VOSEVI 400 MG/100 MG/100 MG FILM-COATED TABLETS

2. What you need to know before you take Vosevi

Do not take Vosevi

• If you are allergicto sofosbuvir, to velpatasvir, to voxilaprevir or to any of the other ingredients of this medicine (listed in section 6 of this leaflet).

If this is the case, do not take Vosevi and tell your doctor immediately.

• If you are currently taking any of the following medicines:
• rifampicin and rifabutin(antibiotics used to treat infections, including tuberculosis);
• St John's Wort(a herbal medicine used to treat depression);
• carbamazepine, phenobarbitaland phenytoin(medicines used to treat epilepsy and prevent seizures);
• rosuvastatin(a medicine used to treat high cholesterol levels and the risk of certain cardiovascular events);
• dabigatran(a medicine used to prevent blood clots);
• medicines that contain ethinylestradiol, including many oral contraceptives.

Warnings and precautions

Tell your doctor if:

• you have liver problemsother than hepatitis C, for example
• if you haveor have had infection with the hepatitis Bvirus, as your doctor may want to monitor you more closely;
• if you have had a liver transplant.
• you are taking treatment for infection with the human immunodeficiency virus (HIV),as your doctor may want to monitor you more closely.

Tell your doctor or pharmacist before you start taking Vosevi if:

• you are currently taking or have recently taken the medicine amiodarone to treat an irregular heartbeat, as it may cause a potentially life-threatening decrease in heart rate. Your doctor may consider alternative treatments if you have taken this medicine. If Vosevi treatment is needed, you may need additional heart monitoring.
• you have diabetes. After starting Vosevi, you may need close monitoring of your blood glucose levels and/or adjustment of your anti-diabetic medication. After starting treatment with medicines like Vosevi, some diabetic patients have experienced low blood sugar levels (hypoglycaemia).

Tell your doctor immediatelyif you are currently taking or have taken in the last few months any medicine for heart problems and, during treatment, you experience:

• slow or irregular heartbeats, or heart rhythm problems;
• shortness of breath or worsening of existing shortness of breath;
• chest pain;
• feeling dizzy;
• palpitations;
• fainting or feeling like you are about to faint.

Blood tests

Your doctor will perform blood tests before, during and after treatment with Vosevi. This is so that:

• Your doctor can decide if you should take Vosevi and for how long.
• Your doctor can confirm that the treatment has worked and you no longer have the hepatitis C virus.

Children and adolescents

Do not give this medicine to children and adolescents under 18 years of age. The use of Vosevi in children and adolescents has not been studied yet.

Other medicines and Vosevi

Tell your doctor or pharmacistif you are taking, have recently taken or might take any other medicines.

If you are not sure, ask your doctor or pharmacist.

Some medicines must not be taken with Vosevi.If you take them with Vosevi, they may not work properly or they may make side effects worse.

• Rifampicin and rifabutin(antibiotics used to treat infections, including tuberculosis);
• St John's Wort(a herbal medicine used to treat depression);
• Carbamazepine, phenobarbitaland phenytoin(medicines used to treat epilepsy and prevent seizures);
• Rosuvastatin(a medicine used to treat high cholesterol levels or the risk of certain cardiovascular events);
• Dabigatran(a medicine used to prevent blood clots);

• Medicines that contain ethinylestradiol, including many oral contraceptives.

Tell your doctor or pharmacistif you are taking any of the following medicines:

• amiodarone,used to treat irregular heartbeat;
• rifapentine(an antibiotic used to treat infections, including tuberculosis);
• oxcarbazepine(a medicine used to treat epilepsy and prevent seizures);
• tenofovir disoproxil fumarateor any medicine that contains tenofovir disoproxil fumarate, used to treat HIV infection;
• atazanavir, efavirenz or lopinavir, used to treat HIV infection;
• digoxin, used to treat heart problems;
• modafinil, used to treat sleep disorders;
• atorvastatin, pravastatinor other statins, used to treat high cholesterol levels;
• ciclosporin, which is used to suppress the immune system.

Taking Vosevi with any of these medicines may stop them from working properly or make any side effects worse. Your doctor may need to give you a different medicine or adjust the dose of the one you are taking.

• Ask your doctor or pharmacist for adviceif you are taking medicines used to treat stomach ulcers, heartburn or acid refluxas they may reduce the amount of velpatasvir in the blood. These medicines include:

• antacids (such as aluminium/magnesium hydroxide or calcium carbonate). These medicines should be taken at least 4 hours before or 4 hours after Vosevi;
• proton pump inhibitors (such as omeprazol, lansoprazol, rabeprazol, pantoprazol and esomeprazol). If you need to take high doses of these medicines, your doctor may give you a different medicine instead, or adjust the dose of the one you are taking;
• H2 receptor antagonists (such as famotidine, cimetidine, nizatidine or ranitidine). If you need to take high doses of these medicines, your doctor may give you a different medicine instead or adjust the dose of the one you are taking.

These medicines may reduce the amount of Vosevi in the blood. If you are taking any of these medicines, your doctor will give you a different medicine for stomach ulcers, heartburn or acid reflux, or recommend how and when to take the medicine.

• Ask your doctor or pharmacist for adviceif you are taking warfarin or other similar medicinesthat are known as vitamin K antagonists, to thin the blood. Your doctor may increase the number of blood tests to check how the blood clots.
• Your liver function may change with hepatitis C treatment and may affect other medicines (e.g. medicines used to suppress your immune system, etc.). Your doctor may need to closely monitor these other medicines you are taking and make adjustments after starting treatment with Vosevi.

Pregnancy, breast-feeding and fertility

If you are pregnant, think you may be pregnant, are breast-feeding or plan to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

Vosevi is not recommended during pregnancy.The effects of Vosevi during pregnancy are not known.

Breast-feeding

Do not breast-feed during treatment with Vosevi.Some of the active substances in Vosevi may pass into breast milk.

Driving and using machines

Vosevi is unlikely to affect your ability to drive or use tools or machines.

Vosevi contains lactose

• If you are intolerant to lactose or to other sugars, you should tell your doctor.Vosevi contains lactose monohydrate. If you are lactose intolerant, or if you have been told that you have an intolerance to other sugars, talk to your doctor before taking this medicine.

3. How to take Vosevi

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.

Recommended dose

The recommended dose is onetabletoncedailyfor 8 or 12weeks.

Swallow the tablet whole with food. Do not chew, crush or break the tablet, as it has a very bitter taste.

Kidney problems

If you have kidney problemsor if you are on dialysistell your doctor, as Vosevi has not been fully evaluated in patients with severe kidney problems.

Liver problems

Do not take Vosevi if you have moderate or severe liver problems.

If you are taking an antacid, take it at least 4 hours before or at least 4 hours after Vosevi.

If you vomit after taking Vosevithis may affect the amount of Vosevi in the blood. This may make Vosevi work less well.

• If you vomit less than 4 hoursafter taking Vosevi, take another tablet.
• If you vomit more than 4 hoursafter taking Vosevi, do not take another tablet until the next one is due.

If you take more Vosevi than you should

If you accidentally take a higher dose than recommended, you may increase the risk of getting side effects from this medicine (see section 4 Possible side effects).

You should contact your doctor or the nearest emergency department immediately for advice. Take the pack with you so that you can show the doctor what you have taken.

If you forget to take Vosevi

It is important that you do not miss any dose of this medicine.

If you miss a dose, calculate how long ago you took the last Vosevi tablet:

• If you realise within 18 hoursof the time you usually take Vosevi, you should take the tablet as soon as possible. Then take the next dose at the usual time.

• If it has been 18 hours or moresince the time you usually take Vosevi, wait and take the next dose at the usual time. Do not take a double dose (two doses together).

Do not stop taking Vosevi

Do not stop taking this medicine unless your doctor tells you to. It is very important that you complete the full treatment course so that the medicine can work as well as possible to treat the hepatitis C infection.

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

4. Possible side effects

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

Very common side effects

(may affect more than 1 in 10 people)

• headache
• diarrhoea
• nausea

Common side effects

(may affect up to 1 in 10 people)

• stomach pain
• loss of appetite
• vomiting
• muscle pain (myalgia)
• abnormal liver function test (total bilirubin).
• rash

Uncommon side effects

(may affect up to 1 in 100 people)

• muscle cramps
• swelling of the face, lips, tongue or throat (angioedema).

Other side effects that may be seen with sofosbuvir:

The following side effects have not been known to occur with sofosbuvir (frequency cannot be estimated from the available data).

• widespread severe skin rash with skin peeling, possibly with fever, flu-like symptoms, blistering of the mouth, eyes and/or genitals (Stevens-Johnson syndrome).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist,even if they are not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Monitoring System for Human Use: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Vosevi

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 blister after “EXP”. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions. Store in the original package to protect from moisture. Keep the bottle tightly closed.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Package Contents and Additional Information

Vosevi Composition

• The active ingredients aresofosbuvir, velpatasvir, and voxilaprevir. Each film-coated tablet contains 400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir.

• The other ingredients are

Tablet core:

Colloidal anhydrous silica, copovidone, sodium croscarmellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose.

Film coating:

Black iron oxide (E172), red iron oxide (E172), yellow iron oxide (E172), macrogol, polyvinyl alcohol, talc, titanium dioxide (E171).

Product Appearance and Package Contents

The film-coated tablets are beige, capsule-shaped tablets with "GSI" engraved on one side and "3" on the other. The tablet measures 20 mm in length and 10 mm in width.

The tablets are presented in plastic bottles with child-resistant closures. All bottles contain a desiccant with silica gel (desiccant) that should remain inside the bottle to protect the tablets. The desiccant with silica gel is in a separate bag or container that should not be swallowed.

The following package sizes are available:

• Boxes with 1 bottle of 28 film-coated tablets.

Marketing Authorization Holder

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

Manufacturer

Gilead Sciences Ireland UC

IDA Business & Technology Park

Carrigtohill

County Cork

Ireland

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.