EZETIMIBE/SIMVASTATIN Aurovitas 10 mg/40 mg Tablets

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

Do not takeEzetimibe/Simvastatin Aurovitasif:

• 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 any of the following medicines:

• 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 (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 condition 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 ezetimibe/simvastatin can cause muscle problems (rhabdomyolysis).

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

Consult your doctor if you are not sure if any of the above applies to you.

Warnings and precautions

Consult your doctor or pharmacist before taking Ezetimibe/Simvastatin Aurovitas:

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 this medicine and if you have any symptoms of liver problems while taking ezetimibe/simvastatin. This is to check how your liver is working.

Your doctor may also want to do blood tests to check how your liver is working after you start taking ezetimibe/simvastatin.

While you are taking this medicine, your doctor will check if you have diabetes or are at risk of developing diabetes. Your risk of diabetes is higher if you have high levels of sugars and fats in your blood, are overweight and have high blood pressure.

Tell 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 with fibrates has not been studied.

Consult your doctor immediately if you experience unexplained muscle pain, tenderness or weakness.This is because, on rare occasions, 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, particularly with the 10 mg/80 mg dose. The risk of muscle breakdown is also greater in certain patients. Tell your doctor if any of the following applies to you:

• 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 muscle problem called hereditary myopathy.

Also, tell your doctor or pharmacist if you experience persistent muscle weakness. You may need further tests and treatment to diagnose and manage this condition.

If you have or have had myasthenia gravis (a disease that causes muscle weakness), or myasthenic syndrome (a condition that causes muscle weakness), as statins can sometimes make these conditions worse or trigger their onset (see section 4).

Children and adolescents

Ezetimibe/simvastatin is not recommended for children under 10 years old.

Other medicines andEzetimibe/Simvastatin Aurovitas

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Taking ezetimibe/simvastatin with any of the following medicines may increase the risk of muscle problems (some of these are already included in the section above “Do not take Ezetimibe/Simvastatin Aurovitas if”).

• If you need 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 taking ezetimibe/simvastatin. Taking ezetimibe/simvastatin with fusidic acid can rarely cause muscle weakness, tenderness or pain (rhabdomyolysis). For more information about rhabdomyolysis, see section 4.
• cyclosporin (often used in patients who have had an organ transplant).
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus).
• medicines with an active substance used to treat fungal infections, such as itraconazole, ketoconazole, fluconazole, posaconazole or voriconazole.
• 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 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 with the active substance 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 conditions).
• lomitapide (used to treat a rare and serious genetic cholesterol disorder).
• daptomycin (a medicine used to treat skin and skin structure infections with complications and bacteraemia). The risk of side effects that affect the muscles may be greater when this medicine is taken during treatment with simvastatin (such as ezetimibe/simvastatin). Your doctor may decide that you need to stop taking ezetimibe/simvastatin 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 listed 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).
• colestyramine (also used to lower cholesterol), as it affects how ezetimibe/simvastatin works.
• fenofibrate (also used to lower cholesterol).
• rifampicin (used to treat tuberculosis).
• ticagrelor (an antiplatelet agent).

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

TakingEzetimibe/Simvastatin Aurovitaswith food and drink

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

Pregnancy and breast-feeding

Do not take ezetimibe/simvastatin 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 taking 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 when taking ezetimibe/simvastatin.

Ezetimibe/Simvastatin Aurovitas contains lactose and sodium

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.

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

3. How to take Ezetimibe/Simvastatin Aurovitas

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

Your doctor will decide on the appropriate dose of ezetimibe/simvastatin for you, depending on your current treatment and your individual risk profile.

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

Adults:the dose is one ezetimibe/simvastatin tablet once a day by mouth.

Use in adolescents(10 to 17 years of age):the dose is one ezetimibe/simvastatin tablet 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.

Not all the recommended doses are possible with these tablets; however, other tablets with different doses are also available (10 mg/80 mg).

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

If your doctor has prescribed ezetimibe/simvastatin 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 moreEzetimibe/Simvastatin Aurovitasthan you should

If you have taken too much of this medicine, contact your doctor or pharmacist immediately or go to the emergency department at your nearest hospital. Take the medicine pack with you.

If you forget to takeEzetimibe/Simvastatin Aurovitas

Do not take a double dose to make up for a forgotten dose. Simply take your normal dose of ezetimibe/simvastatin at the usual time the next day.

If you stop takingEzetimibe/Simvastatin Aurovitas

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

If you have any further questions on the use of this medicine, 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.

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

• Muscle pain.
• Increased blood test results for liver function (transaminases) and/or muscle (CK).

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

• Increased liver function in blood tests; increased uric acid in the blood; increased time 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 arms and legs; back pain.
• Unusual fatigue or weakness; feeling tired; chest pain; swelling, especially of 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), reduced blood cell count that can cause bruising/bleeding (thrombocytopenia).
• Numbness or weakness of 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).
• Rash that can occur on the skin or ulcers in the mouth (drug-induced lichenoid rash) (may affect up to 1 in 10,000 people).
• Blurred vision and visual disturbance (may affect up to 1 in 1,000 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 require immediate treatment (angioedema), pain or inflammation of the joints, inflammation of blood vessels, unusual bruising, skin rashes, and swelling, hives, skin 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, weakness, or cramps; muscle rupture, muscle breakdown (which may affect up to 1 in 10,000 people); tendon problems, which can occasionally be complicated by tendon rupture.
• Gynecomastia (breast enlargement in men) (which 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.

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

• 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, sensitivity, or weakness that may not disappear after stopping treatment with ezetimibe/simvastatin (frequency not known).

If any of these serious adverse effects occur, stop taking the medicine and immediately inform your doctor or go to the emergency department of the nearest hospital:Muscle pain, sensitivity, weakness, or cramps. This is because, in rare cases, muscle problems can be serious, including muscle breakdown that causes kidney damage; and very rarely, deaths have occurred.

Frequency not known (cannot be estimated from 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.

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, 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 Ezetimibe/Simvastatin Aurovitas

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging and blister after CAD. The expiration date is the last day of the month indicated.

This medicine does not require any special storage temperature.

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

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

6. Package Contents and Additional Information

Composition ofEzetimibe/Simvastatin Aurovitas

• The active ingredients are ezetimibe and simvastatin.

Each Ezetimibe/Simvastatin Aurovitas 10 mg/40 mg tablet contains 10 mg of ezetimibe and 40 mg of simvastatin.

• The other ingredients are: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, magnesium stearate, hypromellose 2910, and butylhydroxytoluene (E321). See section 2 "Ezetimibe/Simvastatin Aurovitas contains lactose and sodium".

Appearance of the Product and Package Contents

White or almost white, biconvex, capsule-shaped tablets. The tablet size is 14 mm x 6 mm.

Ezetimibe/Simvastatin Aurovitas 10 mg/40 mg tablets EFG are available in boxes containing 28, 30, 50, 90, 98, and 100 tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Manufacturer:

Krka, d.d., Novo mesto

Šmarješka cesta 6

8501 Novo mesto

Slovenia

or

TAD Pharma GmbH

Heinz-Lohmann-Straße 5

27472 Cuxhaven

Germany

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

Germany: Ezetimib/Simvastatin PUREN 10 mg/40 mg Tablets

Belgium: Ezetimib/Simvastatin AB 10 mg/40 mg tablets

Spain: Ezetimiba/Simvastatina Aurovitas 10 mg/40 mg tablets EFG

France: EZETIMIBE/SIMVASTATINE ARROW 10 mg/40 mg, tablet

Italy: Ezetimibe e Simvastatina Aurobindo

Netherlands: Ezetimibe/Simvastatine Aurobindo 10/40 mg, tablets

Date of the Last Revision of this Leaflet:June 2023

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