ENBREL suppresses the immune system and has been associated with serious and sometimes fatal infections, malignancies, neurologic events, hematologic events, congestive heart failure, hepatitis B reactivation, allergic reactions, lupus-like syndrome and autoimmune hepatitis.

Please see Prescribing Information and Medication Guide.

Anti-tumor necrosis factor (TNF) therapies, including ENBREL, affect host defenses against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses. In a study of 49 RA patients treated with ENBREL, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector cell populations. The impact of treatment with ENBREL on the development and course of malignancies, as well as active and/or chronic infections, is not fully understood. The safety and efficacy of ENBREL in patients with immunosuppression of chronic infections have not been evaluated.

The risks and benefits of ENBREL should be carefully considered in patients with chronic or recurrent infection or underlying conditions that may predispose them to infection (such as advanced or poorly controlled diabetes) or a history of opportunistic infections, and with those who have been exposed to tuberculosis or areas of endemic tuberculosis or mycoses (such as histoplasmosis, coccidioidomycosis, or blastomycosis).

Most psoriatic arthritis patients receiving ENBREL were able to mount effective B-cell immune responses to pneumococcal polysaccharide vaccines, but titers in aggregate were moderately lower, and fewer patients had twofold rises in titers compared with patients not receiving ENBREL. The clinical significance of this is unknown. Patients receiving ENBREL may receive concurrent vaccinations, except for live vaccines. No data are available on the secondary transmission of infection by live vaccines in patients receiving ENBREL.

It is recommended that pediatric patients, if possible, be brought up-to-date with all immunizations in agreement with current immunization guidelines prior to initiating ENBREL therapy.

Live vaccines are not recommended for patients on ENBREL.

A total of 480 RA patients ages 65 years or older have been studied in clinical trials. In plaque psoriasis randomized clinical trials, a total of 138 out of 1,965 subjects treated with ENBREL or placebo were age 65 or older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but the number of geriatric psoriasis subjects is too small to determine whether they respond differently from younger subjects. Because there is a higher incidence of infections in the elderly population in general, caution should be used in treating elderly patients.

In ENBREL clinical trials, patients with RA, psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis were tested at multiple time points for antibodies to ENBREL. Antibodies to the TNF receptor portion or other protein components of the ENBREL drug product were detected at least once in sera of approximately 6% of adult patients with RA, psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis. These antibodies were all non-neutralizing. No apparent correlation of antibody development to clinical response or adverse events was observed. Results from JIA patients were similar to those seen in adult RA patients treated with ENBREL. The long-term immunogenicity of ENBREL is unknown.

Serious Infections
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 infection prior to initiating therapy.

Patients with Heart Failure
Physicians should exercise caution when using ENBREL in patients who also have heart failure, and monitor patients carefully.

See Prescribing Information for additional warnings and precautions.

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of ENBREL or its effect on fertility. Mutagenesis studies were conducted in vitro and in vivo, and no evidence of mutagenic activity was observed.

ENBREL is classified as Pregnancy Category B. Developmental toxicity studies have been performed in rats and rabbits at doses ranging from 60- to 100-fold higher than the human dose, and have revealed no evidence of harm to fetuses due to ENBREL. There are, however, no studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Women who become pregnant during ENBREL treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

It is not known whether ENBREL is excreted in human milk or absorbed systemically after ingestion. Because many drugs and immunoglobulins are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ENBREL, a decision should be made whether to discontinue nursing or to discontinue the drug.

For moderate to severe plaque psoriasis, the recommended starting dose of ENBREL for adult patients is 50 mg, twice a week (3 or 4 days apart), given for 3 months. After 3 months, the recommended dose is to step down to 50 mg once weekly.

Step-down dosing:

• Step 1: ENBREL 50 mg twice weekly for the first 3 months
• Step 2: ENBREL 50 mg once weekly for maintenance after 3 months

A 50-mg dose can be given as one subcutaneous (SC) injection using the Enbrel^® (etanercept) SureClick^® autoinjector or the 50-mg/mL single-use prefilled syringe. 25-mg/0.5-mL prefilled syringes and 25-mg vials of ENBREL are also available.

Yes, the needle covers on the Enbrel^® SureClick^® autoinjector and the single-use prefilled syringes contain dry natural rubber (derivative of latex), which should not be handled by persons sensitive to the substance.

ENBREL should not be administered to patients with sepsis.

Each single-use prefilled syringe and Enbrel^® SureClick^® autoinjector contains 50 mg/mL of etanercept in a single-dose syringe with a 27-gauge, 1/2-inch needle.

ENBREL multiple-use vial is supplied in a carton containing four dose trays. Each dose tray contains one 25-mg vial of etanercept, one diluent syringe (1 mL Sterile Bacteriostatic Water for Injection, USP, containing 0.9% benzyl alcohol), one 27-gauge 1/2-inch needle, one vial adapter, and one plunger. Each carton contains four "Mixing Date:" stickers.

Administration of one 50-mg prefilled syringe or one Enbrel^® SureClick^® autoinjector provides a dose equivalent to two 25-mg prefilled syringes or two multiple-use vials of lyophilized ENBREL, when vials are reconstituted and administered as recommended.

ENBREL must be refrigerated at 2° to 8°C (36° to 46°F). DO NOT FREEZE. The product must be kept in the original carton to protect from light until time of use.

Reconstituted solutions of ENBREL prepared with the supplied Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol), using a 25-gauge needle, may be stored for up to 14 days if refrigerated at 2° to 8°C (36° to 46°F). Discard reconstituted solution after 14 days.

Do not use an ENBREL dose tray beyond the date stamped on the carton or vial label.