Brineura

Patient Information Leaflet

Brineura 150 mg solution for infusion

cerliponase alfa
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before you or the child receive this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor.
• If you or the child experience any side effects, including those not listed in this leaflet, consult your doctor. See section 4.

Contents of this leaflet

1. What Brineura is and what it is used for
2. What you need to know before receiving or giving Brineura to the child
3. How to use Brineura
4. Possible side effects
5. How to store Brineura
6. Contents of the pack and other information

1. What Brineura is and what it is used for

Brineura contains the active substance cerliponase alfa, which belongs to a group of medicines known as enzyme replacement therapy drugs. It is used to treat patients with neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl-peptidase 1 (TPP-1) deficiency.
People with CLN2 either lack an enzyme called TPP1 or have it in reduced amounts, leading to an accumulation of substances known as lysosomal storage materials. In people with CLN2, these substances accumulate in certain parts of the body, primarily in the brain.
How Brineura works
This medicine replaces the missing enzyme, TPP1, thereby reducing lysosomal storage accumulation. This medicine helps slow down the progression of the disease.

2. What you should know before taking or administering Brineura to the child

Do not use Brineura

• If you or the child have experienced severe allergic reactions to cerliponase alfa or to any of the other components of this medicine (listed in section 6), and these reactions recur when cerliponase alfa is administered again.
• If you or the child have an implanted device to drain excess fluid from the brain.
• If you or the child have had symptoms of infection related to the device or have experienced problems with the device. The doctor may decide to continue treatment once the infection or problem has been resolved.

Warnings and precautions
Talk to the doctor before using Brineura.

• You or the child may experience problems with the implanted device used during treatment with Brineura (see section 4 “Possible side effects”), including infections or device malfunction. Signs indicating that you or the child may have an infection include fever, headache, neck stiffness, photophobia, nausea, vomiting, and changes in mental status. Signs of device problems include swelling, redness of the scalp, leakage of fluid from the device, and scalp swelling. Treatment may be interrupted if the device needs to be replaced or until the infection is resolved. Device replacement may be required within 4 years of use; the doctor will assess whether this is necessary. For any questions about the device, consult the doctor.
• Potentially life-threatening allergic reactions (anaphylactic reactions) may occur with this medicine. The doctor will monitor you or the child for symptoms of potentially life-threatening allergic reactions, such as hives, itching or flushing, swelling of the lips, tongue, and/or throat, chills, rapid heartbeat, shortness of breath, hoarseness, bluish discoloration of the fingers or lips, hypotonia, fainting, diarrhea, or incontinence. If these symptoms occur, contact the doctor immediately.
• The doctor will monitor heart rate, blood pressure, respiratory rate, and body temperature before, during, and after treatment. The doctor may decide to further monitor these parameters if necessary.
• The doctor will perform an ECG every 6 months to rule out abnormalities. If you or the child have a history of heart problems, the doctor or nurse will monitor cardiac activity during each infusion.
• The doctor may send samples of cerebrospinal fluid to rule out infections.
• This medicine has not been administered to patients with advanced-stage disease at the start of treatment or to children under 1 year of age. The doctor will determine whether treatment with Brineura is appropriate for you/the child.

Other medicines and Brineura
Inform the doctor if you or the child are taking, have recently taken, or might take any other medicines.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult the doctor before taking this medicine.
You should not receive treatment with this medicine during pregnancy unless clearly necessary. It is unknown whether this medicine may cause harm to the fetus.
You should not receive treatment with this medicine while breastfeeding. It is unknown whether this medicine passes into breast milk.
It is unknown whether this medicine has an effect on male fertility.

Driving and using machines
It is unknown whether this medicine affects the ability to drive or operate machinery. Consult your doctor.

Brineura contains sodium and potassium
This medicine contains 17.4 mg of sodium (a main component of table salt) per vial. This corresponds to 0.87% of the recommended maximum daily dietary intake for an adult.
This medicine contains potassium, less than 1 mmol (39 mg) per vial, i.e., essentially ‘potassium-free’.

3. How to use Brineura

The patient or child must undergo a surgical procedure to implant the device for administering this medicine. This device allows the medicine to reach a specific part of the brain.
This medicine must be administered exclusively in a healthcare setting by a physician experienced in the administration of intracerebroventricular drugs (infusion of fluids into the brain).
This medicine has not been administered in patients below 1 year of age or above 9 years of age (at the start of the clinical study).
The recommended dose of this medicine varies according to the patient's age and must be administered every other week according to the following schedule:

• from birth to < 6 months: 100 mg
• from 6 months to < 1 year: 150 mg
• from 1 year to < 2 years: 200 mg (first 4 doses), 300 mg (all subsequent doses)
• ≥ 2 years: 300 mg

The physician may adjust the dose or the interval between administrations if the infusion is not well tolerated, in case of an allergic reaction, or if there is a possible increase in intracranial pressure.
The medicine is infused slowly through the implanted device. After administration of the medicine, a second, shorter infusion of a solution is performed to flush any residual Brineura from the infusion device, ensuring that the full prescribed dose reaches the brain. This medicine and the solution will be administered over a period of 2 to 4.5 hours, depending on the dose prescribed for the patient or child. The physician may reduce the dose or the infusion rate based on the patient's response during treatment.
Prior to each treatment with this medicine, the physician may administer medications such as antipyretics in case of fever or antihistamines to manage allergic reactions, in order to reduce the undesirable effects that may occur during or immediately after each infusion.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you experience any of the following side effects, contact your doctor or nurse immediately.
Very common side effects (may affect more than 1 in 10 people):

• seizures (convulsive fits)
• reactions during or immediately after administration of the medicine, such as hives, itching or redness, swelling of lips, tongue and/or throat, shortness of breath, hoarseness, blue colouring around fingertips or lips, reduced muscle tone, loss of consciousness or incontinence.
• bacterial infections related to the use of the device

Common side effects (may affect up to 1 in 10 people):

• severe allergic reaction (anaphylactic reactions).

Not known (frequency cannot be estimated from the available data):

• brain inflammation (meningitis) due to an infection related to the device.

This medicine may cause other side effects:
Very common side effects (may affect more than 1 in 10 people):

• fever
• vomiting
• irritability
• headache
• increased or decreased levels of proteins in the cerebrospinal fluid detected by laboratory monitoring
• abnormal electrocardiogram (ECG) results
• increased cells in the cerebrospinal fluid detected by laboratory monitoring
• device malfunction due to blockage detected during preparation for infusion
• loss of the device
• problems related to the needle (infusion needle detaches from the implanted device).

Common side effects (may affect up to 1 in 10 people):

• slow heart rate
• erythema
• hives
• device rupture
• irritation at device site
• nervousness
• stomach and intestinal disorders.

Not known (frequency cannot be estimated from the available data):

• device displacement and incorrect functioning at the time of preparation for infusion.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Brineura

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vials and the outer carton after the symbol "Exp.". The expiry date refers to the last day of that month.
Store frozen in an upright position (-25 °C to -15 °C). Keep in the original packaging to protect the medicine from light. Transport and distribute frozen (-85 °C to -15 °C).
Thawed Brineura and wash solution must be used immediately. The medicine should be withdrawn from closed vials immediately before use. If immediate use is not possible, closed vials of Brineura and wash solution must be stored in a refrigerator (2 °C – 8 °C) and used within 24 hours.
Chemical and physical in-use stability has been demonstrated for up to 12 hours at room temperature (19 °C – 25 °C). From a microbiological standpoint, opened vials or product in syringes should be used immediately. Otherwise, the storage times and conditions prior to use are the sole responsibility of the user.
The physician or pharmacist is responsible for the storage of Brineura and the proper disposal of unused vials.

6. Package contents and other information

What Brineura contains

• The active substance is cerliponase alfa. Each Brineura vial contains 150 mg of cerliponase alfa in 5 mL of solution. Each mL of infusion solution contains 30 mg of cerliponase alfa.
• The other components of Brineura infusion solution and of the wash solution are: disodium phosphate heptahydrate, sodium dihydrogen phosphate monohydrate, sodium chloride, potassium chloride, magnesium chloride hexahydrate, calcium chloride dihydrate, water for injections (see section 2 “Brineura contains sodium and potassium”).

Description of the appearance of Brineura and the contents of the pack
Brineura and the wash solution are both solutions for infusion. The Brineura infusion solution is from clear to slightly opalescent, from colourless to pale yellow, and may contain very fine translucent fibres or opaque particles. The wash solution is clear and colourless.
Pack: each pack contains two vials of Brineura infusion solution and one vial of wash solution, each containing 5 mL of solution.

Marketing Authorisation Holder and Manufacturer
BioMarin International Limited
Shanbally, Ringaskiddy
County Cork
Ireland

This medicinal product has been authorised under “exceptional circumstances”. This means that, due to the rarity of the disease, it has not been possible to obtain complete information on this medicinal product.
The European Medicines Agency will review any new information on this medicinal product annually, and this package leaflet will be updated if necessary.

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.