Leitlinien & Arzneimittelsicherheit

HOS-093082 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile In placebo-controlled studies in RA patients, the most frequently reported adverse reactions with Kineret were injection site reactions (ISRs), which were mild to moderate in the majority of patients. The most common reason for withdrawal from study in Kineret-treated RA patients was injection site reaction. The subject incidence of serious adverse reactions in RA studies at the recommended dose of Kineret (100 mg/day) was comparable with placebo (7.1% compared with 6.5% in the placebo group). The incidence of serious infection was higher in Kineret-treated patients compared to patients receiving placebo (1.8% vs. 0.7%). Neutrophil decreases occurred more frequently in patients receiving Kineret compared with placebo. 8 Adverse reactions data in COVID-19 are based on a randomized placebo-controlled study of 405 Kineret-treated patients with COVID-19 pneumonia (SAVE-MORE study). The incidence of serious adverse reactions in the anakinra-treatment group was comparable with the placebo group. Neutropenia, elevation of liver function test, rash and injection site reactions were reported more frequently in patients receiving Kineret compared with placebo. The overall safety profile in patients with COVID-19 treated with Kineret is similar to that in Kineret-treated patients with RA. Adverse reactions data in CAPS patients are based on an open-label study of 43 patients with NOMID/CINCA treated with Kineret for up to 5 years, with a total Kineret exposure of 159.8 patient years. During the 5-year study 14 patients (32.6%) reported 24 serious events. Eleven serious events in 4 (9.3%) patients were considered related to Kineret. No patient withdrew from Kineret treatment due to adverse reactions. Adverse events data in patients with Still’s disease is based on a partially open-label and partially blinded, placebo-controlled study of 15 SJIA patients, treated for up to 1.5 years and a randomised double blind placebo-controlled study of 11 adult and paediatric patients with Still’s disease (6 Kineret and 5 placebo) treated for 12 weeks and followed for an additional 4 weeks. In addition, a non- interventional long-term safety study in 306 paediatric patients with Still’s disease, post-marketing adverse event reports and published studies constitute supporting data. Adverse events data in patients with FMF are based on post-marketing adverse event reports and published studies. Th

Auszug; vollständigen Abschnitt im Original lesen.

HOS-093078 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to E. coli derived proteins. Kineret treatment must not be initiated in patients with neutropenia (ANC <1.5 x 109/l) (see section 4.4).

HOS-093077 · has-indication-information · PDF-Seite 2

Rheumatoid Arthritis (RA) Kineret is indicated in adults for the treatment of the signs and symptoms of RA in combination with methotrexate, with an inadequate response to methotrexate alone. COVID-19 Kineret is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adult patients with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure determined by plasma concentration of soluble urokinase plasminogen activator receptor (suPAR) ≥ 6 ng/ml (see sections 4.2, 4.4 and 5.1). Periodic fever syndromes Kineret is indicated for the treatment of the following autoinflammatory periodic fever syndromes in adults, adolescents, children and infants aged 8 months and older with a body weight of 10 kg or above: Cryopyrin-Associated Periodic Syndromes (CAPS) Kineret is indicated for the treatment of CAPS, including: - Neonatal-Onset Multisystem Inflammatory Disease (NOMID) / Chronic Infantile Neurological, Cutaneous, Articular Syndrome (CINCA) - Muckle-Wells Syndrome (MWS) - Familial Cold Autoinflammatory Syndrome (FCAS) Familial Mediterranean Fever (FMF) Kineret is indicated for the treatment of Familial Mediterranean Fever (FMF). Kineret should be given in combination with colchicine, if appropriate. 2 Still’s Disease Kineret is indicated in adults, adolescents, children and infants aged 8 months and older with a body weight of 10 kg or above for the treatment of Still’s disease, including Systemic Juvenile Idiopathic Arthritis (SJIA) and Adult-Onset Still’s Disease (AOSD), with active systemic features of moderate to high disease activity, or in patients with continued disease activity after treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids. Kineret can be given as monotherapy or in combination with other anti-inflammatory drugs and disease-modifying antirheumatic drugs (DMARDs).

HOS-093080 · has-interaction-information · PDF-Seite 8

Interactions between Kineret and other medicinal products have not been investigated in formal studies. In clinical studies, interactions between Kineret and other medicinal products (including nonsteroidal anti-inflammatory medicinal products, glucocorticoids, and DMARDs) have not been observed. Concurrent Kineret and TNF-α antagonist treatment In a clinical study with RA patients receiving background methotrexate, patients treated with Kineret and etanercept were observed to have a higher rate of serious infections (7%) and neutropenia than patients treated with etanercept alone and higher than observed in previous studies where Kineret was used alone. Concurrent Kineret and etanercept treatment has not demonstrated increased clinical benefit. The concurrent use of Kineret with etanercept or any other TNF-α antagonist is not recommended (see section 4.4). Cytochrome P450 Substrates The formation of CYP450 enzymes is suppressed by increased levels of cytokines (e.g., IL-1) during chronic inflammation. Thus, it may be expected that for an IL-1 receptor antagonist, such as anakinra, the formation of CYP450 enzymes could be normalized during treatment. This would be clinically relevant for CYP450 substrates with a narrow therapeutic index (e.g. warfarin and phenytoin). Upon start or end of Kineret treatment in patients on these types of medicinal products, it may be relevant to consider therapeutic monitoring of the effect or concentration of these products and the individual dose of the medicinal product may need to be adjusted. For information on vaccinations see section 4.4.

HOS-093081 · has-pregnancy-information · PDF-Seite 8

Pregnancy There are limited amount of data from the use of anakinra in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of anakinra during pregnancy and in woman of childbearing potential not using contraception. Breast-feeding It is unknown whether anakinra/metabolites are excreted in human milk. A risk to the newborns/ infants cannot be excluded. Breast-feeding should be discontinued during treatment with Kineret.

HOS-093079 · has-warning-information · PDF-Seite 5

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Allergic reactions Allergic reactions, including anaphylactic reactions and angioedema have been reported uncommonly. The majority of these reactions were maculopapular or urticarial rashes. If a severe allergic reaction occurs, administration of Kineret should be discontinued and appropriate treatment initiated. Hepatic Events In clinical studies transient elevations of liver enzymes have been seen. These elevations have not been associated with signs or symptoms of hepatocellular damage, except for one patient with SJIA that developed a serious hepatitis in connection with a cytomegalovirus infection. During post-marketing use hepatic events, not affecting liver function, have been reported. The majority of patients have been treated for Still’s disease or have had predisposing factors, e.g. a history of transaminase elevations. In addition cases of non-infectious hepatitis, including occasional events of acute liver failure, have been reported in patients with Still’s disease during Kineret treatment. Hepatic events in patients with Still’s disease predominantly occur during the first month of Kineret treatment. Routine testing of hepatic enzymes during the first month should be considered, especially if the patient has pre-disposing factors or develops symptoms indicating liver dysfunction. The efficacy and safety of Kineret in patients with AST/ALT ≥ 1.5 x upper level of normal have not been evaluated. Serious infections Kineret has been associated with an increased incidence of serious infections (1.8%) vs. placebo (0.7%) in RA patients. For a small number of patients with asthma, the incidence of serious infection was higher in Kineret-treated patients (4.5%) vs. placebo-treated patients (0%), these infections were mainly related to the respiratory tract. The safety and efficacy of Kineret treatment in patients with chronic and serious infections have not been evaluated. Kineret treatment should not be initiated in patients with active infections. Kineret treatment should be discontinued in RA patients if a serious infection develops. In Kineret treated CAPS or FMF patients, there is a risk for disease flares when discontinuing Kineret treatment. With careful monitoring, Kineret treatment can be continued also during a serious infection. Treatment with Kineret for COVID-19 c

Auszug; vollständigen Abschnitt im Original lesen.