ATOZET 10 mg/40 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

ATOZET 10mg/20mg film-coated tablets

ATOZET 10mg/40mg film-coated tablets

ATOZET 10mg/80mg film-coated tablets

ezetimibe/atorvastatin

(ezetimibe/atorvastatin)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is ATOZET and what is it used for
2. What you need to know before you take ATOZET
3. How to take ATOZET
4. Possible side effects
5. Storage of ATOZET
6. Contents of the pack and other information

1. What is ATOZET and what is it used for

ATOZET is a medicine that lowers high cholesterol levels. ATOZET contains ezetimibe and atorvastatin.

ATOZET 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, ATOZET raises the levels of “good” cholesterol (HDL cholesterol).

ATOZET 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, which 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 the bad cholesterol from building up in the arteries and protects them from heart disease.

Triglycerides are another type of fat found in your blood that can increase the risk of heart disease.

ATOZET is used in patients who cannot control their cholesterol levels by diet alone. While taking this medicine, you should follow a cholesterol-lowering diet.

ATOZET is used, along with a cholesterol-lowering diet, if you have:

• high levels of cholesterol in the blood (primary hypercholesterolaemia [heterozygous familial and non-familial]) or high levels of fats in the blood (mixed hyperlipidaemia):

• that are not well controlled with a statin alone
• for which you have taken a statin and ezetimibe in separate tablets

• a hereditary disease (homozygous familial hypercholesterolaemia) that increases the level of cholesterol in the blood. You may also receive other treatments.

• heart disease, ATOZET reduces the risk of heart attack, stroke, surgery to increase blood flow to the heart, or hospitalization for chest pain.

ATOZET does not help you lose weight.

2. What you need to know before you take ATOZET

Do not take ATOZET

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

• if you are pregnant, trying to become pregnant, or breastfeeding,

• if you are taking the combination of glecaprevir/pibrentasvir in the treatment of hepatitis C.

Warnings and precautions

Consult your doctor or pharmacist before starting to take ATOZET

• if you have had a previous stroke with bleeding in the brain, or have small accumulations of fluid in the brain derived from previous strokes,
• if you have kidney problems,
• if your thyroid gland is underactive (hypothyroidism),
• if you have had recurring or unexplained muscle pain or a history of muscle problems,
• if you have experienced muscle problems while taking other lipid-lowering medicines (e.g., other medicines containing "statins" or "fibrates"),
• if you regularly drink large amounts of alcohol,
• if you have a history of liver disease,
• if you are over 70 years old,
• if your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine,

• if you are taking or have taken in the last 7 days a medicine that contains fusidic acid (used to treat bacterial infections) orally or by injection. The combination of fusidic acid and ATOZET can cause serious muscle problems (rhabdomyolysis),

• if you have or have had myasthenia (a disease that causes generalised muscle weakness that can affect the muscles used for breathing) or ocular myasthenia (a disease that causes weakness of the eye muscles), as statins can sometimes worsen the disease or cause myasthenia (see section 4).

Contact your doctor as soon as possible if you experience unexplained muscle pain, tenderness, or muscle weakness while taking ATOZET.This is because muscle problems can be serious, including muscle breakdown that can cause kidney damage. Atorvastatin can cause muscle problems, and muscle problems have also been reported with ezetimibe.

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

Consult your doctor or pharmacist before starting to take ATOZET:

• if you have severe respiratory failure.

If you are in any of the above situations (or are unsure), consult your doctor before starting to take ATOZET, as your doctor will need to perform a blood test before starting your treatment with ATOZET, and possibly during treatment, to predict the risk you have of experiencing muscle side effects. It is known that the risk of muscle side effects, e.g., rhabdomyolysis, increases when certain medicines are taken at the same time (see section 2 “Taking ATOZET with other medicines”).

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 the blood, are overweight, and have high blood pressure.

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

The combined use of ATOZET and fibrates (certain medicines to lower cholesterol) should be avoided, as the combined use of ATOZET and fibrates has not been studied.

Children

ATOZET is not recommended for children and adolescents.

Taking ATOZET with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

There are some medicines that can affect the way ATOZET works or that can increase the risk of side effects (see section 3). This type of interaction could decrease the effectiveness of one or both medicines. On the other hand, it could also increase the risk or severity of side effects, including a serious disorder in which muscle is destroyed, known as “rhabdomyolysis”, which is described in section 4:

• cyclosporin (a medicine often used in transplant patients),
• erythromycin, clarithromycin, telithromycin, fusidic acid**, rifampicin (medicines used to treat bacterial infections),
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medicines used to treat fungal infections),
• gemfibrozil, other fibrates, nicotinic acid, derivatives, colestipol, colestyramine (medicines used to regulate lipid levels),
• certain calcium channel blockers used to treat angina or high blood pressure, e.g., amlodipine, diltiazem,
• digoxin, verapamil, amiodarone (medicines that regulate heart rhythm),
• medicines used in the treatment of HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (used to treat AIDS),
• certain medicines used in the treatment of hepatitis C, e.g., telaprevir, boceprevir, and the combination of elbasvir/grazoprevir,
• daptomycin (a medicine used to treat complicated skin and skin structure infections and bacteremia).

** If you have to take fusidic acid orally to treat a bacterial infection, you will have to stop using this medicine temporarily. Your doctor will tell you when you can restart treatment with ATOZET. The use of ATOZET with fusidic acid can rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4

• Other medicines that are known to interact with ATOZET

• oral contraceptives (medicines that prevent pregnancy),
• stiripentol (an anticonvulsant medicine used to treat epilepsy),
• cimetidine (a medicine used for stomach acidity and peptic ulcers),
• phenazone (a pain reliever),
• antacids (products for the treatment of indigestion that contain aluminium or magnesium),
• warfarin, phenprocoumon, acenocoumarol, or fluindione (medicines that prevent blood clot formation),
• colchicine (used to treat gout),
• St. John's Wort (a medicine used to treat depression).

Taking ATOZET with food and drink

See section 3 for instructions on how to take ATOZET. 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 affect the way ATOZET works.

Alcohol

Avoid excessive alcohol consumption while taking this medicine. For more details, see section 2 “Warnings and precautions”.

Pregnancy and breastfeeding

Do not take ATOZET if you are pregnant, trying to become pregnant, or think you may be pregnant. Do not take ATOZET if you can become pregnant, unless you use reliable contraceptive methods. If you become pregnant while taking ATOZET, stop taking it immediately and inform your doctor.

Do not take ATOZET if you are breastfeeding.

The safety of ATOZET during pregnancy and breastfeeding has not yet been established.

Consult your doctor or pharmacist before taking this medicine.

Driving and using machines

ATOZET 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 ATOZET.

ATOZET contains lactose

ATOZET tablets contain a sugar called lactose. If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

ATOZET contains sodium

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

3. How to take ATOZET

Follow exactly the administration instructions of this medicine given by your doctor. Your doctor will determine the appropriate dose per tablet for you, depending on your current treatment and your personal risk situation. In case of doubt, consult your doctor or pharmacist again.

• Before starting to take ATOZET, you should be following a cholesterol-lowering diet.
• You should continue with this cholesterol-lowering diet while taking ATOZET.

How much to take

The recommended dose is one ATOZET tablet once a day by mouth.

Method of administration

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

If your doctor has prescribed ATOZET along with colestyramine or any other bile acid sequestrant (medicines that lower cholesterol levels), you should take ATOZET at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more ATOZET than you should

Consult your doctor or pharmacist.

If you forget to take ATOZET

Do not take an extra dose; the next day, take your normal amount of ATOZET at the usual time.

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.

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

• 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, pain, or muscle rupture or change in urine color to reddish-brown and especially, if it occurs at the same time, a feeling of discomfort or high temperature that can be caused by abnormal muscle destruction that can be potentially fatal and trigger kidney problems

• lupus-like syndrome (including 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.

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

• diarrhea,
• muscle pain.

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

• flu,
• depression; sleep problems; sleep disorder,
• dizziness; headache; tingling sensation,
• slow heartbeat,
• hot flashes,
• shortness of breath,
• abdominal pain; abdominal swelling; constipation; indigestion; flatulence; frequent bowel movements; stomach inflammation; nausea; stomach discomfort; stomach upset,
• acne; hives,
• joint pain; back pain; muscle cramps in the legs; muscle fatigue, spasms, or muscle weakness; pain in the arms and legs,
• unusual weakness; feeling of tiredness or discomfort; inflammation, especially in the ankles (edema),
• increase or decrease in some liver or muscle function tests (CK) in laboratory blood tests,
• weight gain.

The following adverse effects have been reported with an unknown frequency (the 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 the 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 ATOZET, ezetimibe, or atorvastatin tablets:

• allergic reactions, including inflammation of the face, lips, tongue, and/or throat that can cause difficulty breathing or swallowing (which require immediate medical treatment),
• red, sometimes target-shaped, skin rash,
• liver problems,
• cough,
• heartburn,
• decreased appetite; loss of appetite,
• high blood pressure,
• skin rash and itching; allergic reactions, including the appearance of skin rash and hives,
• tendon injury,
• gallstones or gallbladder inflammation (which can cause abdominal pain, nausea, or vomiting),
• pancreatitis, often accompanied by severe abdominal pain,
• decrease in blood cell count, which can cause bruising/bleeding (thrombocytopenia),
• inflammation of the nasal passages; nosebleeds,
• neck pain; chest pain; throat pain,
• increase or decrease in blood sugar levels (if you have diabetes, you should closely monitor your blood glucose levels),
• nightmares,
• numbness or tingling in the fingers and toes,
• decreased sensitivity to pain or touch,
• alteration of taste; dry mouth,
• memory loss,
• ringing in the ears and/or head; hearing loss,
• vomiting,
• belching,
• hair loss,
• high temperature,
• presence of white blood cells in urine tests,
• blurred vision; visual disturbances,
• gynecomastia (breast enlargement in men).

Possible adverse effects reported with some statins

• sexual dysfunction,
• depression,
• respiratory problems, 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,
• constant muscle pain, sensitivity, or weakness, and especially if it occurs at the same time, a feeling of discomfort or high temperature that may not disappear after stopping treatment with ATOZET (unknown frequency).

Reporting of 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 does 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 ATOZET

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date that appears on the carton or packaging after "CAD" or "EXP". The expiration date is the last day of the month indicated.
• Store in the original packaging to protect it from oxygen.

Medicines should not be thrown away 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 of ATOZET

The active ingredients are ezetimibe and atorvastatin. Each film-coated tablet contains 10 mg of ezetimibe and 20 mg, 40 mg, or 80 mg of atorvastatin (as atorvastatin calcium trihydrate).

The other ingredients are: calcium carbonate; anhydrous colloidal silica; sodium croscarmellose; hydroxypropylcellulose; lactose monohydrate; magnesium stearate; microcrystalline cellulose; polysorbate 80; povidone; sodium lauryl sulfate.

The tablet coating contains: hypromellose, macrogol 8000, titanium dioxide (E-171), and talc.

Appearance of the Product and Package Contents

Film-coated tablets, capsule-shaped, biconvex, and white to bone-colored.

ATOZET10 mg/20 mg tablets: with the code "333" on one side

ATOZET10 mg/40 mg tablets: with the code "337" on one side

ATOZET10 mg/80 mg tablets: with the code "357" on one side

Package sizes:

Packaging of 10, 30, 90, and 100 film-coated tablets in aluminum/aluminum blisters (oriented polyamide-aluminum-PVC with an aluminum cover).

Packaging of 30 x 1 and 45 x 1 film-coated tablets in unit doses, aluminum/aluminum blisters (oriented polyamide-aluminum-PVC with an aluminum cover).

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Organon Salud, S.L.

Paseo de la Castellana, 77

28046 Madrid

Spain

Tel.: 915911279

Manufacturer:

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

Organon Heist bv

Industriepark 30

2220 Heist-op-den-Berg

Belgium

Organon N.V.

Kloosterstraat 6, 5349 AB,

Oss, Netherlands.

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

ATOZET: Austria, Belgium, Bulgaria, Croatia, Denmark, Germany, Iceland, Ireland, Italy, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, and Sweden

LIPTRUZET: Cyprus, France, Greece, and Hungary

ZOLETORV: Czech Republic

Date of the Last Revision of this Leaflet:07/2023.

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