EZETIMIBE/SIMVASTATIN DZ 10 mg/40 mg TABLETS

Introduction

Package Leaflet: Information for the User

Ezetimibe/Simvastatin DZ 10 mg/40 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 DZ and what is it used for
2. What you need to know before you take Ezetimibe/Simvastatin DZ
3. How to take Ezetimibe/Simvastatin DZ
4. Possible side effects
5. Storage of Ezetimibe/Simvastatin DZ
6. Contents of the pack and other information

1. What is Ezetimibe/Simvastatin DZ 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 a type of fat called triglycerides 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 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 fats found 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 slow down or block the blood flow to vital organs such as the heart and brain. This blocking 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 found in the blood. High levels of triglycerides can increase the risk of heart disease.

Ezetimibe/simvastatin 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.

Ezetimibe/simvastatin is used, along with a low-cholesterol diet, if you have:

• high levels of cholesterol in the blood (primary hypercholesterolaemia [heterozygous and non-familial]) or high levels of fats 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, surgery to increase blood flow to the heart, or hospitalisation due to chest pain.

This medicine does not help you lose weight.

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

Do not take Ezetimibe/Simvastatin DZ 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)
• cyclosporine (used in patients with transplanted organs)
• danazol (a synthetic hormone used to treat endometriosis, a disease in which the lining of the uterus grows outside the uterus)

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.

Your doctor will do a blood test before you start taking ezetimibe/simvastatin and also 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 increases 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 muscle problems can be serious, including muscle breakdown resulting in 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:

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 DZ

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

• cyclosporine (often used in patients with transplanted organs)
• 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 conditions)
• lomitapide (used to treat rare and serious genetic cholesterol disorders)
• 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, acenocoumarol, acetylsalicylic acid or phenindione (anticoagulants)
• colestipol (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 DZ with food and drink

Grapefruit juice contains one or more components that alter the metabolism of some medicines, including ezetimibe/simvastatin. You should avoid grapefruit juice, as it may 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 not expected 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.

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.

3. How to take Ezetimibe/Simvastatin DZ

Your doctor will determine the appropriate dose of the tablet 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 unsure, consult your doctor or pharmacist again.

• Before you start taking ezetimibe/simvastatin, you should be following 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 a 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 that contains the active substance colestipol 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 DZ 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 DZ

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

If you stop taking Ezetimibe/Simvastatin DZ

• 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 Ezetimibe/Simvastatin DZ).

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; elevations of uric acid in the blood; elevations 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 ezetimibe/simvastatin or medicines containing the active ingredients ezetimibe or simvastatin:

• Low red blood cell count (anemia), reduction in blood cell count, which can cause bruising/hemorrhage (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; reddened 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, blood vessel inflammation, atypical bruising, skin rashes and swelling, hives, skin sensitivity to sunlight, fever, hot flashes, difficulty breathing, and general discomfort, pseudo-lupus syndrome (including skin rash, joint disorders, and effects on white blood cells))
• Muscle pain, tenderness, 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 (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 ezetimibe/simvastatin (frequency not known)

The following serious rare adverse effects have been reported.

If any of these serious adverse effects occur, stop taking the medicine and inform your doctor immediately or go to the emergency department of the nearest hospital.

• Hypersensitivity reactions (allergic) that include:
• • Swelling of the face, tongue, and throat, which can cause difficulty breathing (angioedema)

The following very rare serious adverse effects have been reported:

A severe allergic reaction that causes difficulty breathing or dizziness (anaphylactic reaction)

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 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 Ezetimibe/Simvastatin DZ

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

Do not use this medicine after the expiration date stated on the carton after CAD. The expiration date is the last day of the month indicated.

Do not store above 25°C.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicines in the pharmacy's SIGRE 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 Ezetimibe/Simvastatin DZ

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

The other ingredients are: lactose monohydrate, hypromellose, sodium croscarmellose,

microcrystalline cellulose, ascorbic acid, anhydrous citric acid, butylated hydroxyanisole, propyl gallate, magnesium stearate, yellow iron oxide, red iron oxide, black iron oxide.

Appearance of the Product and Package Contents

The Ezetimibe/Simvastatin DZ 10/40 mg tablets are round, biconvex, white to bone-colored, speckled, and engraved with "513" on one side.

Package sizes:

28 tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Day Zero ehf.,

Reykjavikurvegur 62

220 Hafnarfjörður

Iceland

Manufacturer

Balkanpharma-Dupnitsa AD,

3 Samokovsko Shosse Street,

Dupnitsa, 2600,

Bulgaria

Date of the Last Revision of this Leaflet: September 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.es