Brineura 150 mg solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Brineura 150 mg solution for infusion

cerliponase alfa

This medicinal product is subject to additional monitoring, which will allow for faster identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read this entire leaflet carefully before this medicine is administered to you, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you or your child experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Brineura is and what it is used for
2. What you need to know before Brineura is administered to you or your child
3. How Brineura is administered
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 called enzyme replacement therapies. It is used to treat patients with neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl-peptidase 1 (TPP1) deficiency.

People with CLN2 disease do not have the enzyme called TPP1, or have too little of it, leading to an accumulation of substances known as lysosomal storage materials. In people with CLN2 disease, these materials build up in certain parts of the body, especially in the brain.

How Brineura works

This medicine replaces the missing enzyme, TPP1, thereby reducing the accumulation of lysosomal storage materials. This medicine acts to slow the progression of the disease.

2. What you need to know before you or your child are given Brineura

Do not administer Brineura:

• If you or your child have had allergic reactions to cerliponase alfa or to any of the other components of this medicine (listed in section 6) that could potentially be life-threatening, and the reactions reappeared when cerliponase alfa was administered again.
• If you or your child have an implanted device to drain excess fluid from the brain.
• If you or your child currently have signs of infection related to the device or problems with the device. Your doctor may decide to continue treatment once the infection or device-related problems have resolved.

Warnings and precautions

Talk to your doctor before you or your child start receiving Brineura.

• You or your child may experience problems with the implanted device used during Brineura treatment (see section 4, "Possible side effects"), including infection or device malfunction. Treatment may be interrupted if the device needs to be replaced or until an infection has healed. Speak to your doctor if you have any questions about the device.
• Brineura may cause potentially life-threatening allergic reactions. Your doctor will monitor you or your child for symptoms of such allergic reactions, including hives, itching or flushing, swelling of the lips, tongue, and/or throat, difficulty breathing, hoarseness, bluish discoloration of the lips or fingertips, low muscle tone, fainting, or incontinence.
• Your doctor will monitor your or your child's heart rate, blood pressure, respiratory rate, and temperature before, during, and after treatment. The doctor may decide to perform additional monitoring if necessary.
• Your doctor will perform a test every 6 months to check for abnormalities in the heart's electrical activity (electrocardiogram or ECG). If you or your child have a history of heart problems, the doctor or nurse will monitor heart activity during each infusion.
• Your doctor may order tests on samples of cerebrospinal fluid to check for signs of infection.
• Brineura has not been administered to patients with advanced disease at the start of treatment or to children under 2 years of age. Your doctor will discuss whether Brineura treatment is appropriate for you or your child.

Other medicines and Brineura

Tell your doctor if you or your child are taking, have recently taken, or might need to take any other medicines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before treatment with this medicine.

You should not receive Brineura during pregnancy unless clearly necessary. It is unknown whether Brineura passes into human breast milk. Breastfeeding must be discontinued during treatment with Brineura. It is unknown whether Brineura affects human fertility.

Driving and using machines

It is unknown whether Brineura affects the ability to drive or operate machinery. Consult your doctor.

Brineura contains sodium:

This medicine contains 44 mg of sodium per vial, which should be taken into consideration for patients on low-sodium diets.

3. How Brineura is administered

You or your child will need to undergo a surgical procedure to implant the device used to administer Brineura. The device helps deliver the medicine to a specific area of the brain.

Brineura will be administered by a physician experienced in the administration of intracerebroventricular infusion (infusion into the fluid of the brain) in a hospital or clinical setting.

Brineura has not been administered to patients under 2 years of age or over 8 years of age (at the start of the clinical trial). Experience in patients under 2 years of age is limited to a few children.

The recommended dose of Brineura to be administered every other week depends on your or your child's age:

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

Your doctor may adjust your or your child's dose or the duration of administration if the infusion is not well tolerated, if an allergic reaction occurs, or if there is a potential increase in intracranial pressure.

The medicine is slowly pumped through the implanted device. After the drug is administered, a shorter infusion of a solution is performed to flush any remaining Brineura from the infusion equipment, ensuring that the full dose reaches the brain. The administration of the medicine and solution will take approximately 2 to 4.5 hours, depending on the dose required by you or your child. Your doctor may reduce the dose or the infusion rate based on your response during treatment.

Your doctor may give you or your child medications, such as antipyretics to reduce fever or antihistamines to manage allergic reactions, before each Brineura treatment to reduce adverse effects that may occur during or shortly after treatment.

If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Immediately consult your doctor or nurse if you experience any of the following adverse effects:

Very common adverse effects (may affect more than 1 in 10 people):

• Fever
• Vomiting
• Irritability
• Seizures
• Reactions during or shortly after administration of the medicine, such as rash, itching or redness, swelling of the lips, tongue and/or throat, difficulty breathing, hoarseness, bluish discoloration of the lips or fingertips, low muscle tone, fainting, or incontinence.

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

• Bacterial infections related to the device
• Slower heartbeats
• Incorrect functioning of the device due to an obstruction detected during preparation for infusion

Frequency not known (cannot be estimated from available data):

• The device moves and does not function properly when being prepared for infusion

This medicine may cause other adverse effects:

Very common adverse effects:

• Headache
• Increase or decrease in proteins in the cerebrospinal fluid
• Abnormal results in the electrical activity of the heart (ECG)
• Increased cells in the cerebrospinal fluid detected in laboratory tests
• Infection of the nose or throat (cold)
• Problems with the needle (infusion needle dislodges from the implanted device)

Common adverse effects:

• Pain
• Skin rash
• Hives
• Head drooping (such that the chin drops toward the chest)
• Stomach pain
• Leakage from the device
• Blisters in the mouth or on the tongue
• Swelling or redness of the eyelid and the white part of the eye
• Nervousness
• Stomach or intestinal disorder

Reporting of adverse effects

If you or your child experience any adverse effects, please consult your doctor, even if they are adverse effects not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 carton after EXP. The expiry date is the last day of the month indicated.

Store in a freezer upright (between -25 °C and -15 °C). Transport and distribute frozen (between -85 °C and -15 °C). Keep in the original packaging to protect from light.

Once thawed, Brineura and the wash solution must be used immediately. The medicine should only be withdrawn from unopened vials immediately before use. If immediate use is not possible, unopened vials of Brineura or the wash solution must be stored at 2-8 °C and used within 24 hours.

Chemical and physical in-use stability has been demonstrated for up to 12 hours at room temperature (19-25 °C). From a microbiological point of view, opened vials or medicine contained in syringes should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user.

The physician or pharmacist is responsible for the storage of Brineura. They are also responsible for the proper disposal of any unused amount of Brineura.

6. Contents of the container and other information

Composition of Brineura

• 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 and the wash solution are: sodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate monohydrate, sodium chloride, potassium chloride, magnesium chloride hexahydrate, calcium chloride dihydrate, and water for injections (see section 2, "Brineura contains sodium").

Appearance of Brineura and contents of the container

Brineura and the wash solution are infusion solutions. The solutions are colourless or pale yellow, clear or slightly opalescent; occasionally the Brineura solution may contain translucent fibrils or opaque particles.

Container size: 3 vials (two vials of Brineura 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

Date of the most recent revision of this leaflet: MM/YYYY

This medicine has been authorised under "exceptional circumstances". This type of approval means that due to the rarity of the disease, it has not been possible to obtain complete information on this medicine.

The European Medicines Agency will review any new information on this medicine annually, and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicinal products.