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 reactions including anaphylaxis

Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with sebelipase alfa; see section 4.8. Therefore, appropriate medical support must be readily available when sebelipase alfa is administered. If severe reactions occur, the sebelipase alfa infusion should be immediately stopped and appropriate medical treatment should be initiated. The risks and benefits of re-administering sebelipase alfa following a severe reaction should be considered.

Following the first sebelipase alfa infusion, including the first infusion after a dose escalation, patients should be observed for 1 hour in order to monitor for any signs or symptoms of anaphylaxis or a severe hypersensitivity reaction.

The management of hypersensitivity reactions may include temporarily interrupting the infusion, lowering the infusion rate, and/or treatment with antihistamines, antipyretics, and/or corticosteroids. For patients who have experienced allergic reactions during infusion, caution should be exercised upon re-administration. If interrupted, the infusion may be resumed at a slower rate with increases as tolerated. Pre-treatment with antipyretics and/or antihistamines may prevent subsequent reactions in those cases where symptomatic treatment was required.

In cases of severe infusion reactions and in cases of lack or loss of effect, patients should be tested for the presence of antibodies.

This medicinal product may contain traces of egg proteins. Patients with known egg allergies were excluded from clinical studies (see section 4.3).

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. In the sebelipase alfa clinical program, patients were routinely tested for anti-sebelipase alfa anti-drug antibodies (ADAs) to determine the immunogenicity potential of sebelipase alfa. Patients who tested positive for ADAs were also tested for inhibitory antibody activity. The presence of inhibitory activity has been detected at some postbaseline timepoints in clinical studies (see section 4.8). Overall, no conclusion on the relationship between development of ADAs/NAbs and associated hypersensitivity reactions or suboptimal clinical response can be made.
In clinical studies, 3 patients homozygous for a deletion affecting both alleles of genes Lipase A, lysosomal acid [LIPA] and Cholesterol 25-Hydroxylase developed inhibitory antibody activity associated with a suboptimal clinical response. These patients underwent either immunomodulatory therapy alone or in combination with haematopoietic stem cell transplant (HSCT) or bone marrow transplant (BMT), resulting in improved clinical response to sebelipase alfa.

Excipients

This medicinal product contains 33 mg sodium per vial equivalent to 1.7% of the WHO recommended maximum daily intake of 2 g sodium for an adult. It is administered in sodium chloride 9 mg/ml (0.9%) solution for infusion (see section 6.6). This should be taken into consideration by patients on a controlled sodium diet.

Effects on Driving

4.7    Effects on ability to drive and use machines

KANUMA may have a minor influence on the ability to drive and use machines.
Adverse events of dizziness have been reported with the use of sebelipase alfa, which could affect the ability to drive or use machines (see section 4.8).