Adalimumab: uses, appearance and warnings

YUFLYMA is a tumor necrosis factor (TNF) blocker indicated for: Reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active r heumatoid arthritis . ( 1.1 ) Reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. ( 1.2 ) Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active p soriatic arthritis . ( 1.3 ) Reducing signs and symptoms in adult patients with active ankylosing spondylitis . ( 1.4 ) Treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and older. ( 1.5 ) Treatment of moderately to severely active ulcerative colitis in adult patients. ( 1.6 ) Limitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers. Treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. ( 1.7 ) Treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older. ( 1.8 ) Treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older. ( 1.9 ) 1.1 Rheumatoid Arthritis YUFLYMA is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. YUFLYMA can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs). 1.2 Juvenile Idiopathic Arthritis YUFLYMA is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. YUFLYMA can be used alone or in combination with methotrexate. 1.3 Psoriatic Arthritis YUFLYMA is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. YUFLYMA can be used alone or in combination with non-biologic DMARDs. 1.4 Ankylosing Spondylitis YUFLYMA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis. 1.5 Crohn's Disease YUFLYMA is indicated for the treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and older. 1.6 Ulcerative Colitis YUFLYMA is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients. Limitations of Use The effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to TNF blockers [see Clinical Studies ( 14.7 )] . 1.7 Plaque Psoriasis YUFLYMA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. YUFLYMA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see Warnings and Precautions ( 5 )] . 1.8 Hidradenitis Suppurativa YUFLYMA is indicated for the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older. 1.9 Uveitis YUFLYMA is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.

YUFLYMA is a clear to opalescent, and colorless to pale brown solution available as: Auto-injector (YUFLYMA AI) Injection: 80 mg/0.8 mL in a single-dose auto-injector. Injection: 40 mg/0.4 mL in a single-dose auto-injector. Prefilled Syringe with Safety Guard Injection: 80 mg/0.8 mL in a single-dose prefilled syringe with safety guard. Injection: 40 mg/0.4 mL in a single-dose prefilled syringe with safety guard. Prefilled Syringe Injection: 80 mg/0.8 mL in a single-dose prefilled syringe. Injection: 40 mg/0.4 mL in a single-dose prefilled syringe. Injection: 20 mg/0.2 mL in a single-dose prefilled syringe. Injection: 10 mg/0.1 mL in a single-dose prefilled syringe. Injection: Single-dose prefilled auto-injector (YUFLYMA AI): 80 mg/0.8 mL, 40 mg/0.4 mL ( 3 ) Single-dose prefilled syringe with safety guard : 80 mg/0.8 mL, 40 mg/0.4 mL ( 3 ) Single-dose prefilled syringe: 80 mg/0.8 mL, 40 mg/0.4 mL, 20 mg/0.2 mL, 10 mg/0.1 mL ( 3 )

YUFLYMA (adalimumab-aaty) is supplied as a preservative-free, sterile, clear to opalescent, and colorless to pale brown solution for subcutaneous administration. The following packaging configurations are available. YUFLYMA AI Carton - 40 mg/0.4 mL (1 Count) YUFLYMA is supplied in a carton containing two alcohol preps and one dose tray. The dose tray consists of a single-dose prefilled auto-injector, containing a 1 mL prefilled syringe with a fixed thin wall, ½ inch needle, providing 40 mg/0.4 mL of YUFLYMA. The NDC number is 72606-030-09. YUFLYMA AI Carton - 40 mg/0.4 mL (2 Count) YUFLYMA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose prefilled auto-injector, containing a 1 mL prefilled syringe with a fixed thin wall, ½ inch needle, providing 40 mg/0.4 mL of YUFLYMA. The NDC number is 72606-030-10. YUFLYMA AI Carton - 40 mg/0.4 mL (4 Count) YUFLYMA is supplied in a carton containing four alcohol preps and four dose trays. Each dose tray consists of a single-dose prefilled auto-injector, containing a 1 mL prefilled syringe with a fixed thin wall, ½ inch needle, providing 40 mg/0.4 mL of YUFLYMA. The NDC number is 72606-030-11. YUFLYMA AI Carton - 40 mg/0.4 mL (6 Count) YUFLYMA is supplied in a carton containing six alcohol preps and six dose trays. Each dose tray consists of a single-dose prefilled auto-injector, containing a 1 mL prefilled syringe with a fixed thin wall, ½ inch needle, providing 40 mg/0.4 mL of YUFLYMA. The NDC number is 72606-030-12. Prefilled Syringe with Safety Guard Carton - 40 mg/0.4 mL (1 Count) YUFLYMA is supplied in a carton containing two alcohol preps and one dose tray. The dose tray consists of a single-dose prefilled syringe with safety guard, containing a 1 mL prefilled syringe with a fixed thin wall, ½ inch needle, providing 40 mg/0.4 mL of YUFLYMA. The NDC number is 72606-030-05. Prefilled Syringe with Safety Guard Carton - 40 mg/0.4 mL (2 Count) YUFLYMA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose prefilled syringe with safety guard, containing a 1 mL prefilled syringe with a fixed thin wall, ½ inch needle, providing 40 mg/0.4 mL of YUFLYMA. The NDC number is 72606-030-06. Prefilled Syringe with Safety Guard Carton - 40 mg/0.4 mL (4 Count) YUFLYMA is supplied in a carton containing four alcohol preps and four dose trays. …

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Serious infections: Do not start YUFLYMA during an active infection. If an infection develops, monitor carefully, and stop YUFLYMA if infection becomes serious ( 5.1 ) Invasive fungal infections: For patients who develop a systemic illness on YUFLYMA, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic ( 5.1 ) Malignancies: Incidence of malignancies was greater in adalimumab-treated patients than in controls ( 5.2 ) Anaphylaxis or serious hypersensitivity reactions may occur ( 5.3 ) Hepatitis B virus reactivation: Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop YUFLYMA and begin anti-viral therapy ( 5.4 ) Demyelinating disease: Exacerbation or new onset, may occur ( 5.5 ) Cytopenias, pancytopenia: Advise patients to seek immediate medical attention if symptoms develop, and consider stopping YUFLYMA ( 5.6 ) Heart failure: Worsening or new onset, may occur ( 5.8 ) Autoimmunity: Stop YUFLYMA if lupus-like syndrome or autoimmune hepatitis develop ( 5.9 ) 5.1 Serious Infections Patients treated with adalimumab products, including YUFLYMA, 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. The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections in patients with rheumatoid arthritis (RA); therefore, the concomitant use of YUFLYMA and these biologic products is not recommended in the treatment of patients with RA [see Warnings and Precautions ( 5.7 , 5.11 ) and Drug Interactions ( 7.2 )] . Treatment with YUFLYMA should not be initiated in patients with an active infection, including localized infections. Patients 65 years of age and older, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Consider the risks and benefits of treatment 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. Tuberculosis Cases of reactivation of tuberculosis and new onset tuberculosis infections have been reported in patients receiving adalimumab products, including patients who have previously received treatment for latent or active tuberculosis. Reports included cases of pulmonary and extrapulmonary (i.e., disseminated) tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating YUFLYMA and periodically during therapy. Treatment of latent tuberculosis infection prior to therapy with TNF blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating YUFLYMA, assess if treatment for latent tuberculosis is needed; and consider an induration of ≥ 5 mm a positive tuberculin skin test result, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG). Consider anti-tuberculosis therapy prior to initiation of YUFLYMA 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. Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with adalimumab products. 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. Strongly consider tuberculosis in the differential diagnosis in patients who develop a new infection during YUFLYMA 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. Monitoring Closely monitor patients for the development of signs and symptoms of infection during and after treatment with YUFLYMA, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with YUFLYMA. Discontinue YUFLYMA if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with YUFLYMA, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy. Invasive Fungal Infections If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider appropriate empiric antifungal therapy, taking into account both the risk for severe fungal infection and the risks of antifungal therapy, while a diagnostic workup is being performed. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections. …

The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions ( 5.1 )] Malignancies [see Warnings and Precautions ( 5.2 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] Hepatitis B Virus Reactivation [see Warnings and Precautions ( 5.4 )] Neurologic Reactions [see Warnings and Precautions ( 5.5 )] Hematological Reactions [see Warnings and Precautions ( 5.6 )] Heart Failure [see Warnings and Precautions ( 5.8 )] Autoimmunity [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (> 10%) are: infections (e.g. upper respiratory, sinusitis), injection site reactions, headache and rash ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact CELLTRION USA Inc., at 1-800-560-9414 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

Abatacept: Increased risk of serious infection ( 5.1 , 5.11 , 7.2 ) Anakinra: Increased risk of serious infection ( 5.1 , 5.7 , 7.2 ) Live vaccines: Avoid use with YUFLYMA ( 5.10 , 7.3 ) 7.1 Methotrexate Adalimumab has been studied in rheumatoid arthritis (RA) patients taking concomitant methotrexate (MTX). Although MTX reduced the apparent clearance of adalimumab, the data do not suggest the need for dose adjustment of either YUFLYMA or MTX [see Clinical Pharmacology ( 12.3 )] . 7.2 Biological Products In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of YUFLYMA with abatacept or anakinra is not recommended in patients with RA [see Warnings and Precautions ( 5.7 , 5.11 )] . …