Atozet

Package leaflet: Information for the user

ATOZET 10 mg/10 mg film-coated tablets, 10 mg/20 mg film-coated tablets, 10 mg/40 mg film-coated tablets, 10 mg/80 mg film-coated tablets

ezetimibe and atorvastatin
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ATOZET is and what it is used for

ATOZET is a medicine used to lower elevated cholesterol levels. ATOZET contains
ezetimibe and atorvastatina.
ATOZET is used in adults to reduce blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fat substances called triglycerides. In addition, ATOZET increases levels of "good" cholesterol (HDL cholesterol).
ATOZET works in two ways to lower cholesterol. It reduces cholesterol absorbed in the gastrointestinal tract as well as cholesterol naturally produced by the body.
Cholesterol is one of several fatty substances found in the bloodstream. Total cholesterol consists mainly of LDL cholesterol and HDL cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can accumulate in the walls of arteries, forming plaques. Over time, this plaque buildup can lead to narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. This blockage of blood flow can cause 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 provides protection against heart disease.
Triglycerides are another form of fat in the blood that can increase the risk of heart disease.
ATOZET is used to treat patients in whom diet alone is not sufficient to control cholesterol levels. While taking this medicine, you must continue to follow a cholesterol-lowering diet.
ATOZET is used as an add-on to diet to lower cholesterol if you have:

• elevated cholesterol levels in the blood (primary hypercholesterolemia [heterozygous familial and non-familial]) or elevated levels of fats in the blood (mixed hyperlipidemia)
• that are not adequately controlled with a statin alone;
• for whom you have previously been treated with a statin and ezetimibe as separate tablets;
• a hereditary disease (homozygous familial hypercholesterolemia) that increases your blood cholesterol levels. You may also be receiving other treatments;
• heart disease. ATOZET reduces the risk of heart attack, stroke, surgery to improve blood flow to the heart, or hospitalization for chest pain.

ATOZET does not help with weight loss.

2. What you need to know before taking 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),
• you have or have ever had liver disease,
• you have had unexplained blood test results indicating impaired liver function,
• you are a woman of childbearing potential and are not using a reliable method of contraception,
• you are pregnant, trying to become pregnant, or breastfeeding,
• you are taking the combination glecaprevir/pibrentasvir for the treatment of hepatitis C.

Warnings and precautions
Talk to your doctor or pharmacist before taking ATOZET if

• you have previously had a stroke with cerebral haemorrhage or if there are small accumulations of fluid in the brain due to prior strokes,
• you have kidney problems,
• you have an underactive thyroid gland (hypothyroidism),
• you have experienced repeated or unexplained episodes of muscle pain or discomfort, or have a personal or family history of muscle disorders,
• you have previously had muscle problems while being treated with other lipid-lowering medicines (e.g. other "statin" or "fibrate" medicines),
• you regularly consume large amounts of alcohol,
• you have a history of liver disease,
• you are over 70 years old,
• your doctor has told you that you have an intolerance to certain sugars, contact your doctor before taking this medicine,
• you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine for bacterial infection). The combination of fusidic acid and ATOZET can lead to serious muscle problems (rhabdomyolysis),
• you have or have had myasthenia gravis (a disease characterized by generalized muscle weakness, sometimes including muscles used for breathing) or ocular myasthenia (a

disease causing weakness of the eye muscles), as statins may sometimes worsen
myasthenia or trigger its onset (see section 4).
Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness
while taking ATOZET. This is because, although rarely, muscle problems can be severe, including muscle breakdown leading to kidney damage. It is known that atorvastatin can cause muscle problems, and cases of muscle problems have also been reported with ezetimibe.
Additionally, inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and treatments may be needed to diagnose and manage this condition.
Before taking ATOZET, check with your doctor or pharmacist:

• if you have severe respiratory insufficiency.

If any of these conditions apply to you (or if you are unsure), consult your doctor or pharmacist
before taking ATOZET, as your doctor may ask you to have a blood test before and possibly during
treatment with ATOZET to assess the risk of muscle-related side effects. It is known that the risk of developing muscle-related side effects, such as rhabdomyolysis, increases when certain medicines are taken concomitantly (see section 2 “Other medicines and ATOZET”).
During treatment with this medicine, your doctor will closely monitor you if you have diabetes or are at risk of developing diabetes. Risk factors for developing diabetes include high blood sugar and lipid levels, being overweight, and having high blood pressure.
Inform your doctor about all your medical conditions, including allergies.
The use of ATOZET together with fibrates (medicines used to lower cholesterol) should be avoided, as the combination has not been studied.
Children
ATOZET is not recommended for use in children and adolescents.
Other medicines and ATOZET
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
Some medicines may alter the effect of ATOZET or their effects may be altered by ATOZET (see section 3). Such interactions could reduce the effectiveness of one or both medicines. Alternatively, they could increase the risk or severity of side effects, including the serious condition of muscle breakdown known as "rhabdomyolysis" described in section 4:

• cyclosporine (a medicine often used in organ 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 and its derivatives, colestipol, cholestyramine (medicines used to regulate lipid levels),
• certain calcium antagonists used to treat angina or hypertension, e.g. amlodipine and diltiazem,
• digoxin, verapamil, amiodarone (medicines used to regulate heart rhythm),
• medicines used to treat HIV, e.g. ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination tipranavir/ritonavir, etc. (medicines for treating AIDS),
• certain medicines used to treat hepatitis C, e.g. telaprevir, boceprevir, and the combination elbasvir/grazoprevir,
• daptomycin (a medicine used to treat complicated skin and soft tissue infections and bacteremia).

**If you need to take oral fusidic acid to treat a bacterial infection,
you must temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart
ATOZET. Taking ATOZET with fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). See
further information on rhabdomyolysis in section 4.

• other medicines known to interact with ATOZET,
• oral contraceptives (medicines to prevent pregnancy),
• stiripentol (an anticonvulsant medicine used to treat epilepsy),
• cimetidine (a medicine used to treat heartburn and peptic ulcers),
• phenazone (a painkiller),
• antacids (medicines for digestive problems containing aluminium or magnesium),
• warfarin, phenprocoumon, acenocoumarol, or fluindione (medicines to prevent blood clots),
• colchicine (used to treat gout),
• St. John’s wort (a herbal medicine used to treat depression).

ATOZET with food and alcohol
For instructions on how to take ATOZET, see section 3. Pay attention to the following:
Grapefruit juice
Do not drink more than one or two small glasses of grapefruit juice per day, as large quantities may alter the effects of ATOZET.
Alcohol
Avoid drinking excessive amounts of alcohol while being treated with this medicine. For further information, consult section 2 “Warnings and precautions”.
Pregnancy and breastfeeding
Do not take ATOZET if you are pregnant, planning to become pregnant, or suspect you may be pregnant. Do not take ATOZET if you are a woman of childbearing potential unless you are using an effective method of contraception. If you become pregnant while taking ATOZET, stop treatment immediately and contact your doctor.
Do not take ATOZET if you are breastfeeding.
The safety of ATOZET during pregnancy and breastfeeding has not been established.
Ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
ATOZET is not expected to affect your ability to drive or operate machinery. However, you should be aware that some people may experience dizziness after taking ATOZET.
ATOZET contains lactose
ATOZET tablets contain a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.
ATOZET contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take ATOZET

Take this medicine exactly as your doctor has told you. Your doctor will determine the appropriate tablet dose for you based on your ongoing treatment and your individual risk profile. If you have any doubts, consult your doctor or pharmacist.

• Before starting treatment with ATOZET, you should already have started a diet aimed at reducing cholesterol levels.
• While taking ATOZET, you must continue to follow this cholesterol-lowering diet.

What dose to take
The recommended dose is one ATOZET tablet taken by mouth once daily.

When to take the dose
Take ATOZET at any time of day. You may take it with or without food.
If your doctor has prescribed ATOZET together with colestyramine or another bile acid sequestrant (medicines used to lower cholesterol levels), you must take ATOZET at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more ATOZET than you should
Contact your doctor or pharmacist.

If you forget to take ATOZET
Do not take a double dose to make up for the missed dose; take only your usual dose of ATOZET at the next scheduled time.

If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, ATOZET may cause side effects, although not everybody experiences them.
If you notice any of the following serious side effects or symptoms, stop taking the tablets and contact your doctor immediately or go to the nearest hospital emergency department.

• severe allergic reaction causing swelling of the face, tongue and throat, which may cause severe breathing difficulties
• severe illness with extensive skin peeling and swelling, blistering of the skin, mouth, eyes, genitals, and fever; skin rash with pink-red pustules, particularly on the palms of the hands or soles of the feet, which may develop into blisters
• muscle weakness, tenderness, pain or muscle breakdown, or red-brown discoloration of the urine, especially if you also feel unwell and have a high fever; this may be due to unusual muscle breakdown that can be life-threatening and may lead to kidney problems
• lupus-like syndrome (characterized by skin rash, joint problems, and effects on blood cells)

If you experience unexpected or unusual bleeding or bruising, consult your doctor as soon as possible, as these may be signs of liver problems.

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

• diarrhoea,
• muscle pain.

The following uncommon side effects have been reported (may affect up to 1 in 100 people):

• influenza,
• depression; difficulty falling asleep; sleep disorders,
• dizziness; headache; tingling sensation,
• slow heart rate,
• hot flushes,
• shortness of breath,
• abdominal pain; abdominal swelling; constipation; indigestion, flatulence; frequent bowel movements; stomach inflammation; nausea; stomach discomfort; stomach disorders,
• acne; urticaria,
• joint pain; back pain; leg cramps; fatigue, muscle spasms or weakness; pain in arms and legs,
• unusual weakness; feeling tired or unwell; swelling, especially in the ankles (oedema),
• increases in certain blood test values indicating liver or muscle (CK) function,
• weight gain.

The following side effects have been reported with unknown frequency (frequency cannot be estimated from the available data):

• myasthenia gravis (a disease causing generalized muscle weakness, including in some cases the muscles used for breathing),
• ocular myasthenia (a disease causing weakness of the eye muscles).

Contact your doctor if you experience worsening weakness in the arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing, or laboured breathing.

In patients treated with ATOZET or with ezetimibe or atorvastatin tablets, the following additional side effects have also been reported:

• allergic reactions including swelling of the face, lips, tongue and/or throat, which may cause difficulty breathing or swallowing (a condition requiring immediate intervention),
• raised, red skin rash, sometimes accompanied by "target-like" lesions,
• liver problems,
• cough,
• heartburn,
• decreased appetite; loss of appetite,
• high blood pressure,
• skin rash and itching; allergic reactions including skin rashes and urticaria,
• tendon injury,
• gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea and vomiting),
• pancreatitis, often with severe abdominal pain,
• reduced number of blood cells, which may lead to bruising/bleeding (thrombocytopenia),
• nasal passage inflammation; nosebleeds,
• neck pain; pain; chest pain; throat pain,
• increased or decreased blood sugar levels (if you have diabetes, you should continue to monitor your blood sugar levels closely),
• nightmares,
• numbness or tingling in fingers and toes,
• reduced sensitivity to pain or touch,
• altered sense of taste; dry mouth,
• memory loss,
• ringing in the ears and/or head; hearing loss,
• vomiting,
• belching,
• hair loss,
• increased body temperature,
• urine tests positive for white blood cells,
• blurred vision; visual disturbances,
• gynaecomastia (enlargement of breast tissue in men).

Possible side effects reported with some statins:

• sexual difficulties,
• depression,
• breathing problems including persistent cough and/or shortness of breath or fever,
• diabetes. More likely if you have high levels of sugar and fats in the blood, are overweight, or have high blood pressure. Your doctor will monitor you during treatment with this medicine,
• muscle pain, tenderness or weakness that is persistent, and especially if you also feel unwell or have a high fever that does not resolve after stopping ATOZET (frequency not known).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco) website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store ATOZET

• Keep this medicine out of the sight and reach of children.
• Do not use ATOZET after the expiry date which is stated on the carton after “Exp.” or on the container after “EXP”. The expiry date refers to the last day of that month.
• Store in the original packaging to protect the medicine from oxygen.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ATOZET contains
The active substances are ezetimibe and atorvastatin. Each film-coated tablet contains 10 mg of
ezetimibe and 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin (as atorvastatin calcium trihydrate).
The other components are: calcium carbonate; anhydrous colloidal silicon dioxide; sodium croscarmellose;
hydroxypropylcellulose; lactose monohydrate; magnesium stearate; microcrystalline cellulose; polysorbate;
povidone; sodium lauryl sulfate.
The film coating contains: hypromellose, macrogol 8000, titanium dioxide (E171), talc.

Description of the appearance of ATOZET and contents of the pack
Film-coated tablets, capsule-shaped, biconvex, white to off-white in colour.
ATOZET 10 mg/10 mg tablets: “257” engraved on one side
ATOZET 10 mg/20 mg tablets: “333” engraved on one side
ATOZET 10 mg/40 mg tablets: “337” engraved on one side
ATOZET 10 mg/80 mg tablets: “357” engraved on one side

Pack sizes:
Blister packs (aluminum/aluminum under nitrogen, with forming film in oPA-Al-PVC and lidding foil in Al) containing 10, 30, 90 or 100 film-coated tablets.
Blister packs containing 30 x 1 and 45 x 1 film-coated tablets in single-dose aluminum/aluminum blisters under nitrogen (forming film in oPA-Al-PVC and lidding foil in Al).

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Organon Italia S.r.l.
Piazza Carlo Magno, 21
00162 Rome, Italy

Manufacturer
Merck Sharp & Dohme B.V.,
Waarderweg 39,
2031 BN Haarlem,
The Netherlands
Organon Heist bv
Industriepark 30
2220 Heist-op-den-Berg
Belgium
Organon N.V.
Kloosterstraat 6, 5349 AB,
Oss, The Netherlands

This medicinal product is authorized in the European Economic Area countries under the
following trade names:
ATOZET: Austria, Belgium, Bulgaria, Croatia, Denmark, Germany, Iceland, Ireland, Italy,
Luxembourg, Malta, The Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic,
Slovenia, Spain, Sweden
LIPTRUZET: Cyprus, France, Greece, Hungary
ZOLETORV: Czech Republic