Etanercept: uses, appearance and warnings

Enbrel is a tumor necrosis factor (TNF) blocker indicated for the treatment of: Adult patients with: Rheumatoid Arthritis (RA) ( 1.1 ) Psoriatic Arthritis (PsA) ( 1.3 ) Ankylosing Spondylitis (AS) ( 1.4 ) Plaque Psoriasis (PsO) ( 1.5 ) Pediatric patients with: Polyarticular Juvenile Idiopathic Arthritis (pJIA), 2 years of age or older ( 1.2 ) Juvenile Psoriatic Arthritis, 2 years of age or older (JPsA) ( 1.6 ) Plaque Psoriasis, 4 years of age or older ( 1.5 ) 1.1 Rheumatoid Arthritis 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 (RA). Enbrel can be initiated in combination with methotrexate (MTX) or used alone. 1.2 Polyarticular Juvenile Idiopathic Arthritis Enbrel is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older. 1.3 Psoriatic Arthritis Enbrel is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in adult patients with psoriatic arthritis (PsA). Enbrel can be used with or without methotrexate. 1.4 Ankylosing Spondylitis Enbrel is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis (AS). 1.5 Plaque Psoriasis Enbrel is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy. 1.6 Juvenile Psoriatic Arthritis Enbrel is indicated for the treatment of active juvenile psoriatic arthritis (JPsA) in pediatric patients 2 years of age and older.

Injection: 25 mg/0.5 mL and 50 mg/mL clear, colorless solution in a single-dose prefilled syringe Injection: 50 mg/mL clear, colorless solution in a single-dose prefilled SureClick autoinjector Injection: 25 mg/0.5 mL clear, colorless solution in a single-dose vial For Injection: 25 mg lyophilized powder in a multiple-dose vial for reconstitution Injection: 50 mg/mL clear, colorless solution in Enbrel Mini single-dose prefilled cartridge for use with the AutoTouch reusable autoinjector only Injection: 25 mg/0.5 mL and 50 mg/mL solution in a single-dose prefilled syringe ( 3 ) Injection: 50 mg/mL solution in single-dose prefilled SureClick ® Autoinjector ( 3 ) Injection: 25 mg/0.5 mL solution in a single-dose vial ( 3 ) For Injection: 25 mg lyophilized powder in a multiple-dose vial for reconstitution ( 3 ) Injection: 50 mg/mL solution in Enbrel Mini ® single-dose prefilled cartridge for use with the AutoTouch ® reusable autoinjector only ( 3 )

Enbrel (etanercept) injection is supplied as a clear and colorless sterile, preservative-free solution for subcutaneous administration in single-dose prefilled syringes, an Enbrel single-dose prefilled SureClick autoinjector with a 27-gauge, ½-inch needle, or a single-dose vial. The prefilled syringe and SureClick autoinjector are not made with natural rubber latex. Each Enbrel ® Mini single-dose prefilled cartridge for use with the AutoTouch ® reusable autoinjector contains 1.0 mL of 50 mg/mL of etanercept. The AutoTouch reusable autoinjector and Enbrel Mini single-dose prefilled cartridge are not made with natural rubber latex. The AutoTouch reusable autoinjector contains no drug and must use an Enbrel Mini single-dose prefilled cartridge. In addition, the AutoTouch Connect ® reusable autoinjector would allow for data connectivity via Bluetooth wireless technology. 50 mg/mL single-dose prefilled syringe Carton of 4 NDC 58406-021-04 50 mg/mL single-dose prefilled SureClick autoinjector Carton of 4 NDC 58406-032-04 25 mg/0.5 mL single-dose prefilled syringe Carton of 4 NDC 58406-010-04 50 mg/mL Enbrel Mini single-dose prefilled cartridge for use with the AutoTouch reusable autoinjector only Cartridges: Carton of 4 NDC 58406-044-04 NDC 58406-044-24 AutoTouch Connect Reusable Autoinjector: Carton of 1 NDC 58406-480-01 25 mg/0.5 mL single-dose vial Carton of 4 NDC 58406-055-04 Enbrel should be refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light or physical damage. Do not store Enbrel in extreme heat or cold. DO NOT SHAKE. DO NOT FREEZE. For convenience, storage of individual single-dose prefilled syringes, SureClick autoinjectors, single-dose vials, or Enbrel Mini cartridges at room temperature at 68°F to 77°F (20°C to 25°C) for a maximum single period of 30 days is permissible, with protection from light and sources of heat. Once a single-dose prefilled syringe, SureClick autoinjector, single-dose vial, or Enbrel Mini cartridge has been stored at room temperature, it should not be placed back into the refrigerator. If not used within 30 days at room temperature, the single-dose prefilled syringe, SureClick autoinjector, single-dose vial, or Enbrel Mini cartridge should be discarded. Do not use Enbrel beyond the expiration date stamped on the carton or barrel/cartridge label. Keep out of the reach of children. The AutoTouch reusable autoinjector should be stored at room temperature. …

Enbrel is contraindicated in patients with sepsis. Enbrel is contraindicated in patients with sepsis. ( 4 )

Do not start Enbrel during an active infection. If an infection develops, monitor carefully and stop Enbrel if infection becomes serious. ( 5.1 ) Consider empiric anti-fungal therapy for patients at risk for invasive fungal infections who develop a severe systemic illness on Enbrel (those who reside or travel to regions where mycoses are endemic). ( 5.1 ) Demyelinating disease, exacerbation or new onset, may occur. ( 5.2 ) Cases of lymphoma have been observed in patients receiving TNF-blocking agents. ( 5.3 ) Congestive heart failure, worsening or new onset, may occur. ( 5.4 ) Advise patients to seek immediate medical attention if symptoms of pancytopenia or aplastic anemia develop, and consider stopping Enbrel. ( 5.5 ) Monitor patients previously infected with hepatitis B virus for reactivation during and several months after therapy. If reactivation occurs, consider stopping Enbrel and beginning anti-viral therapy. ( 5.6 ) Anaphylaxis or serious allergic reactions may occur. ( 5.7 ) Stop Enbrel if lupus-like syndrome or autoimmune hepatitis develops. ( 5.9 ) 5.1 Serious Infections Patients treated with Enbrel are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis have been reported with TNF-blockers. Patients have frequently presented with disseminated rather than localized disease. Treatment with Enbrel should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. The risks and benefits of treatment should be considered prior to initiating therapy in patients: With chronic or recurrent infection; Who have been exposed to tuberculosis; With a history of an opportunistic infection; Who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or With underlying conditions that may predispose them to infection, such as advanced or poorly controlled diabetes [see Adverse Reactions (6.1) ] . Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with Enbrel. Enbrel should be discontinued if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with Enbrel should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and appropriate antimicrobial therapy should be initiated. Tuberculosis Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving Enbrel, including patients who have previously received treatment for latent or active tuberculosis. Data from clinical trials and preclinical studies suggest that the risk of reactivation of latent tuberculosis infection is lower with Enbrel than with TNF-blocking monoclonal antibodies. Nonetheless, postmarketing cases of tuberculosis reactivation have been reported for TNF-blockers, including Enbrel. Tuberculosis has developed in patients who tested negative for latent tuberculosis prior to initiation of therapy. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating Enbrel and periodically during therapy. Tests for latent tuberculosis infection may be falsely negative while on therapy with Enbrel. Treatment of latent tuberculosis infection prior to therapy with TNF-blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy. Induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent tuberculosis is needed prior to initiating Enbrel, even for patients previously vaccinated with Bacillus Calmette-Guerin (BCG). Anti-tuberculosis therapy should also be considered prior to initiation of Enbrel in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient. Tuberculosis should be strongly considered in patients who develop a new infection during Enbrel treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis. Invasive Fungal Infections Cases of serious and sometimes fatal fungal infections, including histoplasmosis, have been reported with TNF-blockers, including Enbrel. For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Appropriate empiric anti-fungal therapy should be considered while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric anti-fungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and the risks of anti-fungal therapy. …

The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Serious Infections [see Warnings and Precautions (5.1) ] Neurologic Reactions [see Warnings and Precautions (5.2) ] Malignancies [see Warnings and Precautions (5.3) ] Patients with Heart Failure [see Warnings and Precautions (5.4) ] Hematologic Reactions [see Warnings and Precautions (5.5) ] Hepatitis B Reactivation [see Warnings and Precautions (5.6) ] Allergic Reactions [see Warnings and Precautions (5.7) ] Autoimmunity [see Warnings and Precautions (5.9) ] Immunosuppression [see Warnings and Precautions (5.10) ] Most common adverse reactions (incidence > 5%): infections and injection site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

Specific drug interaction studies have not been conducted with Enbrel. Live vaccines – Avoid concurrent administration with Enbrel ( 5.8 , 7.1 ) Anakinra – Increased risk of serious infection ( 5.12 , 7.2 ) Abatacept – Increased risk of serious adverse events, including infections ( 5.12 , 7.2 ) Cyclophosphamide – Not recommended for use with Enbrel. ( 7.3 ) 7.1 Vaccines Most PsA patients receiving Enbrel were able to mount effective B-cell immune responses to pneumococcal polysaccharide vaccine, but titers in aggregate were moderately lower and fewer patients had 2-fold rises in titers compared to 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. …