Vytorin

Patient Information Leaflet

VYTORIN 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg, 10 mg/80 mg tablets

ezetimibe and simvastatin
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 other people, even if they have the same symptoms as you, 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 VYTORIN is and what it is used for
2. What you need to know before taking VYTORIN
3. How to take VYTORIN
4. Possible side effects
5. How to store VYTORIN
6. Contents of the pack and other information

1. What VYTORIN is and what it is used for

VYTORIN contains the active substances ezetimibe and simvastatin.
VYTORIN is a medicine used to lower levels of total cholesterol, “bad” cholesterol (LDL cholesterol), and fats known as triglycerides in the blood. In addition, VYTORIN increases levels of “good” cholesterol (HDL cholesterol).
VYTORIN works in two ways to lower cholesterol. The active substance ezetimibe reduces cholesterol absorbed from the gastrointestinal tract. The active substance simvastatin, which belongs to a class of medicines called “statins”, inhibits the body's own production of cholesterol.
Cholesterol is one of several types of fat 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 build up 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.
VYTORIN 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.
VYTORIN is used as an add-on 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 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; VYTORIN reduces the risk of heart attack, stroke, surgical procedures to improve blood flow to the heart, or hospitalization due to chest pain.

VYTORIN does not help with weight loss.

2. What you should know before taking VYTORIN

Do not take VYTORIN if:

• you are allergic (hypersensitive) to ezetimibe, simvastatin, or any of the other ingredients of this medicine (listed in section 6: Contents of the pack and other information);
• 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 infection), ○ nefazodone (used to treat depression), cobicistat, or gemfibrozil (used to lower cholesterol), ○ cyclosporine (often used in patients who have had an organ transplant), ○ danazol (an artificial hormone 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 VYTORIN may lead to serious muscle problems (rhabdomyolysis). Do not take more than 10 mg/40 mg of VYTORIN if you are taking lomitapide (used to treat a rare, genetic condition of severe high cholesterol).

Ask your doctor for advice if you are unsure whether the medicine you are taking is one of those listed above.
Warnings and precautions:
Tell your doctor:

• about all your medical conditions, including allergies;
• if you consume large amounts of alcohol or if you have ever had liver disease. In such cases, VYTORIN may not be suitable for you;
• if you are scheduled for surgery. You may need to stop taking VYTORIN tablets for a short period;
• if you are of Asian origin, as a different dose may be appropriate for you;
• if you have or have had myasthenia (a disease characterized by generalized muscle weakness, including in some cases the muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), since statins may sometimes worsen myasthenia or cause its onset (see section 4).

Your doctor should perform a blood test before you start taking VYTORIN and if you develop symptoms of liver problems while taking VYTORIN. This test is performed to check whether your liver is functioning properly.
Your doctor may also prescribe blood tests to monitor liver function after starting treatment with VYTORIN.
While being treated 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 fats in your blood, are overweight, and have high blood pressure.
Inform your doctor if you have a serious lung disease.
The use of VYTORIN together with fibrates (a type of medicine used to lower cholesterol) should be avoided, as the combination of VYTORIN 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 serious and lead to muscle tissue damage causing kidney damage,
and very rare cases of death have occurred.
The risk of muscle damage is higher at higher doses of VYTORIN, 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 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 had 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.

In addition, inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and medicines may be needed to diagnose and treat this condition.
Children and adolescents
The use of VYTORIN is not recommended in children under 10 years of age.
Other medicines and VYTORIN
Inform your doctor if you are taking, have recently taken, or might take any other medicine containing any of the following active substances. Taking VYTORIN 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 VYTORIN if”):

• 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 VYTORIN treatment. Taking VYTORIN with fusidic acid may rarely lead to muscle weakness, pain, or tenderness (rhabdomyolysis). See more information on rhabdomyolysis in 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);
• 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 of severe high cholesterol);
• daptomycin (a medicine used to treat complicated skin and soft tissue infections and bacteremia). The risk of muscle-related side effects may be increased when this medicine is taken during treatment with simvastatin (e.g., VYTORIN). Your doctor may decide that you should stop taking VYTORIN for a period of time,
• high doses (1 gram 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 to prevent blood clots, such as warfarin, fluindione, phenprocoumon, or acenocoumarol (anticoagulants);
• colestyramine (also used to lower cholesterol), as it affects how VYTORIN works;
• fenofibrate (also used to lower cholesterol);
• rifampicin (used to treat tuberculosis);
• ticagrelor (an antiplatelet medicine).

You should also inform any doctor who prescribes you a new medicine that you are taking VYTORIN.
VYTORIN with food and drinks
Grapefruit juice contains one or more substances that alter the metabolism of certain medicines, including VYTORIN. Consumption of grapefruit juice should be avoided, as it may increase the risk of muscle problems.
Pregnancy and breastfeeding
Do not use VYTORIN if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If you become pregnant while taking VYTORIN, stop treatment immediately and contact your doctor. VYTORIN must not be used during 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
VYTORIN is not expected to affect your ability to drive or use machines.
However, bear in mind that some people have experienced dizziness after taking VYTORIN.
VYTORIN contains lactose
VYTORIN 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.
VYTORIN contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially “sodium-free”.

3. How to take VYTORIN

Your doctor will determine the appropriate tablet dosage for you, based on your current treatment and your individual risk profile.
The tablets do not have a score 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 VYTORIN, you must already be following a cholesterol-lowering diet.
• While taking VYTORIN, you must continue to follow this cholesterol-lowering diet.

Adults: The dose is 1 tablet of VYTORIN taken orally once daily.
Use in adolescents (aged 10 to 17 years): The dose is 1 tablet of VYTORIN taken orally once daily (the maximum dose should not exceed 10 mg/40 mg once daily).
The VYTORIN 10 mg/80 mg dose is recommended only for adult patients with very high cholesterol levels and at high risk for heart disease who have not reached their target cholesterol levels with lower doses.
Take VYTORIN in the evening. You may take it with or without food.
If your doctor has prescribed VYTORIN together with another cholesterol-lowering medicine containing the active substance cholestyramine or any other bile acid sequestrant, you must take VYTORIN at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more VYTORIN than you should:

• Contact your doctor or pharmacist.

If you forget to take VYTORIN:

• Do not take a double dose to make up for the missed tablet. Take your usual dose of VYTORIN at the next scheduled time.

If you stop taking VYTORIN:

• 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, VYTORIN may cause side effects, although not everybody gets them (see section 2, What you need to know before taking VYTORIN).

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

• muscle pain,
• increases in blood laboratory test values indicating liver function (transaminases) and/or muscle function (CK).

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

• increases in blood test values indicating 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; 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 side effects have been reported with unknown frequency (frequency cannot be estimated from the available data):

• myasthenia gravis (a disease causing generalized muscle weakness, including in some cases the muscles used for breathing),
• ocular myasthenia (a disease causing weakness of the eye muscles).

Contact your doctor if you experience arm or leg weakness that worsens after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.
In addition, the following side effects have been reported in people taking VYTORIN or medicines containing the active substances ezetimibe or simvastatin:

• reduction 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,
• breathing problems including persistent cough and/or shortness of breath or fever,
• constipation,
• inflammation of the pancreas, often with severe abdominal pain,
• liver inflammation with the following symptoms: yellowing of the skin and eyes; itching; dark-coloured urine or pale-coloured 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-like lesions (erythema multiforme),
• blurred vision and impaired vision (may affect up to 1 in 1,000 people),
• skin rash which may appear on the skin or ulcers in the mouth (drug-induced lichenoid eruptions) (may affect up to 1 in 10,000 people),
• hypersensitivity reactions including some of the following: 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, abnormal 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). A very rare severe allergic reaction (may affect up to 1 in 10,000 people) may occur, causing difficulty breathing or dizziness, requiring immediate treatment (anaphylaxis),
• muscle pain, tenderness, weakness or cramps; muscle injury; muscle breakdown (may affect up to 1 in 10,000 people); tendon problems, sometimes complicated by tendon rupture,
• gynaecomastia (enlargement of breasts in men) (may affect up to 1 in 10,000 people),
• decreased appetite,
• hot flushes; high blood pressure,
• pain,
• erectile dysfunction,
• depression,
• changes in certain blood test values indicating 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 fat in your blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine,
• persistent muscle pain, tenderness or weakness, which may not resolve after stopping treatment with VYTORIN (frequency not known).

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 damage,
and very rare cases of death have occurred.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
Web: 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 VYTORIN

• 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 the word "Exp".
• Do not store VYTORIN tablets above 30°C.

Blister packs: store in the original packaging to protect the medicine from moisture and light.
Bottles: keep bottles tightly closed to protect the medicine from moisture and light.
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. Pack contents and other information

What VYTORIN contains
The active substances in VYTORIN are ezetimibe and simvastatin. Each tablet contains 10 mg of
ezetimibe and 10 mg, 20 mg, 40 mg or 80 mg of simvastatin.
The other components are: butylhydroxyanisole, citric acid monohydrate, croscarmellose sodium,
hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, propyl gallate.
Description of the appearance of VYTORIN and pack contents
VYTORIN tablets are white to off-white capsule-shaped tablets with the code “311”, “312”, “313” or “315” on one side. The tablets do not have a break line and must not be divided.
Pack sizes:
7, 10, 14, 28, 30, 50, 56, 84, 90, 98, multiple pack containing 98 (2 boxes of 49), 100 or 300
tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 – Milan, Italy
Manufacturer
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands
Organon Heist bv
Industriepark 30
2220 Heist-op-den-Berg
Belgium
Savio Industrial S.r.l.
Via Emilia, 21
27100 – Pavia (PV)
Italy
This medicinal product is authorised in the European Economic Area countries under the
following name:
VYTORIN in Germany, Italy, Portugal and Spain.