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 medicinal product should be clearly recorded.

Absence of blood-brain barrier transfer

Xenpozyme is not expected to cross the blood-brain barrier or modulate the CNS manifestations of the disease.

Infusion associated reactions (IARs)

IARs occurred in approximately 58% of patients treated with Xenpozyme in clinical studies. These IARs included hypersensitivity reactions and acute phase reactions (see section 4.8). The most frequent IARs were headache, urticaria, pyrexia, nausea and vomiting (see section 4.8). IARs typically occurred between the time of infusion and up to 24 hours after infusion completion.

Hypersensitivity/anaphylaxis

Hypersensitivity reactions, including anaphylaxis, have been reported in Xenpozyme-treated patients (see section 4.8). In clinical studies, hypersensitivity reactions occurred in 7 (17.5%) adult and 9 (45%) paediatric patients including one paediatric patient who experienced anaphylaxis.



Management

Patients should be observed closely during and for an appropriate period of time after the infusion, based on clinical judgement. Patients must be informed of the potential symptoms of hypersensitivity/anaphylaxis and instructed to seek immediate medical care should symptoms occur.
IARs management should be based on the severity of signs and symptoms and may include temporarily interrupting the Xenpozyme infusion, lowering the infusion rate, and/or appropriate medical treatment.

If severe hypersensitivity or anaphylaxis occurs, Xenpozyme should be discontinued immediately, and appropriate medical treatment should be initiated. The patient who experienced anaphylaxis in the clinical study underwent a tailored desensitization regimen that enabled the patient to resume long term treatment with Xenpozyme at the recommended maintenance dose. The prescriber should evaluate the risks and benefits of Xenpozyme re-administration following anaphylaxis or severe hypersensitivity reaction. If considering re-administration of Xenpozyme following anaphylaxis, the prescribing physician should contact the local Sanofi representative for advice on re-administration. In such patients, extreme caution should be exercised, with appropriate resuscitation measures available, when Xenpozyme is readministered.

If mild or moderate IARs occur, the infusion rate may be slowed or temporarily stopped, the duration of each step for an individual infusion increased, and/or the Xenpozyme dose reduced. If a patient requires a dose reduction, re-escalation should follow dose escalation described in Table 1 and Table 2 for adult and paediatric patients, respectively (see section 4.2).

Patients may be pre-treated with antihistamines, antipyretics, and/or glucocorticoids to prevent or reduce allergic reactions.

Immunogenicity

Treatment-emergent antidrug antibodies (ADA) were reported in adult and paediatric patients during the clinical trials (see section 4.8). IARs and hypersensitivity reactions may occur independent of the development of ADA. The majority of IARs and hypersensitivity reactions were mild or moderate and were managed with standard clinical practices.
IgE ADA testing may be considered for patients who experienced a severe hypersensitivity reaction to olipudase alfa.
While in clinical studies, no loss of efficacy was reported, IgG ADA testing may be considered in case of loss of response to therapy.

Transient transaminases elevation

Transient transaminase elevations (ALT or AST) within 24 to 48 hours after infusions were reported during the dose escalation phase with Xenpozyme in clinical studies (see section 4.8). At the time of the next scheduled infusion, these elevated transaminase levels generally returned to the levels observed prior to the Xenpozyme infusion.

Transaminases (ALT and AST) levels should be obtained within 1 month prior to Xenpozyme treatment initiation (see section 4.2). During dose escalation or upon resuming treatment following missed doses, transaminases levels should be obtained within 72 hours prior to the next scheduled Xenpozyme infusion. If either the baseline or a pre-infusion transaminase level is > 2 times the ULN during dose escalation, then additional transaminase levels should be obtained within 72 hours after the end of the infusion. If the pre-infusion transaminase levels are elevated above baseline and > 2 times the ULN, the Xenpozyme dose can be adjusted (prior dose repeated or reduced) or treatment can be temporarily withheld in accordance with the degree of transaminase elevation (see section 4.2).
Upon reaching the recommended maintenance dose, transaminase testing can be performed as part of routine clinical management of ASMD.


Sodium content

This medicinal product contains 3.02 mg sodium per 20 mg vial, equivalent to 0.15% of the WHO recommended maximum daily intake of 2 g sodium for an adult or an adolescent, and ≤0.38% of the maximum acceptable daily intake of sodium for children below 16 years of age.

Effects on Driving

4.7    Effects on ability to drive and use machines

Because hypotension has been reported in clinical studies, Xenpozyme may have minor influence on the ability to drive and use machines (see section 4.8).