Ezetimibe and simvastatin Zentiva

Patient Information Leaflet

Ezetimibe and Simvastatin Zentiva 10 mg/10 mg tablets, mg/20 mg tablets, mg/40 mg tablets

Generic medicine
Please read this leaflet carefully before taking this medicine, as 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 others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, speak to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Ezetimibe and Simvastatin Zentiva is and what it is used for
2. What you need to know before taking Ezetimibe and Simvastatin Zentiva
3. How to take Ezetimibe and Simvastatin Zentiva
4. Possible side effects
5. How to store Ezetimibe and Simvastatin Zentiva
6. Contents of the pack and other information

1. What Ezetimibe and Simvastatin Zentiva is and what it is used for

Ezetimibe and Simvastatin Zentiva contains the active substances ezetimibe and simvastatin.
Ezetimibe and Simvastatin Zentiva 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 and Simvastatin Zentiva increases levels of "good" cholesterol (HDL cholesterol).
Ezetimibe and Simvastatin Zentiva works in two ways to lower cholesterol. The active substance ezetimibe reduces the amount of cholesterol absorbed in the gastrointestinal tract. The active substance simvastatin, which belongs to the class of "statins", inhibits the body's own production of cholesterol.
Cholesterol is one of several fatty substances found in the bloodstream. Total cholesterol consists 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. Such blockage of blood flow may 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 type of fat in the blood that may increase the risk of heart disease.
Ezetimibe and Simvastatin Zentiva is used for patients who cannot control their cholesterol levels through diet alone. While taking this medicine, you should still follow a cholesterol-lowering diet.
Ezetimibe and Simvastatin Zentiva is used as an additional therapy to diet to lower cholesterol if you have:

• elevated levels of cholesterol in the blood (primary hypercholesterolaemia) [heterozygous familial and non-familial] or elevated levels of fats in the blood (mixed hyperlipidaemia):
  • that are not adequately controlled by a statin alone
  • for which you have previously been treated with a statin and ezetimibe as separate tablets
• an inherited disease (homozygous familial hypercholesterolaemia) that increases your blood cholesterol levels. You may also be receiving other treatments.
• heart disease; Ezetimibe and Simvastatin Zentiva reduces the risk of heart attack, stroke, surgery to improve blood flow to the heart, or hospitalisation due to chest pain.

Ezetimibe and Simvastatin Zentiva does not help with weight loss.

2. What you should know before taking Ezetimibe and Simvastatin Zentiva

Do not take Ezetimibe and Simvastatin Zentiva if

• you are allergic to ezetimibe, simvastatin, or any of the other ingredients of this medicine (listed in section 6)
• you currently have liver problems
• you are pregnant or breastfeeding
• you are taking a medicine(s) containing one or more 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)
  • ciclosporin (often used in patients who have had an organ transplant)
  • danazol (a hormone produced in the body used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus)
• you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine used to treat bacterial infection). The combination of fusidic acid and Ezetimibe and Simvastatin Zentiva can lead to serious muscle problems (rhabdomyolysis).
• Do not take more than 10 mg/40 mg of Ezetimibe and Simvastatin Zentiva if you are taking lomitapide (used to treat a rare, genetic condition causing severely high cholesterol).

Ask your doctor for advice if you are unsure whether the medicine you are taking is included in the list above.

Warnings and precautions

Tell your doctor or pharmacist before taking Ezetimibe and Simvastatin Zentiva if:

• you have any medical condition, including allergies.
• you consume large amounts of alcohol or have ever had liver disease. In this case, Ezetimibe and Simvastatin Zentiva may not be suitable for you.
• you are scheduled for surgery. You may need to stop taking Ezetimibe and Simvastatin Zentiva tablets for a short period.
• you are of Asian origin, as you may require a different dose.
• you have a severe lung disease.

Your doctor will perform a blood test before starting Ezetimibe and Simvastatin Zentiva and if you develop symptoms of liver problems while taking it. This test checks whether your liver is functioning properly.
Your doctor may also prescribe periodic blood tests to monitor liver function after starting treatment with Ezetimibe and Simvastatin Zentiva.
During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing diabetes. You may be at increased risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, or have high blood pressure.
Concomitant administration of Ezetimibe and Simvastatin Zentiva with fibrates (a type of cholesterol-lowering medicine) should be avoided, as the combination has not been studied.

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness.
Rarely, muscle problems can be severe and include damage to muscle tissue leading to kidney damage; very rarely, cases of death have occurred.
The risk of muscle damage is higher at higher doses of Ezetimibe and Simvastatin Zentiva, particularly with the 10 mg/80 mg dose. The risk of muscle damage 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 during treatment 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.

Additionally, inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and treatment may be needed to diagnose and manage this condition.

Children and adolescents
The use of Ezetimibe and Simvastatin Zentiva is not recommended in children under 10 years of age.

Other medicines and Ezetimibe and Simvastatin Zentiva
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 Zentiva 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 Zentiva”).

• 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 Zentiva. Taking Ezetimibe and Simvastatin Zentiva with fusidic acid may rarely cause muscle weakness, pain, or tenderness (rhabdomyolysis). See more information about rhabdomyolysis in section 4.
• Ciclosporin (often used in patients who have had an organ transplant).
• Danazol (a synthetic 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).
• Antiviral agents for hepatitis C such as boceprevir, telaprevir, elbasvir, or grazoprevir (used to treat hepatitis C virus infection).
• 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, genetic condition causing severely high cholesterol).
• Daptomycin (a medicine used to treat complicated skin and skin structure infections and bacteremia). The risk of muscle-related side effects may be increased when this medicine is taken during treatment with simvastatin (e.g., Ezetimibe and Simvastatin Zentiva). Your doctor may decide that you should temporarily stop taking Ezetimibe and Simvastatin Zentiva.
• 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 or have recently taken 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 Zentiva works.
• fenofibrate (also used to lower cholesterol).
• rifampicin (used to treat tuberculosis).
• ticagrelor (used to prevent heart attack or stroke).

You should also inform any doctor who prescribes you a new medicine that you are taking Ezetimibe and Simvastatin Zentiva.

Ezetimibe and Simvastatin Zentiva with food and drink
Grapefruit juice contains one or more substances that alter the metabolism of certain medicines, including Ezetimibe and Simvastatin Zentiva. Grapefruit juice should be avoided, as it may increase the risk of muscle problems.

Pregnancy and breastfeeding
Do not take Ezetimibe and Simvastatin Zentiva if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If you become pregnant while taking Ezetimibe and Simvastatin Zentiva, stop treatment immediately and contact your doctor. Ezetimibe and Simvastatin Zentiva should not be used if you are breastfeeding, as it is not known whether the medicine passes into human milk.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Ezetimibe and Simvastatin Zentiva is not expected to affect your ability to drive or use machines. However, you should be aware that some people have experienced dizziness after taking Ezetimibe and Simvastatin Zentiva.

Ezetimibe and Simvastatin Zentiva contains lactose and sodium
Ezetimibe and Simvastatin Zentiva tablets contain a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, consult your doctor before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take Ezetimibe and Simvastatin Zentiva

Your doctor will determine the appropriate tablet dose for you, based on your current treatment and your risk profile.
Always take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

• Before starting to take Ezetimibe and Simvastatin Zentiva, you must already be following a cholesterol-lowering diet.
• While being treated with Ezetimibe and Simvastatin Zentiva, you must continue to follow this cholesterol-lowering diet.

Adults: The dose is 1 tablet taken orally once daily.
Use in adolescents (aged 10 to 17 years): The dose is 1 tablet taken orally once daily (a maximum dose of 10 mg/40 mg once daily must not be exceeded).
The 10 mg/80 mg dose of Ezetimibe and Simvastatin Zentiva is recommended only for adult patients with very high cholesterol levels and at high risk for heart disease who have not achieved their target cholesterol levels with lower doses.
If the optimal dose cannot be achieved using Ezetimibe and Simvastatin Zentiva, your doctor may prescribe other tablets containing ezetimibe/simvastatin.
The tablets do not have a break line and must not be divided.
Take Ezetimibe and Simvastatin Zentiva in the evening. You may take it with or without food.
If your doctor has prescribed Ezetimibe and Simvastatin Zentiva together with another cholesterol-lowering medicine containing the active substance colestyramine or any other bile acid sequestrant, you must take Ezetimibe and Simvastatin Zentiva at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more Ezetimibe and Simvastatin Zentiva than you should
Contact your doctor or pharmacist.

If you forget to take Ezetimibe and Simvastatin Zentiva
Do not take a double dose to make up for the forgotten tablet. Take only the usual dose of Ezetimibe and Simvastatin Zentiva at the normal time the next day.

If you stop taking Ezetimibe and Simvastatin Zentiva
Consult your doctor or pharmacist, as your cholesterol levels may rise again.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets 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 function (CK)

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

• increased blood test values indicating liver function abnormalities; increased 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 bloating; diarrhoea; dry mouth; heartburn
• skin rash; itching; urticaria
• joint pain; muscle pain; tenderness; weakness or spasms; neck pain; arm or leg pain; back pain
• unusual tiredness or weakness; feeling of fatigue; chest pain; swelling, especially of the hands and feet
• sleep disorder; difficulty falling asleep

The following rare side effects have been reported (may affect up to 1 in 1,000 people):

• blurred vision and impaired vision
• a hypersensitivity reaction including some of the following features: allergic reactions including swelling of the face, lips, tongue, and/or throat, which may cause difficulty breathing or swallowing and requires immediate treatment (angioedema); joint pain or inflammation; inflammation of blood vessels; unusual bruising; skin rashes and swelling; urticaria; skin sensitivity to sunlight; fever; hot flushes; shortness of breath; feeling unwell; lupus-like illness (including skin rash, joint problems, and effects on white blood cells)
• poor memory, memory loss, confusion

The following very rare side effects have been reported (may affect up to 1 in 10,000 people):

• a severe allergic reaction causing breathing difficulties or dizziness (anaphylaxis)
• gynaecomastia (enlargement of the breast in men)
• Skin rash which may occur on the skin or mouth sores (drug-induced lichenoid eruptions)
• Muscle rupture

In addition, the following side effects have been reported with a frequency not known (cannot be estimated from the available data) in people taking ezetimibe/simvastatin in combination or ezetimibe or simvastatin alone:

• decrease in red blood cell count (anaemia); decrease in blood cells which may lead to bruising/bleeding (thrombocytopenia)
• loss of sensation or weakness in arms and legs
• lung inflammation causing 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 stomach
• liver inflammation with the following symptoms: yellowing of the skin and eyes; itching; dark urine or pale stools; feeling tired or weak; loss of appetite; liver failure; gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea and vomiting)
• hair loss; red, raised skin rash, sometimes with target-shaped lesions (erythema multiforme)
• muscle pain, tenderness, weakness or muscle cramps; muscle damage; 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
• persistent muscle weakness

Additional possible side effects reported with some statins:

• sleep disorders, including nightmares
• sexual difficulties
• diabetes. This is more likely if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine.

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

Reporting of side effects
If you get any side effects, 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 https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ezetimibe and Simvastatin Zentiva

Keep this medicine out of the sight and reach of children.
Do not use Ezetimibe and Simvastatin Zentiva after the expiry date stated on the container after the word “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 and Simvastatin Zentiva 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: lactose monohydrate, hypromellose,
sodium croscarmellose, microcrystalline cellulose, ascorbic acid, anhydrous citric acid,
butylated hydroxyanisole, propyl gallate, magnesium stearate. Pigment mixture:
lactose monohydrate, yellow iron oxide (E172), red iron oxide (E172), and black iron oxide
(E172).

Description of the appearance of Ezetimibe and Simvastatin Zentiva and contents of the pack
Ezetimibe and Simvastatin Zentiva 10 mg/10 mg tablets are light brown, mottled, round, 6 mm in diameter, biconvex, marked with "511" on one side.
Ezetimibe and Simvastatin Zentiva 10 mg/20 mg tablets are light brown, mottled, round, 8 mm in diameter, biconvex, marked with "512" on one side.
Ezetimibe and Simvastatin Zentiva 10 mg/40 mg tablets are light brown, mottled, round, 10 mm in diameter, biconvex, marked with "513" on one side.

Pack sizes
10 mg/10 mg: 10, 30, 50, 100 and 300 tablets
10 mg/20 mg; 10 mg/40 mg: 30, 50, 100 and 300 tablets
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milano
Italy

Manufacturers
Balkanpharma-Dupnitsa AD
3 Samokovsko Shosse Str.,
Dupnitza 2600, Bulgaria

Special Product's Line S.p.A.
Via Fratta Rotonda Vado Largo 1
03012 Anagni (FR)
Italy

This medicinal product is authorised in the European Economic Area Member States under the following names:
Ezimvalla in Denmark;
Ezetimib Simvastatin Zentiva in Germany;
Ezetimibe e Simvastatina Zentiva in Italy;
Ezetimiba + Sinvastatina Zentiva in Portugal;
Cornusan in Slovakia;
Axocar in Poland.