EZETIMIBE/SIMVASTATIN PHARMA COMBIX 10 mg/40 mg TABLETS

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

Do not take Ezetimibe/Simvastatin Pharma Combix 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 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 may also do a blood 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. This risk of diabetes increases if you have high levels of sugar and fat in your 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 cholesterol-lowering medicines) 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.

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. You may need to have tests and additional medicines to diagnose and treat this problem.

Children and adolescents

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

Other medicines and Ezetimibe/Simvastatin Pharma Combix

Tell your doctor if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription. In particular, tell your doctor if you are taking or have taken any of the following:

• 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 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, acenoquinoline or phenprocoumon (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 Pharma Combixwith 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 can increase the risk of muscle problems.

Pregnancy and breast-feeding

Do not take this medicine if you are pregnant, trying to become pregnant or 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.

Ezetimibe/Simvastatin Pharma Combixcontains 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 Pharma Combix

Your doctor will decide on 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 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 old): 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 containing 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 moreEzetimibe/Simvastatin Pharma Combixthan 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 takeEzetimibe/Simvastatin Pharma Combix

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

If you stop takingEzetimibe/Simvastatin Pharma Combix

• Talk to your doctor or pharmacist because your cholesterol levels may rise 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 taking Ezetimiba/Simvastatina Pharma Combix).

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

• Muscle pain
• Elevations in blood test results 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 ezetimiba/simvastatina or medicines containing the active ingredients ezetimiba or simvastatina:

• Low red blood cell count (anemia), reduced 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; red 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 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, joint pain or inflammation, blood vessel inflammation, atypical bruising, skin rash 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))
• Muscle pain, pressure sensitivity, 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 blood tests of liver function

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
• Persistent muscle pain, sensitivity, or weakness that may not disappear after stopping treatment with ezetimiba/simvastatina (frequency not known)
• Severe myasthenia (a disease that causes generalized muscle weakness that, in some cases, affects the muscles used for breathing) (frequency not known)
• Ocular myasthenia (a disease that causes weakness of the eye muscles) (frequency not known)

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

Consult your doctor immediately if you experience unexplained muscle pain, pressure sensitivity, 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 effects, consult your doctor, pharmacist, or nurse, 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 Ezetimiba/Simvastatina Pharma Combix

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 after CAD. The expiration date is the last day of the month indicated

This medicine does not require special storage conditions

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and any unused medicines at the SIGRE collection point in your pharmacy. 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 Ezetimiba/Simvastatina Pharma Combix

• The active ingredients are ezetimiba and simvastatina. Each tablet contains 10 mg of ezetimiba and 40 mg of simvastatina
• The other ingredients are: lactose monohydrate, pregelatinized corn starch (1500), crospovidone type B, hypromellose 3 CPS, sodium lauryl sulfate, microcrystalline cellulose (E460i),

butylated hydroxyanisole, citric acid, ascorbic acid, anhydrous lactose, sodium croscarmellose,

sodium fumarate, magnesium stearate (E470b)

Appearance of the Product and Package Contents

Capsule-shaped tablets, white to off-white in color, with the engraving "14" on one side and smooth on the other

Ezetimiba/Simvastatina Pharma Combix 10 mg/40 mg is available in PVC/Aclar-Al and OPA/Al/PVC-Al blister packs, in packs of 28 tablets

Marketing Authorization Holder

Laboratorios Combix, S.L.U

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

or

Pharmex Advanced Laboratories S.L

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

Date of the Last Revision of this Leaflet: April 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/