EZETIMIBE/SIMVASTATIN CINFAMED 10 mg/20 mg TABLETS

2. What you need to know before you take ezetimibe/simvastatin cinfamed

Do not take ezetimibe/simvastatin cinfamed

• 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 breast-feeding.
• if 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 organ transplant patients),
• danazol (a synthetic hormone used to treat endometriosis, a condition 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 a rare and serious genetic cholesterol disorder).

Consult your doctor if you are not sure if any of your medicines are mentioned above.

Warnings and precautions

Consult your doctor or pharmacist before you start taking ezetimibe/simvastatin cinfamed.

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 problems (myasthenia) or muscle weakness (myasthenic syndrome), as statins can sometimes make these conditions worse or trigger them (see section 4).

Your doctor will do a blood test before you start taking ezetimibe/simvastatin and will also do a test 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. 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 and fibrates together has not been studied.

Tell your doctor immediately if you experience muscle pain, tenderness or weakness that you cannot explain. 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.

The risk of muscle breakdown is higher with higher doses of ezetimibe/simvastatin, especially the 10/80 mg dose. The risk of muscle breakdown is also higher in certain patients. Tell your doctor if:

• you have kidney problems,
• you have thyroid problems,
• you are over 65 years old,
• 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 a close family member have a muscle problem that runs in the family.

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

Children and adolescents

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

Other medicines and ezetimibe/simvastatin cinfamed

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 "Do not take ezetimibe/simvastatin cinfamed" section above).

• if you have 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 the treatment with ezetimibe/simvastatin. The use of ezetimibe/simvastatin with fusidic acid can rarely cause muscle weakness, tenderness or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.

• cyclosporin (often used in patients who have had organ transplants),
• 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 ingredient used to treat fungal infections, such as itraconazole, ketoconazole, fluconazole, posaconazole or voriconazole,
• fibrates with an active ingredient 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 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 conditions),
• 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). The risk of muscle side effects 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, in particular, tell your doctor if you are taking any of the following:

• medicines with an active ingredient used to prevent blood clots, such as warfarin, fludione, 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),
• ticagrelor (an antiplatelet medicine).

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

Taking ezetimibe/simvastatin cinfamedwith food and drink

Grapefruit juice contains one or more ingredients 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

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

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 if this medicine passes into breast milk.

Ask your doctor or pharmacist for advice 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 after taking ezetimibe/simvastatin.

ezetimibe/simvastatin cinfamedcontains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

ezetimibe/simvastatina cinfamedcontains sodium

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

3. How to take ezetimibe/simvastatin cinfamed

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 personal risk situation.

The tablets are not scored and should not be divided.

• Before you start taking ezetimibe/simvastatin, you should be on a diet to lower your cholesterol.
• You should continue with this low-cholesterol diet while you are taking this medicine.

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 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 ingredient 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 more ezetimibe/simvastatin cinfamedthan you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist or call the Toxicology Information Service immediately. telephone: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take ezetimibe/simvastatin cinfamed

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

If you stop taking ezetimibe/simvastatin cinfamed

• 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,
• 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; elevation of uric acid in the blood; elevation 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.

The following adverse effects have been reported with an unknown frequency (cannot be estimated from the 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.

Additionally, the following adverse effects have been reported in people taking ezetimibe/simvastatin or medications containing the active ingredients ezetimibe or simvastatin:

• Low red blood cell count (anemia), reduction in 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,
• 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-shaped lesions (erythema multiforme),
• Blurred vision and vision impairment (may affect up to 1 in 1,000 people)
• Rash that may occur on the skin or ulcers in the mouth (drug-induced lichenoid eruptions) (may affect up to 1 in 10,000 people),
• Hypersensitivity reactions that may include the following: allergic reactions including swelling of the face, lips, tongue, and/or throat, which can cause difficulty breathing or swallowing and requires immediate treatment (angioedema), pain or inflammation of the joints, inflammation of blood vessels, atypical bruising, skin rash, and swelling, urticaria, skin sensitivity to sunlight, fever, hot flashes, difficulty breathing, and general malaise, 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 to pressure, 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 the breast 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 blood tests of liver function,

The following additional adverse events have been reported with some statins:

• Sleep disorders, including nightmares,
• Sexual dysfunction,
• Diabetes. It is more likely if you have high levels of sugars and fats in the blood, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medication,

• Persistent muscle pain, sensitivity, or weakness that may not disappear after discontinuing treatment with ezetimibe/simvastatin (frequency not known: cannot be estimated from the available data).

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

Reporting of Adverse Effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, 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 Cinfamed

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

Do not use this medicine after the expiration date that appears on the packaging or on the blister pack 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 through wastewater or household waste. Deposit the packaging and unused medicines at the SIGRE collection point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Ezetimibe/Simvastatin Cinfamed

The active ingredients are ezetimibe and simvastatin. Each tablet contains 10 mg of ezetimibe and 20 mg of simvastatin.

The other ingredients are: lactose monohydrate, hypromellose, sodium croscarmellose, microcrystalline cellulose, ascorbic acid, citric acid, butylhydroxyanisole, propyl gallate, and magnesium stearate. Pigment mixture: lactose monohydrate, yellow iron oxide (E-172), red iron oxide (E-172), and black iron oxide (E-172).

Appearance of the Product and Package Contents

Round, biconvex tablets, white to bone-colored, speckled, 8 mm in diameter, and engraved with "512" on one side.

OPA/Aluminum/PVC blisters attached to an aluminum sheet.

Package sizes:

10, 14, 28, 30, 50, 56, 90, 98, and 100 tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorios Cinfa, S.A.

Carretera Olaz-Chipi, 10. Polígono Industrial Areta

31620 Huarte (Navarra) - Spain

Manufacturer

Balkanpharma-Dupnitsa AD,

3 Samokovsko Shosse Street,

Dupnitsa, 2600,

Bulgaria

or

Laboratorios Cinfa, S.A.

Carretera Olaz-Chipi, 10. Polígono Industrial Areta

31620 Huarte (Navarra) - Spain

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.

You can access detailed and updated information about this medicine by scanning the QR code included in the leaflet and packaging with your mobile phone (smartphone). You can also access this information at the following internet address: https://cima.aemps.es/cima/dochtml/p/82799/P_82799.html.

QR code to: https://cima.aemps.es/cima/dochtml/p/82799/P_82799.html.