HEPCLUDEX 2 mg powder for solution for injection

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

Hepcludex contains the active substance bulevirtide, which is an antiviral medicine.

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

HDV uses a particular protein in liver cells to enter the cells. Bulevirtide, the active substance in this medicine blocks the protein and so prevents the HDV from getting into liver cells. This reduces the spread of HDV in the liver and reduces inflammation.

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

If you are not sure, speak to your doctor before taking this medicine.

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

Talk to your doctor or pharmacist before taking Hepcludex:

• if your liver is not working well enough – it is not known how well Hepcludex works in these circumstances; if your liver is not functioning well, taking Hepcludex is not recommended.
• if you have had kidney disease or if tests have shown problems with your kidneys. Before and during treatment, your doctor may order blood tests to check how well your kidneys are working;
• if you have HIV infection or hepatitis C - it is not known how well Hepcludex works in these circumstances; your doctor may order blood tests to check the status of your HIV or hepatitis C infection

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

Please tell your doctor if you are taking, have recently taken, or might take any other medicines.

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

• ciclosporin, a medicine that supresses the immune system;
• ezetimibe, used for treating high blood cholesterol;
• irbesartan, used for treating high blood pressure and heart disease;
• ritonavir, used to treat HIV infection;
• sulfasalazine, (used for treating rheumatoid arthritis, ulcerative colitis, and Crohn's disease.

Some medicines can increase or decrease the effects of Hepcludex when taken together. In some cases, you may need to have certain tests or your doctor may change the dose or monitor you regularly:

• cancer treatments (e.g. dasatinib, docetaxel, ibrutinib, paclitaxel);
• antihistamine medicines used for allergies (e.g. ebastine, fexofenadine);
• immune system medicines (e.g. everolimus, sirolimus, tacrolimus);
• medicines for hepatitis C and HIV treatment (e.g. darunavir, glecaprevir, grazoprevir, indinavir, maraviroc, paritaprevir, saquinavir, simeprevir, tipranavir, voxilaprevir);
• medicines for diabetes (e.g. glibenclamide, nateglinide, repaglinide);
• medicines for erectile dysfunction (e.g., avanafil, sildenafil, vardenafil);
• medicines for treating high blood pressure and heart disease (e.g. olmesartan, telmisartan, valsartan);
• statin, medicines used for high blood cholesterol (e.g. atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin);
• thyroid hormones used to treat thyroid problems;
• alfentanil, an opioid medicine used to treat severe pain;
• bosentan, used for pulmonary arterial hypertension;
• buspirone, an anxiety medicine;
• budesonide, used for asthma and chronic obstructive pulmonary disease;
• conivaptan and tolvaptan, used to treat hyponatraemia (low sodium levels);
• darifenacin, used to treat urinary incontinence;
• dronedarone, heart medicine for cardiac arrhythmias;
• eletriptan, used for migraine headaches;
• eplerenone, used for high blood pressure;
• estrone-3-sulfate a menopausal hormone medicine;
• felodipine and nisoldipine (heart medicines);
• lomitapide, used for high blood cholesterol;
• lurasidone and quetiapine, antipsychotic medicines for psychiatric disorders;
• midazolam and triazolam, medicines to treat insomnia (inability to sleep) and for anaesthesia (to avoid pain during surgery);
• naloxegol, used to treat dependence on opioid medicines for severe pain;
• ticagrelor, anticoagulant to prevent blood clotting.

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 taking this medicine. You should not use this medicine unless specifically told to by your doctor.

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

Talk to your doctor to decide whether you should breastfeed while taking Hepcludex.

It is not known whether Hepcludex can pass into breast milk. Therefore, a decision must be made whether to discontinue breast-feeding or to discontinue Hepcludex.

Dizziness and tiredness are side effects which may impair your ability to drive and use machines. If you have any concerns consult your doctor.

This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially "sodium-free".

The recommended dose is 2 mg once daily by subcutaneous injection (just under the skin). Your doctor will say how long you need to take the medicine for.

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

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

If less than 4 hours have passed since your missed dose of Hepcludex, take the missing dose as soon as possible and take your next scheduled dose at the usual time.

If more than 4 hours have passed since your missed dose of 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. Tell your doctor if you have missed a dose of Hepcludex.

If you do not want to take Hepcludex anymore, talk to your doctor before stopping the treatment.

Stopping the treatment can reactivate the infection and worsen your disease. Tell your doctor immediately about any changes in symptoms after stopping treatment.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App.

By reporting side effects, you can help to provide more information on the safety of this medicine.

The active substance is bulevirtide 2 mg. Each vial contains bulevirtide acetate equivalent to 2 mg bulevirtide.

The other ingredients are: sodium carbonate anhydrous, sodium hydrogen carbonate, mannitol, hydrochloric acid, sodium hydroxide.

Bulevirtide is a powder for solution for injection and comes as a white to off-white powder.

Each carton contains 30 single doses.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

In order to reduce injection site reactions, you may change the site of bulevirtide injection regularly.

Do not inject bulevirtide into the following areas: knee, groin, the lower or inner buttocks, directly over a blood vessel, around the navel (belly button), on scar tissue, a bruise, a mole, a surgical scar, tattoo or burn site, or where there is an injection site reaction.

Abdomen

Upper thighs

1A Storage

Bulevirtide vials must be stored in the original packaging in the refrigerator (2–8 °C) in order to protect bulevirtide from light.

1B Preparing doses

The following instructions are for dissolving a single dose.

1C Wash hands

Wash your hands well using soap and warm water and dry them with a clean towel.

Once your hands are clean, do not touch anything else other than the medicine, supplies and the area around the injection site.

1D Clean vial

Wipe the vial top with a new alcohol pad and let the top air-dry.

If you touch the rubber top after cleaning it, clean it again with a new alcohol pad.

2A Draw up sterile water

Pick up the syringe. Put the longer needle on.

Important! Be sure the capped needle is tight by pushing it down slightly while twisting it clockwise.

Pull off the plastic cap.

Open the sterile water for injection. Insert the needle in the vial and gently turn the water vial upside down. Make sure the tip of the needle is always below the surface of the water to help keep air bubbles from entering the syringe.

Slowly pull the plunger back to get 1.0 ml of sterile water into the syringe. Carefully remove the needle and syringe from the vial.

2B Inject sterile water into the powder

Gently tap the bulevirtide vial to loosen the powder.

Insert the needle with sterile water into the bulevirtide vial at an angle.

Inject the sterile water slowly, so it can drip down the side of the vial into the bulevirtide powder.

2C Gently mix bulevirtide

Gently tap the bulevirtide vial with your fingertip for 10 sec to start dissolving the powder. Then gently roll the bulevirtide vial between your hands to ensure thorough mixing. Make sure no bulevirtide powder is stuck to the vial wall.

Important! Do not shake the bulevirtide vial. Shaking will make the medicine foam and it will take much longer to dissolve.

2D Inspect bulevirtide

Once the powder starts to dissolve, just set it aside and it completely will dissolve.

After tapping, it could take up to 3 min to dissolve.

2E Bulevirtide ready for injection

When mixed completely, Clean the bulevirtide the bulevirtide solution should be clear.

Important! Completely dissolved bulevirtide should be clear and without foam.

If the bulevirtide solution appears foamy or yellowish, allow more time for it to dissolve.

If you see bubbles, gently tap the vial until they disappear.

If you see any particles in the bulevirtide solution once it is (completely) dissolved, do not use that vial. Contact your doctor or pharmacist that provided it.

Reconstituted bulevirtide must be used immediately.

2F Clean vial

Clean the bulevirtide vial top again, using a new alcohol pad.

Allow it to air dry.

3A Insert needle into vial

Pick up the syringe.

Insert the needle into the vial of liquid bulevirtide.

3B Draw up bulevirtide

Gently turn the vial upside down. Make sure the tip of the needle is always below the surface of the bulevirtide solution to help keep air bubbles from entering the syringe. Slowly pull the plunger to get 1.0 ml of bulevirtide.

3C Finishing preparation

Gently tap or flick the syringe and push/pull the plunger to remove extra air and bubbles.

To be sure you end up with 1.0 ml of bulevirtide in the syringe, you may need to pull the plunger past the 1.0 ml mark.

Carefully remove the needle and syringe from the vial.

3D Change and discard the needle

Remove the longer needle from the syringe and dispose of it properly so that nobody can be injured.

Important! Do not put the plastic cap back on the needle.

3E Attach needle for injection

Place the shorter needle on the syringe.

Important! Be sure the capped needle is tight by pushing it down slightly while twisting it clockwise.

Pull off the plastic cap.

3F Choose the injection site

Choose a site different from the one you used for your last injection. Clean the injection site with a new alcohol pad. Start in the centre, apply pressure and clean in a circular motion, working outward.

Important! Allow site to air-dry.

3G Prepare injection site

Pinch and hold a fold of skin around the injection site.

3H Inject bulevirtide

Pierce the skin at a 45-degree angle. The needle should be inserted most of the way in.

Slowly push the plunger all the way to inject bulevirtide.

Remove the needle from skin.

Remove the needle from the syringe and dispose of both properly so that nobody can be injured (see 3D).