Hepcludex

Package leaflet: Information for the patient

Hepcludex 2 mg powder for injectable solution

bulevirtide
This medicinal product is subject to additional monitoring. This will allow 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 all of this leaflet carefully before you start using this medicine, as 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 nurse.
• 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 dangerous.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

1. What Hepcludex is and what it is used for
2. What you need to know before using Hepcludex
3. How to use Hepcludex
4. Possible side effects
5. How to store Hepcludex
6. Contents of the pack and other information
7. Step-by-step injection guide

If Hepcludex has been prescribed for your child, please note that all the information in this leaflet applies to your child (in this case, read “your child” instead of “you”).

1. What Hepcludex is and what it is used for

What Hepcludex is
Hepcludex contains the active substance bulevirtide, which is an antiviral medicine.
What Hepcludex is used for
Hepcludex is used for the long-term treatment of hepatitis delta virus (HDV) infection in adults and children aged 3 years and older who weigh at least 10 kg and have compensated liver disease (where the liver still functions well enough).
Hepatitis delta virus infection causes inflammation of the liver.
How Hepcludex works
HDV uses a specific protein on liver cells to enter them.
Bulevirtide, the active substance in this medicine, blocks this protein and thereby prevents HDV from entering liver cells. This action reduces the spread of HDV in the liver and reduces inflammation.

2. What you need to know before using Hepcludex

Do not use Hepcludex:

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

If in doubt, consult your doctor before using this medicine.
Warnings and precautions
Do not stop treatment with Hepcludex unless advised by your doctor.
Stopping treatment may reactivate the infection and worsen the disease.
Talk to your doctor or pharmacist before using Hepcludex:

1. if you have impaired liver function, as it is not known how effective Hepcludex is under such circumstances; use of Hepcludex is not recommended in case of inadequate liver function;
2. if you have had kidney disease or if blood tests have shown kidney problems. Before and during treatment, your doctor may prescribe blood tests to monitor kidney function;
3. if you have HIV or hepatitis C infection, as it is not known how effective Hepcludex is in these circumstances; your doctor may prescribe blood tests to monitor the status of HIV or hepatitis C infection.

Children and adolescents
Children under 3 years of age or weighing less than 10 kg must not be treated with
Hepcludex.
Other medicines and Hepcludex
Inform your doctor if you are taking, have recently taken, or might take any other
medicines.
Some medicines may increase the side effects of Hepcludex and must not be used
at the same time. For this reason, you must inform your doctor if you are taking any of the following
medicines:

1. cyclosporine, a medicine that inhibits the immune system;
2. ezetimibe, used to treat high cholesterol in the blood;
3. irbesartan, used to treat high blood pressure and heart disease;
4. ritonavir, used to treat HIV infection;
5. sulfasalazine, used to treat rheumatoid arthritis, ulcerative colitis, and Crohn’s disease.

Some medicines may increase or decrease the effects of Hepcludex when taken together. In some
cases, you may need to undergo certain tests, or your doctor may adjust your dose or perform regular monitoring:

1. anticancer treatments (e.g., dasatinib, docetaxel, ibrutinib, paclitaxel);
2. antihistamine medicines used for allergies (e.g., ebastine, fexofenadine);
3. medicines for the immune system (e.g., everolimus, sirolimus, tacrolimus);
4. medicines for the treatment of hepatitis C and HIV (e.g., darunavir, glecaprevir, grazoprevir, indinavir, maraviroc, paritaprevir, saquinavir, simeprevir, tipranavir, voxilaprevir);
5. medicines for diabetes (e.g., glibenclamide, nateglinide, repaglinide);
6. medicines for erectile dysfunction (e.g., avanafil, sildenafil, vardenafil);
7. medicines for high blood pressure and heart disease (e.g., olmesartan, telmisartan, valsartan);
8. statins, medicines used for high cholesterol in the blood (e.g., atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin);
9. thyroid hormones used to treat thyroid disorders;
10. alfentanil, an opioid medicine used to treat severe pain;
11. bosentan, used for pulmonary arterial hypertension;
12. buspirone, a medicine for anxiety;
13. budesonide, used for asthma and chronic obstructive pulmonary disease;
14. conivaptan and tolvaptan, used to treat hyponatremia (low sodium levels);
15. darifenacin, used to treat urinary incontinence;
16. dronedarone, a medicine for cardiac arrhythmias;
17. eletriptan, used for migraine headaches;
18. eplerenone, used for high blood pressure;
19. estrone-3-sulfate, a hormonal medicine for menopause;
20. felodipine and nisoldipine (medicines for the heart);
21. lomitapide, used for high cholesterol in the blood;
22. lurasidone and quetiapine, antipsychotic medicines for psychiatric disorders;
23. midazolam and triazolam, medicines used to treat insomnia (inability to sleep) and for anesthesia (to prevent pain during surgical procedures);
24. naloxegol, used to treat opioid dependence for severe pain;
25. ticagrelor, an anticoagulant to prevent blood clotting.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding,
ask your doctor for advice before using this medicine. You must not use this
medicine unless specifically indicated by your doctor.
If you are a woman of childbearing potential, do not take this medicine without using effective contraceptive measures.
Talk to your doctor to decide whether to breastfeed during treatment with Hepcludex.
It is not known whether Hepcludex passes into breast milk. Therefore, a decision must be made whether to discontinue breastfeeding or discontinue treatment with Hepcludex.
Driving and using machines
Dizziness and fatigue are side effects that may impair the ability to drive or use machines. If in doubt, consult your doctor.
Hepcludex contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per mL, i.e., it is essentially “sodium-free”.

3. How to use Hepcludex

Use this medicine exactly as your doctor has instructed you. If you have any doubts, consult your
doctor.
Posology
Hepcludex must be administered once daily as an injection just under the skin (subcutaneous injection).
Your doctor and nurse will show you how to prepare and inject Hepcludex. This patient information leaflet contains a step-by-step injection guide to assist you in administering the medicine (see section 7).
Recommended dose
The recommended dose of Hepcludex in adults is 2 mg once daily.
The recommended dose of Hepcludex in patients aged 3 to less than 18 years depends on body weight, as indicated in the table below.

Age/body weight	Dose	Volume to be injected
Children aged 3 years and older weighing at least 35 kg	2 mg, once daily	1.0 mL
Children aged 3 years and older weighing at least 25 kg but less than 35 kg	1.5 mg, once daily	0.75 mL
Children aged 3 years and older weighing at least 10 kg but less than 25 kg	1 mg, once daily	0.5 mL

Your doctor will inform you how long you should use this medicine.
If you take more Hepcludex than you should
If you think you have taken more Hepcludex than you should, contact your doctor immediately.
If you forget to take Hepcludex
If less than 4 hours have passed since the time you were supposed to take Hepcludex, take the missed dose as soon as possible and then take the next scheduled dose at the usual time.
If more than 4 hours have passed since the time you were supposed to take Hepcludex, do not take the missed dose. Take the next dose the following day at the usual time. Do not take a double dose to make up for the missed dose. Inform your doctor if you have forgotten to take a dose of Hepcludex.
If you stop taking Hepcludex
If you no longer wish to take Hepcludex, consult your doctor before stopping treatment. Stopping treatment may reactivate the infection and worsen the disease. Inform your doctor immediately of any changes in symptoms after stopping treatment.
If you have any doubts about how to use Hepcludex, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Inform your doctor if you experience any side effects or if you notice side effects not listed in
this leaflet.

The following side effect is very common (may affect more than 1 in 10 people):

• headache
• itching
• reactions at the injection site which may include swelling, redness, irritation, bruising, itching sensation, rash, hardening, infection or local pain

The following side effects are common (may affect up to 1 in 10 people):

• dizziness
• nausea
• fatigue
• flu-like illness
• joint pain

The following side effects are uncommon (may affect up to 1 in 100 people):

• allergic reactions, including anaphylactic reaction (a sudden allergic reaction that may be life-threatening). Symptoms of allergic reactions may include:
  • shortness of breath or wheezing
  • swelling of the face, lips, tongue or throat (angioedema)
  • skin rashes
  • changes in blood pressure or heart rate. Symptoms of an anaphylactic reaction are similar to those of an allergic reaction, but are much more severe and require immediate medical attention.

Blood tests may also show:

• increased levels of bile acids in the blood (very common);
• increased white blood cells (eosinophils) (common).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse.
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 Hepcludex

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 after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C). To protect the medicine from light, keep the vials in the outer packaging.
The reconstituted solution should be used immediately. However, if this is not possible, it may be stored for a maximum of 2 hours at a temperature up to 25 °C.
Do not dispose of any medicine or used needle via wastewater or household waste. Ask your pharmacist how to safely dispose of used medicines and needles.

6. Package contents and other information

What Hepcludex contains
The active substance is bulevirtide 2 mg. Each vial contains bulevirtide acetate equivalent to 2 mg
of bulevirtide.
The other components are: anhydrous sodium carbonate, sodium hydrogen carbonate, mannitol,
hydrochloric acid, sodium hydroxide.

Description of the appearance of Hepcludex and package contents
Bulevirtide is a powder for solution for injection and is available as a white to off-white powder.
Each box contains 30 single doses.

Marketing Authorization Holder
Gilead Sciences Ireland UC
Carrigtohill
County Cork, T45 DP77
Ireland

Manufacturer
Gilead Sciences Ireland UC
IDA Business and Technology Park
Carrigtohill
Co. Cork
Ireland

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien
Gilead Sciences Belgium SRL-BV
Tél/Tel: + 32 (0) 24 01 35 50

България (Bulgaria)
Gilead Sciences Ireland UC
Тел.: + 353 (0) 1 686 1888

Česká republika (Czech Republic)
Gilead Sciences s.r.o.
Tel: + 420 (0) 910 871 986

Danmark (Denmark)
Gilead Sciences Sweden AB
Tlf: + 46 (0) 8 5057 1849

Deutschland (Germany)
Gilead Sciences GmbH
Tel: + 49 (0) 89 899890-0

Eesti (Estonia)
Gilead Sciences Ireland UC
Tel.: +353 (0) 1 686 1888

Ελλάδα (Greece)
Gilead Sciences Ελλάς Μ.ΕΠΕ.
Τηλ: + 30 (0) 210 8930 100

España (Spain)
Gilead Sciences, S.L.
Tel: + 34 (0) 91 378 98 30

France
Gilead Sciences
Tél: + 33 (0) 1 46 09 41 00

Hrvatska (Croatia)
Gilead Sciences Ireland UC
Tel: + 353 (0) 1 686 1888

Ireland
Gilead Sciences Ireland UC
Tel: + 353 (0) 214 825 999

Ísland (Iceland)
Gilead Sciences Sweden AB
Sími: + 46 (0) 8 5057 1849

Italia (Italy)
Gilead Sciences S.r.l.
Tel: + 39 02 439201

Κύπρος (Cyprus)
Gilead Sciences Ελλάς Μ.ΕΠΕ.
Τηλ: + 30 (0) 210 8930 100

Latvija (Latvia)
Gilead Sciences Ireland UC
Tel.: + 353 (0) 1 686 1888

Lietuva (Lithuania)
Gilead Sciences Ireland UC
Tel.: + 353 (0) 1 686 1888

Luxembourg/Luxemburg
Gilead Sciences Belgium SRL-BV
Tél/Tel: + 32 (0) 24 01 35 50

Magyarország (Hungary)
Gilead Sciences Ireland UC
Tel.: + 353 (0) 1 686 1888

Malta
Gilead Sciences Ireland UC
Tel: + 353 (0) 1 686 1888

Nederland (Netherlands)
Gilead Sciences Netherlands B.V.
Tel: + 31 (0) 20 718 36 98

Norge (Norway)
Gilead Sciences Sweden AB
Tlf: + 46 (0) 8 5057 1849

Österreich (Austria)
Gilead Sciences GesmbH
Tel: + 43 (0) 1 260 830

Polska (Poland)
Gilead Sciences Poland Sp. z o.o.
Tel.: + 48 (0) 22 262 8702

Portugal
Gilead Sciences, Lda.
Tel: + 351 (0) 21 7928790

România (Romania)
Gilead Sciences (GSR) S.R.L.
Tel: +40 31 631 18 00

Slovenija (Slovenia)
Gilead Sciences Ireland UC
Tel: + 353 (0) 1 686 1888

Slovenská republika (Slovakia)
Gilead Sciences Slovakia s.r.o.
Tel: + 421 (0) 232 121 210

Suomi/Finland (Finland)
Gilead Sciences Sweden AB
Puh/Tel: + 46 (0) 8 5057 1849

Sverige (Sweden)
Gilead Sciences Sweden AB
Tel: + 46 (0) 8 5057 1849

United Kingdom (Northern Ireland)
Gilead Sciences Ireland UC
Tel: + 44 (0) 8000 113 700

7. Step-by-step injection guide for patients/caregivers

Before using Hepcludex, you must first read sections 1–6 of this leaflet.
Before starting treatment with this medicine at home, your doctor or nurse will show you
how to prepare and inject Hepcludex. This guide explains how to prepare and inject Hepcludex.
Contact your doctor or nurse if you have any doubts or questions, or if you need further information or
support. Take your time to carefully prepare and inject Hepcludex.
If Hepcludex has been prescribed for your child, but the child is unable to self-administer,
all the information in this step-by-step injection guide for the administration of Hepcludex
is intended for you, as the caregiver (the person caring for the child).
Children and adolescents should only self-inject the medicine after proper training by a healthcare
professional and under the supervision of an adult caregiver.
Injection sites Abdomen Upper thighs

The most suitable injection sites are the abdomen and the upper part of the thighs, as shown in the images. To reduce injection site reactions, you may periodically change the injection site of Hepcludex. Do not inject Hepcludex into the following areas: knee, groin, lower or inner buttocks, directly over a blood vessel, around the navel, scar tissue, bruised skin, mole, surgical scar, t titiiiddi

tattoo, burn, or at the site of an injection reaction.

1. Before injection

1A 1B 1C 1D
Storage Prepare the doses Wash hands Clean the vial
Hepcludex vials must The following instructions Wash hands thoroughly Clean the vial stopper
be stored in their are for reconstituting a with warm water and with a clean alcohol-
original packaging single dose. soap, and dry them soaked swab and let
in the refrigerator thoroughly. it air-dry.
(2–8 °C) to protect After hands are clean,
Hepcludex from light. touch only the Do not touch the rubber
medication, supplies, stopper after cleaning
and the area around it; if touched, clean it
the injection site. again with a new
alcohol-soaked swab.

2. Prepare the solution

2A 2B 2C
Draw up sterile water Inject sterile water Mix
into the Hepcludex powder gently
Take the syringe. Insert the longer needle. Tap Tap gently on the
gently on the Hepcludex vial to loosen the Hepcludex vial with
Important! Ensure that the needle with cap is powder. your fingertip for
securely inserted by gently pushing it downward 10 seconds to start
while rotating clockwise. Remove the plastic cap. dissolving the powder.
Insert the needle at an angle
Open the vial of sterile water for injectable into the vial of sterile water,
preparations. Insert the needle into the vial and then invert the vial of sterile
and gently turn the vial of sterile water upside water. Ensure that the tip of
down. Make sure the tip of the needle remains the needle remains below the
below the water surface to prevent air bubbles surface of the water to avoid
from entering the syringe. drawing air into the syringe.

Slowly pull back the plunger until the syringe Inject the sterile water slowly along the vial’s inner wall to avoid splashing and to allow the powder to dissolve gradually.

Carefully remove the needle and syringe from the vial. Remove the needle from the vial and place the syringe and needle in a safe place.

Important! Do not shake the vial. Shaking may cause foaming, which prolongs the dissolution time.

2D 2E 2F
Check Hepcludex ready for injection Clean the vial
Hepcludex
Once the powder begins to dissolve, it is sufficient to let it rest to complete the process.

Important! When fully dissolved, Hepcludex solution must be clear and free of foam.

If the solution appears foamy or yellowish, wait longer for complete dissolution. In case of small air bubbles, gently tap the vial until they disappear.

It may take up to 3 minutes for complete dissolution.

If particles remain in the solution after complete dissolution, do not use the vial. Contact the doctor or pharmacist who provided it.

Reconstituted Hepcludex must be used immediately.

Clean the Hepcludex vial stopper again using a new alcohol-impregnated swab. Allow to air dry.

3. Injecting a dose

3A 3B 3C 3D
Insert the needle into Draw up Hepcludex Finalize the Replace and
the vial preparation discard the needle
Take the syringe. Invert Tap or gently shake the Remove the longer
the vial of Hepcludex. syringe gently and pull needle carefully from
the plunger to remove the syringe and
Insert the needle into the air bubbles and excess dispose of it properly
vial. Make sure the air from the syringe. so that no one can be
needle tip remains
injured.
below the surface of
the Hepcludex solution
to prevent air from
entering the syringe.
Important! Do not
re-cap the plastic needle
Check again the dose cap after removal.
to be injected by
referring to the table
titled “Recommended
dose” in section 3 of
the package leaflet.
Carefully remove the
needle and syringe
from the vial.

Important! Dispose
of the vial after use,
including any unused
liquid.

Pull the plunger slowly
to draw up the required
amount of liquid.

3E 3F 3G 3H
Attach the injection Choose the injection Prepare the injection Inject Hepcludex
needle site site
Attach the shorter needle Select an injection site Clean the injection site Pinch and hold a fold
to the syringe. different from the one by wiping with an of skin around the
used for the previous alcohol swab. Start injection site. Insert the
Important! Ensure the from the centre and move needle at a 45-degree
needle with cap is firmly outward in a circular angle. The needle
inserted by slightly motion. should be inserted for
pushing it down while most of its length.
rotating clockwise.
Let the injection site
Remove the plastic cap. dry in the air.
Remove the needle from
the syringe and dispose
of both properly so that
no one can be injured
(see 3D).

Push the plunger slowly
and completely to inject
Hepcludex.

Remove the needle from
the skin.