Ezetimibe and simvastatin EG

Package leaflet: Information for the user

EZETIMIBE AND SIMVASTATIN EG 10 mg/10 mg tablets, mg/20 mg tablets, mg/40 mg tablets

Generic medicine
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.
• 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 EZETIMIBE AND SIMVASTATIN EG is and what it is used for
2. What you need to know before taking EZETIMIBE AND SIMVASTATIN EG
3. How to take EZETIMIBE AND SIMVASTATIN EG
4. Possible side effects
5. How to store EZETIMIBE AND SIMVASTATIN EG
6. Contents of the pack and other information

1. What EZETIMIBE AND SIMVASTATIN EG is and what it is used for

EZETIMIBE AND SIMVASTATIN EG is a medicine used to lower levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fats known as triglycerides in the blood. In addition, EZETIMIBE AND SIMVASTATIN EG increases levels of "good" cholesterol (HDL cholesterol).
EZETIMIBE AND SIMVASTATIN EG contains the active substances ezetimibe and simvastatin.
EZETIMIBE AND SIMVASTATIN EG works in two ways to lower cholesterol. The active substance ezetimibe reduces cholesterol absorbed in the gastrointestinal tract. The active substance simvastatin, which belongs to a class of medicines called "statins", inhibits the body's production of cholesterol.
Cholesterol is one of several fatty substances found in the bloodstream. Total cholesterol is made up mainly of LDL cholesterol and HDL cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can accumulate in the walls of arteries, forming plaques. Over time, this plaque buildup can lead to narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. This blockage of blood flow can cause a heart attack or stroke.
HDL cholesterol is often called "good" cholesterol because it helps prevent "bad" cholesterol from building up in the arteries and protects against heart disease.
Triglycerides are another form of fat in the blood that may increase the risk of heart disease.
EZETIMIBE AND SIMVASTATIN EG is used for patients who cannot control their cholesterol levels with diet alone. While taking this medicine, you must still follow a cholesterol-lowering diet.
EZETIMIBE AND SIMVASTATIN EG is used as an additional therapy to diet to lower cholesterol if you have:

• elevated cholesterol levels in the blood (primary hypercholesterolemia [heterozygous familial and non-familial]) or elevated levels of fats in the blood (mixed hyperlipidemia):
• that are not well controlled by a statin alone,
• for which you have previously been treated with separate tablets containing a statin and ezetimibe;
• a hereditary disease (homozygous familial hypercholesterolemia) that increases your blood cholesterol levels. You may also be receiving other treatments;
• heart disease; EZETIMIBE AND SIMVASTATIN EG reduces the risk of heart attack, stroke, surgical procedures to improve blood flow, or hospitalization due to chest pain.

EZETIMIBE AND SIMVASTATIN EG does not help with weight loss.

2. What you should know before taking EZETIMIBE AND SIMVASTATIN EG

Do not take EZETIMIBE AND SIMVASTATIN EG:

• if you are allergic to ezetimibe, simvastatin, or any of the other ingredients of this medicine (listed in section 6);
• if you currently have liver problems;
• if you are pregnant or breastfeeding;
• if you are taking one or more medicines containing any of the following active substances:
• 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 to treat HIV infections),
• boceprevir or telaprevir (used to treat hepatitis C virus infections),
• nefazodone (used to treat depression),
• cobicistat,
• gemfibrozil (used to lower cholesterol),
• cyclosporine (often used in organ transplant patients),
• danazol (a hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus);
• if you are taking or have taken within the last 7 days a medicine called fusidic acid (used to treat bacterial infection) by mouth or by injection. The combination of fusidic acid and EZETIMIBE AND SIMVASTATIN EG may cause serious muscle problems (rhabdomyolysis);
• do not take more than 10 mg/40 mg of EZETIMIBE AND SIMVASTATIN EG if you are taking lomitapide (used to treat a rare, severe genetic cholesterol condition). Ask your doctor for advice if you are unsure whether the medicine you are taking is one of those listed above.

Warnings and precautions
Talk to your doctor or pharmacist before taking EZETIMIBE AND SIMVASTATIN EG if:

• you suffer from any medical condition, including allergies;
• you consume large amounts of alcohol or have ever had liver disease. EZETIMIBE AND SIMVASTATIN EG may not be suitable for you;
• you are due to undergo surgery. You may need to stop taking EZETIMIBE AND SIMVASTATIN EG temporarily;
• you are of Asian origin, as you may require a different dose.

Your doctor should perform a blood test before you start taking EZETIMIBE AND SIMVASTATIN EG. This test is done to check whether your liver is functioning properly. Your doctor may also order periodic blood tests to monitor liver function after you have started taking EZETIMIBE AND SIMVASTATIN EG. During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing diabetes. You are at risk of developing diabetes if you have high levels of sugar and fat in your blood, are overweight, or have high blood pressure. Inform your doctor if you have a serious lung disease. The combined use of EZETIMIBE AND SIMVASTATIN EG with fibrates (a type of medicine used to lower cholesterol) should be avoided, as the combination has not been studied. Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness, as muscle problems can, rarely, be serious and lead to muscle tissue damage causing kidney injury; very rarely, cases of death have occurred. Always inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and treatments may be needed to diagnose and manage this condition. The risk of muscle injury is higher with higher doses of EZETIMIBE AND SIMVASTATIN EG, particularly with the 10 mg/80 mg dose. The risk of muscle injury is also increased in certain patients. Inform your doctor if any of the following apply to you:

• you have kidney problems;
• you have thyroid problems;
• you are 65 years of age or older;
• you are female;
• you have previously experienced muscle problems while being treated with cholesterol-lowering medicines known as "statins" (such as simvastatin, atorvastatin, and rosuvastatin) or fibrates (such as gemfibrozil and bezafibrate);
• you or your close family members have a hereditary muscle disease.

Children and adolescents
The use of EZETIMIBE AND SIMVASTATIN EG is not recommended in children under 10 years of age.

Other medicines and EZETIMIBE AND SIMVASTATIN EG
Inform your doctor if you are taking, have recently taken, or might take any other medicine containing any of the following active substances. Taking EZETIMIBE AND SIMVASTATIN EG with any of the following medicines may increase the risk of muscle problems (some of which have already been mentioned in the section "Do not take EZETIMIBE AND SIMVASTATIN EG"):

• if you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart EZETIMIBE AND SIMVASTATIN EG. Taking EZETIMIBE AND SIMVASTATIN EG with fusidic acid may, in rare cases, lead to muscle weakness or pain (rhabdomyolysis). For more information on rhabdomyolysis, see also section 4;
• cyclosporine (often used in patients who have received an organ transplant);
• danazol (an artificial hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus);
• medicines containing active substances such as itraconazole, ketoconazole, fluconazole, posaconazole, or voriconazole (used to treat fungal infections);
• fibrates containing active substances such as gemfibrozil and bezafibrate (used to reduce cholesterol);
• erythromycin, clarithromycin, or telithromycin (used to treat bacterial infections);
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat AIDS);
• boceprevir or telaprevir (used to treat hepatitis C virus infections);
• nefazodone (used to treat depression);
• medicines containing the active substance cobicistat;
• amiodarone (used to treat irregular heartbeat);
• verapamil, diltiazem, or amlodipine (used to treat high blood pressure, chest pain associated with heart disease, or other heart conditions);
• lomitapide (used to treat a rare, severe genetic cholesterol condition);
• high doses (1 g or more per day) of niacin or nicotinic acid (also used to lower cholesterol);
• colchicine (used to treat gout).

In addition to the medicines listed above, inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine, including those without a prescription. In particular, tell your doctor if you are taking any of the following:

• medicines containing active substances used to prevent blood clots, such as warfarin, fluindione, phenprocoumon, or acenocoumarol (anticoagulants);
• colestyramine (also used to lower cholesterol), as it affects how EZETIMIBE AND SIMVASTATIN EG works;
• fenofibrate (also used to lower cholesterol);
• rifampicin (used to treat tuberculosis).

You should also inform any doctor who prescribes you a new medicine that you are taking EZETIMIBE AND SIMVASTATIN EG.

EZETIMIBE AND SIMVASTATIN EG with food and drink
Grapefruit juice contains one or more substances that alter the metabolism of certain medicines, including EZETIMIBE AND SIMVASTATIN EG. Consumption of grapefruit juice should be avoided, as it may increase the risk of muscle problems.

Pregnancy and breastfeeding
Do not take EZETIMIBE AND SIMVASTATIN EG if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. If you become pregnant while taking EZETIMIBE AND SIMVASTATIN EG, stop taking it immediately and contact your doctor. Do not take EZETIMIBE AND SIMVASTATIN EG if you are breastfeeding, as it is not known whether the medicine passes into breast milk. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
EZETIMIBE AND SIMVASTATIN EG is not expected to affect your ability to drive or use machines. However, bear in mind that some people have experienced dizziness after taking EZETIMIBE AND SIMVASTATIN EG.

EZETIMIBE AND SIMVASTATIN EG contains lactose and sodium
EZETIMIBE AND SIMVASTATIN EG tablets contain a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine. This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to take EZETIMIBE AND SIMVASTATIN EG

Your doctor will determine the appropriate tablet strength for you, based on your current treatment and individual risk profile.
The tablets do not have a break line and must not be divided.
Take this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.

• Before starting treatment with EZETIMIBE AND SIMVASTATIN EG, you must already be on a cholesterol-lowering diet.
• During treatment with EZETIMIBE AND SIMVASTATIN EG, you must continue this cholesterol-lowering diet.
  Adults: The dose is 1 tablet taken orally once daily.
  Adolescents (aged 10 to 17 years): The dose is 1 tablet taken orally once daily (the maximum dose should not exceed 10 mg/40 mg once daily).

A dose of ezetimibe and simvastatin 10 mg/80 mg is recommended only for adult patients with very high cholesterol levels and high risk of heart disease who have not reached their target cholesterol levels with lower doses.
If optimal dosing cannot be achieved with EZETIMIBE AND SIMVASTATIN EG, your doctor may prescribe other tablets containing ezetimibe/simvastatin.
Take EZETIMIBE AND SIMVASTATIN EG in the evening. It may be taken with or without food.
If your doctor has prescribed EZETIMIBE AND SIMVASTATIN EG together with another cholesterol-lowering medicine containing the active substance colestyramine or any other bile acid sequestrant, you must take EZETIMIBE AND SIMVASTATIN EG at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more EZETIMIBE AND SIMVASTATIN EG than you should
Contact your doctor or pharmacist.

If you forget to take EZETIMIBE AND SIMVASTATIN EG
Do not take a double dose to make up for the missed tablet. Take only the usual dose at the regular time the next day.

If you stop taking EZETIMIBE AND SIMVASTATIN EG
Consult your doctor or pharmacist, as your cholesterol levels may rise again.

If you have any doubts 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 experiences them (see section 2).
The following common side effects have been reported (may affect up to 1 in 10 people):

• muscle pain;
• increases in blood laboratory test values related to liver function (transaminases) and/or muscle (CK).

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

• increases in blood test values related to liver function; increases in blood uric acid levels; prolonged blood clotting time; presence of protein in urine; decrease in body weight;
• dizziness; headache; tingling sensation;
• abdominal pain; indigestion; flatulence; nausea; vomiting; abdominal swelling; diarrhoea; dry mouth; heartburn;
• rash; itching; urticaria;
• joint pain; muscle pain; tenderness; weakness or spasms; neck pain; pain in arms and legs; back pain;
• unusual tiredness or weakness; feeling of fatigue; chest pain; swelling, especially of hands and feet;
• sleep disorders; difficulty falling asleep.

Additionally, the following side effects have been reported in people taking the combination
ezetimibe/simvastatin or medicines containing the active substances ezetimibe or simvastatin:

• reduced number of red blood cells (anaemia); decreased number of blood cells, which may cause bruising/bleeding (thrombocytopenia);
• loss of sensation or weakness in 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 stools; feeling of tiredness or weakness; loss of appetite; liver failure; gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea and vomiting);
• hair loss; red, raised rash, sometimes with target-like lesions (erythema multiforme);
• hypersensitivity reaction including some of the following features: hypersensitivity (allergic reactions including swelling of the face, lips, tongue and/or throat which may cause difficulty breathing or swallowing and requires immediate treatment (angioedema)); a severe allergic reaction, very rare, causing breathing difficulties or dizziness (anaphylaxis); joint pain; inflammation of blood vessels; abnormal bruising; skin rashes and swelling; urticaria; skin sensitivity to sunlight; fever; hot flushes; shortness of breath and feeling unwell; lupus-like symptoms (including skin rash, joint problems, and effects on white blood cells); muscle pain; tenderness; weakness or muscle cramps; muscle injury; tendon problems, sometimes complicated by tendon rupture;
• decreased appetite;
• hot flushes; high blood pressure;
• pain;
• erectile dysfunction;
• depression;
• changes in certain blood test values related to 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 sugar and fats in the blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine;
• muscle pain, tenderness or weakness that is persistent and may not resolve after stopping treatment with EZETIMIBE E SIMVASTATINA EG (frequency not known: cannot be estimated from available data).

Contact your doctor immediately if you experience unexplained muscle pain, tenderness or weakness.
This is because muscle problems can, rarely, be serious and lead to muscle tissue damage causing kidney injury; very rare cases of death have occurred.

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 at: http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store EZETIMIBE AND SIMVASTATIN EG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date 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 dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What EZETIMIBE E SIMVASTATINA EG contains
The active substances are ezetimibe and simvastatin.
Each tablet contains 10 mg of ezetimibe and 10 mg of simvastatin.
Each tablet contains 10 mg of ezetimibe and 20 mg of simvastatin.
Each tablet contains 10 mg of ezetimibe and 40 mg of simvastatin.
The other components are:
Tablet core: monohydrate lactose, hypromellose, sodium croscarmellose, microcrystalline cellulose,
ascorbic acid, anhydrous citric acid, butylhydroxyanisole, propyl gallate, magnesium stearate.
Colouring mixture: monohydrate lactose, yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172).

Description of the appearance of EZETIMIBE E SIMVASTATINA EG and package contents
EZETIMIBE E SIMVASTATINA EG 10 mg/10 mg are light brown, mottled, round, biconvex tablets, 6 mm in diameter, engraved with "511" on one side.
EZETIMIBE E SIMVASTATINA EG 10 mg/20 mg are light brown, mottled, round, biconvex tablets, 8 mm in diameter, engraved with "512" on one side.
EZETIMIBE E SIMVASTATINA EG 10 mg/40 mg are light brown, mottled, round, biconvex tablets, 10 mm in diameter, engraved with "513" on one side.

Pack sizes
Blister packs:
[10 mg/10 mg]
Pack sizes: 14, 28, 30, 50, 98 and 100 tablets.
[10 mg/20 mg; 10 mg/40 mg]
Pack sizes: 28, 30, 50, 98 and 100 tablets.

HDPE bottle:
100 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder
EG S.p.A., Via Pavia 6, 20136 Milano, Italy

Manufacturers
Balkanpharma-Dupnitsa AD, 3 Samokovsko Shosse Str., Dupnitza 2600 – Bulgaria
STADA Arzneimittel AG, Stadastrasse 2–18, 61118 Bad Vilbel – Germany
STADA Arzneimittel GmbH, Muthgasse 36/2, 1190 Wien – Austria
Centrafarm Services B.V., Nieuwe Donk 9, NL-4879 AC Etten-Leur – Netherlands
Clonmel Healthcare Ltd., Waterford Road, Clonmel, Co. Tipperary – Ireland

This medicinal product is authorized in the European Economic Area countries under the following names:
AT Ezetimib/Simvastatin STADA
BE Ezetimibe/Simvastatine EG
CZ Ezetimib/Simvastatin STADA
DE Ezetimib/Simvastatin AL
DK Ezetimib/Simvastatin STADA
ES Ezetimiba/Simvastatina STADA
FR EZETIMIBE/SIMVASTATINE EG
IE Ezetimibe/Simvastatin Clonmel
IT Ezetimibe e Simvastatina EG
LU Ezetimibe/Simvastatine EG
NL Ezetimibe/Simvastatine CF
PT Sinvastatina + Ezetimiba Ciclum
SI Ezetimib/simvastatin STADA