InfoCons Consumer Protection informs you – KYGEVVI – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

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

KYGEVVI contains the active substances doxecitine and doxribtimine. KYGEVVI is known as nucleosides therapy. KYGEVVI is used in children and adults in whom disease symptoms started on or before 12 years of age to treat thymidine kinase 2 deficiency (TK2d), a rare form of inherited mitochondrial DNA depletion and deletion syndrome.

Mitochondria are parts of the cell that produce the cell’s energy and they carry their own genetic material called mitochondrial DNA. TK2d is caused b y mutations (changes) in a gene called TK2 which provides instructions for making a protein known as thymidine kinase 2. This protein helps mitochondria function properly. Mutations in the TK2 gene result in production of a faulty protein. As a result , the mitochondria can’t make enough copies of their own DNA, leading to a gradual loss of energy in patients with TK2d. T K2d mainly affects the muscles, causing weakness, especially in the muscles used for movement, breathing and swallowing .

⚠️ 2. What you need to know before you take KYGEVVI

Do not take KYGEVVI

• if you are allergic to any of the other ingredients of this medicine (listed in section 6) .

Warnings and precautions

Talk to your doctor or nurse before taking KYGEVVI if:

• You have or have had liver problems because increase in liver function tests can occur during KYGEVVI treatment. Your doctor will check your liver both before and during treatment with KYGEVVI.
• You have diarrhoea, as your doctor may need to adjust your dose.

Other medicines and KYGEVVI

Tell your doctor or pharmacist if you are taking, have recently used or might use any other medicines.

In particular, tell your doctor, pharmacist or nurse if you are taking any of the following medicines:

• medicines able to kill cells , such as cancer cells, and antiviral medicines (e.g., cedazuridine, cisplatin, tipiracil, brivudine, stavudine, ribavarin, fludarabine) Pregnancy and breast -feeding If you are pregnant or breast -feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

The effects of KYGEVVI in pregnancy are not known, so do not take this medicine if you are pregnant or think that you may be pregnant unless your doctor specifically recommends it.

If you plan to breast -feed, ask your doctor or pharmacist for advice before taking this medicine. This is because it is not known whether the medicine passes into human breast milk although no effects on the baby are expected .

Driving and using machines

This medicine has no, or almost no effect on your driving and use of machines.

💊 3. How to take KYGEVVI

Always take this medicine, exactly as your doctor, pharmacist or nurse has told you. Check with your doctor, pharmacist or nurse if you are not sure.

Treatment must be started and supervised by a doctor experienced in the management of mitochondrial disorders .

Dosing KYGEVVI

• The dose of KYGEVVI is based on your weight. Your doctor will tell you the number of sachets and volume of water you have to use for the preparation of your daily supply.
• The daily recommended starting dose is 130 mg of doxecitine and 130 mg of doxribtimine for each kg of body weight per day.
• Your doctor may adjust your dose depending on how well you tolerate it .
• Your doctor may change the number of sachets to achieve the recommended dose based on changes in your weight.
• Always take this medicine with food.

Prepare KYGEVVI

• Use the recommended dosing system (mixing bottle and cup) to prepare the reconstituted oral solution.
• KYGEVVI must only be prepared with room temperature water (between 15°C to 25°C) .
• Do not mix KYGEVVI powder with other medic ines, liquids, powders, or foods.
• You must carefully read and follow the enclosed “Instructions for Use (IFU)” on how to prepare and take KYGEVVI.

Take KYGEVVI

• By mouth (oral) 3 times a day in equally divided doses, approximately 6 hours apart ±2 hours,
• You should take KYGEVVI with food.
• If a dose is missed or if you are not sure you took all of the medicine, do not take another dose.

Wait until the next scheduled dose.

• If necessary, this medicine may be given via a feeding tube with or after a feed (see section “Use of feeding tube”).

25 Use of feeding tube

• KYGEVVI oral solution is compatible with most commonly available feeding tubes (polyurethane, polyvinyl chloride, silicone ) from 4 French and up with a maximum length of 125 cm.
• Be sure KYGEVVI is given with or after a feed.
• If you take or give KYGEVVI via a feeding tube, ensure you follow manufacturer’s instructions.

For more information, ask your doctor, pharmacist or nurse.

If you take more KYGEVVI than you should

If you suspect that you have accidentally taken a higher dose of KYGEVVI than prescribed, please contact your doctor for advice, as soon as possible.

If you forget to take KYGEVVI

If you miss a dose, you should take the dose as soon as you remember. However, if it is within 2 hours of the next planned dose, skip the missed dose and take the next dose at the usual time. A double or extra dose should not be taken to make up for a missed dose.

If you stop taking KYGEVVI

Interrupting or stopping treatment with this medicine may cause your symptoms to come back. Talk to your doctor before stopping KYGEVVI. Your doctor will discuss the possible side effects and risks with you. Your doctor may also want to monitor you closely.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

❗ 4. Possible side effects

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

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

• Diarrhoea
• Vomiting (being sick)
• Belly (abdominal) pain

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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 KYGEVVI

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 sachet and carton after “EXP”.

The expiry date refers to the last day of that month.

This medicin e does not require any special storage conditions.

Reconstituted solution After reconstitution, the solution should be used within 16 hours.

Do not store above 25°C. Can be stored in a refrigerator (2°C and 8°C). Do not freeze.

Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

📦 6. Contents of the pack and other information

What KYGEVVI contains

• The active substances are doxecitine and doxribtimine. One sachet contains 2 g of doxecitine and 2 g doxribtimine.
• The other ingredients are silica colloidal anhydrous (E551) , magnesium stearate (E470b) .

What KYGEVVI looks like and contents of the pack

KYGEVVI is a white to off -white powder for oral solution, supplied in a sachet. Each carton contains 30 sachets.

Marketing Authorisation Holder

UCB Pharma S.A.

Allée de la Recherche 60 B-1070 Bruxelles Belgium

Manufacturer

Catalent Germany Schorndorf GmbH Steinbeisstrasse 1 -2 Schorndorf , Baden -Württemberg , 73614 Germany For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien UCB Pharma S.A./NV Tél/Tel: + 32 / (0)2 559 92 00 Lietuva UAB Medfiles Tel: + 370 5 246 16 40 България Ю СИ БИ България ЕООД Teл.: + 359 (0) 2 962 30 49 Luxembourg/Luxemburg UCB Pharma SA/NV Tél/Tel: + 32 / (0)2 559 92 00 ( Belgique/Belgien) Česká republika UCB s.r.o.

Tel: + 420 221 773 411 Magyarország UCB Magyarország Kft. Tel.: + 36 -(1) 391 0060 Danmark UCB Nordic A/S Tlf.: + 45 / 32 46 24 00 Malta Pharmasud Ltd.

Tel: + 356 / 21 37 64 36 Deutschland UCB Pharma GmbH Tel: + 49 /(0) 2173 48 4848 Nederland UCB Pharma B.V.

Tel: + 31 / (0)76 -573 11 40 Eesti OÜ Medfiles Tel: + 372 730 5415 Norge UCB Nordic A/S Tlf: + 47 / 67 16 5880 Ελλάδα UCB Α.Ε.

Τηλ: + 30 / 2109974000 Österreich UCB Pharma GmbH Tel: + 43 -(0)1 291 80 00 España UCB Pharma, S.A.

Tel: + 34 / 91 570 34 44 Polska UCB Pharma Sp. z o.o. / VEDIM Sp. z o.o.

Tel.: + 48 22 696 99 20 France UCB Pharma S.A.

Tél: + 33 / (0)1 47 29 44 35 Portugal UCB Pharma (Produtos Farmacêuticos), Lda Tel: + 351 21 302 5300 Hrvatska Medis Adria d.o.o.

Tel: +385 (0) 1 230 34 46 Ireland UCB (Pharma) Ireland Ltd. Tel: + 353 / (0)1 -46 37 395 România UCB Pharma Romania S.R.L.

Tel: + 40 21 300 29 04 Slovenija Medis, d.o.o.

Tel: + 386 1 589 69 00 Ísland UCB Nordic A/S Sími: + 45 / 32 46 24 00 Slovenská republika UCB s.r.o., organizačná zložka Tel: + 421 (0) 2 5920 2020 Italia UCB Pharma S.p.A.

Tel: + 39 / 02 300 791 Suomi/Finland UCB Pharma Oy Finland Puh/Tel: + 358 9 2514 4221 Κύπρος Lifepharma (Z.A.M.) Ltd Τηλ: + 357 22 056300 Sverige UCB Nordic A/S Tel: + 46 / (0) 40 294 900 Latvija Medfiles SIA Tel: + 371 67 370 250

This leaflet was last revised in

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

28 Instructions for Use Table of contents

• Instructions for use o Important information
• Before you start o Supplies for preparing and taking or giving KYGEVVI
• Important information o What you need to know before preparing and taking or giving KYGEVVI
• Preparing your one -day supply of KYGEVVI o Get supplies ready o Measure water and add powder sachets o Mix and inspect medicine
• Dosing methods o How to measure your individual dose
• Individual doses equal to or greater than 50 ml o Measure and take or give your individual dose
• Individual doses less than 50 ml o Measure and take or give your individual dose
• Between individual doses o Clean up after first and second individual dose
• End-of-day clean up o Pour out and clean up after third individual dose
• Dosing cup maintenance o Replacing the seal if misplaced or damaged
• Contact information o Contact your healthcare provider or pharmacist Instructions For Use Important information

These Instructions for Use contains information on how to prepare and take “or give” a one-day supply of KYGEVVI.

Read these Instructions for Use before taking or giving KYGEVVI and each time you get a refill.

There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

When you are prescribed KYGEVVI for the first time, you will be provided with the carton(s) of 30 KYGEVVI powder sachets and the A dministration device kit (see Figure A ).

Carton of 30 KYGEVVI powder sachets Administration device kit Figure A 30 Before you start Supplies for preparing and taking or giving KYGEVVI Carton of 30 KYGEVVI powder sachets Carton of KYGEVVI powder sachets KYGEVVI powder sachet Instructions for Use Expiration date (see back of the powder sachet) Expiration date (see bottom of the carton) Tamper evident seal Before you start Supplies for preparing and taking or giving KYGEVVI Seal Dosing cup Mixing bottle 2 Spare seals 2 Oral syringes Tip Barrel Plunger 2 Instructions for Use Container with room temperature water Other items needed (not provided) Administration device kit (containing 1 dosing cup, 1 mixing bottle, 2 oral syringes, 2 spare seals and 2 Instructions for Use) 32 Important information What you need to know before preparing and taking or giving KYGEVVI

• You will prepare a one -day supply of KYGEVVI oral solution to be taken in 3 equal doses throughout the day (about 6 hours apart).
• If you or the patient you care for weigh more than 85. 0 kg, your doctor may tell you that you need to prepare your 3 daily doses separately. It is important to talk to your doctor about the detailed preparation steps if this is the case.
• KYGEVVI should be prepared and given by adults only.
• Only use the dosing cup, mixing bottle and oral syringes provided with your Administration device kit .
• Each Administration device kit includes two oral syringes. Keep the second oral syringe as a spare.
• Rinse and dry the mixing bottle and dosing cup before first use. Do not use the dosing cup, mixing bottle or oral syringe if it appears dirty or damaged.
• Each Administration device kit can be used for 6 months. Contact your healthcare provider when you need a replacement.
• Contact your healthcare provider or pharmacist for a replacement if your mixing bottle, dosing cup, or oral syringe is damaged or if the markings are missing or no longer readable.
• Do not use the powder sachets if the tamper evidence seal on the carton is broken.
• Mix KYGEVVI powder only with room temperature water. Do not mix KYGEVVI powder with cold or hot water, milk powders or any other liquids or foods. You may have KYGEVVI oral solution left over after taking your 3 individual doses. Throw away (dispose of) any remaining KYGEVVI oral solution at the end of each day.
• If powder spills out of a sachet before use, do not use the sachet. Throw it away and use a new KYGEVVI powder sachet.

KYGEVVI oral solution is compatible with most feeding tubes. Follow the steps in this instruction booklet to prepare your one -day supply of KYGEVVI and then follow the feeding tube instructions to give KYGEVVI using a feeding tube.

33 Preparing your one -day supply of KYGEVVI Get supplies ready Step 1 a) Wash your hands well with soap and water. b) Place the mixing bottle, dosing cup and the oral syringe (if you need one to measure your individual dose) on a clean, well -lit flat work surface. If the dosing cup is attached to the mixing bottle, unscrew it from the mixing bottle and set it down (see Figure B ). c) When opening the KYGEVVI carton for the first time, break the tamper evidence seal. d) Remove the prescribed number of KYGEVVI powder sachets needed for your one -day supply of KYGEVVI out of the carton. Your one -day supply of KYGEVVI will be divided into 3 individual doses. e) Do not open the KYGEVVI powder sachets until Step 2.

Note: The mixing bottle has markings on the front of the bottle in 40 ml increments, each increment is equal to one sachet of medicine. The dosing cup has markings on the front and back of the cup in 10 ml increments, offset to provide 5 ml increments of measurements.

Figure B Preparing your one -day supply of KYGEVVI Measure water and add powder sachets Step 2 a) On a flat surface, pour the prescribed amount of room temperature water into the mixing bottle (see Figure C ).

• Do not pour the water into the dosing cup.
• Important: Do not add powder sachets to the mixing bottle before this step. b) Check to make sure the mixing bottle is filled with water up to the marking that matches the amount prescribed by your healthcare provider. The marking should also match the number of sachets needed for your one -day supply (see Figure C) . c) Check you have counted out the correct number of KYGEVVI powder sachets for your one -day supply, as shown on your prescription. d) Tap the powder sachet on a hard surface to settle the powder to the bottom of the sachet away from the dotted line (see Figure D). e) Carefully fold and tear or cut along the dotted line (see Figure E ). If you spill any powder, do not use it. Throw the powder sachet away and use a new sachet. f) Empty the entire powder sachet contents into the mixing bottle containing water. Be careful not to drop the powder sachet into the mixing bottle (see Figure F). g) Pour only 1 powder sachet into the mixing bottle at a time. Repeat Steps 2d to 2f, for each powder sachet until you have poured the prescribed number of powder sachets for your one -day supply.

Figure C Figure D Figure E Figure F Check water level in mixing bottle Preparing your one -day supply of KYGEVVI Mix and inspect medicine Step 3 a) Screw the dosing cup tightly onto the mixing bottle (see Figure G ). b) Place one hand at the end of the mixing bottle and the other hand at the end of the dosing cup. Slowly turn the bottle upside down and back. Repeat at least 20 times (see Figure H ). c) Check the solution. If you see any lumps, keep turning until they disappear (see Figure I ). d) The solution will be cloudy and have some powder residue at the bottom or top, this is normal.

You have now prepared your one -day supply of KYGEVVI oral solution for 3 individual doses or your individual dose if your doctor has told you to prepare your individual doses separately. Take KYGEVVI oral solution with a snack or meal.

Figure G Figure H Figure I Dosing cup Mixing Bottle x 20 36 Dosing methods How to measure your individual dose There are 2 different methods to take or give KYGEVVI oral solution depending on your individual dose. Use the table below to identify which steps you should follow:

Doses equal to or greater than 50 ml Doses less than 50 ml (dosing cup used for dose preparation only) Example 100 ml Follow Step 4 Example 14 ml Follow step 5 Individual doses equal to or greater than 50 ml Measure and take or give your individual dose You will need to use the dosing cup to measure and take or give your individual dose.

Step 4. Individual doses equal to or greater than 50 ml a) Check to ensure the dosing cup is closed tightly onto the mixing bottle and mix the already prepared oral solution by slowly turning the mixing bottle upside down and back at least 3 times. b) Unscrew the dosing cup from the mixing bottle and place on a flat surface. c) Pour KYGEVVI oral solution from the mixing bottle into the dosing cup until it reaches the marking on the dosing cup for your prescribed individual dose (see Figure J ). Note: Your dose may be different than the dose shown in Figure J. d) Drink or give the entire oral solution from the dosing cup (see Figure K ). e) When it is time for the second or third individual dose , repeat Steps 4a to 4d for each individual dose. f) After the first or second individual dose , go to Step 6 for instructions on how to clean your supplies and store KYGEVVI oral solution. After the third individual dose , go to Step 7 for instructions on how to clean your supplies and dispose of KYGEVVI oral solution.

Figure J Figure K Individual doses less than 50 ml Measure and take or give your individual dose Step 5 – Individual doses less than 50 ml You will need to use the dosing cup and oral syringe to measure and take or give your individual dose a) Mix the already prepared oral solution by slowly turning the mixing bottle upside down and back at least 3 times. b) Unscrew the dosing cup from the mixing bottle and place on a flat surface. c) Pour slightly more than the amount of oral solution needed for your prescribed individual dose into the dosing cup (see Figure L). d) Push the plunger of the oral syringe all the way down to make sure there is no air in the oral syringe when measuring the dose (see Figure M).

If you are giving the oral solution to young children, they must be seated and held in place to avoid the risk of oral solution going down the wrong pipe or choking. e) Place the tip of the oral syringe into the dosing cup with the oral solution. Fill the oral syringe by pulling the plunger back until it reaches the marking on the oral syringe that matches your prescribed individual dose (see Figure N). Step 5e may need to be repeated depending on your individual dose.

Figure L Figure N Figure M f) Place the tip of the oral syringe into the mouth and point the tip towards the inside of either cheek (see Figure O). g) Slowly push the plunger all the way down until the oral syringe is empty (see Figure O).

Figure O h) If your prescribed dose is more than 10 ml, repeat Steps 5d to 5g until you take or give the full individual dose. i) Pour back any remaining oral solution from the dosing cup into the mixing bottle. j) When it is time for the second or third individual dose , repeat Steps 5a to 5i for each individual dose. k) After the first or second individual dose , go to Step 6 for instructions on how to clean your supplies and store KYGEVVI . After the third individual dose , go to Step 7 for instructions on how to clean your supplies and dispose of KYGEVVI .

40 Between individual doses Clean up after first and second individual dose Step 6.

After you complete the first or second individual dose:

• Rinse the dosing cup with cold water after each use (see Figure P).
• Dry the dosing cup with a clean, dry towel.
• After the dosing cup is dry, screw the dosing cup tightly onto the mixing bottle (see Figure Q) and store it at room temperature or in the refrigerator until it is time for the next individual dose.
• If you used the oral syringe, clean it with cold water: o Rinse the oral syringe with cold water by filling the oral syringe with water and pushing it back out (see Figure R). Then remove the plunger from the barrel and rinse the plunger and barrel (see Figure R) under running tap water until it is clean. o Let the oral syringe barrel and plunger dry in the open air. After the oral syringe barrel and plunger are dry, put the plunger back into the barrel.
• Do not wash the dosing cup or oral syringe in the dishwasher.

Figure P Figure Q Figure R End-of-day clean up Pour out and clean up after third individual dose Step 7 After you take or give the third individual dose, throw away any remaining KYGEVVI oral solution in the sink. Do not save KYGEVVI oral solution for another day.

• Remove the seal from the dosing cup to thoroughly clean it (see Figure S).
• Clean the mixing bottle, dosing cup and seal by hand with soap and warm water. Use a brush to remove any residue left in the mixing bottle or dosing cup (see Figure T).
• Dry the mixing bottle, dosing cup and seal with a clean towel. Put the dry seal back into the dosing cup, with the thin side of the seal facing the groove.
• If you used the oral syringe, clean it with cold water: o Rinse the oral syringe with cold water by filling the oral syringe with water and pushing it back out (see Figure U). Then remove the plunger from the barrel and rinse the plunger and barrel under running tap water until it is clean (see Figure U). o Let the oral syringe barrel and plunger dry in the open air. After the oral syringe barrel and plunger are dry, put the plunger back into the barrel.
• Do not wash the mixing bottle, dosing cup, seal or oral syringe in the dishwasher.
• Store all supplies in a clean, dry area out of the reach of children for the next day’s use.

Figure S Figure T Figure U Dosing cup maintenance Replacing the seal if misplaced or damaged Changing the dosing cup seal If you misplace the dosing cup seal or you notice leakage when the mixing bottle and dosing cup are tightly closed, change the seal using one of the two spare seals provided in the A dministration device kit. Follow these steps to replace the seal:

• Remove the seal in the dosing cup (see Figure V). Skip this step if you misplaced the seal.
• Wash the dosing cup groove with warm water (see Figure W).
• Get a new seal from the spare seal box (see Figure X).
• Insert the seal into the groove of the dosing cup with the thin side of the seal facing the groove (see Figure Y).

Figure V Figure W Figure X Figure Y Contact your healthcare provider or pharmacist if you have any questions about these Instructions for Use.

📄 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 KYGEVVI (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/25/2013).

⚠️ 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.