Hepcludex 2 mg powder for injection solution

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Hepcludex 2 mg powder for injectable solution

bulevirtide

This medicinal product is subject to additional monitoring, which will enable rapid identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as 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 and must not be given to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are side effects not listed in this leaflet. 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

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) hepatitis delta virus (HDV) infection in adults with compensated liver disease (when the liver is still functioning adequately). Hepatitis delta virus infection causes inflammation of the liver.

How Hepcludex works

HDV uses a specific protein on liver cells to enter these cells. Bulevirtide, the active substance in this medicine, blocks this protein and thereby 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 using Hepcludex

Do not take Hepcludex:

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

If you have any doubts, 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 condition.

Consult your doctor or pharmacist before starting Hepcludex:

1. if your liver is not functioning properly – it is not known how Hepcludex works under these circumstances; Hepcludex is not recommended if your liver function is impaired.

2. if you have had kidney disease or if blood tests indicate kidney problems. Before and during treatment, your doctor may request blood tests to monitor proper kidney function.

3. if you have HIV or hepatitis C infection – it is not known how Hepcludex works in these circumstances; your doctor may request blood tests to monitor the status of HIV or hepatitis C infection.

Children and adolescents

Hepcludex should not be used in children and adolescents under 18 years of age.

Other medicines and Hepcludex

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Some medicines may increase the adverse effects of Hepcludex and should not be taken 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 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, tests may be required or your doctor may need to adjust your dose or carry out periodic monitoring:

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 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 hyponatremia (low sodium levels);
15. darifenacin, used to treat urinary incontinence;
16. dronedarone, a medicine for cardiac arrhythmias;
17. eletriptan, used for migraine-type headaches;
18. eplerenone, used for high blood pressure;
19. estrone 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 used to treat insomnia (difficulty sleeping) and for anesthesia (to prevent pain during surgery);
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 or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. You should not use this medicine unless specifically instructed by your doctor.

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

Talk to your doctor to decide whether you can breastfeed during treatment with Hepcludex. It is unknown whether Hepcludex is excreted in breast milk. Therefore, a decision must be made to either discontinue breastfeeding or discontinue treatment with Hepcludex.

Driving and use of machines

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

3. How to use Hepcludex

Follow exactly the instructions for administration of this medicine given by your doctor. If in doubt, 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 for 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 self-administer 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 less than 4 hours have passed since you missed your dose of Hepcludex, the missed dose should be injected as soon as possible, and the next scheduled dose should be taken at the usual time.

If more than 4 hours have passed since you missed your dose of Hepcludex, the missed dose should not be administered. The next dose should be given the following day at the usual time. Do not administer a double dose to make up for missed doses. Inform your doctor if you have missed a dose of Hepcludex.

If you stop using 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 condition. Inform your doctor immediately of any changes in symptoms after stopping treatment.

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

4. Possible side effects

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

If you experience any side effect or notice any 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, skin rash, induration, infection or local pain.

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

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

Symptoms of allergic reactions may include:

• difficulty breathing 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 the same as those of an allergic reaction, but are more intense 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 experience side effects, consult your doctor or nurse, even if they are possible side effects not listed in this leaflet. You may also report them directly through the national reporting system included 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 stated on the carton and vial after "EXP". The expiry date refers to the last day of the stated month.

Store in a refrigerator (between 2 °C and 8 °C). To protect 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 up to 2 hours at a temperature not exceeding 25 °C.

Do not dispose of medicines or used needles via wastewater or household waste. Ask your pharmacist how to dispose of used containers and needles properly.

6. Contents of the pack and other information

Composition of Hepcludex

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, and sodium hydroxide.

Appearance of the medicinal product and contents of the pack

Bulevirtide is a powder for injectable solution and is presented as a white or almost white powder.

Each carton 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

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

Date of the most recent review of this leaflet: <{MM/YYYY}> <{month YYYY}>.

This medicine has been authorised under a "conditional approval". This type of approval means that further information on this medicine is expected.

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

1. Step-by-step injection guide

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

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