Ezetimibe and simvastatin Mylan

Package leaflet: Information for the patient

Ezetimibe and Simvastatin Mylan 10 mg/10 mg Tablets, mg/20 mg Tablets, mg/40 mg Tablets

ezetimibe and simvastatin
equivalent medicinal product
Please read 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 adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Ezetimibe and Simvastatin Mylan contains the two active substances ezetimibe and simvastatin.
Ezetimibe and Simvastatin Mylan 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 Mylan increases levels of "good" cholesterol (HDL cholesterol).
Ezetimibe and Simvastatin Mylan works to reduce your cholesterol in two ways. The active substance ezetimibe reduces the amount of cholesterol absorbed in the digestive tract. The active substance simvastatin, which belongs to the class of medicines known as "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. 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 type of fat present in the blood that may increase the risk of heart disease.
Ezetimibe and Simvastatin Mylan is used in patients who cannot control their cholesterol levels through diet alone. While taking this medicine, you must still follow a cholesterol-lowering diet.
Ezetimibe and Simvastatin Mylan 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):
  • that are not well 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 hypercholesterolemia) that increases your blood cholesterol levels. You may also be receiving other treatments;
• heart disease; Ezetimibe and Simvastatin Mylan reduces the risk of heart attack, stroke, surgery to improve blood flow to the heart, or hospitalization due to chest pain.

Ezetimibe and Simvastatin Mylan does not help with weight loss.

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

Do not take Ezetimibe and Simvastatin Mylan:

• if you are allergic to ezetimibe or simvastatin or to 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(s) 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) or medicines containing cobicistat (also used to treat HIV infections); boceprevir or telaprevir (used to treat hepatitis C virus infections); nefazodone (used to treat depression); gemfibrozil (used to lower cholesterol); cyclosporine (often used in organ transplant patients); danazol (a synthetic androgen hormone used to treat endometriosis, a condition in which uterine lining tissue grows outside the uterus); if you are taking or have taken within the past 7 days a medicine called fusidic acid (used for bacterial infections) by mouth or injection. The combination of fusidic acid and Ezetimibe and Simvastatin Mylan may lead to serious muscle problems (rhabdomyolysis).

Do not take more than 10 mg/40 mg of Ezetimibe and Simvastatin Mylan if you are taking lomitapide (used
to treat a rare and serious genetic disorder affecting cholesterol).
Consult your doctor if you are unsure whether the medicine you are taking is one of those listed above.
Warnings and precautions
Tell your doctor or pharmacist before taking Ezetimibe and Simvastatin Mylan:

• about all your medical conditions, including allergies;
• if you have or have had myasthenia (a disease causing general muscle weakness, which in some cases includes muscles used for breathing) or ocular myasthenia (a disease causing eye muscle weakness), as statins may sometimes worsen these conditions or trigger the onset of myasthenia (see section 4);
• if you consume large amounts of alcohol or have ever had liver disease. In such cases, Ezetimibe and Simvastatin Mylan may not be suitable for you;
• if you are scheduled for surgery. You may need to temporarily stop taking Ezetimibe and Simvastatin Mylan;
• if 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 Mylan and if you
develop symptoms of liver problems while taking Ezetimibe and Simvastatin Mylan.
This test checks whether your liver is functioning properly.
Your doctor may also order periodic blood tests to monitor liver function after starting treatment with
Ezetimibe and Simvastatin Mylan.
During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at
risk of developing diabetes. Risk factors for developing diabetes include high levels of sugar and fats in the
blood, being overweight, and having high blood pressure.
Inform your doctor if you suffer from a serious lung disease.
The use of Ezetimibe and Simvastatin Mylan with fibrates (a class of medicines 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 severe and lead to muscle tissue damage causing kidney damage, and
very rare cases of death have been reported.
The risk of muscle damage is higher at higher doses of ezetimibe/simvastatin, particularly at 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 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 ever 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;
• you are of Asian origin.

Additionally, inform your doctor or pharmacist if you experience persistent muscle weakness. Further tests
and treatments may be needed to diagnose and manage this condition.
Children
The use of Ezetimibe and Simvastatin Mylan is not recommended in children under 10 years of age.
Other medicines and Ezetimibe and Simvastatin Mylan
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including any of the following. Taking Ezetimibe and Simvastatin Mylan with any of these medicines may increase the risk of muscle problems.
Do not take Ezetimibe and Simvastatin Mylan with:

• fusidic acid. 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 treatment with Ezetimibe and Simvastatin Mylan. Taking Ezetimibe and Simvastatin Mylan together with fusidic acid may rarely cause muscle weakness, muscle breakdown, or pain (rhabdomyolysis). More information on rhabdomyolysis is available in section 4;
• cyclosporine (often used in patients receiving an organ transplant);
• danazol (a synthetic hormone used to treat endometriosis, a condition in which uterine lining tissue 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 lower 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, grazoprevir, or glecaprevir/pibrentasvir (used to treat hepatitis C virus infections);
• nefazodone (used to treat depression);
• medicines containing cobicistat (also used to treat HIV infections);
• 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 and serious genetic disorder affecting 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 Mylan). Your doctor may decide to temporarily stop Ezetimibe and Simvastatin Mylan;
• 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 medicines, including those without a prescription. In particular, inform your doctor if you are taking any of the following:

• medicines containing active substances to prevent blood clots, such as warfarin, phenprocoumon, fluindione, acenocoumarol (anticoagulants);
• colestyramine (also used to lower cholesterol), as it affects how Ezetimibe and Simvastatin Mylan works;
• fenofibrate (also used to lower cholesterol);
• rifampicin (used to treat tuberculosis);
• ticagrelor (an anticoagulant medicine).

Inform your doctor if you are also taking niacin (nicotinic acid) or a product containing niacin or a niacin-related product such as acipimox (used to lower cholesterol) and if you are of Asian origin.
You should also inform any doctor prescribing you a new medicine that you are taking Ezetimibe and Simvastatin Mylan.
Ezetimibe and Simvastatin Mylan with food and drinks
Grapefruit juice contains one or more substances that alter the metabolism of certain medicines, including
Ezetimibe and Simvastatin Mylan. Grapefruit juice should be avoided, as it may increase the risk of muscle problems.
Pregnancy and breastfeeding
Do not take Ezetimibe and Simvastatin if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If you become pregnant while taking Ezetimibe and Simvastatin Mylan, stop taking the medicine immediately and contact your doctor.
Do not take Ezetimibe and Simvastatin Mylan while breastfeeding, as it is not known whether the medicine passes into human milk.
Driving and using machines
Ezetimibe and Simvastatin Mylan 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 Mylan. If this occurs, do not drive or operate machinery.
Ezetimibe and Simvastatin Mylan contains lactose monohydrate
If your doctor has diagnosed you with an intolerance to certain sugars, consult him 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 Mylan

Take this medicine exactly as prescribed by your doctor or pharmacist.
Your doctor will determine the appropriate tablet dosage for you, based on your current treatment and your individual risk profile.
If you have any doubts, consult your doctor or pharmacist.

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

Adults
The recommended dose is 1 tablet of Ezetimibe and Simvastatin Mylan taken orally once daily in the evening.
The 10 mg/80 mg dose of Ezetimibe/Simvastatin Mylan is recommended only for adult patients with very high cholesterol levels and a high risk of heart problems who have not achieved their cholesterol targets with lower doses.

Use in adolescents (aged 10 to 17 years)
The recommended dose is 1 tablet of Ezetimibe and Simvastatin Mylan taken orally once daily in the evening (the maximum dose should not exceed 10 mg/40 mg once daily).

• Take Ezetimibe and Simvastatin Mylan in the evening.
• You may take it with or without food.
• The tablets do not have a break line and must not be divided.

If your doctor has prescribed Ezetimibe and Simvastatin Mylan together with another cholesterol-lowering medicine containing the active substance colestyramine or any other bile acid sequestrant, you must take Ezetimibe and Simvastatin Mylan at least 2 hours before or 4 hours after taking these medicines.

If you take more Ezetimibe and Simvastatin Mylan than you should
If you take more Ezetimibe and Simvastatin Mylan than prescribed, contact your doctor.

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

If you stop taking Ezetimibe and Simvastatin Mylan
Inform your doctor before stopping treatment with this medicine, 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.
Tell your doctor or go to the nearest hospital emergency department if you experience any of the
following serious side effects; these effects occur with an unknown frequency (i.e. cannot be
estimated from the available data), but may require medical treatment:

• muscle pain, tenderness, or weakness, particularly persistent unexplained muscle weakness, muscle breakdown (which may affect up to 1 in 10,000 people). This is because, in rare cases, muscle problems, including muscle breakdown leading to kidney damage, can be severe and potentially life-threatening;
• allergic reactions including swelling of the face, lips, tongue and/or throat which may cause difficulty in breathing or swallowing (requiring immediate treatment) (angioedema);
• inflammation of the pancreas, often with severe abdominal pain;
• gallstones or inflammation of the gallbladder (which may cause abdominal pain, feeling unwell);
• raised red skin rash, sometimes with target-like lesions (erythema multiforme), skin rash or mouth ulcers (drug-induced lichenoid eruptions) (which may affect up to 1 in 10,000 people);
• inflammation of the liver (which may cause yellowing of the skin and eyes, itching, dark urine or pale stools, feeling tired or weak, loss of appetite);
• liver failure;
• breathing problems including persistent cough and/or shortness of breath or fever;
• hypersensitivity reaction including some of the following features: hypersensitivity (severe allergic reactions causing difficulty in breathing or dizziness requiring immediate treatment (anaphylaxis, which may affect 1 in 10,000 people, and anaphylactic reactions), 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 and feeling unwell, lupus-like symptoms (including skin rash, joint problems, and effects on white blood cells));
• 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;
• gynaecomastia (enlargement of the breast in men) (which may affect up to 1 in 10,000 people).

Other possible side effects:

Common (may affect up to 1 in 10 people):

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

Uncommon (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; weight loss
• dizziness; headache; tingling sensation
• abdominal pain; indigestion; flatulence; nausea; malaise; abdominal swelling; diarrhoea; dry mouth; heartburn; skin rash; itching; urticaria
• joint pain; muscle pain; sensitivity; weakness or spasms; neck pain; arm or leg pain; back pain
• unusual tiredness or weakness; feeling tired; chest pain; swelling, especially of the hands and feet
• sleep disorder; difficulty falling asleep.

Rare (may affect up to 1 in 1,000 people):

• blurred vision and visual impairment.

Not known (frequency cannot be estimated from the available data):

• 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; poor memory; memory loss; confusion
• constipation
• hair loss
• muscle cramps; muscle inflammation; 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 blood sugar levels
• inflammation of the stomach lining
• shortness of breath
• cough.

Additional possible side effects reported with some statins:
Not known (frequency cannot be estimated from the available data):

• sleep disorders, including nightmares
• sexual difficulties
• severe myasthenia (a disease causing general muscle weakness, including in some cases the muscles used for breathing)
• ocular myasthenia (a disease causing weakness of the eye muscles).

Talk to your doctor if you experience worsening weakness in the arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing, or breathlessness.
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: 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 Mylan

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 blister, carton or bottle after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Bottles: use within 100 days of opening.
Do not dispose of medicines 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 Mylan contains

• The active substances are ezetimibe and simvastatin. Each tablet contains 10 mg of ezetimibe and 10 mg, 20 mg or 40 mg of simvastatin.
• The other components are: monohydrate lactose (see section 2 "Ezetimibe and Simvastatin Mylan contains monohydrate lactose"); monohydrate citric acid, butylated hydroxyanisole (E320), ascorbic acid (E300), sodium lauryl sulfate (E487), sodium croscarmellose, hypromellose (E464), microcrystalline cellulose, magnesium stearate.

Description of the appearance of Ezetimibe and Simvastatin and pack contents
Ezetimibe and Simvastatin Mylan 10 mg/10 mg Tablets are white to off-white, oval-shaped, biconvex tablets, with "M" engraved on one side and "ES1" on the other side.

Ezetimibe and Simvastatin Mylan Tablets are available in the following pack sizes:
Blister packs:
10 mg/10 mg: 14, 28, 30 and 100 tablets
10 mg/20 mg and 10 mg/40 mg: 14, 28, 30, 98, 100 tablets and calendar blister packs of 28 tablets
Unit dose blisters:
10 mg/10 mg: 14 x 1 and 28 x 1 tablets
10 mg/20 mg and 10 mg/40 mg: 14 x 1, 28 x 1, 30 x 1 and 90 x 1 tablets
Plastic bottle, with screw cap, aluminium seal and cotton absorbent pad, containing:
10 mg/10 mg: 30 and 100 tablets
10 mg/20 mg and 10 mg/40 mg: 30, 100, 250 and 500 tablets
Not all pack sizes may be marketed.
Marketing Authorization Holder
Mylan S.p.A.
Via Vittor Pisani, 20
20124 Milan, Italy
Manufacturers
Mylan Hungary Kft, H-2900 Komárom, Mylan utca 1, Hungary
Mylan Germany GmbH, Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1
Bad Homburg v. d. Hoehe, Hessen, 61352, Germany
This medicinal product is authorised in the European Economic Area Member States under the following
names: