Harvoni 90 mg/400 mg film-coated tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

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

This medicine is under additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you experience. Section 4 at the end of this leaflet includes information on how to report side effects.

Read this entire leaflet carefully before you start taking 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 pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Harvoni is and what it is used for
2. What you need to know before taking 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 information in this leaflet applies to your child (in this case, 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 used to treat chronic (long-term) hepatitis C virus infection in adults and children aged 3 years and older.

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

Harvoni is sometimes taken together with another medicine: ribavirin.

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

2. What you need to know before taking Harvoni

Do not take Harvoni

• If you are allergic to ledipasvir, sofosbuvir, or any of the other components 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 (a herbal remedy used to treat depression);

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

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

• If any of these apply to you, do not take Harvoni and inform your doctor immediately.

Warnings and precautions

Your doctor will know if you have any of the following conditions. These will be taken into account before starting treatment with Harvoni.

• other liver problems besides hepatitis C, for example

• if you are awaiting a liver transplant;

• • if you have or have previously had an infection caused by hepatitis B virus, as your doctor may want to monitor you more closely;

• kidney problems or if you are undergoing dialysis, as Harvoni has not been fully studied in patients with severe kidney problems;

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

Consult your doctor or pharmacist before starting Harvoni if:

• you are currently taking or have stopped taking amiodarone, a medicine used to treat irregular heartbeat, within the last few months, as it may cause a potentially life-threatening slow heart rate. Your doctor may consider alternative treatments if you have taken this medicine. If Harvoni treatment is needed, you may require additional heart monitoring.

• you have diabetes. After starting Harvoni, you may need close monitoring of your blood glucose levels and/or adjustment of your antidiabetic medication. After starting treatment with medicines like Harvoni, some diabetic patients have experienced low blood sugar levels (hypoglycaemia).

Contact your doctor immediately if you are currently taking or have taken any medicine for heart problems in the past few months and, during treatment, experience:

• slow or irregular heartbeat, or heart rhythm problems;

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

• chest pain;

• dizziness;

• palpitations;

• fainting or near-fainting.

Blood tests

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

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

• Your doctor can confirm that the treatment has been effective and that you no longer have hepatitis C virus.

Children and adolescents

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

Other medicines and Harvoni

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

Warfarin and other similar medicines called vitamin K antagonists, used to thin the blood. Your doctor may increase the number of blood tests to check how your blood is clotting.

Your liver function may change with hepatitis C treatment and, therefore, 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 Harvoni treatment.

If you are unsure whether you should take any other medicine, consult your doctor or pharmacist.

Some medicines must not be taken with Harvoni.

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

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

• amiodarone, used to treat irregular heartbeat

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

• digoxin, used to treat heart problems

• dabigatran, used to thin the blood

• statins, used to treat high cholesterol levels

• rifapentine (an 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 medicines may prevent them from working properly or worsen their possible side effects. Your doctor may need to prescribe a different medicine or adjust the dose of the one you are taking.

• Seek advice from a doctor or pharmacist if you take medicines used to treat stomach ulcers, heartburn, or acid reflux. These include:

  • antacids (such as aluminium hydroxide/magnesium hydroxide or calcium carbonate). These medicines 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 medicines should be taken at the same time as Harvoni. Do not take proton pump inhibitors before Harvoni. Your doctor may prescribe a different medicine or adjust the dose of the one you are taking;

• H2-receptor antagonists (such as famotidine, cimetidine, nizatidine, or

ranitidine). Your doctor may prescribe a different medicine or adjust the dose of the one you are taking.

These medicines may reduce the amount of ledipasvir 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 will advise you on how and when to take the medicine.

Pregnancy and contraception

The effects of Harvoni during pregnancy are unknown. If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Pregnancy must be avoided if taking Harvoni together with ribavirin. It is very important that you read carefully the "Pregnancy" section of the ribavirin package leaflet. Ribavirin can be very harmful to the unborn child. Therefore, special precautions must be taken regarding sexual activity if there is any possibility of pregnancy.

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

• If you or your partner becomes pregnant during treatment with Harvoni and ribavirin or in the months following, you must contact your doctor immediately.

Breast-feeding

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

Driving and using machines

If you feel tired after taking Harvoni, do not carry out activities that require concentration, for example, do not drive, ride a bicycle, or operate machinery.

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

• If your doctor has told you that you have an intolerance to certain sugars, inform them before taking this medicine.

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

• Inform your doctor if you are allergic to sunset yellow FCF, also known as "E110", before taking this medicine.

3. How to take Harvoni

Harvoni should be taken exactly as prescribed by your doctor. Do not change the dose or stop treatment without consulting your doctor.

• Recommended dose: The usual dose of Harvoni is one tablet taken once daily, with or without food.
• Duration of treatment: The length of treatment depends on whether you have been previously treated for hepatitis C and whether you have cirrhosis. Your doctor will determine the appropriate duration of treatment for you.
• Swallow the tablet whole: Do not crush, chew, or split the tablet.
• If you forget to take a dose: Take the missed dose as soon as you remember, unless it is almost time for your next dose. In that case, skip the missed dose and take your next dose at the regular time. Do not take two doses at the same time to make up for a missed dose.
• If you vomit after taking Harvoni: Take another tablet if you vomit within 4 hours after taking Harvoni. If vomiting occurs more than 4 hours after taking Harvoni, you do not need to take another tablet.

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

Follow exactly the administration instructions for this medicine as indicated by your doctor.

If in doubt, consult your doctor or pharmacist again.

Recommended dose

You must take Harvoni as directed by your physician. The recommended dose of Harvoni in adults is one 90 mg/400 mg film-coated tablet once daily. Your doctor will inform you for how many weeks you should take Harvoni.

The recommended dose of Harvoni in children aged 3 years and older is based on body weight.

Take Harvoni as directed by your physician.

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

If you are taking an antacid, take it at least 4 hours before or at least 4 hours after taking 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 vomit after taking Harvoni, this may affect the amount of Harvoni in your blood. This may cause Harvoni to be less effective.

• If you vomit within 5 hours after taking Harvoni, take another dose.

• If you 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, contact your doctor or the nearest emergency service immediately for advice. Bring the tablet bottle with you to easily describe what you have taken.

If you forget to take Harvoni

It is important not to miss any doses of this medicine.

If you miss a dose, consider how long it has been since you last took Harvoni:

• If you remember within 18 hours of your usual Harvoni intake time, take the missed dose as soon as possible. Then take the next dose at your usual time.
• If 18 hours or more have passed since your usual Harvoni intake time, wait and take the next dose at your usual time. Do not take a double dose (two doses within a short time interval).

Do not interrupt treatment with Harvoni

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 so that the medicine is in the best possible conditions to treat hepatitis C virus infection.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects. If you take

Harvoni, you may experience one or more of the following side effects:

Very common side effects

(may affect more than 1 in 10 people)

• headache

• fatigue

Common side effects

(may affect up to 1 in 10 people)

• skin rash

Other side effects that may occur during treatment with Harvoni

The frequency of the following adverse effects is unknown (cannot be estimated from the available data).

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

Other side effects that may occur during treatment with sofosbuvir:

The frequency of the following adverse effects is unknown (cannot be estimated from the available data).

• severe generalized rash with skin peeling, 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 experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through 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. Harvoni Storage

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 carton after "EXP". The expiry date is the last day of the month indicated.

This medicine does not require any special storage conditions.

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

6. Contents of the pack and other information

Composition of Harvoni

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

• Other components are:
  Tablet core:
  Copovidone, monohydrate lactose, microcrystalline cellulose, sodium croscarmellose, colloidal anhydrous silica, magnesium stearate

Film coating:
Polyvinyl alcohol, titanium dioxide, macrogol, talc, and only for the 90 mg/400 mg tablet: FCF orange-yellow (E110)

Nature of the product and contents of the pack

Harvoni 90 mg/400 mg film-coated tablets are orange-colored, diamond-shaped tablets, with "GSI" engraved on one side and "7985" on the other. The tablet measures approximately 19 mm in length and 10 mm in width.

Harvoni 45 mg/200 mg film-coated tablets are white, capsule-shaped tablets, with "GSI" engraved on one side and "HRV" on the other. The tablet measures approximately 14 mm in length and 7 mm in width.

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

The following pack sizes are available:

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

• packs of 3 bottles containing 28 (84) film-coated tablets, only for 90 mg/400 mg film-coated tablets. Only certain pack sizes may be marketed.

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 more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

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