Amgevita (adalimumab) Brief Prescribing information Please refer to the Summary of Product Characteristics before prescribing Amgevita . Pharmaceutical Form: AMGEVITA 40 mg solution for injection in pre-filled syringe Solution for injection & AMGEVITA 40 mg solution for injection in pre-filled pen (SureClick) Solution for injection. Therapeutic indication: Rheumatoid arthritis: AMGEVITA in combination with methotrexate, is indicated for: the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate. the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. AMGEVITA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. AMGEVITA reduces the rate of progression of joint damage as measured by x-ray and improves physical function, when given in combination with methotrexate. Juvenile idiopathic arthritis: Polyarticular juvenile idiopathic arthritis. AMGEVITA in combination with methotrexate is indicated for the treatment of active polyarticular juvenile idiopathic arthritis, in patients from the age of 2 years who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). AMGEVITA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate (for the efficacy in monotherapy refer to full summary of product characteristics). Adalimumab has not been studied in patients aged less than 2 years. Enthesitis-related arthritis: AMGEVITA is indicated for the treatment of active enthesitis-related arthritis in patients, 6 years of age and older, who have had an inadequate response to, or who are intolerant of, conventional therapy. Axial spondyloarthritis : Ankylosing spondylitis (AS) AMGEVITA is indicated for the treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy. Axial spondyloarthritis without radiographic evidence of AS. AMGEVITA is indicated for the treatment of adults with severe axial spondyloarthritis without radiographic evidence of AS but with objective signs of inflammation by elevated CRP and/or MRI, who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs. Psoriatic arthritis: AMGEVITA is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. AMGEVITA reduces the rate of progression of peripheral joint damage as measured by x-ray in patients with polyarticular symmetrical subtypes of the disease and improves physical function. Psoriasis: AMGEVITA is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy. Paediatric plaque psoriasis: AMGEVITA is indicated for the treatment of severe chronic plaque psoriasis in children and adolescents from 4 years of age who have had an inadequate response to or are inappropriate candidates for topical therapy and phototherapies. Hidradenitis suppurativa (HS): AMGEVITA is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adult patients with an inadequate response to conventional systemic HS therapy. Crohn’s disease: AMGEVITA is indicated for treatment of moderately to severely active Crohn’s disease, in adult patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. Paediatric Crohn's disease: AMGEVITA is indicated for the treatment of moderately to severely active Crohn's disease in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including primary nutrition therapy, a corticosteroid, and an immunomodulator, or who are intolerant to or have contraindications for such therapies. Ulcerative colitis: AMGEVITA is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies. Uveitis: AMGEVITA is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid-sparing, or in whom corticosteroid treatment is inappropriate. Posology and method of administration: Posology: Rheumatoid arthritis: The recommended dose of AMGEVITA for adult patients with rheumatoid arthritis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection. Methotrexate should be continued during treatment with AMGEVITA. Glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs, or analgesics can be continued during treatment with AMGEVITA. Regarding combination with disease-modifying anti-rheumatic drugs other than methotrexate refer to full Summary of Product Characteristics. In monotherapy, some patients who experience a decrease in their response may benefit from an increase in dose intensity to 40 mg adalimumab every week. Available adalimumab data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be reconsidered in a patient not responding within this time period. Dose interruption: There may be a need for dose interruption, for instance before surgery or if a serious infection occurs. Re-introduction of AMGEVITA after discontinuation for 70 days or longer should result in the same magnitudes of clinical response and similar safety profile as before dose interruption. Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and psoriatic arthritis: The recommended dose of AMGEVITA for patients with ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and for patients with psoriatic arthritis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection. For all of the above indications, available data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period. Psoriasis: The recommended dose of AMGEVITA for adult patients is an initial dose of 80 mg administered subcutaneously, followed by 40 mg subcutaneously given every other week starting one week after the initial dose. Continued therapy beyond 16 weeks should be carefully reconsidered in a patient not responding within this time period. Beyond 16 weeks, patients with inadequate response may benefit from an increase in dosing frequency to 40 mg every week. The benefits and risks of continued weekly therapy should be carefully reconsidered in a patient with an inadequate response after the increase in dosing frequency. If adequate response is achieved with an increased dosing frequency, the dose may subsequently be reduced to 40 mg every other week. Hidradenitis suppurativa: The recommended AMGEVITA dose regimen for adult patients with hidradenitis suppurativa (HS) is 160 mg initially at day 1 (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days), followed by 80 mg two weeks later at day 15 (given as two 40 mg injections in one day). Two weeks later (day 29) continue with a dose of 40 mg every week. Antibiotics may be continued during treatment with AMGEVITA if necessary. It is recommended that the patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment with AMGEVITA. Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement within this time period. Should treatment be interrupted, AMGEVITA 40 mg every week may be re-introduced. The benefit and risk of continued long-term treatment should be periodically evaluated. Crohn’s disease: The recommended AMGEVITA induction dose regimen for adult patients with moderately to severely active Crohn’s disease is 80 mg at week 0 followed by 40 mg at week 2. In case there is a need for a more rapid response to therapy, the regimen 160 mg at week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days), 80 mg at week 2, can be used with the awareness that the risk for adverse events is higher during induction. After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. Alternatively, if a patient has stopped AMGEVITA and signs and symptoms of disease recur, AMGEVITA may be re-administered. There is little experience from re-administration after more than 8 weeks since the previous dose. During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines. Some patients who experience decrease in their response may benefit from an increase in dosing frequency to 40 mg AMGEVITA every week. Some patients who have not responded by week 4 may benefit from continued maintenance therapy through week 12. Continued therapy should be carefully reconsidered in a patient not responding within this time period. Ulcerative colitis: The recommended AMGEVITA induction dose regimen for adult patients with moderate to severe ulcerative colitis is 160 mg at week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days) and 80 mg at week 2. After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines. Some patients who experience decrease in their response may benefit from an increase in dosing frequency to 40 mg AMGEVITA every week. Clinical response is usually achieved within 2-8 weeks of treatment. AMGEVITA therapy should not be continued in patients failing to respond within this time period. Uveitis: The recommended dose of AMGEVITA for adult patients with uveitis is an initial dose of 80 mg, followed by 40 mg given every other week starting one week after the initial dose. There is limited experience in the initiation of treatment with adalimumab alone. Treatment with AMGEVITA can be initiated in combination with corticosteroids and/or with other non-biologic immunomodulatory agents. Concomitant corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating treatment with AMGEVITA. It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a yearly basis. Elderly patients: No dose adjustment is required. Impaired renal and/or hepatic function : Adalimumab has not been studied in these patient populations. No dose recommendations can be made. Paediatric population : AMGEVITA is only available as 20 mg and 40 mg pre-filled syringe and 40 mg pre-filled pen. It is not possible to administer AMGEVITA to paediatric patients that require less than a full 20 mg or 40 mg dose. If an alternate dose is required, other adalimumab products offering such an option should be used. Polyarticular juvenile idiopathic arthritis from 2 to 12 years of age: The recommended dose of AMGEVITA for patients with polyarticular juvenile idiopathic arthritis, aged 2 12 years, is 24 mg/m² body surface area up to a maximum single dose of 20 mg adalimumab (for patients aged 2-< 4) and up to a maximum single dose of 40 mg adalimumab (for patients aged 4 12) administered every other week via subcutaneous injection. The administered dose is selected based on the patients' height and weight, refer to full Summary of Product Characteristic. Polyarticular juvenile idiopathic arthritis from 13 years of age: For patients from 13 years of age, a dose of 40 mg is administered every other week regardless of body surface area. Clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period. There is no relevant use of adalimumab in patients aged less than 2 years for this indication. Enthesitis-related arthritis: The recommended dose of AMGEVITA for patients with enthesitis-related arthritis 6 years of age and older is 24 mg/m² body surface area up to a maximum single dose of 40 mg adalimumab administered every other week via subcutaneous injection. The volume for injection is selected based on the patients' height and weight, refer to full prescribing information. Adalimumab has not been studied in patients with enthesitis-related arthritis aged less than 6 years. Paediatric plaque psoriasis : The recommended AMGEVITA dose is 0.8 mg per kg body weight (up to a maximum of 40 mg per dose) administered subcutaneously weekly for the first two doses and every other week thereafter. Continued therapy beyond 16 weeks should be carefully considered in a patient not responding within this time period. If retreatment with AMGEVITA is indicated, the above guidance on dose and treatment duration should be followed. The safety of adalimumab in paediatric patients with plaque psoriasis has been assessed for a mean of 13 months. Patients above 4 years of age but with a weight less than 23 kg or between 29 and 46 kg are not possible to dose with this product. There is no relevant use of adalimumab in children aged less than 4 years in this indication. The administered dose is selected based on the patients' weight refer to full Summary of Product Characteristic. Paediatric Crohn's disease : Paediatric Crohn's disease patients < 40 kg: The recommended AMGEVITA induction dose regimen for paediatric subjects with severe Crohn's disease is 40 mg at week 0 followed by 20 mg at week 2. In case there is a need for a more rapid response to therapy, the regimen 80 mg at week 0 (dose can be administered as two injections in one day), 40 mg at week 2 can be used, with the awareness that the risk for adverse events may be higher with use of the higher induction dose. After induction treatment, the recommended dose is 20 mg every other week via subcutaneous injection. Some subjects who experience insufficient response may benefit from an increase in dosing frequency to 20 mg AMGEVITA every week. Paediatric Crohn's disease patients ≥ 40 kg: The recommended AMGEVITA induction dose regimen for paediatric subjects with severe Crohn's disease is 80 mg at week 0 followed by 40 mg at week 2. In case there is a need for a more rapid response to therapy, the regimen 160 mg at week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days), 80 mg at week 2 can be used, with the awareness that the risk for adverse events may be higher with use of the higher induction dose. After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. Some subjects who experience insufficient response may benefit from an increase in dosing frequency to 40 mg AMGEVITA every week. Continued therapy should be carefully considered in a subject not responding by week 12. There is no relevant use of adalimumab in children aged less than 6 years in this indication. Paediatric hidradenitis suppurativa: The safety and efficacy of adalimumab in children aged 12-17 years have not yet been established for hidradenitis suppurativa. No data are available. There is no relevant use of adalimumab in children aged below 12 years in this indication. Paediatric ulcerative colitis: The safety and efficacy of adalimumab in children aged 4-17 years have not yet been established. No data are available. There is no relevant use of adalimumab in children aged < 4 years in this indication. Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis: There is no relevant use of adalimumab in the paediatric population in the indications, ankylosing spondylitis and psoriatic arthritis. Paediatric uveitis: The safety and efficacy of adalimumab in children aged 2-17 years have not yet been established. No data are available. Method of administration: AMGEVITA is administered by subcutaneous injection. Full instructions for use are provided in the package leaflet. A 40 mg pen and 40 mg pre-filled syringe are available for patients to administer a full 40 mg dose. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active tuberculosis or other severe infections such as sepsis, and opportunistic infections. Moderate to severe heart failure (NYHA class III/IV). Special warnings and precautions for use: In order to improve traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded. Infections: Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may increase the risk for developing infections. Patients must therefore be monitored closely for infections, including tuberculosis, before, during and after treatment with AMGEVITA. Because the elimination of adalimumab may take up to four months, monitoring should be continued throughout this period. Treatment with AMGEVITA should not be initiated in patients with active infections including chronic or localised infections until infections are controlled. In patients who have been exposed to tuberculosis and patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis, the risk and benefits of treatment with AMGEVITA should be considered prior to initiating therapy (see Other opportunistic infections). Patients who develop a new infection while undergoing treatment with AMGEVITA, should be monitored closely and undergo a complete diagnostic evaluation. Administration of AMGEVITA should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled. Physicians should exercise caution when considering the use of AMGEVITA in patients with a history of recurring infection or with underlying conditions which may predispose patients to infections, including the use of concomitant immunosuppressive medications. Serious infections: Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in patients receiving adalimumab. Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported. Tuberculosis: Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving adalimumab. Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis. Before initiation of therapy with AMGEVITA, all patients must be evaluated for both active or inactive (“latent”) tuberculosis infection. This evaluation should include a detailed medical assessment of patient history of tuberculosis or possible previous exposure to people with active tuberculosis and previous and/or current immunosuppressive therapy. Appropriate screening tests (i.e. tuberculin skin test and chest x-ray) should be performed in all patients (local recommendations may apply). It is recommended that the conduct and results of these tests are recorded in the patient alert card. Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised. If active tuberculosis is diagnosed, AMGEVITA therapy must not be initiated. In all situations described below, the benefit/risk balance of therapy should be very carefully considered. If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted. If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis prophylaxis treatment before the initiation of AMGEVITA, and in accordance with local recommendations. Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of AMGEVITA in patients with several or significant risk factors for tuberculosis despite a negative test for tuberculosis and in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with adalimumab. Some patients who have been successfully treated for active tuberculosis have redeveloped tuberculosis while being treated with adalimumab. Patients should be instructed to seek medical advice if signs/symptoms suggestive of a tuberculosis infection (e.g. persistent cough, wasting/weight loss, low grade fever, listlessness) occur during or after therapy with AMGEVITA. Other opportunistic infections: Opportunistic infections, including invasive fungal infections have been observed in patients receiving adalimumab. These infections have not consistently been recognised in patients taking TNF-antagonists and this has resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes. For patients who develop the signs and symptoms such as fever, malaise, weight loss, sweats, cough, dyspnoea, and/or pulmonary infiltrates or other serious systemic illness with or without concomitant shock an invasive fungal infection should be suspected and administration of AMGEVITA should be promptly discontinued. Diagnosis and administration of empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the care of patients with invasive fungal infections. Hepatitis B reactivation: Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including adalimumab, who are chronic carriers of this virus (i.e. surface antigen positive). Some cases have had a fatal outcome. Patients should be tested for HBV infection before initiating treatment with AMGEVITA. For patients who test positive for hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Carriers of HBV who require treatment with AMGEVITA should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. Adequate data from treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV reactivation, AMGEVITA should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated. Neurological events: TNF-antagonists including adalimumab have been associated in rare instances with new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome. Prescribers should exercise caution in considering the use of AMGEVITA in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of AMGEVITA should be considered if any of these disorders develop. There is a known association between intermediate uveitis and central demyelinating disorders. Neurologic evaluation should be performed in patients with non-infectious intermediate uveitis prior to the initiation of AMGEVITA therapy and regularly during treatment to assess for pre-existing or developing central demyelinating disorders. Allergic reactions : Serious allergic reactions associated with adalimumab were rare during clinical trials. Non-serious allergic reactions associated with adalimumab were uncommon during clinical trials. Reports of serious allergic reactions including anaphylaxis have been received following adalimumab administration. If an anaphylactic reaction or other serious allergic reaction occurs, administration of AMGEVITA should be discontinued immediately and appropriate therapy initiated. Dry natural rubber: The needle cover of the pre-filled syringe or pen is made from dry natural rubber (a derivative of latex), which may cause allergic reactions. Immunosuppression : In a study of 64 patients with rheumatoid arthritis that were treated with adalimumab, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T-, B-, NK-cells, monocyte/macrophages, and neutrophils. Malignancies and lymphoproliferative disorders : In the controlled portions of adalimumab clinical trials of TNF-antagonists, more cases of malignancies including lymphoma have been observed among patients receiving a TNF-antagonist compared with control patients. However, the occurrence was rare. In the post-marketing setting, cases of leukaemia have been reported in patients treated with a TNF-antagonist. There is an increased background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-standing highly active, inflammatory disease, which complicates the risk estimation. With the current knowledge, a possible risk for the development of lymphomas, leukaemia, and other malignancies in patients treated with a TNF-antagonist cannot be excluded. Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including adalimumab in the post-marketing setting. Approximately half the cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression. A risk for the development of malignancies in children and adolescents treated with TNF-antagonists cannot be excluded. Rare post-marketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Some of these hepatosplenic T-cell lymphomas with adalimumab have occurred in young adult patients on concomitant treatment with azathioprine or 6-mercaptopurine used for inflammatory bowel disease. The potential risk with the combination of azathioprine or 6 mercaptopurine and AMGEVITA should be carefully considered. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with AMGEVITA cannot be excluded. No studies have been conducted that include patients with a history of malignancy or in whom treatment with adalimumab is continued following development of malignancy. Thus additional caution should be exercised in considering AMGEVITA treatment of these patients. All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of PUVA treatment should be examined for the presence of non-melanoma skin cancer prior to and during treatment with AMGEVITA. Melanoma and Merkel cell carcinoma have also been reported in patients treated with TNF-antagonists including adalimumab. In an exploratory clinical trial evaluating the use of another TNF-antagonist, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab-treated patients compared with control patients. All patients had a history of heavy smoking. Therefore, caution should be exercised when using any TNF-antagonist in COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking. With current data it is not known if adalimumab treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per local recommendations. Haematologic reactions : Rare reports of pancytopenia including aplastic anaemia have been reported with TNF-antagonists. Adverse events of the haematologic system, including medically significant cytopenia (e.g. thrombocytopaenia, leucopenia) have been reported with adalimumab. All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor) while on AMGEVITA. Discontinuation of AMGEVITA therapy should be considered in patients with confirmed significant haematologic abnormalities. Vaccinations : Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were treated with adalimumab or placebo. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab. It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating AMGEVITA therapy. Patients on AMGEVITA may receive concurrent vaccinations, except for live vaccines. Administration of live vaccines to infants exposed to AMGEVITA in utero is not recommended for 5 months following the mother’s last AMGEVITA injection during pregnancy. Congestive heart failure : In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality due to congestive heart failure have been observed. Cases of worsening congestive heart failure have also been reported in patients receiving adalimumab. AMGEVITA should be used with caution in patients with mild heart failure (NYHA class I/II). AMGEVITA is contraindicated in moderate to severe heart failure . Treatment with AMGEVITA must be discontinued in patients who develop new or worsening symptoms of congestive heart failure. Autoimmune processes :Treatment with AMGEVITA may result in the formation of autoimmune antibodies. The impact of long-term treatment with AMGEVITA on the development of autoimmune diseases is unknown. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with AMGEVITA and is positive for antibodies against double-stranded DNA, further treatment with AMGEVITA should not be given.Concurrent administration of biologic DMARDS or TNF-antagonists : Serious infections were seen in clinical studies with concurrent use of anakinra and another TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNF-antagonists. Therefore, the combination of AMGEVITA and anakinra is not recommended Concomitant administration of AMGEVITA with other biologic DMARDS (e.g. anakinra and abatacept) or other TNF-antagonists is not recommended based upon the possible increased risk for infections, including serious infections and other potential pharmacological interactions. Surgery : There is limited safety experience of surgical procedures in patients treated with adalimumab. The long half-life of adalimumab should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on AMGEVITA should be closely monitored for infections, and appropriate actions should be taken. There is limited safety experience in patients undergoing arthroplasty while receiving adalimumab. Small bowel obstruction: Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture that may require surgical treatment. Available data suggest that adalimumab does not worsen or cause strictures. Elderly patients : The frequency of serious infections among adalimumab-treated subjects over 65 years of age (3.7%) was higher than for those under 65 years of age (1.5%). Some of those had a fatal outcome. Particular attention regarding the risk for infection should be paid when treating the elderly. Paediatric population : See Vaccinations above. Interaction with other medicinal products and other forms of interaction: Adalimumab has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic arthritis patients taking adalimumab as monotherapy and those taking concomitant methotrexate. Antibody formation was lower when adalimumab was given together with methotrexate in comparison with use as monotherapy. Administration of adalimumab without methotrexate resulted in increased formation of antibodies, increased clearance and reduced efficacy of adalimumab. The combination of AMGEVITA and anakinra is not recommended (refer to Full Summary of Product Characteristics) The combination of AMGEVITA and abatacept is not recommended (refer to Full Summary of Product Characteristics). Fertility, pregnancy and lactation: Women of child bearing potential/Contraception in males and females: Women of childbearing potential are strongly recommended to use adequate contraception to prevent pregnancy and continue its use for at least five months after the last AMGEVITA treatment. Pregnancy : For adalimumab, limited clinical data on exposed pregnancies are available. In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity of adalimumab are not available. Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal immune responses in the newborn. Administration of AMGEVITA is not recommended during pregnancy. Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of live vaccines to infants exposed to adalimumab in utero is not recommended for 5 months following the mother’s last adalimumab injection during pregnancy. Breast-feeding : It is not known whether adalimumab is excreted in human milk or absorbed systemically after ingestion. However, because human immunoglobulins are excreted in milk, women must not breast-feed for at least five months after the last AMGEVITA treatment. Fertility: Preclinical data on fertility effects of adalimumab are not available. Effects on ability to drive and use machines: AMGEVITA may have a minor influence on the ability to drive and use machines. Vertigo and visual impairment may occur following administration of AMGEVITA). Undesirable effects: very common (≥ 1/10): Respiratory tract infections (including lower and upper respiratory tract infection, pneumonia, sinusitis, pharyngitis, nasopharyngitis and pneumonia herpes viral), Leucopenia (including neutropenia and agranulocytosis), Anaemia, Lipids increased, Headache, Abdominal pain, Nausea and vomiting, Elevated liver enzymes, Rash (including exfoliative rash), Musculoskeletal pain, Injection site reaction (including injection site erythema). common (≥ 1/100 to < 1/10): Systemic infections (including sepsis, candidiasis and influenza), Intestinal infections (including gastroenteritis viral), Skin and soft tissue infections (including paronychia, cellulitis, impetigo, necrotising fasciitis and herpes zoster), Ear infections, Oral infections (including herpes simplex, oral herpes and tooth infections), Reproductive tract infections (including vulvovaginal mycotic infection), Urinary tract infections (including pyelonephritis), Fungal infections, Joint infection, Skin cancer excluding melanoma (including basal cell carcinoma and squamous cell carcinoma), Benign neoplasm,Leucocytosis,Thrombocytopaenia, Hypersensitivity, Allergies (including seasonal allergy), Hypokalaemia, Uric acid increased, Blood sodium abnormal, Hypocalcaemia, Hyperglycaemia, Hypophosphataemia, Dehydration, Mood alterations (including depression), Anxiety, Insomnia, Paraesthesias (including hypoaesthesia), Migraine, Nerve root compression, Visual impairment, Conjunctivitis, Blepharitis, Eye swelling, Vertigo, Tachycardia, Hypertension, Flushing, Haematoma, Asthma, Dyspnoea, Cough, GI haemorrhage, Dyspepsia, Gastroesophageal reflux disease, Sicca syndrome, Worsening or new onset of psoriasis (including palmoplantar pustular psoriasis), Urticaria, Bruising (including purpura), Dermatitis (including eczema), Onychoclasis, Hyperhidrosis, Alopecia, Pruritus, Muscle spasms (including blood creatine phosphokinase increased), Renal impairment, Haematuria, Chest pain, Oedema, Pyrexia, Coagulation and bleeding disorders (including activated partial thromboplastin time prolonged), Autoantibody test positive (including double stranded DNA antibody), Blood lactate dehydrogenase increased, Impaired healing. uncommon (≥ 1/1,000 to < 1/100): Neurological infections (including viral meningitis), Opportunistic infections and tuberculosis (including coccidioidomycosis, histoplasmosis and mycobacterium avium complex infection), Bacterial infections, Eye infections, Diverticulitis, Lymphoma, Solid organ neoplasm (including breast cancer, lung neoplasm and thyroid neoplasm), Melanoma, Idiopathic thrombocytopenic purpura, Sarcoidosis, Vasculitis, Cerebrovascular accident, Tremor, Neuropathy, Diplopia, Deafness, Tinnitus, Myocardial infarction1), Arrhythmia, Congestive heart failure, Aortic aneurysm, Vascular arterial occlusion, Thrombophlebitis, Pulmonary embolism, Interstitial lung disease, Chronic obstructive pulmonary disease, Pneumonitis, Pleural effusion, Pancreatitis, Dysphagia, Face oedema, Cholecystitis and cholelithiasis, Hepatic steatosis, Bilirubin increased, Night sweats, Scar, Rhabdomyolysis, Systemic lupus erythematosus, Nocturia, Erectile dysfunction, Inflammation, rare (≥ 1/10,000 to < 1/1,000): Leukaemia, Pancytopenia, Anaphylaxis, Multiple sclerosis, Demyelinating disorders (e.g. optic neuritis, Guillain-Barré syndrome), Cardiac arrest, Pulmonary fibrosis, Intestinal perforation, Hepatitis, Reactivation of hepatitis B, Autoimmune hepatitis, Erythema multiforme, Stevens-Johnson syndrome, Angioedema, Cutaneous vasculitis, Lupus-like syndrome. Overdose : No dose-limiting toxicity was observed during clinical trials. The highest dose level evaluated has been multiple intravenous doses of 10 mg/kg, which is approximately 15 times the recommended dose. Special precautions for storage: Store in a refrigerator (2°C – 8°C). Do not freeze. Keep AMGEVITA in the outer carton in order to protect from light. The pre-filled syringe or pre-filled pen may be stored at temperatures up to a maximum of 25°C for a period of up to 14 days. The pre-filled syringe or pre-filled pen must be protected from light, and discarded if not used within the 14-day period. Special precautions for disposal and other handling: Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Legal Category: POM.
Any suspected adverse reactions should be reported immediately to Amgen in accordance with local spontaneous reporting requirements. Amgen Global Fax: +44 2071361046 or send to AGS mailbox: firstname.lastname@example.org and Safety-MEA@amgen.com and/or National Pharmacovigilance Centre (NPC), Email: email@example.com, Fax: +966-11- 2057662