Vosevi

Patient Information Leaflet

Vosevi 400 mg/100 mg/100 mg film-coated tablets, 200 mg/50 mg/50 mg film-coated tablets

sofosbuvir/velpatasvir/voxilaprevir
Please read all of this leaflet carefully before you start taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Vosevi is and what it is used for
2. What you need to know before taking Vosevi
3. How to take Vosevi
4. Possible side effects
5. How to store Vosevi
6. Contents of the pack and other information

If Vosevi has been prescribed for a child, all the information in this leaflet is directed to the child (in this case, read “the child” instead of “you”).

1. What Vosevi is and what it is used for

Vosevi is a medicine that contains the active substances sofosbuvir, velpatasvir and voxilaprevir in a single tablet. It is administered for the treatment of chronic (long-term) viral liver infection called hepatitis C in patients aged 12 years and older who weigh at least 30 kg.
The active substances in this medicine work together by blocking three different proteins necessary for the hepatitis C virus to grow and reproduce, leading to the elimination of the infection from the body.

2. What you should know before taking Vosevi

Do not take Vosevi

• if you are allergic to sofosbuvir, velpatasvir, voxilaprevir, or any of the other components of this medicine (listed in section 6 of this leaflet).

If this applies to you, do not take Vosevi and inform your doctor immediately.

• if you are currently taking any of the following medicines:
• rifampicin and rifabutin (antibiotics used to treat infections such as tuberculosis);
• St. John’s wort (Hypericum perforatum) (a herbal remedy used to treat depression);
• carbamazepine, phenobarbital, and phenytoin (used to treat epilepsy and prevent seizures);
• rosuvastatin (used to treat high blood cholesterol or to reduce the risk of certain cardiovascular events);
• dabigatran etexilate (used to prevent blood clots);
• medicines containing ethinylestradiol, including many contraceptives.

Warnings and precautions
Consult your doctor if:

• you have liver problems other than hepatitis C, for example
• you currently have or have had hepatitis B virus infection, as your doctor may wish to monitor you more closely;
• you have had a liver transplant;
• you are receiving treatment for human immunodeficiency virus (HIV) infection, as your doctor may wish to monitor you more closely.

Talk to your doctor or pharmacist before taking Vosevi if:

• you are taking or have taken amiodarone in the past few months, a medicine used to treat irregular heartbeat, as it may cause a life-threatening slowing of the heart rate. Your doctor may consider alternative treatments if you have taken this medicine. If treatment with Vosevi is necessary, you may require additional cardiac monitoring.
• you have diabetes. After starting therapy with Vosevi, more frequent monitoring of blood glucose levels and/or adjustment of antidiabetic therapy may be needed. Some diabetic patients have experienced low blood sugar levels (hypoglycaemia) after starting treatment with medicines such as Vosevi.

Inform your doctor immediately if you are taking or have taken medicines for
heart problems in the past few months and during treatment you experience:

• slow or irregular heartbeat, or heart rhythm disturbances;
• shortness of breath or worsening of existing shortness of breath;
• chest pain;
• dizziness;
• palpitations;
• near-fainting or fainting.

Blood tests
Your doctor will perform blood tests before, during, and after treatment with Vosevi. This will allow:

• your doctor to determine whether you should take Vosevi and for how long;
• your doctor to confirm that the treatment has been effective and that the hepatitis C virus is no longer present.

Children and adolescents
Do not give this medicine to children under 12 years of age and weighing less than 30 kg. The use of
Vosevi in these patients has not yet been studied.
Other medicines and Vosevi
Inform your doctor or pharmacist if you are taking, have recently taken, or might take
any other medicine.
If you are unsure, consult your doctor or pharmacist.
Some medicines must not be taken with Vosevi. Taking Vosevi with any of these medicines may make them less effective, or may worsen side effects:

• rifampicin and rifabutin (antibiotics used to treat infections such as tuberculosis);
• St. John’s wort (Hypericum perforatum) (a herbal remedy used to treat depression);
• carbamazepine, phenobarbital, and phenytoin (used to treat epilepsy and prevent seizures);
• rosuvastatin (used to treat high blood cholesterol or to reduce the risk of certain cardiovascular events);
• dabigatran etexilate (used to prevent blood clots);
• medicines containing ethinylestradiol, including many contraceptives.

Inform your doctor or pharmacist if you are taking any of the following medicines:

• amiodarone, used to treat irregular heartbeat;

• rifapentine (an antibiotic used to treat infections such as tuberculosis);

• oxcarbazepine (used to treat epilepsy and prevent seizures);

• tenofovir disoproxil fumarate, or any medicine containing tenofovir disoproxil fumarate, used to treat HIV infection;

• atazanavir, efavirenz, or lopinavir, used to treat HIV infection;

• digoxin, used to treat certain heart conditions;

• modafinil, used to treat sleep disorders;

• atorvastatin, pravastatin, or other statins, used to treat high cholesterol;

• cyclosporine, used for immunosuppression. Taking Vosevi with any of these medicines may reduce their effectiveness or worsen side effects. Your doctor may need to prescribe a different medicine or adjust the dose of the medicine you are taking.

• Ask your doctor or pharmacist if you are taking medicines used to treat gastric ulcer, heartburn, or acid reflux, as these 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 omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole). If you require high doses of these medicines, your doctor may prescribe an alternative medicine or adjust the dose of the medicine you are already taking;

• H(_2)-receptor antagonists (such as famotidine, cimetidine, nizatidine, or ranitidine). If you require high doses of these medicines, your doctor may prescribe a different medicine or adjust the dose of the medicine you are taking. These medicines may reduce Vosevi levels in the blood. If you are taking one of these medicines, your doctor will prescribe a different medicine for gastric ulcer, heartburn, or acid reflux, or will advise you on how and when to take the medicine.

• Ask your doctor or pharmacist if you are taking warfarin or similar medicines known as vitamin K antagonists, used to thin the blood. Your doctor may increase the frequency of blood tests to ensure your blood clots properly.

Liver function may change during hepatitis C treatment, which could affect other medicines (e.g., medicines used to suppress the immune system, etc.). Your doctor may need to closely monitor these other medicines you are taking and adjust their doses after starting treatment with Vosevi.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are breastfeeding, or are planning to become pregnant, consult your doctor before taking this medicine.
Pregnancy
Vosevi is not recommended during pregnancy. The effects of Vosevi during pregnancy are unknown.
Breastfeeding
Do not breastfeed during treatment with Vosevi. Some of the active substances in Vosevi may pass into breast milk.
Driving and using machines
Vosevi has no effect on the ability to drive or use tools and machinery.
Vosevi contains lactose
Inform your doctor if you are lactose intolerant or have other sugar intolerances. Vosevi contains lactose monohydrate. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Vosevi contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., it is essentially ‘sodium-free’.

3. How to take Vosevi

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.
Recommended dose
The recommended dose of Vosevi is one 400 mg/100 mg/100 mg tablet or two 200 mg/50 mg/50 mg tablets taken once daily for 8 or 12 weeks.
Take Vosevi exactly as prescribed by your doctor.
Swallow the tablet(s) whole with food. Do not chew, split, or crush the tablet(s), as they have a very bitter taste.
Kidney problems
Inform your doctor if you have kidney problems or are undergoing renal dialysis, as Vosevi has not been fully studied in patients with severe kidney problems.
Liver problems
Vosevi must not be used 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 taking Vosevi.
If you vomit after taking Vosevi, the amount of Vosevi in your blood may be affected.
The effectiveness of Vosevi may therefore be reduced.

• If you vomit within 4 hours after taking Vosevi, take another dose.
• If you vomit more than 4 hours after taking Vosevi, do not take another dose; wait and take your next dose at the usual time.

If you take more Vosevi than you should
If you accidentally take more than the recommended dose of Vosevi, you may be at increased risk of side effects with the use of this medicine (see section 4 Possible side effects).
Contact your doctor or the nearest emergency department immediately. Take the bottle containing the tablets with you so you can easily explain what has been taken.
If you forget to take Vosevi
It is important not to miss any dose of this medicine.
If you forget a dose, consider how much time has passed since you last took Vosevi:

• If you remember within 18 hours of your usual dosing time, take the missed dose as soon as possible. Then take your next dose at the usual time.
• If 18 hours or more have passed since your usual dosing time, wait and take your next dose at the usual time. Do not take a double dose (two doses close together) to make up for the missed dose.

Do not stop treatment with Vosevi
Do not stop treatment with this medicine unless your doctor tells you to do so.
It is very important to complete the full course of treatment to give the medicine the chance to fight the hepatitis C virus infection.
If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some side effects may be serious
Stop taking Vosevi and contact your doctor immediately if you develop any of the
following symptoms:

• Swelling of the face, lips, tongue or throat (angioedema) ( an uncommon adverse event, may affect up to 1 in 100 people )
• Severe widespread skin rash with peeling of the skin which may be accompanied by fever, flu-like symptoms, blisters in the mouth, eyes and/or genitals (Stevens-Johnson syndrome) ( frequency of this adverse event is not known )

Other possible side effects
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
• Malaise (vomiting)
• Muscle pain (myalgia)
• Abnormal result in a liver function laboratory test (total bilirubin)
• Rash

Uncommon side effects
(may affect up to 1 in 100 people)

• Muscle spasms

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Vosevi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and outer carton after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature. Store in the original packaging to protect the medicine from moisture. Keep the bottle tightly closed.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Vosevi contains

• The active substances are sofosbuvir, velpatasvir and voxilaprevir. Each film-coated tablet contains either 400 mg of sofosbuvir, 100 mg of velpatasvir and 100 mg of voxilaprevir, or 200 mg of sofosbuvir, 50 mg of velpatasvir and 50 mg of voxilaprevir.
• The other components are
  Tablet core:
  Anhydrous colloidal silica, copovidone, sodium croscarmellose (E468) (see section 2 of this leaflet), lactose monohydrate (see section 2 of this leaflet), magnesium stearate, microcrystalline cellulose (E460)

Film coating:
Black iron oxide (E172), red iron oxide (E172), yellow iron oxide (E172),
macrogol (E1521), polyvinyl alcohol (E1203), talc (E553b), titanium dioxide (E171)

Description of the appearance of Vosevi and pack contents
The 400 mg/100 mg/100 mg film-coated tablets of Vosevi are beige, capsule-shaped tablets,
imprinted with “GSI” on one side and “3” on the other side. The tablet is 20 mm long and 10 mm wide.
The 200 mg/50 mg/50 mg film-coated tablets of Vosevi are beige, oval-shaped tablets,
imprinted with “GSI” on one side and “SVV” on the other side. The tablet is 15 mm long and 8 mm wide.
The tablets are packed in plastic bottles with child-resistant caps. Each bottle contains a silica gel desiccant (drying agent), which must remain in the bottle to ensure proper storage of the tablets. The silica gel desiccant is contained in a separate sachet or container and must not be ingested.

For both the 400 mg/100 mg/100 mg and 200 mg/50 mg/50 mg film-coated tablets, the following pack is available:

• Outer cartons containing 1 bottle with 28 film-coated tablets

Marketing Authorisation 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 Authorisation Holder:

België/Belgique/Belgien Lietuva
Gilead Sciences Belgium SRL-BV Gilead Sciences Ireland UC
Tél/Tel: + 32 (0) 24 01 35 50 Tel: + 353 (0) 1 686 1888

България Luxembourg/Luxemburg
Gilead Sciences Ireland UC Gilead Sciences Belgium SRL-BV
Тел.: + 353 (0) 1 686 1888 Tél/Tel: + 32 (0) 24 01 35 50

Česká republika Magyarország
Gilead Sciences s.r.o. Gilead Sciences Ireland UC
Tel: + 420 910 871 986 Tel: + 353 (0) 1 686 1888

Danmark Malta
Gilead Sciences Sweden AB Gilead Sciences Ireland UC
Tlf: + 46 (0) 8 5057 1849 Tel: + 353 (0) 1 686 1888

Deutschland Nederland
Gilead Sciences GmbH Gilead Sciences Netherlands B.V.
Tel: + 49 (0) 89 899890-0 Tel: + 31 (0) 20 718 36 98

Eesti Norge
Gilead Sciences Ireland UC Gilead Sciences Sweden AB
Tel: + 353 (0) 1 686 1888 Tlf: + 46 (0) 8 5057 1849

Ελλάδα Österreich
Gilead Sciences Ελλάς Μ.ΕΠΕ. Gilead Sciences GesmbH
Τηλ: + 30 210 8930 100 Tel: + 43 1 260 830

España Polska
Gilead Sciences, S.L. Gilead Sciences Poland Sp. z o.o.
Tel: + 34 91 378 98 30 Tel: + 48 22 262 8702

France Portugal
Gilead Sciences Gilead Sciences, Lda.
Tél: + 33 (0) 1 46 09 41 00 Tel: + 351 21 7928790

Hrvatska România
Gilead Sciences Ireland UC Gilead Sciences (GSR) S.R.L.
Tel: + 353 (0) 1 686 1888 Tel: + 40 31 631 18 00

Ireland Slovenija
Gilead Sciences Ireland UC Gilead Sciences Ireland UC
Tel: +353 (0) 214 825 999 Tel: + 353 (0) 1 686 1888

Ísland Slovenská republika
Gilead Sciences Sweden AB Gilead Sciences Slovakia s.r.o.
Sími: + 46 (0) 8 5057 1849 Tel: + 421 232 121 210

Italia Suomi/Finland
Gilead Sciences S.r.l. Gilead Sciences Sweden AB
Tel: + 39 02 439201 Puh/Tel: + 46 (0) 8 5057 1849

Κύπρος Sverige
Gilead Sciences Ελλάς Μ.ΕΠΕ. Gilead Sciences Sweden AB
Τηλ: + 30 210 8930 100 Tel: + 46 (0) 8 5057 1849

Latvija United Kingdom (Northern Ireland)
Gilead Sciences Ireland UC Gilead Sciences Ireland UC
Tel: + 353 (0) 1 686 1888 Tel: + 44 (0) 8000 113 700

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