EZETIMIBE/SIMVASTATIN STADA 10 mg/40 mg TABLETS

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

Do not take Ezetimibe/Simvastatin Stada 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 organ transplant patients)
• 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 called 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 10/40 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 going 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
• if you have or have had muscle weakness (myasthenia gravis) or eye muscle weakness (ocular myasthenia), as statins can sometimes make these conditions worse or trigger the onset of myasthenia (see section 4).

Your doctor will do a blood test before you start 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 taking 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 sugar 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 with 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.

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

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 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 relatives have a hereditary muscle problem

Children and adolescents

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

Other medicines and Ezetimibe/Simvastatin Stada

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 section above "Do not take Ezetimibe/Simvastatin Stada if").

• if you need to take fusidic acid by mouth to treat a bacterial infection, you will have to stop taking this medicine temporarily. Your doctor will tell you when it is safe to restart ezetimibe/simvastatin. The combination of ezetimibe/simvastatin and fusidic acid can cause, on rare occasions, muscle weakness, tenderness or pain (rhabdomyolysis). See more information about rhabdomyolysis in section 4.
• cyclosporin (used in transplant patients)
• 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 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 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)
• daptomycin (a medicine used to treat skin and skin structure infections with complications and bacteraemia). It is possible that the adverse effects that affect the muscles may be greater when this medicine is taken during treatment with simvastatin (e.g. ezetimibe/simvastatin). Your doctor may decide that you should 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 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, fluvastatin, 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 Stada 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 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 interfere with 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 and sodium

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 23 mg of sodium (1 mmol) per tablet; this is essentially "sodium-free".

3. How to take Ezetimibe/Simvastatin Stada

Your doctor will determine the appropriate dose of ezetimibe/simvastatin 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 in doubt, consult your doctor or pharmacist again.

• before starting to take 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.

If the optimal dose cannot be achieved using ezetimibe/simvastatin 10 mg/40 mg, your doctor may prescribe other tablets containing ezetimibe/simvastatin.

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 cholestyramine 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 Stada than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service, Tel. 91 562 04 20, indicating the medicine and the amount taken. It is recommended to take the package and the package leaflet of the medicine to the healthcare professional.

If you forget to take Ezetimibe/Simvastatin Stada

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

If you stop taking Ezetimibe/Simvastatin Stada

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 (see section 2).

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

• Muscle pain
• Increased blood test results in laboratory 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; prolongation of blood coagulation time; 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, which can cause bruising/hemorrhage (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; red, 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 (angioedema), a very rare severe allergic reaction that causes difficulty breathing or dizziness (anaphylaxis), joint pain or inflammation, blood vessel inflammation, unusual bruising, skin rash and swelling, urticaria, 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))
• 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
• Abnormal liver function test results
• Severe myasthenia (a disease that causes generalized muscle weakness, which in some cases affects the muscles used for breathing) (frequency not known: cannot be estimated from available data)*
• Ocular myasthenia (a disease that causes weakness of the eye muscles) (frequency not known: cannot be estimated from available data)*

• 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.

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

• Sleep disorders, including nightmares
• Sexual dysfunction
• 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
• Constant muscle pain, tenderness, or weakness that may not disappear after stopping treatment with ezetimibe/simvastatin (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 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 Medicines Surveillance System: 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 Stada

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

Do not use this medicine after the expiration date stated on the packaging 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 collection point. Ask your pharmacist how to dispose of the packaging and any medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Ezetimibe/Simvastatin Stada

The active ingredients are ezetimibe and simvastatin.

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

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

The other ingredients are: Tablet core: lactose monohydrate, hypromellose, sodium croscarmellose, microcrystalline cellulose, ascorbic acid, citric acid, butylated hydroxyanisole, propyl gallate, magnesium stearate. Pigment mixture: lactose monohydrate, yellow iron oxide (E172), red iron oxide (E172), and black iron oxide (E172).

Appearance of the Product and Package Contents

10 mg/20 mg: The tablets of Ezetimibe/Simvastatin Stada 10 mg/20 mg are light brown, speckled, round, 8 mm in diameter, biconvex, and marked with "512" on one side.

10 mg/40 mg: The tablets of Ezetimibe/Simvastatin Stada 10 mg/40 mg are light brown, speckled, round, 10 mm in diameter, biconvex, and marked with "513" on one side.

Package sizes:

Blister: 28, 30, 50, 90, 98, and 100 tablets.

HDPE bottle: 90 and 100 tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorio STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Manufacturer

Balkanpharma-Dupnitsa AD

3 Samokovsko Shosse Str.,

Dupnitza 2600

Bulgaria

or

STADA Arzneimittel AG

Stadastrasse 2 – 18

61118 Bad Vilbel

Germany

or

STADA Arzneimittel GmbH

Muthgasse 36/2

1190 Wien

Austria

or

Centrafarm Services B.V.

Van de Reijtstraat 31-E

4814 NE Breda

Netherlands

or

Clonmel Healthcare Ltd.

Waterford Road

Clonmel, Co. Tipperary

Ireland

or

Sanico N.V.

Veedijk 59

2300 Turnhout

Belgium

or

Actavis Ltd.

BLB015-016, Bulebel Industrial Estate

Zejtun ZTN 3000

Malta

Date of the Last Revision of this Leaflet:May 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.gob.es/