HARVONI 90 mg/400 mg FILM-COATED TABLETS

2. What you need to know before you take Harvoni

Do not take Harvoni

• If you are allergicto 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(a 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 levels).

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

Warnings and precautions

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

• other liver problemsapart from hepatitis C, for example

• if you are waiting for a liver transplant;

• if you have had a hepatitis B virus infection in the past,as your doctor may want to monitor you more closely;
• kidney problems or if you are on dialysis treatment,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.

Tell your doctor or pharmacist before starting treatment with Harvoni if:

• you are currently taking or have recently stopped taking the medicine amiodarone to treat irregular heart rhythm, 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 Harvoni treatment is needed, you may need additional heart monitoring.

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

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;

• dizziness;

• palpitations;

• fainting or feeling like you are about to faint.

Blood tests

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

• allow your doctor to decide if you should take Harvoni and for how long;

• allow your doctor to confirm that the treatment has worked and that you no longer have the hepatitis C virus.

Children and adolescents

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

Other medicines and Harvoni

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

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

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

If you are not sure if you should take any other medicine, ask your doctor or pharmacist.

Some medicines must not be taken with Harvoni.

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

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

• amiodarone,used to treat irregular heart rhythm

• tenofovir disoproxil fumarateor any medicine that contains 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 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 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 give you a different medicine or adjust the dose of the one you are taking;

• histamine H2-receptor antagonists (such as famotidine, cimetidine, nizatidine or ranitidine). Your doctor may give you 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 advise you on how and when to take it.

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 should be avoided if you are taking Harvoni with ribavirin. It is very important that you carefully read the section "Pregnancy" in the package leaflet of ribavirin. Ribavirin can be very harmful to the unborn baby. Special precautions should be taken in sexual activity if there is any possibility of pregnancy.

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

• If you or your partner become pregnant during treatment with Harvoni and ribavirin or in the months after treatment, you should contact your doctor immediately.

Breast-feeding

Do not breast-feed during treatment with Harvoni.It is not known if 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, do not perform activities that require concentration, such as driving, cycling or using machines.

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 some sugars, inform them before taking this medicine.

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

• Tell your doctor if you are allergicto orange yellow S (E110) before taking this medicine.

3. How to take Harvoni

Take this medicine exactly as your doctor has told you.

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

Recommended dose

You must take Harvoni as directed by your doctor.The recommended dose of Harvoni in adultsis one 90 mg/400 mg film-coated tablet once a day. Your doctor will tell you how many weeks you need to take Harvoni.

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

Take Harvoni as directed by your doctor.

Swallow the tablet(s) whole, with or without food. Do not chew, crush or break the tablet, as it has a very bitter taste. Tell your doctor or pharmacist if you have problems swallowing the 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 vomit after taking Harvonithis may affect the amount of Harvoni in the blood. This may make Harvoni work less well.

• If you vomit less than 5 hours aftertaking Harvoni, take another dose.

• If you vomit more than 5 hours aftertaking 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 department immediately for advice. Take the pack of tablets with you to show the doctor what you have taken.

If you forget to take Harvoni

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

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

• If it is within 18 hoursof when you usually take Harvoni, take the dose as soon as possible. Then take the next dose at the usual time.
• If it has been 18 hours or moresince you usually take Harvoni, wait and take the next dose at the usual time. Do not take a double dose (two doses in a short period of time).

Do not stop treatment with Harvoni

Do not stop treatment with 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 virus infection.

If you have any other 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, although not everybody gets them.

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 side effects 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 side effects cannot be estimated from the available data.

• widespread severe skin rash with skin peeling, possibly with fever, flu-like symptoms, blisters in 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. 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. Storage of 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 carton and blister after "EXP". The expiry date refers to the last day of the month stated.

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 no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

Composition of Harvoni

• The active ingredients areledipasvir 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.

• The other ingredients are:Core of the tablet:

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

Film coating:

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

Appearance of the Product and Container Content

Harvoni 90 mg/400 mg film-coated tablets are orange, rhombus-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 pouch or container and should not be swallowed.

The following package sizes are available:

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

• 3 bottles of 28 (84) film-coated tablets only for 90 mg/400 mg film-coated tablets. Not all package 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 further information on 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