Kyntheum · 4.6 Fertility, pregnancy and lactation · 1

HOS-097387 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile The most commonly reported adverse reactions are arthralgia (4.6%), headache (4.3%), fatigue (2.6%), diarrhoea (2.2%), and oropharyngeal pain (2.1%). Tabulated list of adverse reactions Adverse reactions from clinical trials and post-marketing experience (Table 1) are listed by MedDRA system organ class (SOC). Within each SOC, the adverse reactions are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category for each adverse reaction is based on 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) and not known (cannot be estimated from the available data). Within each frequency grouping adverse reactions are presented in order of decreasing seriousness. 5 Table 1: List of adverse reactions in clinical trials and post-marketing experience System Organ Class Frequency Adverse reaction Infections and infestations Common Influenza Tinea infections (including tinea pedis, tinea versicolor, tinea cruris) Uncommon Candida infections (including oral, genital, and oesophageal infections) Blood and lymphatic system Uncommon Neutropenia disorders Immune system disorders Rare Anaphylactic reaction Nervous system disorders Common Headache Eye disorders Uncommon Conjunctivitis Respiratory, thoracic and Common Oropharyngeal pain mediastinal disorders Gastrointestinal disorders Common Diarrhoea Nausea Musculoskeletal and Common Arthralgia connective tissue disorders Myalgia General disorders and Common Fatigue administration site conditions Injection site reactions (including injection site erythema, pain, pruritus, bruising, haemorrhage) Skin and subcutaneous tissue

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HOS-097383 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Active Crohn’s disease. Clinically important active infections (e.g. active tuberculosis, see section 4.4).

HOS-097382 · has-indication-information · PDF-Seite 2

Kyntheum is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy.

HOS-097385 · has-interaction-information · PDF-Seite 4

Live vaccines should not be given concurrently with brodalumab (see section 4.4). The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g. IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Although a role for interleukin (IL)-17A and IL-17RA in the regulation of CYP450 enzymes has not been reported, the effect of brodalumab on CYP3A4/3A5 activity was evaluated in a disease-drug-drug interaction study. In patients with moderate to severe plaque psoriasis, a single subcutaneous dose of 210 mg brodalumab increased the exposure of midazolam, a CYP3A4/3A5 substrate by 24%. Based on the magnitude of change in exposure of midazolam, no dose adjustment of CYP3A4/3A5 substrates is necessary when administered concomitantly with brodalumab.

HOS-097386 · has-pregnancy-information · PDF-Seite 4

Women of childbearing potential Women of childbearing potential should use an effective method of contraception during treatment and for at least 12 weeks after treatment. Pregnancy There are no or limited amount of data from the use of brodalumab in pregnant women. 4 Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Human IgG2 is known to cross the placental barrier and brodalumab is a human IgG2, therefore, brodalumab has the potential to be transmitted from the mother to the developing foetus. As a precautionary measure, it is preferable to avoid the use of Kyntheum in pregnancy. As the metabolism of brodalumab is unknown in infants, benefit risk for exposure of the infant to live vaccines following third trimester exposure to Kyntheum should be discussed with a physician. Breast-feeding It is unknown whether brodalumab is excreted in human milk. Brodalumab is a monoclonal antibody and is expected to be present in the first milk and at low levels afterwards. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Kyntheum therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility No data are available on the effect of brodalumab on human fertility. Animal studies did not show any effects on male and female reproductive organs and on sperm count, motility and morphology (see section 5.3).

HOS-097384 · has-warning-information · PDF-Seite 3

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. Inflammatory bowel disease (including Crohn's disease and ulcerative colitis) Cases of new or exacerbations of inflammatory bowel disease have been reported with IL-17 inhibitors. Therefore, brodalumab is not recommended in patients with inflammatory bowel disease (see section 4.8). If a patient develops signs and symptoms of inflammatory bowel disease, or experiences an exacerbation of pre-existing inflammatory bowel disease, treatment should be discontinued and appropriate medical management should be initiated. Suicidal ideation and behaviour Suicidal ideation and behaviour, including completed suicide, have been reported in patients treated with brodalumab. The majority of patients with suicidal behaviour had a history of depression and/or suicidal ideation or behaviour. A causal association between treatment with brodalumab and increased risk of suicidal ideation and behaviour has not been established. The risk and benefit of treatment with brodalumab should be carefully weighed for patients with a history of depression and/or suicidal ideation or behaviour, or for patients who develop such symptoms. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal ideation, anxiety, or other mood changes, and they should contact their healthcare provider if such events occur. If a patient suffers from new or worsening symptoms of depression and/or suicidal ideation or behaviour is identified, it is recommended to discontinue treatment. Hypersensitivity reactions Rare cases of anaphylactic reactions have been reported in the post-marketing setting. In the event of an anaphylactic reaction, or any other serious allergic reaction, administration of brodalumab should be discontinued and appropriate therapy initiated. 3 Infections Brodalumab may increase the risk of infections. During the 12-week placebo-controlled clinical trial period in patients with psoriasis, serious infections were observed in 0.5% of patients receiving brodalumab (see section 4.8). Caution should be exercised when considering the use of brodalumab in patients with a chronic infection or a history of recurrent infection. Patients should be instructed to seek medical advice if signs o

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