JIVI

Package leaflet: Information for the user

Jivi 250 IU powder and solvent for solution for injection, 500 IU powder and solvent for solution for injection, 1000 IU powder and solvent for solution for injection, 2000 IU powder and solvent for solution for injection, 3000 IU powder and solvent for solution for injection, 4000 IU powder and solvent for solution for injection

recombinant human coagulation factor VIII, PEGylated, with B-domain deletion
(damoctocog alfa pegol)
Read this entire leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Jivi is and what it is used for

Jivi contains the active substance damoctocog alfa pegol. It is produced using recombinant DNA technology, without the addition of any human or animal components during the manufacturing process.
Factor VIII is a protein normally present in the blood that helps promote blood clotting. The protein in damoctocog alfa pegol has been modified (pegylated) to prolong its action in the body.
Jivi is used for the treatment and prevention of bleeding episodes in previously treated adults, adolescents, and children aged 7 years and older with haemophilia A (hereditary factor VIII deficiency). It is not indicated for use in children under 7 years of age.

2. What you should know before using Jivi

Do not use Jivi if you are

• allergic to damoctocog alfa pegol or to any of the other ingredients of this medicine (listed in section 6)
• allergic to murine or hamster proteins

Warnings and precautions
Contact your doctor or pharmacist if you experience

• chest tightness, low blood pressure (often manifested as dizziness when standing up quickly), hives with itching, shortness of breath, malaise, or a feeling of weakness. These could be symptoms of a rare and serious sudden allergic reaction to this medicine. If this occurs, immediately stop the infusion of the medicine and contact a doctor.
• bleeding that is not controlled by the usual dose of this medicine. If this occurs, speak to your doctor immediately. You may have developed antibodies directed against factor VIII (inhibitors) or antibodies against polyethylene glycol (PEG). These antibodies make Jivi less effective in preventing and controlling bleeding episodes. Your doctor may perform tests to confirm the presence of such antibodies and verify that your dose of Jivi achieves adequate factor VIII levels. If necessary, your doctor may switch back to your previous factor VIII-based treatment. Once the immune response has resolved, your doctor may consider restarting Jivi.
• previously developed inhibitors against factor VIII while using other medicinal products.
• heart problems or are at risk of developing heart disease.
• require the use of a central venous access device for this medicine. You may be at risk of device-related complications at the catheter site, including:
  • local infections
  • presence of bacteria in the blood
  • blood clot formation in the blood vessel

Children
Jivi is not indicated for use in children under 7 years of age.
Other medicines and Jivi
No interactions between Jivi and other medicines are known. Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before using this medicine.
Driving and using machines
Jivi does not impair the ability to drive or operate machinery.
Jivi contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.
Jivi contains polysorbate 80 (E 433)
This medicine contains 0.2 mg of polysorbate 80 per vial of 250/500/1,000/2,000/3,000 IU and 0.4 mg of polysorbate 80 per vial of 4,000 IU, equivalent to 0.08 mg/mL of injectable solution. Polysorbates may cause allergic reactions. Inform your doctor if you or your child has known allergies.

3. How to use Jivi

Treatment with Jivi will be initiated by a doctor experienced in the treatment of patients with haemophilia A. After appropriate training, patients or their caregivers may be able to use Jivi at home.
Always use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist. The number of factor VIII units is expressed in International Units (IU).

Treatment of bleeding
To treat bleeding, your doctor will calculate and adjust the dose and frequency of administration based on factors such as:

• your body weight
• the severity of haemophilia A
• the location and severity of the bleed
• whether you have developed factor VIII inhibitors and their levels
• the required factor VIII levels

Prevention of bleeding
To prevent bleeding, your doctor will determine the appropriate dose and frequency according to your individual needs. Your doctor may adjust the dose and frequency based on achieved factor VIII levels and your individual predisposition to bleeding.

• For adults and adolescents aged 12 years and older:
• 45–60 IU per kg body weight every 5 days, or
• 60 IU per kg body weight every 7 days, or
• 30–40 IU per kg body weight twice weekly.
• For children aged 7 to less than 12 years:
• 40–60 IU per kg body weight twice weekly.
• 60 IU per kg body weight twice weekly as initial dose.

Laboratory tests
Regular laboratory tests help ensure adequate factor VIII levels are maintained. In particular, your coagulation must be closely monitored during major surgical procedures.

Duration of treatment
Treatment with Jivi for haemophilia is usually required for life.

How Jivi is administered
Jivi is administered by intravenous infusion over 2–5 minutes, depending on the total volume and your comfort level. The maximum infusion rate is 2.5 mL per minute. Jivi must be used within 3 hours after reconstitution.

How Jivi is prepared for infusion
Use only the components provided in each package (the vial adapter, the pre-filled syringe containing the solvent, and the intravenous infusion set). If these components cannot be used, consult your doctor. Do not use the medicine if any component of the package is open or damaged.

Before infusion, the reconstituted medicine must be filtered using the vial adapter to remove any particulate matter possibly present in the solution.

This medicine must not be mixed with other injectable products. Do not use solutions containing visible particles or that appear cloudy. Follow the instructions for use provided by your doctor and included in the annex to this patient information leaflet.

If you use more Jivi than you should
If this happens, inform your doctor. Symptoms of overdose have not been reported.

If you forget to use Jivi
Infuse the next dose immediately and continue at regular intervals as advised by your doctor.
Do not use a double dose to make up for the missed dose.

If you stop treatment with Jivi
Do not stop treatment with this medicine without consulting your doctor.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this one can cause side effects, although not everyone experiences them.
The most serious side effects are allergic reactions or severe allergic reaction. If
such reactions occur, stop the Jivi infusion immediately and consult your doctor. The following symptoms may be early signs of such reactions:

• tightness in the chest / general feeling of discomfort
• burning and stinging pain at the site of administration
• hives, flushing
• drop in blood pressure which may make you feel weak when standing
• nausea

In patients who have received prior treatment with factor VIII (more than 150 days of treatment), inhibitor antibodies may uncommonly develop (in less than 1 in 100 patients) (see section 2). If this happens, the medicine may no longer work properly and you may experience persistent bleeding. In this case, contact your doctor immediately.
The following side effects may occur with this medicine:
Very common (may affect more than 1 in 10 people):

• headache

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

• stomach pain
• nausea, vomiting
• fever
• allergic reactions (may present as hives, generalized hives, tightness in the chest, dyspnea, shortness of breath, low blood pressure; for early symptoms see above)
• local reactions at the infusion site such as bruising (bleeding under the skin), intense itching, swelling, burning sensation, temporary redness
• dizziness
• difficulty sleeping
• cough
• skin rash, flushed skin

Uncommon (may affect up to 1 in 100 people):

• inhibition of coagulation factor VIII (FVIII)
• taste disturbances
• flushing
• itching

Reporting of side effects
If you experience any side effect, 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 Jivi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the labels and cartons. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the vial and the pre-filled syringe in the outer carton to protect them from light.
This medicine can be stored at room temperature (up to 25 °C) for a maximum of 6 months, provided it is kept in the outer carton. If the medicine is stored at room temperature, its validity will end after 6 months or on the expiry date, whichever comes first.
The new expiry date must be recorded on the outer carton when the medicine is removed from the refrigerator.
Do not refrigerate the solution after reconstitution. The reconstituted solution must be used within 3 hours.
Do not use this medicine if you see visible particles or if the solution is cloudy.
This medicine is for single use only. Any unused solution must be discarded.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist or doctor how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Jivi contains

• The active substance is recombinant human coagulation factor VIII, PEGylated and B-domain deleted (damoctocog alfa pegol). Each vial of Jivi contains nominally 250, 500, 1,000, 2,000, 3,000 or 4,000 IU of damoctocog alfa pegol. After reconstitution with the provided solvent (water for injections), the resulting solutions have the following concentrations:

• The other ingredients are sucrose, histidine, glycine (E 640), sodium chloride, calcium chloride dihydrate (E 509), polysorbate 80 (E 433), glacial acetic acid (E 260), and water for injections. See section 2 “Jivi contains sodium” and “Jivi contains polysorbate 80 (E 433)”.

Description of the appearance of Jivi and contents of the pack
Jivi is supplied as a powder and solvent for injectable solution. The powder is dry and white to pale yellow in colour. The solvent is a clear liquid. After reconstitution, the solution is clear.
Each single pack of Jivi contains:

• a glass vial with powder
• a pre-filled syringe with solvent
• a separate plunger
• a vial adapter
• an intravenous infusion set.

Jivi is available in the following pack sizes:

• single pack
• multiple pack containing 30 single packs
  Not all pack sizes may be marketed.

Marketing Authorisation Holder
Bayer AG
51368 Leverkusen
Germany
Manufacturer
Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Bayer SA-NV UAB Bayer
Tél/Tel: +32-(0)2-535 63 11 Tel. +37 05 23 36 868
България Luxembourg/Luxemburg
Байер България ЕООД Bayer SA-NV
Tел.: +359-(0)2-424 72 80 Tél/Tel: +32-(0)2-535 63 11
Česká republika Magyarország
Bayer s.r.o. Bayer Hungária KFT
Tel: +420 266 101 111 Tel:+36 14 87-41 00
Danmark Malta
Bayer A/S Alfred Gera and Sons Ltd.
Tlf: +45 45 23 50 00 Tel: +35 621 44 62 05
Deutschland Nederland
Bayer Vital GmbH Bayer B.V.
Tel: +49 (0)214-30 513 48 Tel: +31-23–799 1 000
Eesti Norge
Bayer OÜ Bayer AS
Tel: +372 655 8565 Tlf: +47 23 13 05 00
Ελλάδα Österreich
Bayer Ελλάς ΑΒΕΕ Bayer Austria Ges.m.b.H.
Τηλ: +30-210-61 87 500 Tel: +43-(0)1-711 46-0
España Polska
Bayer Hispania S.L. Bayer Sp. z o.o.
Tel: +34-93-495 65 00 Tel: +48 22 572 35 00
France Portugal
Bayer HealthCare Bayer Portugal, Lda.
Tél (N° vert): +33-(0)800 87 54 54 Tel: +351 21 416 42 00
Hrvatska România
Bayer d.o.o. SC Bayer SRL
Tel: +385-(0)1-6599 900 Tel: +40 21 529 59 00
Ireland Slovenija
Bayer Limited Bayer d. o. o.
Tel: +353 1 216 3300 Tel: +386 (0)1 58 14 400
Ísland Slovenská republika
Icepharma hf. Bayer spol. s r.o.
Sími: +354 540 8000 Tel. +421 2 59 21 31 11
Italia Suomi/Finland
Bayer S.p.A. Bayer Oy
Tel: +39 02 397 8 1 Puh/Tel: +358- 20 785 21
Κύπρος Sverige
NOVAGEM Limited Bayer AB
Tηλ: +357 22 48 38 58 Tel: +46 (0) 8 580 223 00
Latvija
SIA Bayer
Tel: +371 67 84 55 63
More detailed information on this medicinal product is available on the European Medicines Agency website at https://www.ema.europa.eu/

Detailed instructions for reconstitution and administration of Jivi
You will need alcohol swabs, dry swabs, adhesive bandages, and a tourniquet. These materials are not included in the Jivi pack.

1. Wash hands thoroughly with soap and warm water.
2. Hold a vial and a syringe in your hands to warm them until they reach an appropriate temperature (do not exceed 37 °C).
3. Remove the protective cap from the vial (A). Clean the vial rubber stopper with an alcohol swab and allow the stopper to air dry before use.
4. Place the vial containing the powder on a stable, non-slip surface. Remove the paper cap from the plastic carrier of the vial adapter. Do not remove the adapter from the plastic carrier. Hold the adapter carrier, place it over the vial containing the powder, and press firmly downward (B). The adapter will snap onto the vial closure cap. Do not remove the adapter carrier yet.
5. Hold the prefilled syringe with solvent in an upright position. Grasp the plunger as shown in the figure and attach it to the threaded cap by turning firmly clockwise (C).
6. Hold the syringe body and remove, by breaking off, the closure cap from the tip of the syringe (D). Do not touch the syringe tip with hands or any other surface. Set the syringe aside for later use.
7. Now remove and discard the adapter carrier (E).
8. Connect the prefilled syringe to the threaded vial adapter by turning it clockwise (F).
9. Inject the solvent by gently pushing the plunger down (G).
10. Gently rotate the vial until all the powder is dissolved (H). Do not shake the vial. Ensure that the powder is completely dissolved. Check for the presence of particles or any change in color before using the solution. Do not use solutions containing visible particles or that appear cloudy.
11. Hold the vial at the end above the vial adapter and the syringe (I). Fill the syringe by slowly and smoothly pulling back the plunger. Make sure the entire contents of the vial have been completely drawn into the syringe. Keep the syringe in an upright position and push the plunger until all air is expelled from the syringe.
12. Apply a tourniquet to the arm.
13. Identify the infusion site and clean the skin.
14. Insert the needle into the vein and secure the intravenous infusion set with adhesive tape.
15. While holding the vial adapter steady, remove the syringe from the vial adapter (which should remain attached to the vial). Connect the syringe to the intravenous infusion set (J). Ensure that no blood enters the syringe.
16. Remove the tourniquet.
17. Infuse the solution intravenously over 2–5 minutes, monitoring the needle position. The infusion rate should be based on patient comfort but must not exceed 2.5 mL per minute.
18. If an additional dose is required, use a new syringe with reconstituted powder as described above.
19. If no additional dose is required, remove the intravenous infusion set and the syringe. Press a dry swab firmly on the infusion site for about 2 minutes, keeping the arm extended. Then apply a small compressive dressing to the infusion site and, if necessary, adhesive tape.
20. It is recommended to record the name and batch number of the medicine each time Jivi is used.
21. Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist or doctor how to properly dispose of medicines no longer in use. This will help protect the environment.