HEPCLUDEX 2 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Hepcludex 2 mg powder for solution for injection

bulevirtide

This medicinal product is subject to additional monitoring, which will allow for the quick identification of new safety information. You can help by reporting any side effects you may get. The last section of the leaflet contains information on how to report side effects.

Read all of this leaflet carefully before you start using 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 or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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 to treat long-term (chronic) infection with the hepatitis delta virus (HDV) in adults with compensated liver disease (when the liver is still working properly). Hepatitis delta virus infection causes liver inflammation.

How Hepcludex works

HDV uses a specific protein from liver cells to enter these cells. Bulevirtide, the active substance in this medicine, blocks the protein and thus prevents HDV from entering liver cells. This reduces the spread of HDV in the liver and reduces inflammation.

2. What you need to know before you use Hepcludex

Do not use Hepcludex:

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

If you are unsure, consult your doctor before taking this medicine.

Warnings and precautions

Do not stop treatment with Hepcludex unless your doctor advises you to do so. Stopping treatment may reactivate the infection and worsen your disease.

Consult your doctor or pharmacist before starting treatment with Hepcludex:

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

1. if you have had kidney disease or if blood tests show kidney problems. Before and during treatment, your doctor may ask for blood tests to check that your kidneys are working properly;

1. if you have HIV or hepatitis C infection - it is not known how Hepcludex works in these circumstances; your doctor may ask for blood tests to check the status of your HIV or hepatitis C infection.

Children and adolescents

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

Other medicines and Hepcludex

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

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

1. ciclosporin, a medicine that suppresses the immune system;
2. ezetimibe, used to treat high blood cholesterol levels;
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 have some tests or your doctor may need to change the dose or monitor you regularly:

1. cancer treatments (e.g. dasatinib, docetaxel, ibrutinib or paclitaxel);
2. antihistamines used for allergies (e.g. ebastine or fexofenadine);
3. medicines for the immune system (e.g. everolimus, sirolimus or tacrolimus);
4. medicines for the treatment of hepatitis C and HIV (e.g. darunavir, glecaprevir, grazoprevir, indinavir, maraviroc, paritaprevir, saquinavir, simeprevir, tipranavir or voxilaprevir);
5. medicines for diabetes (e.g. glibenclamide, nateglinide or repaglinide);
6. medicines for erectile dysfunction (e.g. avanafil, sildenafil or vardenafil);
7. medicines for the treatment of high blood pressure and heart disease (e.g. olmesartan, telmisartan or valsartan);
8. statins, medicines used for high blood cholesterol levels (e.g. atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin or simvastatin);
9. thyroid hormones used to treat thyroid problems;
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 hyponatraemia (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 hypertension;
19. estra-3-sulfate, a hormonal medicine for menopause;
20. felodipine and nisoldipine (heart medicines);
21. lomitapide, used for high blood cholesterol levels;
22. lurasidone and quetiapine, antipsychotic medicines for psychiatric disorders;
23. midazolam and triazolam, medicines for insomnia (inability to sleep) and for anaesthesia (to prevent pain during surgery);
24. naloxegol, used to treat opioid dependence for severe pain;
25. ticagrelor, an anticoagulant to prevent blood clotting.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine. You should not use this medicine unless your doctor specifically advises you to do so.

If you are a woman of childbearing potential, you should not use this medicine without using an effective method of contraception.

Talk to your doctor to decide whether you can breast-feed during treatment with Hepcludex. It is not known whether Hepcludex is excreted in breast milk. Therefore, a decision must be made whether to discontinue breast-feeding or to discontinue Hepcludex treatment.

Driving and using machines

Dizziness and fatigue are side effects that may affect your ability to drive and use machines. If you are unsure, consult your doctor.

Hepcludex contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per ml, which is essentially ‘sodium-free’.

3. How to use Hepcludex

Follow the instructions for administration of this medicine exactly as advised by your doctor. If you are unsure, consult your doctor again.

Dosage

The recommended dose is 2 mg once daily by subcutaneous injection (just under the skin). Your doctor will tell you how long you should use the medicine.

Your doctor and nurse will teach you how to prepare and inject Hepcludex. This leaflet contains a step-by-step injection guide to help you inject the medicine (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 been less than 4 hours since you missed a 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 been more than 4 hours since you missed a dose of Hepcludex, do not inject the missed dose. You should administer the next dose the following day at the usual time. Do not inject a double dose to make up for a missed dose. Inform your doctor if you have missed a dose of Hepcludex.

If you stop treatment with Hepcludex

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

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

4. Possible side effects

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

If you experience any side effect or if you notice any side effect not mentioned in this leaflet, consult your doctor.

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

• headache.

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

• dizziness
• nausea
• fatigue
• flu-like illness
• itching
• joint pain
• injection site reactions which may include swelling, redness, irritation, bruising, itching, rash, induration, infection or pain at the injection site.

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

• allergic reactions, including anaphylactic reaction (a life-threatening allergic reaction).

Symptoms of allergic reactions may include:

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

Symptoms of an anaphylactic reaction are the same as those of an allergic reaction, but are more severe and require immediate medical attention.

Blood tests may also show:

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

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. 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. Storage of 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 to 8°C). To protect from light, keep the vials in the outer carton.

The reconstituted solution should 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.

Medicines or needles should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines or needles no longer required.

6. Container Contents and Additional Information

Hepcludex Composition

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

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

Product Appearance and Container Contents

Bulevirtida is a powder for solution for injection and is presented as a white or off-white powder.

Each box contains 30 individual doses.

Marketing Authorization Holder

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

Manufacturer

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 medication by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet: <{MM/AAAA}> <{mes AAAA}>.

This medicinal product has been authorized with a "conditional approval". This approval mechanism means that more information on this medicinal product is expected.

The European Medicines Agency will review the new information on this medicinal product at least once a year, and this leaflet will be updated as necessary.

1. Step-by-Step Injection Guide

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

Before starting treatment with this medication at home, your doctor or nurse will teach you how to prepare and inject Hepcludex. This guide indicates how you should inject the medication yourself. Consult your doctor or nurse if there is anything you do not understand, if you have any questions, or if you need more information or help. Take the time to prepare and inject Hepcludex carefully.