Strensiq

Treatment should be initiated by a physician experienced in the management of patients with metabolic or bone disorders. 3 Posology Recommended dosage regimen of asfotase alfa is 2 mg/kg of body weight administered subcutaneously three times per week, or a dosage regimen of 1 mg/kg of body weight administered subcutaneously six times per week.

1). Refer to the dosing chart below for more details. Missed dose If a dose of asfotase alfa is missed, a double dose should not be injected to make up for the missed dose. 8 ml (x2) 4 Special population Adult patients The pharmacokinetics, pharmacodynamics, and safety of asfotase alfa have been studied in patients with hypophosphatasia > 18 years old.

2). Elderly The safety and efficacy of asfotase alfa in elderly patients have not been established and no specific dose regimen can be recommended for these patients. Renal impairment The safety and efficacy of asfotase alfa in patients with renal impairment have not been evaluated and no specific dose regimen can be recommended for these patients.

Hepatic impairment The safety and efficacy of asfotase alfa in patients with hepatic impairment have not been evaluated and no specific dose regimen can be recommended for these patients. Method of administration Strensiq is for subcutaneous use only.

It is not intended for intravenous or intramuscular injection. The maximum volume of medicinal product per injection should not exceed 1 ml. If more than 1 ml is required, multiple injections may be administered at the same time. Strensiq should be administered using sterile disposable syringes and injection needles.

The syringes should be of small enough volume that the prescribed dose can be withdrawn from the vial with reasonable accuracy. 4). Patients can self-inject only if they have properly been trained on administration procedures. 6.

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 category Adverse reaction Infections and infestations Common Injection site cellulitis Blood and lymphatic system disorders Common Increased tendency to bruise Immune system disorders Common Anaphylactoid reactions Hypersensitivity2 Metabolism and nutrition disorders Common Hypocalcaemia Nervous system disorders Very common Headache Vascular disorders Common Hot flush Gastrointestinal disorders Common Hypoaesthesia oral Nausea Skin and subcutaneous tissue disorders Very common Erythema Common Skin discolouration Skin disorder (stretched skin) Musculoskeletal and connective tissue disorders Very common Pain in extremity Common Myalgia Renal and urinary disorders Common Nephrolithiasis General disorders and administration site conditions Very common Injection site reactions1 Pyrexia Irritability Common Chills Injury, poisoning and procedural complications Very common Contusion Common Scar 1- Preferred terms considered as injection site reactions are presented in section below 2- Preferred terms considered as hypersensitivity are presented in the section below 8 Description of selected adverse reactions Injection site reactions Injection site reactions (including injection site atrophy, abscess, erythema, discolouration, pain, pruritus, macule, swelling, contusion, bruising, lipodystrophy (lipoatrophy or lipohypertrophy), induration, reaction, nodule, rash, papule, haematoma, inflammation, urticarial, calcification, warmth, haemorrhage, cellulitis, scar, mass, extravasation, exfoliation and vesicles) are the most common adverse reactions observed in about 74% of the patients in clinical studies.

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. 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 5 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. 3). 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.

8). 2). Craniosynostosis In asfotase alfa clinical studies adverse events of craniosynostosis (associated with increased intracranial pressure), including worsening of pre-existing craniosynostosis and occurrence of Arnold- Chiari malformation, have been reported in hypophosphatasia patients < 5 years of age.

4).