InfoCons Consumer Protection informs you – NULIBRY – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start using this medicine because it contains important information for you or your child.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you or your child get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

ℹ️ 1. What NULIBRY is and what it is used for

What NULIBRY is NULIBRY contains the active substance fosdenopterin.

NULIBRY is given to people with the genetic disease molybdenum cofactor deficiency (MoCD) Type A. It is given to people when doctors suspect that they might have MoCD Type A. It needs to be continued for life if MoCD Type A is confirmed by genetic testing.

What molybdenum cofactor deficiency (MoCD) Type A is MoCD Type A is a rare inborn error of the natural chemical processes needed for your body to work (metabolism). Signs of this genetic disease usually appear shortly after birth and include difficulty feeding and seizures. Other signs are a decreased awareness or reaction to the environment, an increase in startle reactions to a sudden event, and weak or stiff muscles.

MoCD type A results from an error in the gene called MOCS1 . This stops the body from making an essential substance called cyclic pyranopterin monophosphate. When this substance is missing, certain compounds (sulphites) formed in the body cannot be broken down. These compounds are toxic to the brain and can negatively affect or delay the development of a child.

How NULIBRY works

NULIBRY provides the missing substance that you or your child’s body needs to break down the harmful sulphite compounds.

⚠️ 2. What you need to know before you use NULIBRY

Do not use NULIBRY

• if you or your child is allergic to fosdenopterin or any of the other ingredients of this medicine (listed in section 6).

21 Warnings and precautions Talk to your doctor or nurse before using NULIBRY.

Patients who use NULIBRY may become sensitive to direct sunlight and ultraviolet light. During treatment with fosdenopterin, patients should avoid exposure to sunlight, and wear sunscreen, protective clothing, and sunglasses when exposed to the sun. Tell your doctor immediately if you or your child develops a rash, redness or blisters on sun-exposed areas of the skin, or if you or your child experience a burning sensation of the skin.

Due to the use of sunscreens and sun protective clothing your doctor may prescribe additional vitamin D as necessary.

Other medicines and NULIBRY

It is unlikely that NULIBRY has an influence on or is influenced by other medicines. However, tell your doctor if your child is taking, has recently taken, or might take any other medicines.

NULIBRY contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium -free’.

💊 3. How to use NULIBRY

How NULIBRY is given NULIBRY is injected into a vein through a catheter.

A doctor who is experienced in the management of inborn errors of metabolism will start and supervise the treatment with NULIBRY.

NULIBRY can be given at home. Before you do this for the first time, your doctor or nurse will train you in how to prepare the medicine and give you or your child a dose of NULIBRY.

Always use this medicine exactly as your doctor or nurse has instructed. Check with your doctor if you or your child are not sure about how to use NULIBRY.

How much to use The dose depends on your child’s age and body weight. You will need to give the dose once each day.

Your doctor will work out the dose you need to give.

If you use more NULIBRY than you should

If you think you or your child may have been given more NULIBRY than prescribed, tell your doctor immediately.

If you forgot to give a dose of NULIBRY.

If a dose of NULIBRY is missed, give the missed dose as soon as possible. Wait at least 6 hours before you give the next dose.

❗ 4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or nurse immediately if any of the side effects occur, or if you notice any side effects not listed in this leaflet.

22 The following side effects are very common and are related to the injection device (catheter) and not to the medicine . These may affect more than 1 in 10 people:

• Catheter-related problems, such as pain, discharge, redness, or inflammation Complications related to catheter You or your child will have an injection device (catheter -type device). This is used to inject medicines into you or your child’s blood. You or your child may develop complications related to the catheter. Please follow the instructions from your doctor or nurse on how to care for this device before and after giving a dose of NULIBRY.

Reporting of side effects

If you notice any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly the national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.

🌡️ 5. How to store NULIBRY

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial label after EXP. The expiry date refers to the last day of that month.

Unopened vial Store in a freezer at -25 °C to -10 °C.

Keep the vial in the outer carton in order to protect from light.

Storage of the reconstituted (mixed) NULIBRY Reconstituted NULIBRY may be stored at room temperature (15 °C-25 °C) or refrigerated (2 °C-8 °C) for up to 4 hours including the time needed to give NULIBRY.

If reconstituted NULIBRY is refrigerated, allow it to come to room temperature (by rolling each vial gently between your hands for 3 to 5 minutes (do not shake) or by leaving it at room temperature for approximately 30 minutes) before giving NULIBRY. – Do not heat.

• Do not freeze NULIBRY after reconstitution.
• Do not shake.

The reconstituted solution must be a clear and colourless to pale yellow solution. Do not use this medicine if you notice any particles or if the solution is discoloured.

Do not throw away any medicines or waste material, including materials used for reconstitution and administration via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the env ironment.

📦 6. Contents of the pack and other information

What NULIBRY contains

• The active substance is fosdenopterin 9.5 mg. Each vial contains fosdenopterin hydrobromide dihydrate equivalent to 9.5 mg fosdenopterin.
• The other ingredients are: ascorbic acid (E300), mannitol (E421), sucrose, hydrochloric acid

(E507), sodium hydroxide (E524) (see section 2 “NULIBRY contains sodium”).

23 What NULIBRY looks like and contents of the pack NULIBRY is a white to pale yellow powder for solution for injection (powder for injection).

Each pack contains one vial.

Marketing Authorisation Holder

Integral Pharma Solutions EU Limited 1 Windmill Lane Dublin 2 D02 F206 Ireland

Manufacturer

Sciensus International B.V.

Bijsterhuizen 3142 6604 LV Wijchen, The Netherlands This leaflet was last revised in This medicine has been authorised under ‘exceptional circumstances’. This means that because of the rarity of this disease it has been impossible to get complete information on this medicine.

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

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu . There are also links to other websites about rare diseases and treatments.

This leaflet is available in all EU/EEA languages on the European Medicines Agency website. ———————————————————————————————————————— The following information is intended for preparation and administration of NULIBRY:

24 Instructions for use on how to prepare and give NULIBRY.

Read these instructions for use before you reconstitute (mix) and give a dose of NULIBRY for the first time and each time you get a NULIBRY refill. This information does not replace talking to your doctor about your child’s medical condition or their treat ment. Always talk to your doctor if you are unsure.

Your doctor should show you the right way to prepare and give your child’s prescribed dose of NULIBRY before you do this for the first time.

NULIBRY is given into your child’s vein (intravenously), through a catheter -type device which is placed by your doctor or nurse. Always follow the specific instructions given by your doctor or nurse.

Important information you need to know before preparing and giving NULIBRY

• Your child’s dose of NULIBRY is based on their age and body weight. Your doctor or nurse will work out the amount of NULIBRY needed for each dose for your child. The amount of NULIBRY needed for each dose and the number of vials needed to prepare each dose may change at each visit with your doctor. The dose will be measured as the number of millilitres (mL) of solution that you need to give.
• If you or your child’s caregiver are administering NULIBRY at home, your doctor or nurse will suggest that you keep an infusion diary including at minimum: o date of each dose of NULIBRY o number of vials used to prepare each dose o lot number from each NULIBRY vial used o total amount (number of mL) of NULIBRY that was given o start and end time of the dose o a place to capture adverse events, medication errors, and complications with the administration Be sure to keep this information up to date when the dose changes. Bring your infusion diary to each follow -up visit with your doctor . Be sure to have your doctor or pharmacist fill in the following information on your infusion diary: o your child’s dose of NULIBRY in millilitres (mL) o number of vials needed to prepare each dose
• NULIBRY comes as a powder in a vial. Each vial of NULIBRY must be made up with 5 mL of sterile water for injection to dissolve the powder and make a solution before use.

Do not prepare the solution with anything other than sterile water for injections .

NULIBRY must be given within 4 hours of preparing the solution. You may keep the prepared solution of NULIBRY at room temperature or refrigerated for up to 4 hours, including the time necessary to give the dose. If you do not give the prepared dose of NULIBRY within 4 hours, all the solution you have made must be thr own away. See section 5 of the package leaflet “How to store NULIBRY”.

Preparing to give NULIBRY Step 1: Gather Supplies

• Use a clean, flat work surface.
• Remove from the freezer the correct number of NULIBRY vials needed to prepare your child’s prescribed dose. You may need more than 1 vial to prepare the total amount needed for 1 dose. Allow the NULIBRY vials to reach room temperature. This can be done by rolling each vial gently between your hands for 3 to 5 minutes as shown, or by allowing the vials to sit at room temperature for about 30 minutes.

25 • Gather supplies needed to prepare and give a dose of NULIBRY: o 1 vial of sterile water for injection for each vial of NULIBRY needed for 1 dose.  Check the expiry date on the NULIBRY vial. Do not use the vial if the expiry date has passed.  Do not use the vial if the flip -off seal on the vial is broken or missing. o 1 sterile 5 mL syringe for each vial of NULIBRY needed for 1 dose, used to prepare NULIBRY with sterile water for injection o A second sterile syringe large enough to hold the total amount of NULIBRY needed for one dose. Your doctor, nurse or pharmacist should tell you what size and type of syringe to use. o sterile needles (18 -gauge recommended) o alcohol wipes o gloves, if your doctor or nurse has instructed you to wear gloves when preparing and giving NULIBRY o 1 intravenous administration set requires specific tubing [di(2 -ethylhexyl)phthalate (DEHP) -free tubing with a 0.2 micron filter] o 1 infusion pump used to give the dose of NULIBRY as instructed by your doctor o other materials, if recommended by your doctor to properly care for your child’s intravenous catheter -type device before and after giving a dose of NULIBRY o Any other materials provided by your pharmacist to throw away medicines you no longer use. These measures will help protect the environment.

Step 2: Wash your hands

• Wash your hands well with soap and water. Use a clean towel to dry your hands or allow them to air dry.
• If you have been told to wear gloves to prepare and give NULIBRY, put them on now.

Step 3: Prepare the vials

• Remove the flip -off cap from each vial of sterile water for injection needed.
• Clean the rubber stopper of each vial with an alcohol wipe and allow to air dry. Do not blow on the stopper to dry it faster.

Note: If you touch the vial stopper, you will need to clean it again with an alcohol wipe.

26 Step 4: Prepare the syringe used for drawing up sterile water for injection

• Open the wrapper that contains a needle. Do not remove the needle cover yet.
• Open the wrapper that contains a 5 mL syringe. Attach the needle to the syringe tip by screwing it on, turning in the direction of the arrow as shown. Your needle and syringe may look different to those shown.

Step 5: Fill syringe with sterile water for injection

• Remove the needle cover by pulling the cover straight off. Do not touch the needle or let the needle touch any surface.
• Hold the body of the syringe with one hand. Use your other hand to pull back the plunger of the syringe until the top of the plunger reaches the 5 mL line on the syringe.

27 • Hold the vial of sterile water for injection firmly on your work surface and insert the needle into the centre of the vial stopper.

• Slowly turn the vial upside down. Check that the tip of the needle is not in the water. Then, push up on the plunger to push all of the air from the syringe into the vial.
• Next, move the needle so that the tip is in the water. Slowly pull down on the plunger of the syringe to fill the syringe with 5 mL of sterile water for injection.

28 • Tap the syringe with your fingers until any air bubbles rise to the top of the syringe then gently push up on the plunger to push the air out of the syringe.

• After removing the air bubbles, check the syringe to be sure that 5 mL of solution is in the syringe before removing the needle from the vial. Continue to draw fluid until you reach 5 mL. Do not use less.

Step 6: Reconstitute NULIBRY

• Remove the flip -off cap from the vial of NULIBRY.
• Wipe the rubber stopper on the vial of NULIBRY with a new alcohol wipe.
• Hold the NULIBRY vial firmly on your work surface. Take the syringe with the sterile water for injection and slowly insert the needle into the centre of the vial stopper.
• Slowly push down on the plunger all the way to push the sterile water for injection into the vial. Then carefully remove the needle from the vial. Throw away the used needle and syringe right away as your pharmacist instructed you, so that 29 nobody can be injured. Do not try to recap the needle. See section 5 “How to store NULIBRY ”
• Gently swirl the vial continuously until the powder is completely dissolved. Do not shake the vial.
• Repeat steps 4 through 6 if more than 1 vial of NULIBRY is needed to prepare your child’s prescribed NULIBRY dose.
• Use a new 5 mL syringe and new needle for each vial of NULIBRY.

Note: Once prepared, the NULIBRY solution should be clear, and colourless to pale yellow.

• Do not use the solution if it is discoloured or cloudy, or if there are any particles in it. If the solution is discoloured or cloudy or there are particles in it: o Do not throw the vial away because the pharmacist may ask that you return it. o Tell your pharmacist and ask for a replacement vial.

Step 7: Prepare a syringe with the prescribed dose of NULIBRY

• If you stored the prepared NULIBRY solution in the refrigerator, remove the vials of prepared NULIBRY solution from the refrigerator and allow them to reach room temperature. This can be done by rolling each vial gently between your hands for 3 to 5 minute s as shown (do not shake), or by allowing the vials to sit at room temperature for about 30 minutes.
• Open the wrapper that contains a new sterile needle. Do not remove the needle cover yet.
• Open the wrapper that contains a sterile disposable syringe that is large enough to hold the total volume of NULIBRY needed for one dose. Attach the needle to the syringe tip with a screw action. Do not remove the needle cover yet.
• Wipe the vial stopper of each prepared NULIBRY vial with a new alcohol wipe.
• Remove the needle cover by pulling the cover straight off. Do not touch the needle or let the needle touch any surface.
• Hold the syringe with one hand. Insert the needle into the centre of the NULIBRY vial stopper then slowly turn the vial upside down.
• Next, move the needle so that the tip is in the NULIBRY solution. Slowly pull back on the syringe plunger to fill the syringe with the amount of NULIBRY solution in mL for your child’s prescribed dose.

30 • Remove any air bubbles from the syringe. Tap on the syringe barrel so that any bubbles rise to the top of the vial. Push up on the plunger to push any air bubbles back into the vial.

Check to make sure that the correct amount of NULIBRY solution has been drawn into the syringe. If needed, pull down slightly on the plunger until the prescribed amount of NULIBRY solution is in the syringe.

Follow the steps below if more than 1 vial of NULIBRY is needed to make up the total amount of solution needed for 1 daily dose.

• Remove the needle and syringe from the first vial of NULIBRY. Hold the syringe with one hand. Insert the needle into the centre of the next NULIBRY vial stopper then slowly turn the vial upside down.
• Next, move the needle so that the tip is in the NULIBRY solution. Slowly pull back on the syringe plunger to fill the syringe with the amount of NULIBRY solution in mL for your child’s prescribed dose.
• Remove any air bubbles from the syringe. Tap on the syringe barrel so that any bubbles rise to the top of the vial. Push up on the plunger to push any air bubbles back into the vial.

Then check to be sure that the prescribed amount of NULIBRY solution has been drawn into the syringe. If needed, pull down slightly on the plunger until the total prescribed amount of NULIBRY solution is in the syringe.

• Repeat this step if additional vials of NULIBRY are needed to make up your child’s dose.
• When the needle is removed from the last vial of NULIBRY, all of the prepared dose of NULIBRY is in 1 syringe.

31 • Replace the needle cover before removing the needle from the syringe by placing the cover on a flat surface and sliding the needle into the cover as shown. With one hand, hold the syringe and use the needle to “scoop up” the cover. Once the cover is on the needle, use the other hand to secure the cover on the needle hub.

• Remove the covered needle from the syringe tip with a screw action in the direction of the arrow as shown.

Do not touch the tip of the syringe after removing the needle.

• Throw away the needle properly. See section 5 “How to store NULIBRY”
• Throw away the used NULIBRY vial(s) after use, even if there is medicine left in the vial as instructed by your pharmacist. Do not throw it out with the household waste.
• The dose of NULIBRY is now ready to be given to your child.

Step 8: Giving a dose of NULIBRY

• NULIBRY is given into your child’s vein (intravenously) through a catheter -type device placed by your doctor.
• When NULIBRY is given through an infusion pump, infuse NULIBRY at a rate of 1.5 mL per minute.

32 • If the amount (volume) in mL for your child’s prescribed dose of NULIBRY is less than 2 mL, your doctor may tell you to give NULIBRY by injecting it slowly using a syringe. Follow your doctor’s instructions for how to give your child’s dose of NULIBRY by s low injection.

• Follow your doctor’s instructions for proper care of your child’s intravenous access catheter -type device before and after giving a dose of NULIBRY.

Step 9: Record the injection After giving each dose of NULIBRY, record information about the dose in an infusion diary. See the section of this instructions for use called “Important information you need to know before preparing and giving NULIBRY. ” Step 10: Disposal After injection, safely throw away all unused NULIBRY solution, the syringe with the injection set, the vial and other waste materials as instructed by your pharmacist.

Do not throw it out with the household waste. These measures will help protect the environment.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information NULIBRY (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/22/1684).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.