Brineura · 4.5 Interaction with other medicinal products and other forms of interaction · 1

HOS-217189 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The adverse reactions described in this section were evaluated in 38 patients with CLN2 disease who received at least one dose of Brineura in clinical studies of up to 309 weeks or in post-marketing experience. The most frequent (>20%) adverse reactions observed during Brineura clinical trials include pyrexia, convulsions, low CSF protein, ECG abnormalities, vomiting, needle issues, device related infections, and hypersensitivity. No patients had to have their treatment discontinued due to adverse events. Tabulated list of adverse reactions Adverse reactions observed are listed below, by system organ class and frequency, following the MedDRA frequency convention defined as: 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), not known (cannot be estimated from the available data). 7 Table 2: Frequency of adverse reactions with Brineura MedDRA MedDRA Frequency System organ class Preferred term Infections and infestations Device-related infectiona Very common Meningitis Not known Immune system disorders Hypersensitivity Very common Anaphylactic reaction Common Psychiatric disorders Irritability Very common Nervous system disorders Convulsion eventsb Very common Headache Very common CSF Pleocytosis Very common Cardiac disorders Bradycardia Common Gastrointestinal disorders Vomiting Very common Gastrointestinal disorder Common Skin and subcutaneous tissue disorders Rash Common Urticaria Common General disorders and administration Pyrexiac

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HOS-217185 · has-contraindication-information · PDF-Seite 5

Life-threatening anaphylactic reaction to the active substance or to any of the excipients listed in section 6.1, if re-challenge is unsuccessful (see section 4.4). CLN2 patients with ventriculo-peritoneal shunts. Brineura must not be administered as long as there are signs of acute intracerebroventricular access device leakage, device failure, or device-related infection (see sections 4.2 and 4.4).

HOS-217184 · has-indication-information · PDF-Seite 2

Brineura is indicated for the treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease, also known as tripeptidyl peptidase 1 (TPP1) deficiency.

HOS-217187 · has-interaction-information · PDF-Seite 7

No interaction studies have been performed. Cerliponase alfa is a recombinant human protein and systemic exposure is limited due to intracerebroventricular administration, therefore interactions between cerliponase alfa and medicinal products metabolised by cytochrome P450 enzymes are unlikely to occur.

HOS-217188 · has-pregnancy-information · PDF-Seite 7

Pregnancy There are no data from the use of cerliponase alfa in pregnant women. Animal reproduction studies have not been conducted using cerliponase alfa. It is not known whether cerliponase alfa can cause foetal harm when administered to a pregnant woman or can affect reproductive capacity. Brineura should be given to a pregnant woman only if clearly needed. Breast-feeding There is insufficient information on the excretion of cerliponase alfa/metabolites in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Brineura. Fertility No fertility studies with cerliponase alfa have been conducted in animals or humans.

HOS-217186 · has-warning-information · PDF-Seite 5

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. 5 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 ac

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