Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

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 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 lipoatrophy and lipohypertrophy, has been reported at injection sites after several months in patients treated with asfotase alfa in clinical trials (see section 4.8).
Patients are advised to follow proper injection technique and to rotate injection sites (see section 4.2).

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. There are insufficient data to establish a causal relationship between exposure to Strensiq and progression of craniosynostosis. Craniosynostosis as a manifestation of hypophosphatasia is documented in published literature and occurred in 61.3% of patients between birth and 5 years of age in a natural history study of untreated infantile-onset hypophosphatasia patients. Craniosynostosis can lead to increased intracranial pressure. Periodic monitoring (including fundoscopy for signs of papilloedema) and prompt intervention for increased intracranial pressure is recommended in hypophosphatasia patients below 5 years of age.

Ectopic calcification
In asfotase alfa clinical studies ophthalmic (conjunctival and corneal) calcification and nephrocalcinosis have been reported in patients with hypophosphatasia. There are insufficient data to establish a causal relationship between exposure to asfotase alfa and ectopic calcification. Ophthalmic (conjunctival and corneal) calcification and nephrocalcinosis as manifestations of hypophosphatasia are documented in published literature. Nephrocalcinosis occurred in 51.6% of patients between birth and 5 years of age in a natural history study of untreated infantile-onset hypophosphatasia patients.
Ophthalmology examination and renal ultrasounds are recommended at baseline and periodically in hypophosphatasia patients.

Serum Parathyroid Hormone and Calcium
Serum parathyroid hormone concentration may increase in hypophosphatasia patients administered asfotase alfa, most notably during the first 12 weeks of treatment. It is recommended that serum parathyroid hormone and calcium be monitored in patients treated with asfotase alfa. Supplements of calcium and oral vitamin D may be required. See section 5.1.

Disproportionate weight gain
Patients may display disproportionate weight increase. Dietary supervision is recommended.

Excipients
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. the product is essentially ‘sodium-free’.

Effects on Driving

4.7   Effects on ability to drive and use machines

Strensiq has no or negligible influence on the ability to drive and use machines.