Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.3 · PDF-Seite 5

HOS-108736 · Präparat HOS-093075

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to E. coli derived proteins.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Gegenanzeigen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.3 · PDF-Seite 5

HOS-108737 · Präparat HOS-093075

Kineret treatment must not be initiated in patients with neutropenia (ANC <1.5 x 109/l) (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.5 · PDF-Seite 8

HOS-108738 · Präparat HOS-093075

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.5 · PDF-Seite 8

HOS-108739 · Präparat HOS-093075

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): etanercept (HOS-090237) methotrexate (HOS-087522)

Wechselwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.5 · PDF-Seite 8

HOS-108742 · Präparat HOS-093075

The concurrent use of Kineret with etanercept or any other TNF-α antagonist is not recommended (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): etanercept (HOS-090237)

Wechselwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.5 · PDF-Seite 8

HOS-108743 · Präparat HOS-093075

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): phenytoin (HOS-084531) warfarin (HOS-085950)

Wechselwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.5 · PDF-Seite 8

HOS-108746 · Präparat HOS-093075

For information on vaccinations see section 4.4.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 8

HOS-108747 · Präparat HOS-093075

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 8–9

HOS-108748 · Präparat HOS-093075

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 9

HOS-108749 · Präparat HOS-093075

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 9

HOS-108750 · Präparat HOS-093075

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 9

HOS-108751 · Präparat HOS-093075

Adverse events data in patients with FMF are based on post-marketing adverse event reports and published studies.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 9

HOS-108752 · Präparat HOS-093075

There are no indications either from these studies or from post-marketing adverse reaction reports that the overall safety profile in patients with CAPS, FMF or Still’s disease is different from that in patients with RA, with the exception of the postmarketing observation of a higher frequency of reported hepatic events in patients with Still’s disease. The adverse reactions table below therefore applies to Kineret treatment of RA, CAPS, FMF and Still’s disease. During long term treatment of RA, CAPS, and Still’s disease the safety profile remains unchanged over time.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 9

HOS-108753 · Präparat HOS-093075

Tabulated list of adverse reactions Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 9–10

HOS-108754 · Präparat HOS-093075

9  MedDRA Organ System Frequency Undesirable Effect Infections and infestations Common (≥ 1/100 to < 1/10) Serious infections Blood and lymphatic system Common (≥ 1/100 to < 1/10) Neutropenia disorders Thrombocytopenia Immune system disorders Uncommon (≥ 1/1 000 to < 1/100) Allergic reactions including anaphylactic reactions, angioedema, urticaria and pruritus Nervous system disorders Very common (≥ 1/10) Headache Hepatobiliary disorders Uncommon (≥ 1/1 000 to < 1/100) Hepatic enzyme increased Not known (cannot be estimated Non-infectious hepatitis from the available data) General disorders and Very common (≥ 1/10) Injection site reaction administration site conditions Skin and subcutaneous tissue Uncommon (≥ 1/1 000 to < 1/100) Rash disorders Not known (cannot be estimated Injection site amyloid deposits from the available data) Drug reaction with eosinophilia and systemic symptoms (DRESS) Investigations Very common (≥ 1/10) Blood cholesterol increased

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 10

HOS-108755 · Präparat HOS-093075

Serious infections The incidence of serious infections in RA studies conducted at the recommended dose (100 mg/day) was 1.8% in Kineret treated patients and 0.7% in placebo-treated patients. In observations up to 3 years, the serious infection rate remained stable over time. The infections observed consisted primarily of bacterial events such as cellulitis, pneumonia, and bone and joint infections. Most patients continued on study medicinal product after the infection resolved.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 10

HOS-108756 · Präparat HOS-093075

In the clinical study in COVID-19, secondary serious infections were common, however less frequently observed in patients treated with Kineret compared to placebo-treated patients.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 10

HOS-108757 · Präparat HOS-093075

In a study with 43 CAPS patients followed for up to 5 years the frequency of serious infections was 0.1/year, the most common being pneumonia and gastroenteritis. Kineret was temporarily stopped in one patient, all other patients continued Kineret treatment during the infections.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 10

HOS-108758 · Präparat HOS-093075

In a study with 15 SJIA patients followed for up to 1.5 years, one patient developed a serious hepatitis in connection with a cytomegalovirus infection. In a study with 11 patients with Still’s disease (SJIA and AOSD) randomized to Kineret (6 patients) or Placebo (5 patients) and followed for 16 weeks, no serious infections were reported. In a non-interventional long-term safety study of Kineret in 306 paediatric patients with Still’s disease followed for up to more than 9 years (mean duration of a treatment course with Kineret was 17.0 (standard deviation 21.1) months and the median duration was 8.9 months), serious infections were reported in 13 patients. There are no indications from post- marketing adverse event reports and published studies that types and severity of infections in patients with FMF differ from those in patients with RA, CAPS or Still’s disease.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Kineret

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. · Abschnitt 4.8 · PDF-Seite 10

HOS-108759 · Präparat HOS-093075

In clinical studies and during post-marketing use, rare cases of opportunistic infections have been observed and have included fungal, mycobacterial, bacterial, and viral pathogens. Infections have been noted in all organ systems and have been reported in patients receiving Kineret alone or in combination with immunosuppressive agents.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.