EZETIMIBE/SIMVASTATIN TECNIGEN 10 mg/20 mg TABLETS

Introduction

Package Leaflet: Information for the User

Ezetimibe/Simvastatin Tecnigen 10 mg/20 mg tablets EFG

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 thepackage leaflet

1. What is Ezetimibe/Simvastatin Tecnigen and what is it used for
2. What you need to know before you take Ezetimibe/Simvastatin Tecnigen
3. How to take Ezetimibe/Simvastatin Tecnigen
4. Possible side effects
5. Storage of Ezetimibe/Simvastatin Tecnigen

Contents of the pack and other information

1. What is Ezetimibe/Simvastatin Tecnigen and what is it used for

This medicine contains the active substances ezetimibe and simvastatin. It is used to reduce the levels of total cholesterol, "bad" cholesterol (LDL cholesterol) and substances called triglycerides that are circulating in the blood. It also increases the levels of "good" cholesterol (HDL cholesterol).

Ezetimibe/simvastatin works by reducing cholesterol in two ways. The active substance ezetimibe reduces the cholesterol that is absorbed in 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 itself.

Cholesterol is one of the fatty substances that can be found in the blood. 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 flow of blood 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.

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

Ezetimibe/simvastatin 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 fatty substances 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, ezetimibe/simvastatin reduces the risk of heart attack, stroke, the need for surgery to increase blood flow to the heart, or hospitalisation due to chest pain.

This medicine does not help you to lose weight.

2. What you need to know before you take Ezetimibe/Simvastatin Tecnigen

Do not take Ezetimibe/Simvastatin Tecnigen 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 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)
• cyclosporin (used in patients who have had an organ transplant)
• danazol (a synthetic hormone used to treat endometriosis, a disease in which the lining of the uterus grows outside the uterus)

• if 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 ezetimibe/simvastatin can cause serious muscle problems (rhabdomyolysis)

Do not take more than 10/40 mg of ezetimibe/simvastatin 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 conditions, including allergies.
• if you drink large amounts of alcohol or if you have ever had liver disease. Ezetimibe/Simvastatin may not be suitable for you.
• if you are due to have an operation. You may need to stop taking the ezetimibe/simvastatin tablets for a short time.
• if you are Asian, as you may need a different dose.

Your doctor will do a blood test before you start taking ezetimibe/simvastatin and will also do a test if you have any symptoms of liver problems while taking ezetimibe/simvastatin. 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 ezetimibe/simvastatin.

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 is increased if you have high levels of sugars and fats in the blood, are overweight and have high blood pressure.

Talk to your doctor if you have severe lung disease.

The combined use of ezetimibe/simvastatin and fibrates (certain medicines used to lower cholesterol) should be avoided, as the use of ezetimibe/simvastatin 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 ezetimibe/simvastatin, 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 while taking medicines to lower cholesterol called "statins" (such as simvastatin, atorvastatin and rosuvastatin) or fibrates (such as gemfibrozil or bezafibrate).
• you or a close family member have a muscle problem that runs in the family

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

• Ezetimibe/simvastatin is not recommended in children under 10 years of age.

Other medicines and Ezetimibe/Simvastatin Tecnigen

Tell your doctor if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription. In particular, tell your doctor if you are taking or have taken any of the following:

• 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 the treatment with ezetimibe/simvastatin. Taking ezetimibe/simvastatin with fusidic acid can rarely cause muscle weakness, tenderness or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4

• cyclosporin (often used in patients who have had an organ transplant)
• 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 such as itraconazole, ketoconazole, fluconazole, posaconazole or voriconazole (used to treat fungal infections)
• fibrates with an active substance 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)
• 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)
• large 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 how ezetimibe/simvastatin works
• fenofibrate (also used to lower cholesterol)
• rifampicin (used to treat tuberculosis).

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

Taking Ezetimibe/Simvastatin Tecnigen with food and drink

Grapefruit juice contains one or more components that alter the metabolism of some medicines, including ezetimibe/simvastatin. You should avoid drinking grapefruit juice, as it can increase the risk of muscle problems.

Pregnancy and breast-feeding

Do not take this medicine 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 ezetimibe/simvastatin, stop taking it immediately and tell your doctor. Do not take ezetimibe/simvastatin 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

Ezetimibe/simvastatin is unlikely to affect your ability to drive or use machines. However, it should be taken into account that some people experience dizziness after taking ezetimibe/simvastatin.

Ezetimibe/Simvastatin Tecnigen 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.

Ezetimibe/Simvastatin Tecnigen contains sodium

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

3. How to take Ezetimibe/Simvastatin Tecnigen

Your doctor will decide on 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 your doctor has told you. If you are unsure, consult your doctor or pharmacist again.

• Before you start taking ezetimibe/simvastatin, you should be on a cholesterol-lowering diet.
• You should continue with this cholesterol-lowering diet while taking ezetimibe/simvastatin.

Adults: the dose is 1 tabletof ezetimibe/simvastatin once a day by mouth.

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

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

Take ezetimibe/simvastatin in the evening. You can take it with or without food.

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

If you take more Ezetimibe/Simvastatin Tecnigen 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 Ezetimibe/Simvastatin Tecnigen

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

If you stop taking Ezetimibe/Simvastatin Tecnigen

• 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 Ezetimiba/Simvastatina Tecnigen).

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

• Muscle pain
• Increases in laboratory blood 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

Additionally, the following adverse effects have been reported in people taking ezetimiba/simvastatina or medicines containing the active ingredients ezetimiba or simvastatina:

• 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-like 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)
• A hypersensitivity reaction that can include the following: hypersensitivity (allergic reactions including swelling of the face, lips, tongue, and/or throat, which can cause difficulty breathing or swallowing and requires immediate treatment, pain or inflammation of the joints, inflammation of blood vessels, unusual bruising, skin rash and swelling, hives, sensitivity to sunlight, fever, hot flashes, difficulty breathing, and general discomfort, pseudolupus syndrome (including skin rash, joint disorders, and effects on white blood cells))
• Muscle pain, tenderness, weakness, or cramps; muscle failure; muscle rupture (may affect up to 1 in 10,000 people); tendon problems, sometimes complicated by tendon rupture
• Gynecomastia (enlargement of breast tissue 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 liver function blood tests

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 sugar and fat in the blood, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine
• Persistent muscle pain, tenderness, or weakness that may not disappear after stopping treatment with ezetimiba/simvastatina (frequency not known).

Consult your doctor immediately if you experience unexplained muscle pain, tenderness, 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 type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed 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 Ezetimiba/Simvastatina Tecnigen

Keep this medicine out of the sight and reach of children.

This medicine does not require any special storage temperature.

Store in the original packaging to protect it from light.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medicines in the pharmacy's SIGRE collection point. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Ezetimiba/Simvastatina TecniGen 10 mg/ 20 mg

• The active ingredients are ezetimiba and simvastatina. Each tablet contains 10 mg of ezetimiba and 20 mg of simvastatina.
• The other ingredients are lactose monohydrate, lactose anhydrous, hypromellose, butylhydroxytoluene, sodium croscarmellose, sodium fumarate.

Appearance of the Product and Package Contents

White, oblong tablets with dimensions of 10.0 mm ± 0.2 mm in length and 5.5 mm ± 0.2 mm in width. The score line should not be used to break the tablet.

Ezetimiba/Simvastatina TecniGen is available in blister packs of 28 and 30 tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Holder

Tecnimede España Industria Farmacéutica S.A..

Avda. de Bruselas, 13-3ºD. Edificio América.

Polígono Arroyo de la Vega.

Alcobendas, 28108 – Madrid

Spain

Manufacturer

Atlantic Pharma – Produções Farmacêuticas, S.A.

Rua da Tapada Grande, n.º 2 Abrunheira,

2710-089 Sintra

Portugal

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

Portugal: Sinvastatina + Ezetimiba Tecnigen

Italy: Ezetimibe e Simvastatina TecniGen

Date of the last revision of this leaflet:January 2019

Other sources of information:

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/