Package leaflet: Information for the user

Ezetimibe/Simvastatin 10 mg/20 mg Tablets Ezetimibe/Simvastatin 10 mg/40 mg Tablets Ezetimibe/Simvastatin 10 mg/80 mg Tablets

Read all of this leaflet carefully before you start using 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 Ezetimibe/Simvastatin Tablets is and what it is used for

2.    What you need to know before you take Ezetimibe/Simvastatin Tablets

3.    How to take Ezetimibe/Simvastatin Tablets

4.    Possible side effects

5.    How to store Ezetimibe/Simvastatin Tablets

6.    Contents of the pack and other information

1. What Ezetimibe/Simvastatin Tablets is and what it is used for

Ezetimibe/Simvastatin Tablets is a medicine used to lower levels of total cholesterol, “bad” cholesterol (LDL cholesterol), and fatty substances called triglycerides in the blood. In addition, Ezetimibe/Simvastatin raises levels of “good” cholesterol (HDL cholesterol).

Ezetimibe/Simvastatin works to reduce your cholesterol in two ways. The active ingredient ezetimibe reduces the cholesterol absorbed in your digestive tract. The active ingredient simvastatin belonging to the class of “statins” inhibits the production of the cholesterol your body makes by itself.

Cholesterol is one of several fatty substances found in the bloodstream. Your total cholesterol is made up mainly of LDL and HDL cholesterol.

LDL cholesterol is often called “bad” cholesterol because it can build up in the walls of your arteries forming plaque. Eventually this plaque build-up can lead to a narrowing of the arteries. This narrowing can slow or block blood flow to vital organs such as the heart and brain. This blocking of blood flow can result in a heart attack or stroke.

HDL cholesterol is often called “good” cholesterol because it helps keep the bad cholesterol from building up in the arteries and protects against heart disease.

Triglycerides are another form of fat in your blood that may increase your risk for heart disease.

Ezetimibe/Simvastatin is used for patients who cannot control their cholesterol levels by diet alone. You should stay on a cholesterol-lowering diet while taking this medicine.

Ezetimibe/Simvastatin is used in addition to your cholesterol-lowering diet if you have:

•    a raised cholesterol level in your blood (primary hypercholesterolaemia [heterozygous familial and non-familial]) or elevated fat levels in your blood (mixed hyperlipidaemia):

-    that is not well controlled with a statin alone

-    for which you have used a statin and ezetimibe as separate tablets

•    a hereditary illness (homozygous familial hypercholesterolaemia) that increases the cholesterol level in your blood. You may also receive other treatments.

Ezetimibe/Simvastatin does not help you lose weight.

2. What you need to know before you take Ezetimibe/Simvastatin Tablets Do not take Ezetimibe/Simvastatin if you:

•    are allergic to ezetimibe, simvastatin, or any of the other ingredients of this medicine (listed in section 6)

•    currently have liver problems

•    are pregnant or breast-feeding

•    are taking medicine(s) with one or more than one of the following active ingredients:

-    itraconazole, ketoconazole, posaconazole or voriconazole (used to treat fungal infections)

-    erythromycin, clarithromycin, or telithromycin (used to treat infections)

-    HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (HIV protease inhibitors are used for HIV infections)

-    boceprevir or telaprevir (used to treat hepatitis C virus infection)

-    nefazodone (used to treat depression)

-    gemfibrozil (used to lower cholesterol)

-    ciclosporin (often used in organ transplant patients)

-    danazol (a man-made hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus)

•    are taking or, in the last 7 days, have taken or been given a medicine called fusidic acid (used to treat bacterial infection).

Ask your doctor if you are not sure if your medicine is listed above.

Warnings and precautions

Talk to your doctor or pharmacist before taking Ezetimibe/Simvastatin if you:

•    have any medicinal conditions including allergies

•    drink large amounts of alcohol or have ever had liver disease. Ezetimibe/Simvastatin may not be right for you

•    are due to have an operation. You may need to stop taking Ezetimibe/Simvastatin for a short time

•    are Asian, because a different dose may be applicable to you

•    have severe lung disease.

Your doctor should do a blood test before you start taking Ezetimibe/Simvastatin. This is to check how well your liver is working.

Your doctor may also want you to have blood tests to check how well your liver is working after you start taking Ezetimibe/Simvastatin.

While you are on this medicine your doctor will monitor you closely if you have diabetes or are at risk of developing diabetes. You are likely to be at risk of developing diabetes if you have high levels of sugars and fats in your blood, are overweight and have high blood pressure.

Tell your doctor if you have severe lung disease.

The combined use of Ezetimibe/Simvastatin and fibrates (certain medicines for lowering cholesterol) should be avoided since the combined use of Ezetimibe/Simvastatin and fibrates has not been studied.

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. This is because on rare occasions, muscle problems can be serious, including muscle breakdown resulting in kidney damage; and very rare deaths have occurred.

Also tell your doctor or pharmacist if you have a muscle weakness that is constant. Additional tests and medicines may be needed to diagnose and treat this.

The risk of muscle breakdown is greater at higher doses of Ezetimibe/Simvastatin, particularly the 10 mg/80 mg dose. The risk of muscle breakdown is also greater in certain patients. Talk with your doctor if any of the following applies:

•    you have kidney problems

•    you have thyroid problems

•    you are 65 years or older

•    you are female

•    you have ever had muscle problems during treatment with cholesterol lowering medicines called “statins” (like simvastatin, atorvastatin, and rosuvastatin) or fibrates (like gemfibrozil and bezafibrate)

•    you or close family members have a hereditary muscle disorder.

Children and adolescents

Ezetimibe/Simvastatin is not recommended for children under age 10.

Other medicines and Ezetimibe/Simvastatin

It is particularly important to tell your doctor if you are taking medicine(s) with any of the following active ingredients. Taking Ezetimibe/Simvastatin with any of these drugs can increase the risk of muscle problems (some of these have already been listed in the above section “Do not take Ezetimibe/Simvastatin").

•    ciclosporin (often used in organ transplant patients)

•    danazol (a man-made hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus)

•    medicines with an active ingredient like itraconazole, ketoconazole, fluconazole, posaconazole, or voriconazole (used to treat fungal infections)

•    fibrates with active ingredients like gemfibrozil and bezafibrate (used to lower cholesterol)

•    erythromycin, clarithromycin, telithromycin, or fusidic acid (used to treat bacterial infections). Do not take fusidic acid while using this medicine. Also see section 4 of this leaflet.

•    HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat AIDS)

•    boceprevir or telaprevir (used to treat hepatitis C virus infection)

•    nefazodone (used to treat depression)

•    amiodarone (used to treat an irregular heartbeat)

•    verapamil, diltiazem, or amlodipine (used to treat high blood pressure, chest pain associated with heart disease, or other heart conditions)

•    large amounts (1 gram or more each day) of niacin or nicotinic acid (also used to lower cholesterol)

•    colchicine (used to treat gout).

As well as the medicines listed above, tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. In particular, tell your doctor if you are taking any of the following:

•    medicines with an active ingredient to prevent blood clots, such as warfarin, fluindione, phenprocoumon or acenocoumarol (anticoagulants)

•    colestyramine (also used to lower cholesterol), because it affects the way Ezetimibe/Simvastatin works

•    fenofibrate (also used to lower cholesterol)

•    rifampicin (used to treat tuberculosis).

You should also tell any doctor who is prescribing a new medicine for you that you are taking Ezetimibe/Simvastatin.

Ezetimibe/Simvastatin with food and drink

Grapefruit juice contains one or more components that alter the metabolism of some medications, including Ezetimibe/Simvastatin. Consuming grapefruit juice should be avoided as it may increase your risk of muscle problems.

Pregnancy and breast-feeding

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

Do not take Ezetimibe/Simvastatinif you are pregnant. If you get pregnant while taking Ezetimibe/Simvastatin, stop taking it immediately and tell your doctor. Do not take Ezetimibe/Simvastatin if you are breast-feeding, because it is not known if the medicine is passed into breast milk.

Driving and using machines

Ezetimibe/Simvastatin is not expected to interfere with your ability to drive or to use machinery. However, it should be taken into account that some people get dizzy after taking Ezetimibe/Simvastatin.

Ezetimibe/Simvastatin Tablets contains lactose

Ezetimibe/Simvastatin tablets contain a sugar called 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.

3. How to take Ezetimibe/Simvastatin Tablets

Your doctor will determine the appropriate tablet strength for you, depending on your current treatment and your personal risk status.

The tablets are not scored and should not be divided.

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

•    Before starting Ezetimibe/Simvastatin, you should be on a diet to lower your cholesterol.

•    You should keep on this cholesterol-lowering diet while taking Ezetimibe/Simvastatin.

Adults: The dose is 1 tablet by mouth once a day.

Adolescents (10 to 17 years of age): The dose is 1 tablet by mouth once a day (a maximum dose of 10 mg/40 mg once daily must not be exceeded).

The Ezetimibe/Simvastatin 10 mg/80 mg dose is only recommended for adult patients with very high cholesterol levels and at high risk of heart disease problems who have not reached their cholesterol goal on lower doses.

Your doctor will determine the appropriate tablet strength for you, depending on your current treatment and your personal risk status.

Take Ezetimibe/Simvastatin in the evening. You can take it with or without food.

If your doctor has prescribed Ezetimibe/Simvastatin along with another medicine for lowering cholesterol containing the active ingredient colestyramine or any other bile acid sequestrant, you should take Ezetimibe/Simvastatin at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more Ezetimibe/Simvastatin Tablets than you should

Please contact your doctor or pharmacist.

If you forget to take Ezetimibe/Simvastatin Tablets

Do not take an extra dose, just take your normal amount of Ezetimibe/Simvastatin at the usual time the next day.

If you stop taking Ezetimibe/Simvastatin Tablets

Talk to your doctor or pharmacist because your cholesterol may rise again.

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 (see section

2).

The following common side effects were reported (may affect up to 1 in 10 people):

•    muscle aches

•    elevations in laboratory blood tests of liver (transaminases) and/or muscle (CK) function

The following uncommon side effects were reported (may affect up to 1 in 100 people):

•    elevations in blood tests of liver function; elevations in blood uric acid; elevations in the time it takes for blood to clot; protein in urine; weight decreased

•    dizziness; headache; tingling    sensation

•    abdominal pain; indigestion;    flatulence; nausea; vomiting; abdominal bloating; diarrhoea; dry

mouth; heartburn

•    rash; itching; hives

•    joint pain; muscle pain, tenderness, weakness or spasms; neck pain; pain in arms and legs; back pain

•    unusual tiredness or weakness; feeling tired; chest pain; swelling, especially in the hands and feet

•    sleep disorder; trouble sleeping

Additionally, the following side effects have been reported in people taking either combination of

ezetimibe and simvastatin or ezetimibe or simvastatin:

•    low red blood cell count (anaemia); reduction in blood cell counts, which may cause bruising/bleeding (thrombocytopenia)

•    numbness or weakness of the arms and legs; poor memory, memory loss, confusion

•    breathing problems including persistent cough and/or shortness of breath or fever

•    constipation

•    inflammation of the pancreas often with severe abdominal pain

•    inflammation of the liver with the following symptoms: yellowing of the skin and eyes; itching, dark coloured urine or pale coloured stool, feeling tired or weak, loss of appetite; liver failure; gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea, vomiting)

•    hair loss; raised red rash, sometimes with target-shaped lesions (erythema multiforme)

•    a hypersensitivity reaction including some of the following: hypersensitivity (allergic reactions including swelling of the face, lips, tongue and/or throat which may cause difficulty in breathing or swallowing and requires treatment immediately, pain or inflammation of the joints, inflammation of blood vessels, unusual bruising, skin eruptions and swelling, hives, skin sensitivity to the sun, fever, flushing, shortness of breath and feeling unwell, lupus-like disease picture (including rash, joint disorders, and effects on white blood cells))

•    muscle pain, tenderness, weakness or cramps; muscle breakdown; tendon problems, sometimes complicated by rupture of the tendon.

•    decreased appetite

•    hot flush; high blood pressure

•    pain

•    erectile dysfunction

•    depression

•    alterations in some    laboratory blood tests for liver function

Additional possible side effects reported with some statins:

•    sleep disturbances,    including nightmares

•    sexual difficulties

•    diabetes. This is more likely if you have high levels of sugars and fats in your blood, are overweight and have high blood pressure. Your doctor will monitor you while you are taking this medicine.

•    Muscle weakness that is constant (not known: cannot be estimated from the available data)

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. This is because on rare occasions, muscle problems can be serious, including muscle breakdown resulting in kidney damage; and very rare deaths have occurred.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Ezetimibe/Simvastatin Tablets Keep this medicine out of the sight and reach of children.

Do not use Ezetimibe/Simvastatin Tablets after the expiry date which is stated on the carton or container after EXP. The expiry date refers to the last day of that month.

Do not store above 25°C.

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 to protect the environment.

6. Contents of the pack and other information

What Ezetimibe/Simvastatin Tablets contains

The active substances are ezetimibe and simvastatin.

Each 10    mg / 20 mg Ezetimibe/Simvastatin tablet contains    10 mg    ezetimibe and    20 mg simvastatin.

Each 10    mg / 40 mg Ezetimibe/Simvastatin tablet contains    10 mg    ezetimibe and    40 mg simvastatin.

Each 10    mg / 80 mg Ezetimibe/Simvastatin tablet contains    10 mg    ezetimibe and    80 mg simvastatin.

The other ingredients are:

Tablet core: lactose monohydrate, hypromellose, croscarmellose sodium, microcrystalline cellulose, ascorbic acid, citric acid anhydrous, butylated hydroxyanisole, propyl gallate, magnesium stearate. Pigment blend: iron oxide yellow, iron oxide red and iron oxide black.

What Ezetimibe/Simvastatin Tablets looks like and contents of the pack

Ezetimibe/Simvastatin Tablets 10 mg/20 mg tablets are light tan, mottled, round, 8 mm in diameter, biconvex tablets, market with “512” on one side.

Ezetimibe/Simvastatin Tablets 10 mg/40 mg tablets are light tan, mottled, round, 10 mm in diameter, biconvex tablets, market with “513” on one side.

Ezetimibe/Simvastatin Tablets 10 mg/80 mg tablets are light tan, mottled, capsule shaped, 17.5 x 7.55 mm, biconvex tablets, market with “515” on one side.

Pack sizes:

Blister packs: 30 and 100 tablets HDPE tablet container: 100 and 180 tablets

Not all packs may be marketed.

Marketing Authorisation Holder

Actavis Group PTC ehf., Reykjavikurvegi 76-78, 220 Hafnarfjordur, Iceland Manufacturer

Balkanpharma-Dupnitsa AD, Balkanpharma-Dupnitsa AD, Dupnitza 2600, Bulgaria

This leaflet was last revised in 10/2016

PL 30306/0797 PL 30306/0798 PL 30306/0799