Indication
Brineura® (cerliponase alfa) injection for intraventricular use is indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as
tripeptidyl peptidase 1 (TPP1) deficiency.
Important Safety Information
Brineura is contraindicated in patients with acute intraventricular access device-related complications and with
ventriculoperitoneal shunts.
Brineura must only be administered via the intraventricular route and using aseptic technique to reduce the risk of
infection. Healthcare professionals should inspect the scalp for skin integrity to ensure the intraventricular access device
is not compromised prior to each infusion. Brineura is contraindicated if there are signs of acute intraventricular access
device-related complications (e.g., leakage, device failure or signs of device-related infection such as swelling, erythema
of the scalp, extravasation of fluid, or bulging of the scalp around or above the intraventricular access device). In case of
intraventricular access device complications, discontinue the Brineura infusion and refer to the manufacturer’s labeling for
further instructions. Routinely send cerebrospinal fluid (CSF) samples for testing to detect subclinical device infections.
Material degradation of the intraventricular access device reservoir may occur after approximately 105 perforations of the
intraventricular access device and may require replacement as soon as, or prior to, 105 administrations of Brineura.
Monitor vital signs before infusion starts, periodically during infusion, and post-infusion in a healthcare setting. Perform
electrocardiogram (ECG) monitoring during infusion in patients with a history of bradycardia, conduction disorder, or with
structural heart disease. In patients without cardiac abnormalities, regular 12-lead ECG evaluations should be performed
every 6 months.
Hypotension occurred in 2 patients during or up to 8 hours after Brineura infusion. Patients did not require alteration in
treatment, and reactions resolved spontaneously or after intravenous fluid administration.
One patient experienced hypoxia 8 hours after Brineura infusion, followed by a low mean arterial pressure at 15 hours
post infusion. Symptoms resolved after oxygen administration, airway repositioning, and normal saline infusion. One
patient reported decreased oxygen saturation, 45 minutes after starting Brineura, with associated low diastolic blood
pressure. Hypoxia resolved after oxygen administration. No treatment was administered for the low diastolic blood
pressure, which returned to normal while the patient continued to receive Brineura infusion without change to the infusion
rate or dose.
Due to the potential for anaphylaxis, appropriate medical support should be readily available when Brineura is
administered. If anaphylaxis occurs, immediately discontinue the infusion and initiate appropriate medical treatment.
Observe patients closely during and after the infusion.
Hypersensitivity reactions were reported in 11 patients during or within 24 hours after completion of the Brineura infusion.
The signs and symptoms observed concomitantly with hypersensitivity reactions include pyrexia, vomiting, pleocytosis, or
irritability. Patients were routinely premedicated with antihistamines with or without antipyretics or corticosteroids, prior to
infusion of Brineura.
The management of hypersensitivity reactions should be based on the severity of the reaction and may include
temporarily interrupting the infusion, and/or treatment with antihistamines, antipyretics, and/or corticosteroids. If a severe
hypersensitivity reaction occurs, immediately discontinue the infusion and initiate appropriate medical treatment.
Brineura has not been studied in pregnancy or lactation.
Safety and effectiveness in pediatric patients below 3 years of age have not been established.
In clinical trials, the most frequently reported adverse reactions (≥8%) were pyrexia, ECG abnormalities, CSF protein
decreased, vomiting, seizures, hypersensitivity, CSF protein increased, hematoma, headache, irritability, pleocytosis,
device-related infection, bradycardia, feeling jittery, and hypotension.
Seizures were reported in 12 patients and included atonic, generalized tonic-clonic, focal, and absence. Seizures were
managed with standard anticonvulsive therapies and did not result in discontinuation of Brineura treatment.
Device-related adverse reactions were reported in 12 patients and included infection, delivery system–related
complications, and pleocytosis. Intraventricular access device-related CNS infections were observed in 2 patients. In both
cases, antibiotics were administered, the intraventricular access device was replaced, and treatment continued. Device-related
complications did not result in discontinuation of Brineura treatment. Other device-related adverse reactions
included 1 patient with leakage of the intraventricular access device and 1 with pleocytosis.
Hematoma adverse reactions were reported in 5 patients and presented as hematoma, post procedural hematoma,
traumatic hematoma, and subdural hematoma. Hematomas did not require treatment and did not interfere with Brineura
infusion.
Anti-drug antibodies (ADAs) were detected in serum (79%) and CSF (33.3%) in patients treated with Brineura. No
association was found between serum or CSF ADA titers and incidence or severity of hypersensitivity.
Inform caregivers of the signs and symptoms of anaphylaxis, hypotension, bradycardia, and device-related complications. Instruct them to seek immediate medical care should any of these signs and symptoms occur.
To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA
at 1-800-FDA-1088, or go to www.fda.gov/medwatch.
Please see full Prescribing Information.
Indication
Brineura® (cerliponase alfa) is a prescription medication used to slow loss of ability to walk or crawl (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.
Important Safety Information
Brineura is a prescription medicine. Before treatment with Brineura, it is important to discuss your child’s medical history with their doctor. Tell the doctor if they are sick or taking any medication and if they are allergic to any medicines. Your child’s doctor will decide if Brineura is right for them. If you have questions or would like more information about Brineura, contact your child’s doctor.
Brineura is only given by infusion into the fluid of the brain (known as an intraventricular injection) and using sterile technique to reduce the risk of infection. An intraventricular access device or port must be in place at least 5 to 7 days prior to the first infusion. Intraventricular access device-related infections were observed with Brineura treatment. If any signs of infection occur, contact your child’s doctor immediately. Your child’s intraventricular access device may need to be replaced over time.
Brineura should not be used in patients with active intraventricular access device-related complications (e.g., leakage, device failure, or device-related infection) and with shunts used to drain extra fluid around the brain.
Low blood pressure and/or slow heart rate may occur during and following the Brineura infusion. Contact your child’s doctor immediately if these reactions occur.
Undesirable or hypersensitivity reactions related to Brineura treatment, including fever, vomiting, and irritability, may occur during treatment and as late as 24 hours after infusion. Your child may receive medication such as antihistamines before Brineura infusions to reduce the risk of reactions. Serious and severe allergic reactions (anaphylaxis) may occur. If a reaction occurs, the infusion will be stopped and your child may be given additional medication. If a severe reaction occurs, the infusion will be stopped and your child will receive appropriate medical treatment. If any signs of anaphylaxis occur, immediately seek medical care.
Safety and effectiveness in pediatric patients below 3 years of age have not been established.
The most common side effects reported during Brineura infusions included fever, problems with the electrical activity of the heart, decreased or increased protein in the fluid of the brain, vomiting, seizures, hypersensitivity, collection of blood outside of blood vessels (hematoma), headache, irritability, and increased white blood cell count in the fluid of the brain, device-related infection, slow heart rate, feeling jittery, and low blood pressure. Intraventricular device-related side effects included infection, delivery system-related complications, and increased white blood cell count in fluid of the brain.
These are not all of the possible side effects with Brineura. Talk to your child’s doctor if they have any symptoms that bother them or that do not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Please see full Prescribing Information.