Package leaflet: Information for the user

Harvoni 90 mg/400 mg film-coated tablets Harvoni 45 mg/200 mg film-coated tablets ledipasvir/sofosbuvir

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 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.

What is in this leaflet

1. What Harvoni is and what it is used for

2. What you need to know before you take Harvoni

3. How to take Harvoni

4. Possible side effects

5. How to store Harvoni

6. Contents of the pack and other information

If Harvoni has been prescribed for your child, please note that all the information in this leaflet is applicable to your child (in this case please read “your child” instead of “you”).

1. What Harvoni is and what it is used for

   
   

   Harvoni is a medicine that contains the active substances ledipasvir and sofosbuvir. Harvoni is given to treat chronic (long-term) hepatitis C virus infection in adults and children 3 years of age and older.

   
   

   Hepatitis C is a virus that infects the liver. The active substances in the medicine work together by blocking two different proteins that the virus needs to grow and reproduce itself, allowing the infection to be permanently eliminated from the body.

   
   

   Harvoni is sometimes taken with another medicine, ribavirin.

   
   

   It is very important that you also read the leaflets for the other medicines that you will be taking with Harvoni. If you have any questions about your medicines, please ask your doctor or pharmacist.

   
   

2. What you need to know before you take Harvoni Do not take Harvoni

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

     
     

   • If you are currently taking any of the following medicines:

     • rifampicin and rifabutin (antibiotics used to treat infections, including tuberculosis);

     • St. John’s wort (herbal medicine used to treat depression);

     • carbamazepine, phenobarbital and phenytoin (medicines used to treat epilepsy and prevent seizures);

     • rosuvastatin (a medicine used to treat high cholesterol).

        If any of these conditions apply to you, do not take Harvoni and tell your doctor immediately. Warnings and precautions

       Your doctor will know if any of the following conditions apply to you. These will be considered before treatment with Harvoni is started.

   • other liver problems apart from hepatitis C, for instance

     • if you are awaiting a liver transplant;

     • if you have a current or previous infection with the hepatitis B virus, since your doctor may want to monitor you more closely;

   • kidney problems or if you are on kidney dialysis, since Harvoni has not been fully tested in patients with severe kidney problems;

   • ongoing treatment for HIV infection, since your doctor may want to monitor you more closely.

     
     

     Talk to your doctor or pharmacist before taking Harvoni if:

   • you currently take, or have taken in the last few months, the medicine amiodarone to treat irregular heartbeats, as it may result in a life-threatening slowing of your heart beat. Your doctor may consider different treatments if you have taken this medicine. If treatment with Harvoni is needed, you may require additional heart monitoring.

   • you have diabetes. You may need closer monitoring of your blood glucose levels and/or adjustment of your diabetes medication after starting Harvoni. Some diabetic patients have experienced low sugar levels in the blood (hypoglycaemia) after starting treatment with medicines like Harvoni.

     
     

     Tell your doctor immediately if you currently take, or have taken in the last months, any medicines for heart problems and during treatment you experience:

   • slow or irregular heartbeat, or heart rhythm problems;

   • shortness of breath or worsening of existing shortness of breath;

   • chest-pain;

   • light-headedness

   • palpitations

   • near fainting or fainting

     
     

     Blood tests

     
     

     Your doctor will test your blood before, during and after your treatment with Harvoni. This is so that:

   • Your doctor can decide if you should take Harvoni and for how long;

   • Your doctor can confirm that your treatment has worked and you are free of the hepatitis C virus.

     
     

     Children and adolescents

     
     

     Do not give this medicine to children under 3 years of age. The use of Harvoni in children under 3 years of age has not yet been studied.

     
     

     Other medicines and Harvoni

     
     

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

     
     

     Warfarin and other similar medicines called vitamin K antagonists used to thin the blood. Your doctor may need to increase the frequency of your blood tests to check how well your blood can clot.

     Your liver function may change with treatment of hepatitis C and therefore may affect other medications (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 Harvoni.

     
     

     If you are not sure about taking any other medicines, talk to your doctor or pharmacist.

     
     

     Some medicines should not be taken with Harvoni.

     
     

   • Do not take any other medicine that contains sofosbuvir, one of the active substances in Harvoni.

     
     

   • Tell your doctor or pharmacist if you are taking any of the medicines below:

     • amiodarone used to treat irregular heartbeats

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

     • digoxin used to treat heart conditions

     • dabigatran used to thin the blood

     • statins used to treat high cholesterol

     • rifapentine (antibiotic used to treat infections, including tuberculosis)

     • oxcarbazepine (a medicine used to treat epilepsy and prevent seizures)

     • tipranavir (used to treat HIV infection).

       
       

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

       
       

   • Get advice from a doctor or pharmacist if you take medicines used to treat stomach ulcers, heartburn or acid reflux. This includes:

     • antacids (such as aluminium/magnesium hydroxide or calcium carbonate). These should be taken at least 4 hours before or 4 hours after Harvoni;

     • proton pump inhibitors (such as omeprazole, lansoprazole, rabeprazole, pantoprazole and esomeprazole). These should be taken at the same time as Harvoni. Do not take proton pump inhibitors before Harvoni. Your doctor may give you a different medicine or adjust the dose of the medicine you are taking;

     • H2-receptor antagonists (such as famotidine, cimetidine, nizatidine or ranitidine). Your doctor may give you a different medicine or adjust the dose of the medicine you are taking.

       These medicines can decrease the amount of ledipasvir in your blood. If you are taking one of these medicines your doctor will either give you a different medicine for stomach ulcers, heartburn or acid reflux, or recommend how and when you take that medicine.

       
       

       Pregnancy and contraception

       
       

       The effects of Harvoni during pregnancy are not known. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

       
       

       Pregnancy must be avoided if Harvoni is taken together with ribavirin. It is very important that you read the "Pregnancy" section in the ribavirin package leaflet very carefully. Ribavirin can be very damaging to an unborn baby. Therefore, special precautions in sexual activity must be taken if there is any chance for pregnancy to occur.

       
       

   • You or your partner must use an effective birth control method during treatment with Harvoni together with ribavirin and for some time afterwards. It is very important that you read the “Pregnancy” section in the ribavirin package leaflet very carefully. Ask your doctor for an effective contraceptive method suitable for you.

   • If you or your partner become pregnant during Harvoni and ribavirin treatment or in the months that follow, you must contact your doctor immediately.

     
     

     Breast-feeding

     
     

     Do not breast-feed during treatment with Harvoni. It is not known whether ledipasvir or sofosbuvir, the two active substances of Harvoni, pass into human breast milk.

     
     

     Driving and using machines

     
     

     If you feel tired after taking Harvoni you should not take part in activities that require concentration, for example, do not drive, ride a bike or operate machines.

     
     

     Harvoni 90 mg/400 mg and 45 mg/200 mg film-coated tablets contain lactose

   • If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

     
     

     Harvoni 90 mg/400 mg film-coated tablets contains sunset yellow FCF (E110) which can cause allergic reactions

   • Tell your doctor if you are allergic to sunset yellow FCF, also called “E110” before taking this medicine.

     
     

     Harvoni contains sodium

     
     

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

     
     

3. How to take Harvoni

   
   

   Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

   
   

   Recommended dose

   
   

   Harvoni is to be taken as advised by your doctor. The recommended dose of Harvoni in adults is one 90 mg/400 mg film-coated tablet once a day. Your doctor will tell you for how many weeks you should take Harvoni.

   
   

   The recommended dose of Harvoni in children aged 3 years and above is based on weight. Take Harvoni as advised by your doctor.

   
   

   Swallow the tablet(s) whole with or without food. Do not chew, crush or split the tablet as it has a very bitter taste. Tell your doctor or pharmacist if you have problems swallowing tablets.

   
   

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

   
   

   If you are taking a proton pump inhibitor, take the proton pump inhibitor at the same time as Harvoni. Do not take it before Harvoni.

   
   

   If you are sick (vomit) after taking Harvoni it may affect the amount of Harvoni in your blood. This may make Harvoni work less well.

   • If you are sick (vomit) less than 5 hours after taking Harvoni, take another dose.

   • If you are sick (vomit) more than 5 hours after taking Harvoni, you do not need to take another dose until your next scheduled dose.

     If you take more Harvoni than you should

     
     

     If you accidentally take more than the recommended dose you should contact your doctor or nearest emergency department immediately for advice. Keep the tablet bottle with you so that you can easily describe what you have taken.

     
     

     If you forget to take Harvoni

     
     

     It is important not to miss a dose of this medicine.

     
     

     If you do miss a dose, work out how long it is since you last took your Harvoni:

   • If you notice within 18 hours of the time you usually take Harvoni, you must take the dose as soon as possible. Then take the next dose at your usual time.

   • If it’s 18 hours or more after the time you usually take Harvoni, wait and take the next dose at your usual time. Do not take a double dose (two doses close together).

     
     

     Do not stop taking Harvoni

     
     

     Do not stop taking this medicine unless your doctor tells you to. It is very important that you complete the full course of treatment to give the medicine the best chance to treat your hepatitis C virus 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 may cause side effects. If you take Harvoni you may get one or more of the side effects below:

   
   

   Very common side effects

   (may affect more than 1 in 10 people)

   • headache

   • feeling tired

     
     

     Common side effects

     (may affect up to 1 in 10 people)

   • rash

     
     

     Other effects that may be seen during treatment with Harvoni

     
     

     The frequency of the following side effects is not known (frequency cannot be estimated from the available data).

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

     
     

     Other effects that may be seen during treatment with sofosbuvir:

     
     

     The frequency of the following side effects is not known (frequency cannot be estimated from the available data).

   • a wide-spread severe rash with peeling skin which may be accompanied by fever, flu-like symptoms, blisters in the mouth, eyes, and/or genitals (Stevens-Johnson syndrome).

     
     

     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. How to store Harvoni

   
   

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

   
   

   This medicine does not require any special storage conditions.

   
   

   Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

   
   

6. Contents of the pack and other information

What Harvoni contains

• The active substances are ledipasvir and sofosbuvir. Each film-coated tablet contains 90 mg ledipasvir and 400 mg sofosbuvir or 45 mg ledipasvir and 200 mg sofosbuvir.

  
  

• The other ingredients are

  Tablet core:

  Copovidone, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate

  
  

  Film-coating:

  Polyvinyl alcohol, titanium dioxide, macrogol, talc, and for the 90 mg/400 mg tablet only; sunset yellow FCF (E110)

  
  

  What Harvoni looks like and contents of the pack

  
  

  Harvoni 90 mg/400 mg film-coated tablets are orange, diamond-shaped tablets debossed with “GSI” on one side and “7985” on the other side. The tablet is approximately 19 mm long and 10 mm wide.

  
  

  Harvoni 45 mg/200 mg film-coated tablets are white, capsule-shaped, debossed with “GSI” on one side and “HRV” on the other side. The tablet is approximately 14 mm long and 7 mm wide.

  
  

  Each bottle contains a silica gel desiccant (drying agent) that must be kept in the bottle to help protect your tablets. The silica gel desiccant is contained in a separate sachet or canister and should not be swallowed.

  The following pack sizes are available:

• outer cartons containing 1 bottle of 28 film-coated tablets for the 90 mg/400 mg and the 45 mg/ 200 mg film-coated tablets.

• outer cartons containing 3 bottles of 28 (84) film-coated tablets for the 90 mg/400 mg film-coated tablets only. Not all pack sizes may be marketed.

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

België/Belgique/Belgien

Gilead Sciences Belgium SRL-BV Tél/Tel: + 32 (0) 24 01 35 50

Lietuva

Gilead Sciences Poland Sp. z o.o. Tel: + 48 22 262 8702

България

Gilead Sciences Ireland UC

Тел.: + 353 (0) 1 686 1888

Luxembourg/Luxemburg

Gilead Sciences Belgium SRL-BV Tél/Tel: + 32 (0) 24 01 35 50

Česká republika Gilead Sciences s.r.o. Tel: + 420 910 871 986

Magyarország

Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888

Danmark

Gilead Sciences Sweden AB Tlf: + 46 (0) 8 5057 1849

Malta

Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888

Deutschland

Gilead Sciences GmbH Tel: + 49 (0) 89 899890-0

Nederland

Gilead Sciences Netherlands B.V. Tel: + 31 (0) 20 718 36 98

Eesti

Gilead Sciences Poland Sp. z o.o. Tel: + 48 22 262 8702

Norge

Gilead Sciences Sweden AB Tlf: + 46 (0) 8 5057 1849

Ελλάδα

Gilead Sciences Ελλάς Μ.ΕΠΕ. Τηλ: + 30 210 8930 100

Österreich

Gilead Sciences GesmbH Tel: + 43 1 260 830

España

Gilead Sciences, S.L. Tel: + 34 91 378 98 30

Polska

Gilead Sciences Poland Sp. z o.o. Tel: + 48 22 262 8702

France

Gilead Sciences

Tél: + 33 (0) 1 46 09 41 00

Portugal

Gilead Sciences, Lda. Tel: + 351 21 7928790

Hrvatska

Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888

România

Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888

Ireland

Gilead Sciences Ireland UC Tel: + 353 (0) 214 825 999

Slovenija

Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888

Ísland

Gilead Sciences Sweden AB Sími: + 46 (0) 8 5057 1849

Slovenská republika

Gilead Sciences Slovakia s.r.o. Tel: + 421 232 121 210

Italia

Gilead Sciences S.r.l. Tel: + 39 02 439201

Suomi/Finland

Gilead Sciences Sweden AB Puh/Tel: + 46 (0) 8 5057 1849

Κύπρος

Gilead Sciences Ελλάς Μ.ΕΠΕ. Τηλ: + 30 210 8930 100

Sverige

Gilead Sciences Sweden AB Tel: + 46 (0) 8 5057 1849

Latvija

Gilead Sciences Poland Sp. z o.o. Tel: + 48 22 262 8702

United Kingdom (Northern Ireland)

Gilead Sciences Ireland UC Tel: + 44 (0) 8000 113700

This leaflet was last revised in