(5%) Pyrexia (2%) Urticaria (2%) Hypersensitivity (1%) PsO (Enbrel and Eticovo only) Diarrhea (3%) Rash (1%) Pruritus (1%) Urticaria (1%) Hypersensitivity (1%) Postmarketing Reports Blood and lymphatic system disorders: Pancytopenia, anemia, leukopenia, neutropenia, thrombocytopenia, lymphadenopathy, aplastic anemia Cardiac disorders: Congestive heart failure Gastrointestinal disorders: Inflammatory bowel disease (IBD General disorders: Angioedema, chest pain Hepatobiliary disorders: Autoimmune hepatitis, elevated transaminases Immune disorders: macrophage activation syndrome, systemic vasculitis Musculoskeletal and connective tissue disorders: Lupus-like syndrome Neoplasms benign, malignant, and unspecified: Melanoma and non-melanoma skin cancers, Merkel cell carcinoma Nervous system disorders: Convulsions, multiple sclerosis, demyelination, optic neuritis, transverse myelitis, paresthesias, headache Ocular disorders: Uveitis, scleritis Respiratory, thoracic and mediastinal disorders: Interstitial lung disease Skin and subcutaneous tissue disorders: Cutaneous lupus erythematosus, cutaneous vasculitis (including leukocytoclastic vasculitis), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, subcutaneous nodule, new or worsening psoriasis (all sub-types including pustular and palmoplantar) SC nodule, new or worsening psoriasis (all sub-types including pustular and palmoplantar) Opportunistic infections, including atypical mycobacterial infection, herpes zoster, aspergillosis and Pneumocystis jiroveci pneumonia, and protozoal infections Black Box Warnings Serious infection risk Increased risk of developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids) Patients older than 65 years may be at greater risk Discontinue if patient develops serious infection or sepsis Reported infections include the following Active tuberculosis (TB), including reactivation of latent TB (frequently present with disseminated or extrapulmonary disease); test for latent TB before use and during therapy; treat latent infection before use Invasive fungal infections (eg, histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis); may present with disseminated, rather than localized, disease; antigen/antibody testing for histoplasmosis may be negative in some patients with active infection; initiate empiric antifungal therapy if severe systemic illness develops Infections caused by other bacterial (eg, Legionella, Listeria), mycobacterial (eg, Mycobacterium tuberculosis), and viral (eg, hepatitis B virus) opportunistic pathogens Malignancy Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF) blockers Cases of acute and chronic leukemia have been reported in association with postmarketing TNF-blocker use in rheumatoid arthritis (RA) and other indications; patients with RA may be at higher (approximately 2-fold greater) risk for leukemia than general population Manufacturer required to report all malignancies to FDA for complete and consistent analysis Contraindications Sepsis Hypersensitivity Cautions HBV-positive status, history of or susceptibility to recurring infections, history of blood dyscrasias Consider empiric anti-fungal therapy for patients at risk for invasive fungal infections who develop a systemic severe illness while receiving therapy Monitor closely for signs or symptoms of demyelinating disease (eg, confusion, numbness, vision changes); use caution in patients with preexisting or recent-onset CNS demyelinating disorders; therapy 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-Barre syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders reported in postmarketing experience with etanercept products therapy Increased risk of TB; monitor for TB Possibility of lupuslike symptoms or development of autoimmune hepatitis; discontinue if such symptoms develop Use with caution in patients with history of significant hematologic abnormalities; consider discontinuing if hematologic disorders (eg, pancytopenia, leukopenia, thrombocytopenia, aplastic anemia) occur; consider stopping therapy Diluent for multidose vial contains benzyl alcohol as preservative Children should be up to date with immunizations before starting drug Increased risk of lymphoma and other cancers reported in children and adolescents; occurrence of leukemia and new-onset psoriasis reported in patients treated with TNF blockers Enhanced safety surveillance requirements to capture malignancy data; manufacturers required to report all malignancies to FDA for complete and consistent analysis Worsening or new onset congestive heart failure reported with TNF blockers; Exercise caution when using in patients who have heart failure; TNFalpha inhibitors should only be considered in patients with HF if there are no other reasonable treatment options, and then only consider in patients with compensated HF Reactivation of hepatitis B (HBV) in chronic carriers of the virus reported; fatal in patients receiving concomitant immunosuppressants; evaluate for HBV prior to initiation in all patients Use caution in patients with moderate to severe alcoholic hepatitis; significant higher rate of mortality reported at 6 months of therapy Use caution in patients with history of seizures, new onset or exacerbatin of seizures reported with therapy Therapy not recommended in patients with Wegener granulomatosis receiving immunosuppressive therapy due to higher incidence of noncutaneous solid malignancies Use in patients with granulomatosis with polyangiitis receiving immunosuppressive agents not recommended; use is associated with a higher incidence of non-cutaneous solid malignancies and not associated with improved clinical outcomes when compared with standard therapy alone Children with significant exposure to varicella virus should temporarely discontinue therapy; consider administering varicella zoster immune globulin Hepatosplenic T-cell lymphoma Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL; an aggressive, rare, and usually fatal type of T-cell lymphoma) have been reported, primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with TNF blockers but also in 1 patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis Most reported cases with TNF blockers have occurred with concomitant treatment with azathioprine or 6-mercaptopurine (6-MP), though some cases have been reported with azathioprine or 6-MP alone Drug interaction overview Vaccines Avoid coadministration of live vaccines No data are available on the secondary transmission of infection by live vaccines in patients receiving etanercept Patients with a significant exposure to varicella virus should temporarily discontinue etanercept and be considered for prophylactic treatment with varicella zoster immune globulin Cyclophosphamide Use of etanercept with cyclophosphamide therapy is not recommended Sulfasalazine Patients in a clinical study who were on established therapy with sulfasalazine, to which etanercept was added, were noted to develop a mild decrease in mean neutrophil counts in comparison to groups treated with either etanercept or sulfasalazine alone Clinical significance of this observation is unknown Pregnancy Available studies during pregnancy do not reliably support an association between therapy and major birth defects; clinical data are available from the Organization of Teratology Information Specialists (OTIS) Enbrel Pregnancy Registry in women with rheumatic diseases or psoriasis and a Scandinavian study in pregnant women with chronic inflammatory disease; Both studies showed the proportion of liveborn infants with major birth defects was higher for women exposed to etanercept compared to diseased etanercept unexposed women; however, the lack of pattern of major birth defects is reassuring and differences between exposure groups (e.g. disease severity) may have impacted the occurrence of birth defects The risk of fetal/neonatal adverse reactions with in utero exposure to therapy is unknown; risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to drug in utero Lactation Limited data from published literature show that etanercept is present in low levels in human milk and minimally absorbed by a breastfed infant; no data are available on effects of therapy on breastfed child or on milk productionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Binds and inactivates TNF, thereby preventing synovial inflammation Absorption Bioavailability: 60% Onset: 1-2 weeks Peak plasma time (single 25-mg dose): 69 ± 34 hr Peak plasma concentration (single 25-mg dose): 1.1 ± 0.6 mcg/mL Distribution Vd: 12 L Elimination Half-life: ~5 days Clearance: 160 mL/hr (varies) SC Preparation For a more comfortable injection, leave prefilled syringe/autoinjector/reconstituted vial at room temperature for ~15-30 minutes before injecting Do not remove the needle cover while allowing to reach room temperature Reconstitution of vial Reconstituted vial powder with 1 mL of the supplied sterile bacteriostatic water for injection Dissolution generally takes <10 minutes; resulting concentration is 25 mg/mL Do not use if discolored or cloudy, or if particulate matter remains Withdraw correct dose of reconstituted solution into the syringe, some foam or bubbles may remain in the vial Remove syringe from the vial adapter or remove the 25-gauge needle from the syringe; attach a 27-gauge needle for SC injection Vial contents should not be mixed with, or transferred into, the contents of another vial of etanercept No other medications should be added to solutions containing etanercept, and do not reconstitute with other diluents Do not filter reconstituted solution during preparation or administration SC Administration Rotate injection sites Clean injection site area with alcohol wipe and let skin dry Inject SC in top of thighs, abdomen (avoid 2-inch area around navel), or outer area of upper arm Do not inject areas of skin that are tender, bruised, red, or hard Avoid injecting area with scars or stretch marks For psoriasis, avoid injecting directly into raised, thick, red, or scaly skin patch or lesion Storage Refrigerate at 36-46ºF (2-8ºC) Do not shake Store in the original carton to protect from light or physical damage For convenience, storage of individual syringes, autoinjectors, or vials at room temperature for a maximum single period of 14 days is permissible, with protection from light and sources of heat Once stored at room temperature, do not place back in the refrigerator Discard if not used within 14 days at room temperature Once a vial has been reconstituted, the solution must be used immediately or may be refrigerated for up to 14 days Do not store in extreme heat or cold Do not freeze BRAND FORM. UNIT PRICE PILL IMAGE Enbrel subcutaneous- 25 mg/0.5 mL (0.5) solutionEnbrel subcutaneous- 50 mg/mL (1 mL) solutionEnbrel subcutaneous- 50 mg/mL (1 mL) solutionEnbrel subcutaneous- 25 mg/0.5 mL vialEnbrel subcutaneous- 50 mg/mL (1 mL) solutionEnbrel subcutaneous- 25 mg (1 mL) vialEnbrel subcutaneous- 25 mg/0.5 mL vialEnbrel SureClick subcutaneous- 50 mg/mL (1 mL) injectionCopyright © 2010 First DataBank, Inc.Print Patient Educationetanercept subcutaneous ETANERCEPT - INJECTION (ee-TAN-er-sept) COMMON BRAND NAME(S): Enbrel WARNING: Because etanercept works by blocking the immune system, it may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection (such as fungal infections, bacterial infections including tuberculosis) or make any infection you have worse. Tell your doctor your medical history, especially of past/recent/current infections. Also, tell your doctor if you have lived or traveled in areas where certain fungal infections (such as coccidioidomycosis, histoplasmosis) are common or if you have been near someone with tuberculosis. Areas where these types of fungal infections are commonly found include the Ohio and Mississippi River valleys and the southwestern United States. You should be tested for tuberculosis (TB skin test or chest X-ray) before and during treatment with etanercept. See Side Effects section for symptoms of infections to watch out for, and get medical help right away if you develop any of these symptoms.The immune system is also important in preventing and controlling cancer. Though it is very unlikely to happen, there is a risk (especially in children/teens/young adults) of developing cancer (such as lymphoma, skin) due to this medication or due to your medical condition. Discuss the risks and benefits of treatment with your doctor. Tell your doctor right away if you develop symptoms such as fever that doesn't go away, unusual lumps/growths, swollen or painful abdomen, unexplained weight loss, or night sweats. USES: This medication is used alone or in combination with an immunosuppressant (such as methotrexate) to treat certain types of arthritis (such as rheumatoid, psoriatic, juvenile idiopathic, and ankylosing spondylitis). Some brands of this medication are also used to treat a skin condition called psoriasis. These conditions are caused by an overactive immune system (autoimmune disease). The immune system attacks the body's own healthy cells, causing inflammation in the joints and skin.Etanercept controls your body's defensive response by blocking the action of a certain natural substance (TNF) that is used by the immune system. Treatment