Prospect: Patient Information

Hepcludex 2 mg Powder for Injectable Solution

bulevirtida

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You may contribute by reporting any adverse effects you experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, as it contains important information for you.

• Keep this prospect, as you may need to refer to it again.
• If you have any questions, consult your doctor or nurse.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

What is Hepcludex

Hepcludex contains the active ingredient bulevirtida, which is an antiviral medication.

What is Hepcludex used for

Hepcludex is used to treat long-term (chronic) infection by the hepatitis delta virus (HDV) in adults with compensated liver disease (when the liver still functions properly). Infection with the hepatitis delta virus causes liver inflammation.

How Hepcludex works

The HDV uses a specific protein from liver cells to enter these cells. Bulevirtida, the active ingredient in this medication, blocks the protein and thereby prevents the HDV from entering liver cells. This reduces the spread of HDV in the liver and reduces inflammation.

Do not take Hepcludex:

1. if you are allergic to bulevirtida or any of the other components of this medication (listed in section 6).

Consult your doctor if you have any doubts before taking this medication.

Warnings and precautions

Do not interrupt treatment with Hepcludex unless your doctor recommends it. Interrupting treatment may reactivate the infection and worsen your condition.

Consult your doctor or pharmacist before starting to use Hepcludex:

1. if your liver does not function properly – it is not known how Hepcludex acts in these circumstances; if your liver does not function well, it is not recommended to use Hepcludex.

1. if you have had kidney disease or if blood tests indicate kidney problems. Before and during treatment, your doctor may request blood tests to check the proper functioning of the kidneys;

1. if you have an HIV or hepatitis C infection - it is not known how Hepcludex acts in these circumstances; your doctor may request blood tests to check the state of the HIV or hepatitis C infection.

Children and adolescents

Children and adolescents under 18 years of age should not be treated with Hepcludex.

Other medications and Hepcludex

Inform your doctor if you are using, have used recently, or may have to use any other medication.

Some medications may increase the adverse effects of Hepcludex and should not be taken at the same time. This is why you should inform your doctor if you are taking any of these medications:

1. ciclosporina, a medication that inhibits the immune system;
2. ezetimiba, used to treat high levels of cholesterol in the blood;
3. irbesartán, used to treat high blood pressure and heart disease;
4. ritonavir, used to treat HIV infection;
5. sulfasalazina, used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease.

Some medications may increase or decrease the effects of Hepcludex when taken together. In some cases, you may need to undergo some tests or your doctor may need to modify the dose or perform regular check-ups:

1. cancer treatments (e.g., dasatinib, docetaxel, ibrutinib, or paclitaxel);
2. antihistamines used for allergies (e.g., ebastina or fexofenadina);
3. immunosuppressive medications (e.g., everolimús, sirolimús, or tacrolimús);
4. medications for hepatitis C and HIV treatment (e.g., darunavir, glecaprevir, grazoprevir, indinavir, maraviroc, paritaprevir, saquinavir, simeprevir, tipranavir, or voxilaprevir);
5. diabetes medications (e.g., glibenclamida, nateglinida, or repaglinida);
6. erectile dysfunction medications (e.g., avanafilo, sildenafilo, or vardenafilo);
7. medications for high blood pressure and heart disease (e.g., olmesartán, telmisartán, or valsartán);
8. statins, medications used for high cholesterol in the blood (e.g., atorvastatina, fluvastatina, lovastatina, pitavastatina, pravastatina, rosuvastatina, or simvastatina);
9. thyroid hormones used to treat thyroid problems;
10. alfentanilo, an opioid medication used to treat intense pain;
11. bosentán, used to treat pulmonary hypertension;
12. buspirona, an anxiolytic medication;
13. budesonida, used for asthma and chronic obstructive pulmonary disease;
14. conivaptán and tolvaptán, used to treat hyponatremia (low sodium levels);
15. darifenacina, used to treat urinary incontinence;
16. dronedarona, a medication for cardiac arrhythmias;
17. eletriptán, used for migraines;
18. eplerenona, used to treat high blood pressure;
19. estrona 3-sulfato, a hormonal medication for menopause;
20. felodipino and nisoldipino (heart medications);
21. lomitapida, used to treat high cholesterol in the blood;
22. lurasidona and quetiapina, antipsychotic medications for psychiatric disorders;
23. midazolam and triazolam, medications for insomnia and anesthesia;
24. naloxegol, used to treat opioid dependence for intense pain;
25. ticagrelor, an anticoagulant to prevent blood coagulation.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medication. Do not use this medication unless your doctor specifically recommends it.

If you are a fertile woman, do not use this medication without using an effective contraceptive method.

Discuss with your doctor whether you can breastfeed during treatment with Hepcludex. It is unknown whether Hepcludex is excreted in breast milk. Therefore, you should decide to stop breastfeeding or stop treatment with Hepcludex.

Driving and operating machinery

Dizziness and fatigue are adverse effects that may affect your ability to drive and operate machinery. If you have any doubts, consult your doctor.

Hepcludex contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per ml; it is essentially "sodium-free".

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

Dosage

The recommended dose is 2 mg once a day by subcutaneous injection (just below the skin). Your doctor will tell you how long you should use the medication.

Your doctor and nurse will teach you how to prepare and inject Hepcludex. This leaflet contains a step-by-step guide for injection to help you inject the medication (see section 7).

If you use more Hepcludex than you should

The usual dose is 2 mg (1 vial) per day. If you think you may have received more than you should, tell your doctor immediately.

If you forget to use Hepcludex

If it has beenless than 4 hourssince you forgot the dose of Hepcludex, you should inject the missed dose as soon as possible and administer the next scheduled dose at the usual time.

If it has beenmore than 4 hourssince you forgot the dose of Hepcludex, do not administer the missed dose. You should administer the next dose the following day at the usual time. Do not administer a double dose to compensate for the missed doses. Inform your doctor if you have forgotten a dose of Hepcludex.

If you interrupt treatment with Hepcludex

If you no longer want to continue using Hepcludex, consult your doctor before stopping treatment. Stopping treatment may reactivate the infection and worsen your condition. Inform your doctor immediately about any changes in symptoms after stopping treatment.

If you have any other questions about using Hepcludex, ask your doctor or nurse.

Like all medications, this medication may produce adverse effects, although not all people will experience them.

If you experience any adverse effect or if you observe any not mentioned in this prospectus, consult your doctor.

The following adverse effect isvery frequent(may affect more than 1 in 10 people):

• headache.

The following adverse effects arecommon(may affect up to 1 in 10 people):

• dizziness.
• nausea.
• fatigue.
• influenza-like illness.
• itching.
• joint pain.
• reactions at the injection site that may include swelling, redness, irritation, hematomas, itching, skin rash, induration, infection, or local pain.

The following adverse effects areinfrequent(may affect up to 1 in 100 people):

• allergic reactions, including anaphylactic reaction (potentially fatal sudden allergic reaction).

The symptoms of allergic reactions may include:

• shortness of breath or wheezing.
• swelling of face, lips, tongue, or throat (angioedema).
• skin rashes.
• changes in blood pressure or heart rate.

The symptoms of anaphylactic reaction are the same as those of an allergic reaction, but are more intense and require immediate medical assistance.

Blood tests may also indicate:

• an increase in bile acids in the blood (very frequent).
• an increase in white blood cells (eosinophils) (common).

Reporting Adverse Effects

If you experience adverse effects, consult your doctor or nurse, even if they are possible adverse effects not listed in this prospectus. You can also report them directly through thenational reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medication after the expiration date that appears on the box and vial after "CAD". The expiration date is the last day of the month indicated.

Store in the refrigerator (between 2 °C and 8 °C). To protect them from light, keep the vials in the outer packaging.

The reconstituted solution must be used immediately. However, if this is not possible, it can be stored for a maximum of 2 hours at a temperature of up to 25 °C.

Used medications or needles should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of used containers and needles.

Composition of Hepcludex

The active ingredient is bulevirtida 2 mg. Each vial contains bulevirtida acetate equivalent to 2 mg of bulevirtida.

The other components are anhydrous sodium carbonate, sodium hydrogenocarbonate, mannitol, hydrochloric acid, and sodium hydroxide.

Appearance of the product and contents of the package

Bulevirtida is a powder for injectable solution and is presented in the form of a white or off-white powder.

Each box contains 30 individual doses.

Holder of the marketing authorization

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

Responsible for manufacturing

LYOCONTRACT GmbH

Pulverwiese 1

38871 Ilsenburg

Germany

or

Gilead Sciences Ireland UC

IDA Business and Technology Park

Carrigtohill

Co. Cork

Ireland

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the last review of this leaflet: <{MM/AAAA}>.

This medicine has been authorized under a conditional approval. This type of approval means that more information is expected to be obtained about this medicine.

The European Medicines Agency will review the new information about this medicine at least once a year and this leaflet will be updated as necessary.

7. Step-by-step guide for injection

Before using Hepcludex, you should read the sections 1-6 of this leaflet first.

Before starting treatment with this medicine at home, your doctor or nurse will teach you how to prepare and inject Hepcludex. In this guide, it is indicated how you should inject the medicine yourself. Consult your doctor or nurse if anything is unclear, if you have any questions or if you need more information or help. Take the time necessary to prepare and inject Hepcludex carefully.