Package Insert: Information for the User

Ezetimiba/simvastatina Tecnigen 10 mg/20 mg tablets EFG

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert.See section 4.

Package Insert Content

1. What isEzetimiba/SimvastatinaTecnigenand for what it is used
2. What you need to know before starting to takeEzetimiba/SimvastatinaTecnigen
3. How to takeEzetimiba/SimvastatinaTecnigen
4. Possible adverse effects
5. Storage ofEzetimiba/SimvastatinaTecnigen

Package contents and additional information

This medicationcontains the active principles ezetimiba and simvastatina.It is used to reduce total cholesterol, "bad" cholesterol (LDL cholesterol) and certain fatty substances called triglycerides that circulate in the blood. Additionally, it increases the concentrations of "good" cholesterol (HDL cholesterol).

Ezetimiba/simvastatinaacts by reducing cholesterol in two ways. The active principle ezetimiba reduces the cholesterol absorbed in the digestive tract. The active principle simvastatina, which belongs to the group of "statins", inhibits the production of cholesterol produced by the body itself.

Cholesterol is one of the fatty substances found in the bloodstream. Its total cholesterol is composed mainly of LDL and HDL cholesterol.

LDL cholesterol is often referred to as "bad" cholesterol because it can accumulate in the walls of your arteries, forming plaques. Over time, this accumulation of plaque can cause a narrowing of the arteries. This narrowing can slow down or interrupt blood flow to vital organs such as the heart and brain. This interruption of blood flow can cause a heart attack or stroke.

HDL cholesterol is often referred to as "good" cholesterol because it helps prevent bad cholesterol from accumulating in the arteries and protects them from heart disease.

Triglycerides are another type of fat in your blood that can increase the risk of heart disease.

Ezetimiba/simvastatinais used in patients who cannot control their cholesterol levels solely with diet. While taking this medication, you must follow a cholesterol-reducing diet.

Ezetimiba/simvastatinais used, along with a cholesterol-reducing diet,if you have:

• elevated blood levels of cholesterol (primary hypercholesterolemia [familial heterozygous and non-familial]) or elevated blood levels of fatty substances (mixed hyperlipidemia):
• that are not well controlled with a single statin
• for whom a statin and ezetimiba in separate tablets have been used

• a genetic disorder (familial hypercholesterolemia), which increases the level of cholesterol in the blood. You may also receive other treatments.

• heart disease,ezetimiba/simvastatinareduces the risk of heart attack, stroke, coronary artery bypass surgery, or hospitalization for chest pain.

This medicationdoes not help you lose weight.

Do not take Ezetimiba/Simvastatina Tecnigen if:

• You are allergic to ezetimiba, simvastatina, or any of the other components of this medication (listed in section 6)
• You currently have liver problems
• You are pregnant or breastfeeding
• You are taking medications with one or more of the following active ingredients:

• Itraconazole, ketoconazole, posaconazole, or voriconazole (used to treat fungal infections)
• Erythromycin, clarithromycin, or telithromycin (used to treat infections)
• Protease inhibitors for HIV such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat HIV infections)
• Boceprevir or telaprevir (used to treat hepatitis C infection)
• Nefazodone (used to treat depression)
• Cobicistat
• Gemfibrozil (used to reduce cholesterol)
• Ciclosporin (used in patients with organ transplants)
• Danazol (a synthetic hormone used to treat endometriosis, a condition in which the inner lining of the uterus grows outside the uterus)

• If you are taking or have taken within the last 7 days a medication containing fusidic acid (used to treat bacterial infections) by mouth or injection. The combination of fusidic acid and ezetimiba/simvastatina may cause severe muscle problems (rhabdomyolysis)

Do not take more than 10/40 mg of ezetimiba/simvastatina if you are taking lomitapida (used to treat rare and severe cholesterol disorders).

Consult your doctor if you are unsure if your medication is mentioned above.

Warnings and precautions

Inform your doctor:

• About all your medical conditions, including allergies
• If you consume large amounts of alcohol or have ever had liver disease. Ezetimiba/Simvastatina may not be suitable for you.
• If you are scheduled for surgery. You may need to stop taking ezetimiba/simvastatina for a short period of time.
• If you are Asian, as you may need a different dose.

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

Your doctor may also want to perform blood tests to check how well your liver is working after you start treatment with ezetimiba/simvastatina.

While you are taking this medication, your doctor will monitor 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 your blood, overweight, and high blood pressure.

Consult your doctor if you have a severe lung disease.

Avoid taking ezetimiba/simvastatina with fibrates (certain medications to reduce cholesterol), as this combination has not been studied.

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

The risk of muscle failure is higher with high doses of ezetimiba/simvastatina, especially the 10/80 mg dose. The risk of muscle failure is also higher in certain patients. Inform 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 medications called "statins" (such as simvastatina, atorvastatina, and rosuvastatina) or fibrates (such as gemfibrozilo or bezafibrato).
• If you or your close relatives have a hereditary muscle disorder

Also inform your doctor or pharmacist if you experience persistent muscle weakness. Additional tests and medications may be necessary to diagnose and treat this problem.

Children and adolescents

• Ezetimiba/simvastatina is not recommended for children under 10 years old.

Other medications and Ezetimiba/Simvastatina Tecnigen

Inform your doctor if you are taking, have taken recently, or may need to take any other medication with any of the following active ingredients. Taking ezetimiba/simvastatina with any of the following medications may increase the risk of muscle problems (some of these are already included in the section above "Do not take X if").

• If you need to take oral fusidic acid to treat a bacterial infection, you will need to temporarily stop taking ezetimiba/simvastatina. Your doctor will tell you when you can restart the treatment with ezetimiba/simvastatina. The use of ezetimiba/simvastatina with fusidic acid rarely may cause muscle weakness, sensitivity, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4

• Ciclosporin (often used in transplant patients)
• Danazol (a synthetic hormone used to treat endometriosis, a condition in which the inner lining of the uterus grows outside the uterus)
• Medications with an active ingredient such as itraconazole, ketoconazole, fluconazole, posaconazole, or voriconazole (used to treat fungal infections)
• Fibrates with an active ingredient such as gemfibrozil and bezafibrato (used to reduce cholesterol)
• Erythromycin, clarithromycin, or telithromycin (used to treat bacterial infections)
• Protease inhibitors for HIV, such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat HIV infections)
• Antivirals for hepatitis C, such as boceprevir, telaprevir, elbasvir, or grazoprevir (used to treat hepatitis C infection)
• Nefazodone (used to treat depression)
• Medications with the active ingredient cobicistat
• Amiodarone (used to treat irregular heart rhythm)
• Verapamil, diltiazem, or amlodipine (used to treat high blood pressure, chest pain associated with heart disease, or other heart diseases)
• Lomitapida (used to treat rare and severe cholesterol disorders)
• Large doses (1 gram or more per day) of niacin or nicotinic acid (also used to reduce cholesterol)
• Colchicine (used to treat gout)

As with the medications mentioned above, inform your doctor or pharmacist if you are taking or have taken recently other medications, even those purchased without a prescription. In particular, inform your doctor if you are taking any of the following:

• Medications with an active ingredient to prevent blood clot formation, such as warfarin, fluindione, fenprocomon, or acenocoumarol (anticoagulants)
• Colestiramine (also used to reduce cholesterol), as it affects how ezetimiba/simvastatina works
• Fenofibrate (also used to reduce cholesterol)
• Rifampicin (used to treat tuberculosis)

You must also inform any doctor who prescribes a new medication that you are taking ezetimiba/simvastatina.

Taking Ezetimiba/Simvastatina Tecnigen with food and drinks

Orange juice contains one or more components that alter the metabolism of some medications, including ezetimiba/simvastatina. You should avoid consuming orange juice, as it may increase the risk of muscle problems.

Pregnancy and breastfeeding

Do not take this medication if you are pregnant, trying to become pregnant, or think you may be pregnant. If you become pregnant while taking ezetimiba/simvastatina, stop taking it immediately and inform your doctor. Do not take ezetimiba/simvastatina if you are breastfeeding, as it is unknown whether this medication passes into breast milk.

Consult your doctor or pharmacist before using any medication.

Driving and operating machines

Ezetimiba/simvastatina is not expected to interfere with your ability to drive or operate machines. However, some people may experience dizziness after taking ezetimiba/simvastatina.

Ezetimiba/Simvastatina Tecnigen contains lactose

This medication contains lactose. If your doctor has told you that you have a certain sugar intolerance, consult with them before taking this medication.

Ezetimiba/Simvastatina Tecnigen contains sodium

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

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

The tablets are not scored and should not be divided.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

• Before starting to take ezetimiba/simvastatina, you must be following a diet to reduce cholesterol.
• You will need to continue with this cholesterol-lowering diet while taking ezetimiba/simvastatina.

Adults: the dose is1 tabletof ezetimiba/simvastatina once a day by mouth.

Use in adolescents(10 to 17 years old): the dose is1 tabletof ezetimiba/simvastatina once a day by mouth (do not exceed a maximum dose of 10mg/40mg once a day).

The dose of ezetimiba/simvastatina 10mg/80mg is only recommended for adult patients with very high cholesterol levels and a high risk of heart disease problems who have not achieved treatment goals with lower doses.

Take ezetimiba/simvastatina at night. You can take it with or without food.

If your doctor has prescribed ezetimiba/simvastatina together with another cholesterol-lowering medication that contains the active ingredient colestiramine or any other bile acid sequestrant, you should take ezetimiba/simvastatina at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more Ezetimiba/Simvastatina Tecnigen than you should

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

If you forgot to take Ezetimiba/Simvastatina Tecnigen

• Do not take a double dose to make up for the missed doses, take your usual amount of Ezetimiba/Simvastatina Tecnigen at the usual time.

If you interrupt the treatment with Ezetimiba/Simvastatina Tecnigen

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them (see section 2. What you need to know before you start taking Ezetimiba/Simvastatina Tecnigen).

The following side effects were reported frequently (can affect up to 1 in 10 people):

• Muscle pain
• Laboratory blood test abnormalities in liver function (transaminases) and/or muscle (CK)

The following side effects were reported infrequently (can affect up to 1 in 100 people):

• Liver function abnormalities in blood tests; elevated uric acid in the blood; prolonged blood clotting time; protein in the urine; weight loss
• Dizziness; headache; tingling sensation
• Abdominal pain; indigestion; flatulence; nausea; vomiting; abdominal swelling; diarrhea; dry mouth; heartburn
• Rash; itching; urticaria
• Joint pain; muscle pain, weakness, or spasms; neck pain; arm and leg pain; back pain
• Unusual fatigue or weakness; feeling tired; chest pain; swelling, especially of the hands and feet
• Sleep disturbances; difficulty sleeping

In addition, the following side effects were reported in people taking ezetimiba/simvastatina or medications containing the active ingredients ezetimiba or simvastatina:

• Low red blood cell count (anemia), reduced white 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
• Hepatitis with the following symptoms: yellowing of the skin and eyes, itching, dark urine, pale stools, feeling tired or weak, loss of appetite; liver insufficiency; gallstones or inflammation of the gallbladder (which can cause abdominal pain, nausea, vomiting)
• Hair loss; red, swollen, and sometimes blistered rash (erythema multiforme)
• Blurred vision and vision deterioration (can affect up to 1 in 1,000 people)
• Rash that can occur on the skin or ulcers in the mouth (medication-induced lichenoid eruptions) (can affect up to 1 in 10,000 people)
• 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, joint pain, inflammation of blood vessels, unusual bruising, skin rash, urticaria, sensitivity to sunlight, fever, hot flashes, difficulty breathing, and general discomfort, pseudolupus-like syndrome, including skin rash, joint problems, and effects on white blood cells)
• Muscle pain, sensitivity to pressure, weakness, or muscle cramps; muscle failure; muscle rupture (can affect up to 1 in 10,000 people); tendon problems, sometimes complicated by tendon rupture
• Gynecomastia (breast enlargement in men) (can affect up to 1 in 10,000 people)
• Loss of appetite
• Hot flashes; high blood pressure
• Pain
• Erectile dysfunction
• Depression
• Abnormalities in some liver function blood tests

With some statins, the following additional adverse events have been reported:

• Sleep disturbances, including nightmares
• Sexual dysfunction
• Diabetes. It is more likely if you have high blood sugar and fat levels, obesity, and high blood pressure. Your doctor will monitor you while taking this medication
• Constant muscle pain, weakness, or sensitivity that may not disappear after stopping ezetimiba/simvastatina treatment (unknown frequency)

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 severe, including muscle failure, which can cause kidney damage; and very rarely, deaths have occurred.

Reporting of side effects:

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:

https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

This medication does not require any special storage temperature.

Store in the original packaging to protect it from light.

Do not dispose of medications through drains or trash. Deposit containers and unused medications at the SIGRE point of your pharmacy.If in doubt, ask your pharmacist how to dispose of containers and unused medications. By doing so, you will help protect the environment.

Composition of Ezetimiba/Simvastatina TecniGen 10 mg/ 20 mg

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

Appearance of the product and contents of the packaging

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

Ezetimiba/Simvastatina TecniGen is available in packaging containing blisters of 28 and 30 tablets.

Only some sizes of packaging may be commercially marketed.

Holder of the marketing authorization and responsible manufacturer

Holder

Tecnimede España Industria Farmacéutica S.A.

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

Polígono Arroyo de la Vega.

Alcobendas, 28108 – Madrid

Spain

Responsible 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 with the following names:

Portugal: Sinvastatina + Ezetimiba Tecnigen

Italy: Ezetimibe e Simvastatina TecniGen

Revision date of this leaflet: January 2019

Other sources of information:

The detailed and updated information of this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http: //www.aemps.gob.es/