receiving immunosuppressive agents (eg, cyclophosphamide)
is not recommended.
MODERATE TO SEVERE ALCOHOLIC HEPATITIS
Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with
moderate to severe alcoholic hepatitis.
ADVERSE REACTIONS
The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In
clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical
trials.
In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult
patients. The types of infections reported in pediatric patients were generally mild and consistent with those
commonly seen in the general pediatric population.
DRUG INTERACTIONS
The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious
infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not
recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication
for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.
Please see Prescribing Information and Medication Guide.
INDICATIONS
ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of
structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis.
ENBREL can be initiated in combination with methotrexate (MTX) or used alone.
ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active
arthritis, and improving physical function in patients with psoriatic arthritis. ENBREL can be used with or
without MTX.
ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile
idiopathic arthritis in patients ages 2 and older.
