Ezetimibe/simvastatin Krka 10 mg/40 mg tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Ezetimibe/Simvastatin Krka 10 mg/20 mg tablets EFG

Ezetimibe/Simvastatin Krka 10 mg/40 mg tablets EFG

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Ezetimibe/Simvastatin Krka is and what it is used for
2. What you need to know before taking Ezetimibe/Simvastatin Krka
3. How to take Ezetimibe/Simvastatin Krka
4. Possible adverse effects
5. How to store Ezetimibe/Simvastatin Krka
6. Contents of the pack and other information

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

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

Ezetimibe/simvastatin works to reduce cholesterol in two ways. The active substance ezetimibe reduces the cholesterol absorbed in the gastrointestinal tract. The active substance simvastatin, which belongs to the group of drugs known as "statins", inhibits the production of cholesterol made by the body itself.

Cholesterol is one of the fatty substances present in the bloodstream. Your 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 your arteries, forming plaques. Over time, this plaque buildup can cause narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. Such blockage of blood flow may lead to 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 your blood that may increase the risk of heart disease.

Ezetimibe/simvastatin is used in patients who cannot control their cholesterol levels with diet alone. While taking this medicine, you must continue to follow a cholesterol-lowering diet.

Ezetimibe/simvastatin is used, together with a cholesterol-lowering diet, if you have:

• high blood levels of cholesterol (primary hypercholesterolemia [heterozygous familial and non-familial]) or high blood levels of fatty substances (mixed hyperlipidemia):
• that are not well controlled by a statin alone
• for whom a statin and ezetimibe have previously been used as separate tablets
• a hereditary condition (homozygous familial hypercholesterolemia), which increases cholesterol levels in the blood. You may also receive other treatments.
• heart disease; in such cases, ezetimibe/simvastatin reduces the risk of heart attack, stroke, surgery to improve blood flow to the heart, or hospitalization due to chest pain.

This medicine does not help you to lose weight.

2. What you need to know before taking Ezetimiba/Simvastatina Krka

Do not take Ezetimiba/Simvastatina Krka

• if you are allergic to ezetimibe, simvastatin, or any of the other ingredients of this medicine (listed in section 6),
• if you currently have liver problems,
• if you are pregnant or breastfeeding,
• if you are taking medicines 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,
  • gemfibrozil (used to reduce cholesterol),
  • cyclosporine (often used in organ transplant patients),
  • 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 medicine containing fusidic acid (used to treat bacterial infection) taken orally or by injection. The combination of fusidic acid and ezetimibe/simvastatin may cause serious muscle problems (rhabdomyolysis).

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

Consult your doctor if you are unsure whether your medicine is listed above.

Warnings and precautions

Tell your doctor or pharmacist before taking Ezetimiba/Simvastatina Krka:

• about all your medical conditions, including allergies,
• if you consume large amounts of alcohol or have ever had liver disease. Ezetimiba/Simvastatina Krka may not be suitable for you,
• if you are scheduled for surgery. You may need to stop taking Ezetimiba/Simvastatina Krka tablets for a short period,
• if you are of Asian descent, as you may require a different dose,
• if you have or have had myasthenia (a disease characterized by generalized muscle weakness, which in some cases affects the muscles used for breathing), or ocular myasthenia (a disease causing weakness of the eye muscles), as these conditions may sometimes worsen or lead to the development of myasthenia (see section 4).

Your doctor should perform a blood test before you start taking Ezetimiba/Simvastatina Krka and also if you develop any symptoms of liver problems while taking it. This is to monitor liver function.

Your doctor may also wish to perform blood tests to monitor liver function after you start treatment with Ezetimiba/Simvastatina Krka.

While taking this medicine, your doctor will monitor you for diabetes or risk of developing diabetes. This risk increases if you have high levels of blood sugar and fats, are overweight, or have high blood pressure.

Talk to your doctor if you have a serious lung disease.

The combined use of Ezetimiba/Simvastatina Krka and fibrates (certain medicines to reduce cholesterol) should be avoided, as the combination has not been studied.

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. This is because, in rare cases, muscle problems can be serious—for example, muscle breakdown leading to kidney damage—and very rarely, deaths have occurred.

The risk of muscle breakdown is higher with higher doses of Ezetimiba/Simvastatina Krka, especially the 10 mg/80 mg dose. The risk of muscle breakdown is also higher in certain patients. Inform your doctor in the following situations:

• 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 called "statins" (such as simvastatin, atorvastatin, and rosuvastatin) or fibrates (such as gemfibrozil or bezafibrate),
• you or your close family members have an inherited muscle disorder.

Also inform your doctor or pharmacist if you have persistent muscle weakness. Additional tests and treatments may be needed for diagnosis and management.

Paediatric population

Ezetimiba/Simvastatina Krka is not recommended for children under 10 years of age.

Taking Ezetimiba/Simvastatina Krka with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines containing any of the following active substances. Taking Ezetimiba/Simvastatina Krka 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 Ezetimiba/Simvastatina Krka").

• If you need to take oral fusidic acid to treat a bacterial infection, you will need to temporarily stop using this medicine. Your doctor will advise you when you can restart treatment. The use of this medicine with fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). For further information on rhabdomyolysis, see section 4.
• cyclosporine (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),
• medicines containing active substances such as itraconazole, ketoconazole, posaconazole, or voriconazole (used to treat fungal infections),
• fibrates with 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 HIV infections),
• antivirals for hepatitis C such as boceprevir, telaprevir, elbasvir, or grazoprevir (used to treat hepatitis C virus infection),
• nefazodone (used to treat depression),
• medicines containing cobicistat,
• amiodarone (used to treat cardiac arrhythmias),
• 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, serious genetic cholesterol disorders),
• daptomycin (a medicine used to treat complicated skin and skin structure infections and bacteremia). Adverse effects affecting muscles may be increased when this medicine is taken during treatment with simvastatin (e.g., this medicine). Your doctor may decide that you should temporarily stop taking this medicine,
• high doses (1 gram or more per day) of niacin or nicotinic acid (also used to reduce 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 medicines, including those obtained without a prescription. In particular, inform your doctor if you are taking any of the following:

• medicines containing active substances to prevent blood clotting, such as warfarin, fluindione, phenprocoumon, or acenocoumarol (anticoagulants),
• colestyramine (also used to reduce cholesterol), as it affects how Ezetimiba/Simvastatina Krka works,
• fenofibrate (also used to reduce cholesterol),
• rifampicin (used to treat tuberculosis),
• ticagrelor (an antiplatelet medicine).

You should also inform any doctor prescribing a new medicine that you are taking Ezetimiba/Simvastatina Krka.

Taking Ezetimiba/Simvastatina Krka with food and drinks

Grapefruit juice contains one or more components that alter the metabolism of certain medicines, including Ezetimiba/Simvastatina Krka. Consumption of grapefruit juice should be avoided, as it may increase the risk of muscle problems.

Pregnancy and breastfeeding

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

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Ezetimiba/Simvastatina Krka is not expected to affect your ability to drive or use machines. However, some people may experience dizziness after taking Ezetimiba/Simvastatina Krka.

Ezetimiba/Simvastatina Krka contains lactose and sodium

If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.

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

3. How to take Ezetimiba/Simvastatina Krka

Follow exactly the instructions for use of this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.

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

• Before starting to take Ezetimiba/Simvastatina Krka, you should already be on a cholesterol-lowering diet.
• You must continue this cholesterol-lowering diet while taking Ezetimiba/Simvastatina Krka.

Adults: The recommended dose is one tablet of Ezetimiba/Simvastatina Krka taken once daily by mouth.

Use in adolescents (10 to 17 years of age): the dose is one tablet of ezetimiba/simvastatina once daily by mouth (the maximum dose should not exceed 10 mg/40 mg once daily).

The 10 mg/80 mg dose is only recommended for adults with very high cholesterol levels and a high risk of heart problems who have not achieved their cholesterol goal with lower doses.

Not all recommended dose strengths are available with these products; however, other products with different dosing (10 mg/80 mg) are also available.

Take Ezetimiba/Simvastatina Krka in the evening. It may be taken with or without food.

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

If you take more Ezetimiba/Simvastatina Krka than you should

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

If you forget to take Ezetimiba/Simvastatina Krka

Do not take a double dose to make up for forgotten doses. Take your usual amount of Ezetimiba/Simvastatina Krka at the usual time.

If you stop taking Ezetimiba/Simvastatina Krka

Talk to your doctor or pharmacist, as your cholesterol levels may rise again.

If you have any further questions about 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 everyone experiences them.

If you experience any of the following, stop taking the medicine and contact your doctor immediately:

• muscle pain (common: may affect up to 1 in 10 people),
• signs indicating blood disorders, e.g. fatigue, unexplained bleeding or bruising, mouth ulcers (frequency not known: cannot be estimated from available data),
• inflammation of the pancreas which may cause severe abdominal and back pain accompanied by a general feeling of discomfort (frequency not known: cannot be estimated from available data),
• signs indicating liver problems, gallstones, or inflammation of the gallbladder, e.g. yellowing of the skin, stomach pain, itching, dark urine, or pale stools (frequency not known: cannot be estimated from available data),
• angioedema (stop taking Ezetimibe/Simvastatin Krka and contact your doctor immediately if you experience any of the following symptoms: swelling of the face, tongue, or throat, difficulty swallowing, hives, or breathing difficulties) (rare: may affect up to 1 in 1,000 people).

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. The reason is that, in rare cases, muscle problems can be serious, for example, muscle breakdown leading to kidney damage; and very rarely, deaths have occurred.

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

• increased laboratory blood test values for liver function (transaminases) and/or muscle function (CK).

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

• increased blood values indicating liver function; increased blood uric acid levels; prolonged blood clotting time; presence of protein in urine; weight loss.
• dizziness; headache; tingling sensation.
• abdominal pain; indigestion; flatulence; nausea; vomiting; abdominal swelling; diarrhea; dry mouth; heartburn.
• skin rash; itching; hives.
• joint pain; muscle pain, tenderness, weakness, or muscle 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 disorders; difficulty sleeping.

Additionally, the following adverse effects have been reported in people taking Ezetimibe/Simvastatin Krka or medicines containing the active substances ezetimibe or simvastatin:

• numbness or weakness in arms and legs; memory impairment, memory loss, confusion.
• breathing problems including persistent cough and/or difficulty breathing or fever.
• constipation.
• hair loss; raised red rash, sometimes with target-like lesions (erythema multiforme).
• blurred vision and vision problems (may affect up to 1 in 1,000 people).
• skin rash that may appear on the skin or mouth sores (lichenoid drug eruptions) (may affect up to 1 in 10,000 people).
• hypersensitivity reactions including some of the following: an allergic reaction accompanied by 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, unusual bruising, skin rashes and swelling, hives, skin sensitivity to sunlight, fever, hot flushes, difficulty breathing, and malaise, lupus-like illness (including skin rash, joint disorders, and effects on white blood cells). A very rare but serious adverse reaction (may affect up to 1 in 10,000 people) may occur, causing difficulty breathing or dizziness, and requires immediate treatment (anaphylaxis).
• 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.
• gynaecomastia (enlargement of breasts in men) (may affect up to 1 in 10,000 people).
• decreased appetite.
• hot flushes; elevated blood pressure.
• pain.
• erectile dysfunction.
• depression.
• changes in certain blood laboratory tests for liver function.
• myasthenia gravis (a disease causing generalized muscle weakness which, in some cases, affects the muscles used for breathing).
• ocular myasthenia (a disease causing weakness of the eye muscles).

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

Other possible adverse effects reported with some statins:

• sleep disorders; including nightmares.
• sexual problems.
• 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 while you are taking this medicine.
• persistent muscle pain, tenderness, or weakness that may not resolve after stopping Ezetimibe/Simvastatin Krka (frequency unknown).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist. This includes any possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Ezetimibe/Simvastatin Krka

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage temperature conditions.

Store in the original packaging to protect it from light and moisture.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE Point in your pharmacy. If you are in doubt, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Ezetimiba/Simvastatina Krka

• The active substances are ezetimibe and simvastatin.

Each tablet contains 10 mg of ezetimibe and 20 mg of simvastatin.

Each tablet contains 10 mg of ezetimibe and 40 mg of simvastatin.

• The other components are lactose, microcrystalline cellulose, sodium croscarmellose, magnesium stearate, hypromellose 2910 and red iron oxide (E172) – for the 10 mg/20 mg tablets only. See section 2 "Ezetimiba/Simvastatina Krka contains lactose and sodium".

Appearance of the product and contents of the pack

10 mg/20 mg tablets: pinkish-white, oval, biconvex tablets. Tablet length 11 mm, width 5.5 mm.

10 mg/40 mg tablets: white to almost white, capsule-shaped, biconvex tablets. Tablet dimensions 14 x 6 mm.

Ezetimiba/Simvastatina Krka is available in packs containing:

• 14, 28, 30, 50, 56, 60, 90, 98 or 100 tablets in blisters,
  • 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 90 x 1, 98 x 1 or 100 x 1 tablets in perforated unit-dose blisters.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer:

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

or

TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For more information about this medicine, contact the local representative of the Marketing Authorization Holder:

KRKA Farmacéutica, S.L., Calle de Anabel Segura 10, 28108 Alcobendas, Madrid, Spain

This medicine is authorized in the European Economic Area member states under the following names:

Date of the most recent review of this leaflet: November 2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es