Strensiq

HOS-097123 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile Supportive safety data reflect exposure in 112 patients with perinatal/infantile (n=89), juvenile-onset (n = 22), adult onset (n = 1) HPP (age at enrollment from 1 day to 66.5 years) treated with asfotase alfa, with a treatment duration range from 1 day to 391.9 weeks [7.5 years]). The most common adverse reactions observed were injection site reactions (74%). A few case reports of anaphylactoid/hypersensitivity reaction have been received. Tabulated list of adverse reactions Adverse reactions with asfotase alfa are listed by system organ class and preferred term using MedDRA frequency 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. Table 1: Adverse Reactions Reported in clinical trials in hypophosphatasia patients System Organ Class Frequency Adverse reaction category Infections and infestations Common Injection site cellulitis Blood and lymphatic system Common Increased tendency to bruise disorders Immune system disorders Common Anaphylactoid reactions Hypersensitivity2 Metabolism and nutrition Common Hypocalcaemia disorders Nervous system disorders Very common Headache Vascular disorders Common Hot flush Gastrointestinal disorders Common Hypoaesthesia oral Nausea Skin and subcutaneous Very common Erythema tissue disorders Common Skin discolouration Skin disorder (stretched skin) Musculoskeletal and Very common Pain in extremity connective tissue disorders Common Myalgia Renal and urinary disorders Common Nephrolithiasis General disorders and Very common Injection site reactions1 administration site

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HOS-097119 · has-contraindication-information · PDF-Seite 4

Severe or life-threatening hypersensitivity to the active substance or to any of the excipients if hypersensitivity is not controllable (see section 4.4).

HOS-097118 · has-indication-information · PDF-Seite 2

Strensiq is indicated for long-term enzyme replacement therapy in patients of all ages with paediatric- onset hypophosphatasia to treat the bone manifestations of the disease (see section 5.1).

HOS-097121 · has-interaction-information · PDF-Seite 6

No interaction studies have been performed with asfotase alfa. Based on its structure and pharmacokinetics, asfotase alfa is unlikely to affect Cytochrome P-450 related metabolism. Asfotase alfa contains a catalytic domain of tissue non-specific alkaline phosphatase. Administration of asfotase alfa will interfere with routine measurement of serum alkaline phosphatase by hospital laboratories resulting in serum alkaline phosphatase activity measurements of several thousand units per litre. Asfotase alfa activity results must not be interpreted as the same measure as serum alkaline phosphatase activity owing to differences in enzyme characteristics. Alkaline Phosphatase (ALP) is used as the detection reagent in many routine laboratory assays. If asfotase alfa is present in clinical laboratory samples, aberrant values could be reported. The treating physician should inform the testing lab that the patient is treated with medication affecting the ALP levels. Alternative assays (i.e. not utilizing an ALP-conjugated reporter system) may be considered in patients treated with Strensiq.

HOS-097122 · has-pregnancy-information · PDF-Seite 6

Pregnancy There are insufficient data from the use of asfotase alfa in pregnant women. Following repeated subcutaneous administration to pregnant mice in the therapeutic dose range (>0.5 mg/kg), asfotase alfa levels were quantifiable in fetuses at all doses tested, suggesting cross-placental transport of asfotase alfa. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Asfotase alfa is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding There is insufficient information on the excretion of asfotase alfa in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from asfotase alfa therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility Preclinical fertility studies were conducted and showed no evidence of effect on fertility and embryo-fetal development (see section 5.3). 6

HOS-097120 · has-warning-information · PDF-Seite 4

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. Hypersensitivity Hypersensitivity reactions including signs and symptoms consistent with anaphylaxis have been reported in patients treated with asfotase alfa (see section 4.8). These symptoms included difficulty breathing, choking sensation, periorbital edema, and dizziness. The reactions have occurred within minutes after subcutaneous administration of asfotase alfa and can occur in patients on treatment for more than 1 year. Other hypersensitivity reactions included vomiting, nausea, fever, headache, flushing, irritability, chills, skin erythema, rash, pruritus, and oral hypoaesthesia. If these reactions 4 occur, immediate discontinuation of treatment is recommended and appropriate medical treatment should be initiated. The current medical standards for emergency treatment should be observed. Consider the risks and benefits of re-administering asfotase alfa to individual patients following a severe reaction, taking other factors into account that may contribute to the risk of a hypersensitivity reaction, such as concurrent infection and/ or use of antibiotics. If the decision is made to re- administer the product, the re-challenge should be made under medical supervision and consideration may be given to use of appropriate pre-medication. Patients should be monitored for recurrence of signs and symptoms of a severe hypersensitivity reaction. The need for supervision for subsequent administrations and need for emergency treatment for home care should be at the discretion of the treating physician. Severe or potentially life-threatening hypersensitivity is a contraindication to re-challenge, if hypersensitivity is not controllable (see section 4.3). Injection reaction Administration of asfotase alfa may result in local injection site reactions (including, but not limited to, erythema, rash, discoloration, pruritus, pain, papule, nodule, atrophy) defined as any related adverse event occurring during the injection or until the end of the injection day (see section 4.8). Rotation of injection sites may help to minimize these reactions. Strensiq administration should be interrupted in any patient experiencing severe injection reactions and appropriate medical therapy administered. Lipodystrophy Localized lipodystrophy, including

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