ENBREL

Enbrel treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of juvenile idiopathic arthritis or paediatric plaque psoriasis. Patients treated with Enbrel should be given the Patient Card.

Posology Special populations Renal and hepatic impairment No dose adjustment is required. Paediatric population The 10 mg presentation is for paediatric patients prescribed a dose of 10 mg or less. Each vial of Enbrel 10 mg should be used on a single occasion in a single patient, and the remainder of the vial should be discarded.

8 mg/kg (up to a maximum of 50 mg per dose) given once weekly. Discontinuation of treatment should be considered in patients who show no response after 4 months. No formal clinical trials have been conducted in children aged 2 to 3 years.

1). There is generally no applicable use of Enbrel in children aged below 2 years in the indication juvenile idiopathic arthritis. 8 mg/kg (up to a maximum of 50 mg per dose) once weekly for up to 24 weeks. Treatment should be discontinued in patients who show no response after 12 weeks.

If re-treatment with Enbrel is indicated, the above guidance on treatment duration should be followed. 8 mg/kg (up to a maximum of 50 mg per dose) once weekly. There is generally no applicable use of Enbrel in children aged below 6 years in the indication plaque psoriasis.

Method of administration Enbrel is administered by subcutaneous injection. 6). " Detailed instructions on unintentional dosing or scheduling variations, including missed doses, are provided in section 3 of the package leaflet.

Summary of the safety profile Paediatric population Undesirable effects in paediatric patients with juvenile idiopathic arthritis In general, the adverse events in paediatric patients with juvenile idiopathic arthritis were similar in frequency and type to those seen in adult patients (see below, Undesirable effects in adults).

Differences from adults and other special considerations are discussed in the following paragraphs. The types of infections seen in clinical trials in juvenile idiopathic arthritis patients aged 2 to 18 years were generally mild to moderate and consistent with those commonly seen in outpatient paediatric populations.

4), appendicitis, gastroenteritis, depression/personality disorder, cutaneous ulcer, oesophagitis/gastritis, group A streptococcal septic shock, type I diabetes mellitus, and soft tissue and post-operative wound infection. In one study in children with juvenile idiopathic arthritis aged 4 to 17 years, 43 of 69 (62%) children experienced an infection while receiving Enbrel during 3 months of the study (part 1, open-label), and the frequency and severity of infections was similar in 58 patients completing 12 months of open-label extension therapy.

The types and proportion of adverse events in juvenile idiopathic arthritis patients were similar to those seen in trials of Enbrel in adult patients with rheumatoid arthritis, and the majority were mild. Several adverse events were reported more commonly in 69 juvenile idiopathic arthritis patients receiving 3 months of Enbrel compared to the 349 adult rheumatoid arthritis patients.

74 events per patient year). There were 4 reports of macrophage activation syndrome in juvenile idiopathic arthritis clinical trials. Undesirable effects in paediatric patients with plaque psoriasis In a 48-week study in 211 children aged 4 to 17 years with paediatric plaque psoriasis, the adverse events reported were similar to those seen in previous studies in adults with plaque psoriasis.

Adult population Undesirable effects in adults The most commonly reported adverse reactions are injection site reactions (such as pain, swelling, itching, reddening and bleeding at the puncture site), infections (such as upper respiratory infections, bronchitis, bladder infections and skin infections), headache, allergic reactions, development of autoantibodies, itching, and fever.

Serious adverse reactions have also been reported for Enbrel. TNF-antagonists, such as Enbrel, affect the immune system and their use may affect the body’s defenses against infection and cancer. Serious infections affect fewer than 1 in 100 patients treated with Enbrel.

Reports have included fatal and life-threatening infections and sepsis. Various malignancies have also been reported with use of Enbrel, including cancers of the breast, lung, skin and lymph glands (lymphoma). Serious haematological, neurological and autoimmune reactions have also been reported.

These include rare reports of pancytopenia and very rare reports of aplastic anaemia. Central and peripheral demyelinating events have been seen rarely and very rarely, respectively, with Enbrel use. There have been rare reports of lupus, lupus-related conditions, and vasculitis.

Tabulated list of adverse reactions The following list of adverse reactions is based on experience from clinical trials and on postmarketing experience. Within the organ system classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

4), peripheral demyelinating events, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy, and multifocal motor […]

In order to improve the traceability of biological medicinal products, the brand name and batch number of the administered product should be clearly recorded (or stated) in the patient file. Infections Patients should be evaluated for infections before, during, and after treatment with Enbrel, taking into consideration that the mean elimination half-life of etanercept is approximately 70 hours (range 7 to 300 hours).

8). These infections were due to bacteria, mycobacteria, fungi, viruses and parasites (including protozoa). In some cases, particular fungal and other opportunistic infections have not been recognised, resulting in delay of appropriate treatment and sometimes death.

, exposure to endemic mycoses) should be considered. Patients who develop a new infection while undergoing treatment with Enbrel should be monitored closely. Administration of Enbrel should be discontinued if a patient develops a serious infection.

The safety and efficacy of Enbrel in patients with chronic infections have not been evaluated. Physicians should exercise caution when considering the use of Enbrel in patients with a history of recurring or chronic infections or with underlying conditions that may predispose patients to infections, such as advanced or poorly controlled diabetes.

Tuberculosis Cases of active tuberculosis, including miliary tuberculosis and tuberculosis with extra- pulmonary location, have been reported in patients treated with Enbrel. Before starting treatment with Enbrel, all patients must be evaluated for both active and inactive (‘latent’) tuberculosis.

This evaluation should include a detailed medical history with personal history of tuberculosis or possible previous contact with tuberculosis and previous and/or current immunosuppressive therapy. , tuberculin skin test and chest X-ray, should be performed in all patients (local recommendations may apply).

It is recommended that the conduct of these tests should be recorded in the Patient 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, Enbrel therapy must not be initiated. If inactive (‘latent’) tuberculosis is diagnosed, treatment for latent tuberculosis must be started with anti- tuberculosis therapy before the initiation of Enbrel, and in accordance with local recommendations.

In this situation, the benefit/risk balance of Enbrel therapy should be very carefully considered. , persistent cough, wasting/weight loss, low-grade fever) appear during or after Enbrel treatment. Hepatitis B reactivation Reactivation of hepatitis B in patients who were previously infected with the hepatitis B virus (HBV) and had received concomitant TNF-antagonists, including Enbrel, has been reported.

This includes reports of reactivation of hepatitis B in patients who were anti-HBc positive but HBsAg negative. Patients should be tested for HBV infection before initiating treatment with Enbrel. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended.

Caution should be exercised when administering Enbrel in patients previously infected with HBV. These patients should be monitored for signs and symptoms of active HBV infection throughout therapy and for several weeks following termination of therapy.

Adequate data from treating patients infected with HBV with anti-viral therapy in conjunction with TNF-antagonist therapy are not available. In patients who develop HBV infection, Enbrel should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.

Worsening of hepatitis C There have been reports of worsening of hepatitis C in patients receiving Enbrel. Enbrel should be used with caution in patients with a history of hepatitis C. Concurrent treatment with anakinra Concurrent administration of Enbrel and anakinra has been associated with an increased risk of serious infections and neutropenia compared to Enbrel alone.

This combination has not demonstrated increased clinical benefit. 8). Concurrent treatment with abatacept In clinical studies, concurrent administration of abatacept and Enbrel resulted in increased incidences of serious adverse events.

5). Allergic reactions Allergic reactions associated with Enbrel administration have been reported commonly. Allergic reactions have included angioedema and urticaria; serious reactions have occurred. If any serious allergic or anaphylactic reaction occurs, Enbrel therapy should be discontinued immediately and appropriate therapy initiated.

The rubber tip cap (closure) of the diluent syringe contains latex (dry natural rubber) that may cause hypersensitivity reactions when handled by, or when Enbrel is administered to, persons with known or possible latex sensitivity.

Immunosuppression The possibility exists for TNF-antagonists, including Enbrel, to affect host defences against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses. In a study of 49 adult patients with rheumatoid arthritis 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.

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1. Sepsis or risk of sepsis. Treatment with Enbrel should not be initiated in patients with active infections, including chronic or localised infections.