Ezetimibe and simvastatin Alter

Package leaflet: Information for the patient

Ezetimibe and Simvastatin Alter 10 mg/10 mg tablets

Ezetimibe and Simvastatin Alter 10 mg/20 mg tablets, Alter 10 mg/40 mg tablets
Ezetimibe/simvastatin
Generic medicine
Please read all of this leaflet carefully before 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 others, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

Ezetimibe and Simvastatin Alter contains the active substances ezetimibe and simvastatin.
Ezetimibe and Simvastatin Alter 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 Alter increases levels of "good" cholesterol (HDL cholesterol).
Ezetimibe and Simvastatin Alter 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 the class of medicines known as "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 present in the blood that may increase the risk of heart disease.
Ezetimibe and Simvastatin Alter 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 Alter is used as an additional therapy to diet to lower cholesterol if you have:

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

Ezetimibe and Simvastatin Alter does not help with weight loss.

2. What you need to know before taking Ezetimibe and Simvastatin Alter

Do not take Ezetimibe and Simvastatin Alter:

• 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 a medicine or medicines containing one or more of the following active substances:
  o itraconazole, ketoconazole, posaconazole or voriconazole (used to treat fungal infections)
  o erythromycin, clarithromycin or telithromycin (used to treat infections)
  o HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir (HIV protease inhibitors are used to treat HIV infections)
  o boceprevir or telaprevir (used to treat hepatitis C virus infections)
  o nefazodone (used to treat depression)
  o cobicistat or gemfibrozil (used to lower cholesterol)

  o cyclosporine (often used in patients who have had an organ transplant)
  o danazol (a male hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus).

• if you are currently 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 Alter can cause serious muscle problems (rhabdomyolysis).

Do not take more than 10 mg/40 mg of Ezetimibe and Simvastatin Alter 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 Alter if:

• you suffer from any medical condition, including allergies.
• you consume large amounts of alcohol or have ever had a liver disease. Ezetimibe and Simvastatin Alter may not be suitable for you.
• you are due to undergo surgery. You may need to stop taking Ezetimibe and Simvastatin Alter for a short period.
• you are of Asian origin, as you may require a different dose.

Your doctor should perform a blood test before starting Ezetimibe and Simvastatin Alter and if you develop symptoms of liver problems while taking Ezetimibe and Simvastatin Alter. 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 Alter.
While taking 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 fats 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 Alter with fibrates (some types of medicines used to lower cholesterol) should be avoided, as the combination of Ezetimibe and Simvastatin Alter with fibrates has not been studied.
Contact your doctor immediately if you experience unexplained muscle pain, tenderness or weakness, as muscle problems can rarely be severe and lead to muscle tissue damage causing kidney damage; very rarely, cases of death have occurred.
The risk of muscle damage is higher with higher doses of Ezetimibe and Simvastatin Alter, particularly with the 10/80 mg dose. The risk of muscle damage is also increased in certain patients. Inform your doctor if any of the following conditions 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.

Always inform your doctor or pharmacist if you have persistent muscle weakness.
Additional tests and treatments may be needed to diagnose and manage this condition.

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

Other medicines and Ezetimibe and Simvastatin Alter
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 Alter with any of the following medicines may increase the risk of muscle problems (some have already been mentioned in the section “Do not take Ezetimibe and Simvastatin Alter”):

• 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 you can safely restart Ezetimibe and Simvastatin Alter. Taking Ezetimibe and Simvastatin Alter with fusidic acid can rarely lead to muscle weakness or pain (rhabdomyolysis). For more information about rhabdomyolysis, see also section 4.
• cyclosporine (often used in patients who have received 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 with 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, 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 with an active substance 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 Alter 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 Alter.

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

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take Ezetimibe and Simvastatin Alter if you are pregnant, suspect you may be pregnant, or are planning to become pregnant. If you become pregnant while taking Ezetimibe and Simvastatin Alter, stop taking it immediately and contact your doctor. Do not take Ezetimibe and Simvastatin Alter if you are breastfeeding, as it is not known whether the medicine passes into breast milk.

Driving and using machines
Ezetimibe and Simvastatin Alter is not expected to affect your ability to drive or operate machinery. However, bear in mind that some people have experienced dizziness after taking Ezetimibe and Simvastatin Alter.

Ezetimibe and Simvastatin Alter contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Ezetimibe and Simvastatin Alter

Your doctor will determine the appropriate tablet dosage for you, based on your current treatment and individual risk profile.
The tablets do not have a break line and must not be divided.
Always take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

• Before starting treatment with Ezetimibe and Simvastatin Alter, you must already be following a cholesterol-lowering diet.
• During treatment with Ezetimibe and Simvastatin Alter, you must continue to follow this cholesterol-lowering diet.

Adults: The dose is 1 tablet of Ezetimibe and Simvastatin Alter taken orally once daily.
Use in adolescents (aged 10 to 17 years): The dose is 1 tablet of Ezetimibe and Simvastatin Alter taken orally once daily (the maximum dose must not exceed 10 mg/40 mg once daily).
The 10 mg/80 mg dose of Ezetimibe and Simvastatin Alter 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.
Take Ezetimibe and Simvastatin Alter in the evening. It can be taken with or without food.
If your doctor has prescribed Ezetimibe and Simvastatin Alter together with another cholesterol-lowering medicine containing the active ingredient colestyramine or any other bile acid sequestrant, you must take Ezetimibe and Simvastatin Alter at least 2 hours before or 4 hours after taking the bile acid sequestrant.

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

If you forget to take Ezetimibe and Simvastatin Alter
Do not take a double dose to make up for the missed tablet. Take only the next normal dose at your usual time the following day.

If you stop taking Ezetimibe and Simvastatin Alter
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 everybody gets them (see section 2. What you need to know before taking Ezetimibe and Simvastatin Alter).

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
• skin 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 of fatigue; chest pain; swelling, especially of the hands and feet
• sleep disorders; difficulty falling asleep

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

• decrease in red blood cell count (anaemia); decrease in 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 urine or pale 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 skin rash, sometimes with target-like lesions (erythema multiforme)
• hypersensitivity reaction which has included some of the following features: hypersensitivity (allergic reactions including swelling of the face, lips, tongue and/or throat which may cause difficulty in breathing or swallowing and requires immediate treatment (angioedema), a severe allergic reaction causing breathing difficulties or dizziness (anaphylaxis, which may affect up to 1 in 10,000 people and anaphylactic reactions), joint pain, inflammation of blood vessels, unusual bruising, skin rashes and swelling, hives, 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 disorders, including nightmares
• sexual difficulties
• diabetes. This is more likely if you have high levels of sugar and fat in your 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 this medicine (frequency not known)

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 damage; 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 the following website: 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 Alter

Keep this medicine out of the sight and reach of children.
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the carton, bottle, or blister after "Exp.".
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Ezetimibe and Simvastatina Alter contains

• The active substances are ezetimibe and simvastatin. Each tablet contains 10 mg of ezetimibe and either 10 mg, 20 mg or 40 mg of simvastatin.
• The other components are: Tablet core: monohydrate lactose, hypromellose, croscarmellose sodium, microcrystalline cellulose, ascorbic acid, anhydrous citric acid, butylated hydroxyanisole (E320), 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 and Simvastatina Alter and contents of the
packaging
Ezetimibe and Simvastatina Alter 10 mg/10 mg are light brown, mottled, round, 6 mm in diameter, biconvex tablets, marked with “511” on one side.
Ezetimibe and Simvastatina Alter 10 mg/20 mg are light brown, mottled, round, 8 mm in diameter, biconvex tablets, marked with “512” on one side.
Ezetimibe and Simvastatina Alter 10 mg/40 mg are light brown, mottled, round, 10 mm in diameter, biconvex tablets, marked with “513” on one side.
Blister packs in OPA/aluminum/PVC with aluminum foil and/or HDPE bottles with desiccant. Pack sizes:
10 mg/10 mg: 28 and 30 tablets.
10 mg/20 mg: 28, 30 and 90 tablets.
10 mg/40 mg: 28, 30 and 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Laboratori Alter S.r.l.
Via Egadi 7 – 20144 Milano
Manufacturer
Balkanpharma-Dupnitsa AD
3 Samokovsko Shosse Street, Dupnitsa, 2600 – Bulgaria

This medicinal product is authorized in the European Economic Area countries under the following names:
France EZETIMIBE/SIMVASTATINE ALTER, comprimé
Italy Ezetimibe e Simvastatina Alter compresse
Spain Ezetimiba/Simvastatina Alter comprimidos EFG

More detailed information on this medicinal product is available on the AIFA website
www.agenziafarmaco.gov.it