EZETIMIBE/ATORVASTATIN STADAFARMA 10 mg/80 mg FILM-COATED TABLETS

1. What is Ezetimibe/Atorvastatin Stadafarma and what is it used for

Ezetimibe/Atorvastatin Stadafarma is a medicine that lowers high cholesterol levels. This medicine contains ezetimibe and atorvastatin.

Ezetimibe/atorvastatin is used in adults to lower the levels of total cholesterol, "bad" cholesterol (LDL cholesterol) and substances called triglycerides that circulate in the blood. In addition, ezetimibe/atorvastatin raises the levels of "good" cholesterol (HDL cholesterol).

Ezetimibe/atorvastatin works by reducing cholesterol in two ways. It reduces the cholesterol absorbed in the digestive tract, as well as the cholesterol produced by your body.

Cholesterol is one of the fatty substances that are found in the bloodstream. Your total cholesterol is mainly made up of LDL 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 buildup of plaque can cause the arteries to narrow. This narrowing can slow down or block the blood flow to vital organs such as the heart and brain. This interruption of blood flow can trigger 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 present in your blood that can increase the risk of heart disease.

Your doctor may prescribe you ezetimibe/atorvastatin if you are already taking the same doses of atorvastatin and ezetimibe separately, in addition to your cholesterol-reducing diet, if you have:

• high blood cholesterol levels (primary heterozygous and homozygous familial and non-familial hypercholesterolemia) or high blood fat levels (mixed hyperlipidemia)

• heart disease

Ezetimibe/atorvastatin does not help you lose weight.

2. What you need to know before you take Ezetimibe/Atorvastatin Stadafarma

Do not take Ezetimibe/Atorvastatin Stadafarma if:

• you are allergic to atorvastatin, ezetimibe or any of the other ingredients of this medicine (listed in section 6).
• you have or have ever had a disease that affects the liver
• you have had any unexplained abnormal blood test results for liver function
• you are a woman who can become pregnant and are not using reliable contraceptive methods
• you are pregnant, trying to become pregnant or are breastfeeding
• you are taking the combination of glecaprevir/pibrentasvir for the treatment of hepatitis C

Warnings and precautions

Consult your doctor or pharmacist before starting to take Ezetimibe/Atorvastatin

• if you have had a previous stroke with intracranial hemorrhage, or have small accumulations of fluid in the brain derived from previous strokes
• if you have kidney problems
• if your thyroid gland has low activity (hypothyroidism)
• if you have had recurring or unexplained muscle pain or discomfort, or a personal or family history of muscle problems
• if you have experienced muscle problems while taking other lipid-lowering medications (e.g., other medications containing "statins" or "fibrates")
• if you have or have had myasthenia (a disease characterized by generalized muscle weakness that, in some cases, affects the muscles used for breathing) or ocular myasthenia (a disease that causes weakness of the eye muscles), as statins can sometimes exacerbate the disease or cause myasthenia to appear (see section 4).
• if you are taking or have taken in the last 7 days a medicine called fusidic acid (used to treat bacterial infections) orally or by injection. The combination of fusidic acid and medications containing ezetimibe/atorvastatin can cause serious muscle problems (rhabdomyolysis)
• if you regularly consume large amounts of alcohol
• if you have a history of liver disease
• if you are over 70 years old

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness while taking ezetimibe/atorvastatin.This is because, in rare cases, muscle problems can be serious, including muscle breakdown and kidney damage. Atorvastatin is known to cause muscle problems, and cases of muscle problems have also been reported with ezetimibe.

Also, talk to your doctor or pharmacist if you have constant muscle weakness. You may need additional tests and medications to diagnose and treat it.

Consult your doctor or pharmacist before starting to take ezetimibe/atorvastatin

• if you have severe respiratory failure

If any of the above applies to you (or you are not sure), consult your doctor or pharmacist before starting to take ezetimibe/atorvastatin, as your doctor will need to perform a blood test before starting your treatment, and possibly during it, to predict the risk of experiencing muscle side effects. It is known that the risk of experiencing muscle side effects, e.g., rhabdomyolysis (degradation of damaged skeletal muscle), increases when certain medications are taken simultaneously (see section 2 "Taking Ezetimibe/Atorvastatin Stadafarma with other medications").

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

Tell your doctor about all your medical problems, including allergies.

Children and adolescents

Ezetimibe/atorvastatin is not recommended for children and adolescents.

Taking Ezetimibe/Atorvastatin Stadafarma with other medications

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medications.

Fibrates (medications to lower cholesterol) should be avoided while taking ezetimibe/atorvastatin.

There are some medications that can modify the effect of ezetimibe/atorvastatin or whose effects may be affected by ezetimibe/atorvastatin (see section 3). This type of interaction could decrease the effectiveness of one or both medications. On the other hand, it could also increase the risk or severity of side effects, including a serious disorder in which muscle breakdown occurs, known as "rhabdomyolysis", which is described in section 4:

• cyclosporine (a medication often used in transplanted patients)
• erythromycin, clarithromycin, telithromycin, fusidic acid, rifampicin (medications used to treat bacterial infections)
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medications used to treat fungal infections)
• gemfibrozil, other fibrates, nicotinic acid, derivatives, colestipol, cholestyramine (medications used to regulate lipid levels)
• certain calcium channel blockers used to treat angina or high blood pressure, e.g., amlodipine, diltiazem
• digoxin, verapamil, amiodarone (medications that regulate heart rhythm)
• letermovir (a medication that helps prevent you from getting sick with cytomegalovirus)
• medications used to treat HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (used to treat AIDS)
• certain medications used to treat hepatitis C, e.g., telaprevir, boceprevir, and the combination of elbasvir, grazoprevir, ledipasvir/sofosbuvir
• daptomycin (a medication used to treat complicated skin and skin structure infections and bacteremia).
• if you need to take oral fusidic acid to treat a bacterial infection, you will temporarily need to stop using this medication. Your doctor will tell you when you can restart treatment with ezetimibe/atorvastatin. Taking this medication with fusidic acid can rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.

• Other medications that are known to interact with the combination ezetimibe/atorvastatin
• • oral contraceptives (medications that prevent pregnancy)
  • stiripentol (an anticonvulsant medication used to treat epilepsy)
  • cimetidine (a medication used for stomach acidity and peptic ulcers)
  • phenazone (a pain reliever)
  • antacids (medications for the treatment of indigestion that contain aluminum or magnesium)
  • warfarin, phenprocoumon, acenocoumarol, or fluindione (medications that prevent blood clot formation)
  • colchicine (used to treat gout)
  • St. John's Wort (a medication used to treat depression)

Taking Ezetimibe/Atorvastatin Stadafarma with food, drinks, and alcohol

See section 3 for instructions on how to take ezetimibe/atorvastatin. Please note the following:

Grapefruit juice

Do not drink more than one or two small glasses of grapefruit juice per day, as large amounts of grapefruit juice can alter the effects of ezetimibe/atorvastatin.

Alcohol

Avoid excessive alcohol consumption while taking this medication. For more details, see section 2 "Warnings and precautions".

Pregnancy, breastfeeding, and fertility

Do not take ezetimibe/atorvastatin if you are pregnant, think you may be pregnant, or are planning to become pregnant.

Do not take ezetimibe/atorvastatin if you can become pregnant, unless you are using reliable contraceptive methods. If you become pregnant while taking this medication, stop taking it immediately and inform your doctor.

Do not take Ezetimibe/Atorvastatin Stadafarma if you are breastfeeding.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and using machines

Ezetimibe/atorvastatin is not expected to interfere with your ability to drive or use machines. However, it should be noted that some people experience dizziness after taking ezetimibe/atorvastatin. If you feel dizzy after taking this medication, do not drive or use machinery.

Ezetimibe/Atorvastatin Stadafarma 10 mg/10 mg, 10 mg/20 mg, and 10 mg/40 mg contains lactose

If your doctor has told you that you are intolerant to certain sugars, contact them before taking this medication.

Ezetimibe/Atorvastatin Stadafarma contains sodium

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

3. How to take Ezetimibe/Atorvastatin Stadafarma

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor will determine the appropriate dose per tablet for you, depending on your current treatment and personal risk situation.

• Before starting to take ezetimibe/atorvastatin, you should be following a cholesterol-reducing diet.
• You should continue with this cholesterol-reducing diet while taking ezetimibe/atorvastatin.

How much to take

The recommended dose is one tablet of ezetimibe/atorvastatin once a day, preferably always at the same time. The tablet should be taken with a sufficient amount of liquid (e.g., a glass of water).

When to take it

Take ezetimibe/atorvastatin at any time of the day. You can take it with or without food.

If your doctor has prescribed you ezetimibe/atorvastatin along with cholestyramine or any other bile acid sequestrant (medications that reduce cholesterol levels), you should take ezetimibe/atorvastatin at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more Ezetimibe/Atorvastatin Stadafarma than you should

Consult your doctor or pharmacist.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Ezetimibe/Atorvastatin Stadafarma

Do not take a double dose to make up for forgotten doses. Take the normal dose at the usual time the next day.

If you have any other questions about the use of this medication, 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.

If you experience any of the following adverse effects or severe symptoms, stop taking your tablets and immediately inform your doctor, or go to the emergency department of the nearest hospital and take the tablets with you.

• severe allergic reactions that cause swelling of the face, tongue, and throat and can cause great difficulty breathing
• severe disease whose symptoms are intense exfoliation and skin inflammation, blister formation on the skin, mouth, eyes, genitals, and fever; skin rash with pink or red spots, especially on the palms of the hands or soles of the feet, which can lead to blisters
• weakness, sensitivity, rupture, or muscle pain, change in urine color to reddish-brown, and especially if it occurs at the same time, a feeling of discomfort or high temperature that may be caused by abnormal muscle destruction that can be potentially fatal and trigger kidney problems
• lupus-like syndrome (which includes skin rash, joint disorders, and effects on blood cells)

Consult your doctor as soon as possible if you experience problems associated with the unexpected or unusual appearance of bleeding or bruising, as this fact may be indicative of a liver condition.

Other possible adverse effects with Ezetimibe/Atorvastatin:

Frequent(may affect up to 1 in 10 people)

• inflammation of the nasal passage, sore throat, nosebleeds
• allergic reactions
• increased glucose level in the blood, diabetic patients must control their blood glucose level
• headache
• nausea, constipation, flatulence, diarrhea, indigestion, abdominal pain
• pain in the pharynx and/or larynx
• pain in the joints and/or hands or feet, back pain, muscle pain (myalgia), muscle spasms, joint swelling
• increases in some blood tests of muscle function (CK)
• abnormal liver function test results, increases in some blood tests of liver function (transaminases)
• fatigue

Uncommon(may affect up to 1 in 100 people):

• swelling due to an allergic reaction
• reduced blood glucose level, diabetic patients must control their blood glucose level
• loss of appetite, weight gain
• cough
• muscle weakness, neck pain, chest pain
• hot flashes, high blood pressure
• vomiting
• belching
• inflammation of the pancreas and liver
• heartburn
• inflammation of the stomach lining
• dry mouth
• redness of the skin, hives, skin rash, itching
• hair loss
• nightmares, difficulty sleeping
• dizziness
• numbness
• altered sense of taste
• amnesia
• abnormal local sensations
• blurred vision
• ringing in the ears
• general feeling of discomfort, restlessness, or pain
• weakness
• increase in the liver enzyme gamma-glutamyl transferase
• positive urine test for white blood cells

Rare(may affect up to 1 in 1,000 people)

• reduction in blood platelets
• inflammation of the lower layer of skin tissue on the face, tongue, throat, abdomen, arms, or legs (angioedema)
• generalized rash in the form of delimited red spots or rash with blisters and skin peeling, particularly around the mouth, nose, eyes, and genitals due to an allergic reaction
• visual disturbances
• yellowing of the skin and whites of the eyes

Very Rare(may affect up to 1 in 10,000 people)

• anaphylactic shock due to an allergic reaction
• hearing loss
• liver failure
• increase in male breast size

Frequency Not Known(cannot be estimated from the available data)

• allergic reaction, including rash and swelling of the lower layers of the skin
• shortness of breath, inflammation of the gallbladder, gallstones
• physical weakness and loss of strength, loss of muscle tissue due to autoimmune antibodies
• depression
• 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 during the post-marketing of some statins (medicines used to reduce cholesterol):

• difficulty breathing, including persistent cough and/or shortness of breath or fever,
• 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 medicine
• sexual dysfunction

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 it 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/Atorvastatin Stadafarma

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 and blister, 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 medicines you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Ezetimibe/Atorvastatin Stadafarma

• The active ingredients are ezetimibe and atorvastatin.

10 mg/10 mg: Each tablet contains 10 mg of ezetimibe and 10 mg of atorvastatin (as atorvastatin calcium trihydrate).

10 mg/20 mg: Each tablet contains 10 mg of ezetimibe and 20 mg of atorvastatin (as atorvastatin calcium trihydrate).

10 mg/40 mg: Each tablet contains 10 mg of ezetimibe and 40 mg of atorvastatin (as atorvastatin calcium trihydrate).

10 mg/80 mg: Each tablet contains 10 mg of ezetimibe and 80 mg of atorvastatin (as atorvastatin calcium trihydrate).

• The other ingredients are:

Core of the tablet

Microcrystalline cellulose 101, mannitol, calcium carbonate, sodium croscarmellose, hydroxypropylcellulose, polysorbate 80, yellow iron oxide (E172), magnesium stearate, povidone K-29/32, sodium lauryl sulfate.

Coating of the tablet

10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg - Opadry white OY-L-28900 containing: lactose monohydrate, hypromellose 2910 (E464), titanium dioxide (E171), macrogol 4000 (E1521)

10 mg/80 mg – DrCoat FCU containing: hypromellose 2910, titanium dioxide (E171), talc (E553b), macrogol 400, yellow iron oxide (E172)

Appearance of the Product and Package Contents

10 mg/10 mg tablet: white, round, biconvex, film-coated with a diameter of approximately 8.1 mm

10 mg/20 mg tablet: white, oval, biconvex, film-coated with a size of approximately 11.6 x 7.1 mm

10 mg/40 mg tablet: white, capsule-shaped, biconvex, film-coated with a size of approximately 16.1 x 6.1 mm

10 mg/80 mg tablet: yellow, oblong, biconvex, film-coated with a size of approximately 19.1 x 7.6 mm

Blister packs (unit dose and non-unit dose) of OPA/AL/PVC//Al packaged in cardboard boxes.

Packages containing 30, 30x1 film-coated tablets.

For 10 mg/20 mg and 10 mg/40 mg, also 100, 100x1 film-coated tablets.

Only some 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

ELPEN Pharmaceutical Co. Inc.

Marathonos Ave. 95, Pikermi Attiki, 19009

Greece

or

STADA Arzneimittel AG

Stadastrasse 2-18

61118 Bad Vilbel

Germany

or

ELPEN Pharmaceutical Co. Inc.

Zapani, Block 1048

Keratea 19001

Greece

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

Date of the Last Revision of this Leaflet:

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/