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.

Device-related complications

Brineura must be administered using aseptic technique to reduce the risk of infection. Intracerebroventricular access device-related infections, including sub-clinical infections and meningitis, have been observed in patients treated with Brineura (see section 4.8). Meningitis may present with the following symptoms: fever, headache, neck stiffness, light sensitivity, nausea, vomiting, and change in mental status. CSF samples should routinely be sent for testing to detect subclinical device infections. In clinical studies, antibiotics were administered, the intracerebroventricular access device was replaced, and Brineura treatment was continued.

Healthcare professionals should inspect the scalp for skin integrity to ensure the intracerebroventricular access device is not compromised prior to each infusion. Common signs of device leakage and device failure include swelling, erythema of the scalp, extravasation of fluid, or bulging of the scalp around or above the intracerebroventricular access device. However, these signs may also occur in the context of device-related infections.

Inspection of the infusion site and a patency check must be performed to detect intracerebroventricular access device leakage and/or failure prior to initiation of Brineura infusion (see sections 4.2 and 4.3). The signs and symptoms of device-related infections may not be apparent, therefore, CSF samples should routinely be sent for testing to detect subclinical device infections. Consultation with a neurosurgeon may be needed to confirm the integrity of the device. Brineura treatment should be interrupted in cases of device failure and may require replacement of the access device prior to subsequent infusions.

Material degradation of the intracerebroventricular access device reservoir occurs after long periods of use according to preliminary results of benchtop testing and as observed in clinical trials with approximately 4 years of use. In two clinical cases, the intracerebroventricular access devices did not show signs of failure at the time of infusion; however, after removal, material degradation of the devices were apparent and consistent with data from benchtop testing of intracerebroventricular access devices. The access devices were replaced and patients resumed treatment with Brineura.
Access device replacement should be considered prior to 4 years of regular administration of Brineura, however it must always be ensured, that the intracerebroventricular access device is used in accordance with the provisions of the respective medical device manufacturer.

In case of intracerebroventricular access device-related complications, refer to the manufacturer’s labelling for further instruction.

Caution should be taken in patients prone to complications from intracerebroventricular medicinal product administration, including patients with obstructive hydrocephalus.

Clinical and laboratory monitoring

Vital signs should be monitored before infusion starts, periodically during infusion, and post-infusion in a healthcare setting. Upon completion of the infusion, the patient status should be clinically assessed and observation may be necessary for longer periods if clinically indicated, particularly in patients less than 3 years.

Electrocardiogram (ECG) monitoring during infusion should be performed in patients with a history of bradycardia, conduction disorder, or with structural heart disease, as some patients with CLN2 disease may 
develop conduction disorders or heart disease. In cardiac normal patients, regular 12-lead ECG evaluations should be performed every 6 months.

CSF samples should routinely be sent for testing to detect subclinical device infections (see section 4.2).


Anaphylactic reactions

Anaphylactic reactions have been reported with Brineura. As a precautionary measure, appropriate medical support should be readily available when Brineura is administered. If anaphylactic reactions occur, the infusion should be immediately discontinued and appropriate medical treatment should be initiated. Patients should be observed closely during and after the infusion. If anaphylaxis occurs, caution should be exercised upon re-administration.

Sodium and potassium content

This medicinal product contains 17.4 mg sodium per vial of Brineura and flushing solution, equivalent to 0.87% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
This medicinal product contains potassium, less than 1 mmol (39 mg) per vial, i.e. essentially ‘potassium- free’.

Paediatric population

There were no patients with advanced disease progression at treatment initiation who were included in clinical trials and no clinical data is available in children < 2 years. Patients with advanced CLN2 disease and newborns may have decreased integrity of the blood-brain barrier. Effects of the potentially increased medicinal product exposure on the periphery are unknown.

Effects on Driving

4.7    Effects on ability to drive and use machines

No studies on the effect of cerliponase alfa on the ability to drive or use machines have been performed.