VYTORIN 10 mg/40 mg TABLETS

Introduction

Package Leaflet: Information for the User

VYTORIN 10mg/20mg tablets

VYTORIN 10mg/40mg tablets

Ezetimibe and simvastatin

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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is VYTORIN and what is it used for
2. What you need to know before you take VYTORIN
3. How to take VYTORIN
4. Possible side effects
5. Storing VYTORIN

1. Contents of the pack and other information

1. What is VYTORIN and what is it used for

VYTORIN contains the active substances ezetimibe and simvastatin. VYTORIN is a medicine used to lower the levels of total cholesterol, "bad" cholesterol (LDL cholesterol) and substances called triglycerides in the blood. It also raises the levels of "good" cholesterol (HDL cholesterol).

VYTORIN works by reducing cholesterol in two ways. The active substance ezetimibe reduces the amount of cholesterol absorbed from the gut. The active substance simvastatin, which belongs to a group of medicines known as "statins", inhibits the production of cholesterol made by the body.

Cholesterol is one of the fatty substances that occur naturally in the bloodstream. Your total cholesterol is made up mainly of LDL and HDL cholesterol.

LDL cholesterol is often called "bad" cholesterol because it can build up in the walls of your arteries, forming plaques. Over time, this can lead to a narrowing of the arteries. This narrowing can reduce or completely block the blood flow to vital organs such as the heart and brain. This blockage 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 in the blood that can increase the risk of heart disease.

VYTORIN is used in patients who cannot control their cholesterol levels by diet alone. While taking this medicine, you should also follow a low-cholesterol diet.

VYTORIN is used, along with a low-cholesterol diet, if you have:

• high levels of cholesterol in the blood (primary hypercholesterolaemia [heterozygous familial and non-familial]) or high levels of triglycerides in the blood (mixed hyperlipidaemia):
• that are not well controlled with a statin alone,
• for which you have taken a statin and ezetimibe in separate tablets.

• a hereditary disease (homozygous familial hypercholesterolaemia) that increases the level of cholesterol in the blood. You may also receive other treatments.
• heart disease, VYTORIN reduces the risk of heart attack, stroke, surgery to increase blood flow to the heart or hospitalisation due to chest pain.

VYTORIN does not help you lose weight.

2. What you need to know before you take 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 breast-feeding,
• you are taking medicines with 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,
• gemfibrozil (used to lower cholesterol),
• cyclosporine (used in organ transplant patients),
• danazol (a synthetic hormone used to treat endometriosis, a disease in which the lining of the uterus grows outside the uterus).

• you are taking or have taken in the last 7 days a medicine containing fusidic acid (used to treat bacterial infections) by mouth or by injection. The combination of fusidic acid and VYTORIN can cause muscle problems (rhabdomyolysis).

Do not take more than 10/40 mg of VYTORIN if you are taking lomitapide (used to treat rare and serious genetic cholesterol disorders).

Consult your doctor if you are not sure if your medicine is mentioned above.

Warnings and precautions

Tell your doctor:

• about all your medical problems, including allergies,
• if you drink large amounts of alcohol or if you have ever had liver disease. VYTORIN may not be suitable for you,
• if you are due to have an operation. You may need to stop taking VYTORIN tablets for a short time,
• if you are Asian, as you may need a different dose
• if you have or have had myasthenia (a disease that causes generalised muscle weakness that can affect the muscles used for breathing) or ocular myasthenia (a disease that causes weakness of the eye muscles), as statins can sometimes make these conditions worse or trigger myasthenia (see section 4).

Your doctor will do a blood test before you start taking VYTORIN and may also do a blood test if you have any symptoms of liver problems while taking VYTORIN. This is to check how well your liver is working.

Your doctor may also want to do blood tests to check how well your liver is working after you start treatment with VYTORIN.

While you are taking this medicine, your doctor will check if you have diabetes or are at risk of developing diabetes. This risk of diabetes increases if you have high levels of sugar and fat in the blood, are overweight and have high blood pressure.

Talk to your doctor if you have severe lung disease.

The combined use of VYTORIN and fibrates (certain cholesterol-lowering medicines) should be avoided, as the use of VYTORIN and fibrates has not been studied.

Tell your doctor immediately if you experience muscle pain, tenderness or weakness. This is because, on rare occasions, muscle problems can be serious, including muscle breakdown, which can cause kidney damage; and, very rarely, deaths have occurred.

The risk of muscle breakdown is greater with higher doses of VYTORIN, especially the 10/80 mg dose. The risk of muscle breakdown is also greater in certain patients. Tell your doctor in the following situations:

• if you have kidney problems,
• if you have thyroid problems,
• if you are over 65 years old,
• if you are female,
• if you have ever had muscle problems during treatment with cholesterol-lowering medicines called "statins" (such as simvastatin, atorvastatin and rosuvastatin) or fibrates (such as gemfibrozil or bezafibrate),
• you or a close family member have a hereditary muscle problem.

Also, tell your doctor or pharmacist if you experience persistent muscle weakness. Further tests and additional medicines may be needed to diagnose and treat this condition.

Children and adolescents

• VYTORIN is not recommended for children under 10 years of age.

Taking VYTORIN with other medicines

Tell your doctor if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription. Taking VYTORIN with any of the following medicines can increase the risk of muscle problems (some of these are already included in the "Do not take VYTORIN" section above).

• if you have to take fusidic acid by mouth to treat a bacterial infection, you will need to stop taking this medicine temporarily. Your doctor will tell you when you can restart VYTORIN treatment. Taking VYTORIN with fusidic acid can rarely cause muscle weakness, tenderness or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.
• cyclosporine (used in organ transplant patients),
• danazol (a synthetic hormone used to treat endometriosis, a disease in which the lining of the uterus grows outside the uterus),
• medicines with an active substance like itraconazole, ketoconazole, fluconazole, posaconazole or voriconazole (used to treat fungal infections),
• fibrates with an active substance like 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),
• antivirals for hepatitis C such as boceprevir, telaprevir, elbasvir or grazoprevir (used to treat hepatitis C virus infection),
• nefazodone (used to treat depression),
• medicines with 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 diseases),
• lomitapide (used to treat rare and serious genetic cholesterol disorders),
• daptomycin (a medicine used to treat skin and skin structure infections with complications and bacteremia). It is possible that the side effects that affect the muscles may be greater when this medicine is taken during treatment with simvastatin (e.g. VYTORIN). Your doctor may decide that you should stop taking VYTORIN for a while,
• high doses (1 gram or more per day) of niacin or nicotinic acid (also used to lower cholesterol),
• colchicine (used to treat gout).

As well as the medicines mentioned above, tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription. In particular, tell your doctor if you are taking any of the following:

• medicines with an active substance used to prevent blood clots, such as warfarin, flindione, phenprocoumon or acenocoumarol (anticoagulants),
• cholestyramine (also used to lower cholesterol), as it affects the way VYTORIN works,
• fenofibrate (also used to lower cholesterol),
• rifampicin (used to treat tuberculosis)
• ticagrelor (an antiplatelet medicine).

You should also tell any doctor who prescribes you a new medicine that you are taking VYTORIN.

Taking VYTORIN with food and drink

Grapefruit juice contains one or more components that alter the metabolism of some medicines, including VYTORIN. You should avoid grapefruit juice, as it may increase the risk of muscle problems.

Pregnancy and breast-feeding

Do not take VYTORIN if you are pregnant, if you are trying to become pregnant or if you think you may be pregnant. If you become pregnant while taking VYTORIN, stop taking it immediately and tell your doctor. Do not take VYTORIN if you are breast-feeding, as it is not known whether this medicine passes into breast milk.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

VYTORIN is not expected to interfere with your ability to drive or use machines. However, it should be taken into account that some people experience dizziness after taking VYTORIN.

VYTORIN contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

VYTORIN contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; this is essentially "sodium-free".

3. How to take VYTORIN

Your doctor will determine the appropriate tablet dose for you, depending on your current treatment and your personal risk situation.

The tablets are not scored and should not be divided.

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are in doubt, consult your doctor or pharmacist again.

• Before starting to take VYTORIN, you should be following a cholesterol-lowering diet.
• You should continue with this cholesterol-lowering diet while taking VYTORIN.

Adults: the dose is 1 tabletof VYTORIN once a day by mouth.

Use in adolescents(10 to 17 years of age): the dose is 1 tabletof VYTORIN once a day by mouth (do not exceed a maximum dose of 10 mg/40 mg once a day).

The dose of VYTORIN 10 mg/80 mg is only recommended for adult patients with very high cholesterol levels and a high risk of heart disease who have not reached their treatment goal with lower doses.

Take VYTORIN in the evening. You can take it with or without food.

If your doctor has prescribed VYTORIN along with another cholesterol-lowering medicine containing the active substance colestyramine or any other bile acid sequestrant, you should take VYTORIN at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more VYTORIN than you should

• In case of overdose or accidental ingestion, contact the Toxicology Information Service. Telephone: 91 562 04 20, consult your doctor or pharmacist

If you forget to take VYTORIN

• Do not take a double dose to make up for forgotten doses, take your normal dose of VYTORIN at the usual time

If you stop taking VYTORIN

• Talk to your doctor or pharmacist because your cholesterol levels may increase again.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them (see section 2. What you need to know before starting to take VYTORIN).

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

• Muscle pain,
• Increases in blood test results in laboratory tests of liver function (transaminases) and/or muscle (CK).

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

• Elevation of liver function in blood tests; elevation of uric acid in the blood; elevation in the time it takes for blood to clot; protein in urine; weight loss,
• Dizziness; headache; tingling sensation,
• Abdominal pain; indigestion; flatulence; nausea; vomiting; abdominal swelling; diarrhea; dry mouth; heartburn,
• Rash; itching; hives,
• Joint pain; pain, hypersensitivity, weakness, or muscle spasms; neck pain; pain in the arms and legs; back pain,
• Unusual fatigue or weakness; feeling tired; chest pain; swelling, especially of the hands and feet,
• Sleep disorder; difficulty sleeping.

The following adverse effects have been reported with an unknown frequency (frequency cannot be estimated from the available data):

• Severe myasthenia (a disease that causes generalized muscle weakness that, in some cases, affects the muscles used for breathing),
• Ocular myasthenia (a disease that causes weakness of the eye muscles).

Consult your doctor if you experience weakness in your arms or legs that worsens after periods of activity, double vision, or drooping eyelids, difficulty swallowing, or difficulty breathing.

Additionally, the following adverse effects have been reported in people taking VYTORIN or medicines that contain the active ingredients ezetimibe or simvastatin:

• Low red blood cell count (anemia), reduction in blood cell count, which can cause bruising/bleeding (thrombocytopenia),
• Numbness or weakness of the arms and legs; poor memory, memory loss, confusion,
• Respiratory problems including persistent cough and/or difficulty breathing or fever,
• Constipation,
• Pancreatitis, often with severe abdominal pain,
• Liver inflammation with the following symptoms: yellowing of the skin and eyes, itching, dark-colored urine or pale-colored stools, feeling tired or weak, loss of appetite; liver failure; gallstones or gallbladder inflammation (which can cause abdominal pain, nausea, vomiting),
• Hair loss; red and swollen rash, sometimes with target-shaped lesions (erythema multiforme),
• Blurred vision and vision impairment (may affect up to 1 in 1,000 people),
• Rash that can occur on the skin or ulcers in the mouth (drug-induced lichenoid eruptions) (may affect up to 1 in 10,000 people),
• Hypersensitivity reactions that can include the following: allergic reactions including swelling of the face, lips, tongue, and/or throat, which can cause difficulty breathing or swallowing and requires immediate treatment (angioedema), pain or inflammation of the joints, inflammation of blood vessels, atypical bruising, skin rash, and swelling, urticaria, sensitivity to sunlight, fever, hot flashes, difficulty breathing, and general discomfort, pseudolupus syndrome (including skin rash, joint disorders, and effects on white blood cells). A very rare severe allergic reaction (may affect up to 1 in 10,000 people) that causes difficulty breathing or dizziness and requires immediate treatment (anaphylaxis),
• Muscle pain, sensitivity to pressure, weakness, or muscle cramps; muscle failure; muscle rupture (may affect up to 1 in 10,000 people); tendon problems, sometimes complicated by tendon rupture,
• Gynecomastia (breast enlargement in men) (may affect up to 1 in 10,000 people),
• Decreased appetite,
• Hot flashes; high blood pressure,
• Pain,
• Erectile dysfunction,
• Depression,
• Abnormalities in some blood tests of liver function.

The following additional adverse events have been reported with some statins:

• Sleep disorders, including nightmares,
• Sexual dysfunction,
• Diabetes. This is more likely if you have high levels of sugars and fats in the blood, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine,
• Constant muscle pain, sensitivity, or weakness that may not disappear after stopping treatment with VYTORIN (frequency not known).

Consult your doctor immediately if you experience unexplained muscle pain, sensitivity to pressure, or weakness. This is because, in rare cases, muscle problems can be serious, including muscle failure, which can cause kidney damage; and very rarely, deaths have occurred.

Reporting of Adverse Effects:

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects that do not appear in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of VYTORIN

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date that appears on the packaging or on the container after [EXP].
• Do not store VYTORIN tablets at a temperature above 30°C.

Blister packs: Store in the original package to protect them from moisture and light. Bottles: Keep the bottles tightly closed to protect them from moisture and light.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition ofVYTORIN

The active ingredients are ezetimibe and simvastatin. Each tablet contains 10 mg of ezetimibe and 20 mg or 40 mg of simvastatin.

The other ingredients are: butylhydroxyanisole, citric acid monohydrate, sodium croscarmellose, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and propyl gallate.

Appearance of the Product and Package Contents

VYTORIN tablets are capsule-shaped, white to off-white in color, with the code "312" on the VYTORIN 10 mg/20 mg tablet or "313" on the VYTORIN 10 mg/40 mg tablet on one side. The tablets are not scored and should not be divided.

Package sizes:

7, 10, 14, 28, 30, 50, 56, 84, 90, 98, multiple package containing 98 tablets (2 packs of 49), 100, or 300 tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Organon Salud, S.L.

Paseo de la Castellana, 77

28046 Madrid

Spain

Tel.: 915911279

Manufacturer

Organon Heist bv

Industriepark 30

2220 Heist-op-den-Berg

Belgium

Or

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

This medicine is authorized in the Member States of the European Economic Area under the following names:

INEGY in: Austria, Belgium, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, and the United Kingdom.

VYTORIN in: Germany, Italy, Portugal, and Spain.

GOLTOR in: Germany and Italy.

Date of the Last Revision of this Leaflet:07/2023.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)