Stezerol

Package leaflet: Information for the user

Stezerol 5 mg/10 mg film-coated tablets, 10 mg/10 mg film-coated tablets, 20 mg/10 mg film-coated tablets, 40 mg/10 mg film-coated tablets

Rosuvastatin and Ezetimibe
Please read this leaflet carefully before you start using 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 other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Stezerol is and what it is used for

Stezerol contains two different active substances in a single film-coated tablet. One of the active substances is rosuvastatin calcium, belonging to the group of medicines known as statins; the other active substance is ezetimibe.
Stezerol is a medicine used to lower total cholesterol levels, "bad" cholesterol (LDL cholesterol), and fat substances called triglycerides in the blood. In addition, it also increases levels of "good" cholesterol (HDL cholesterol). This medicine works by reducing cholesterol in two ways: by reducing the cholesterol absorbed in the digestive tract and by reducing the cholesterol produced by the body.
For most people, high cholesterol does not affect how they feel, as it does not cause symptoms. However, if left untreated, fat deposits can build up in the walls of blood vessels, causing them to narrow.
Sometimes, these narrowed blood vessels can become blocked, interrupting blood flow to the heart or brain, leading to a heart attack or stroke. By lowering cholesterol levels, the risk of having a heart attack, stroke, or other related health problems is reduced.
Stezerol is used in patients whose cholesterol levels cannot be sufficiently controlled by a cholesterol-lowering diet alone. You must continue to follow a cholesterol-lowering diet while taking this medicine.
Your doctor may prescribe Stezerol if you are already taking both rosuvastatin and ezetimibe at the same doses.
Stezerol is used if you have:

• high cholesterol levels in the blood (primary hypercholesterolemia).
• heart disease. Stezerol reduces the risk of heart attack, stroke, surgical intervention to increase blood flow to the heart, or hospitalization due to chest pain.

Stezerol does not help with weight loss.

2. What you need to know before taking Stezerol

Do not take Stezerol:

• if you are allergic to rosuvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6).
• if you have liver disease.
• if you have severe kidney impairment.
• if you have recurrent, unexplained muscle pain (myopathy).
• if you are taking a medicine called cyclosporine (used, for example, after organ transplants).
• if you are pregnant or breastfeeding. If you become pregnant while taking Stezerol, stop taking it immediately and contact your doctor. Women must avoid becoming pregnant while taking Stezerol by using appropriate contraceptive methods.

Additionally, do not take rosuvastatin 40 mg (the highest dose):

• if you have moderate kidney problems (if in doubt, consult your doctor).
• if you have an underactive thyroid gland (hypothyroidism).
• if you regularly drink large amounts of alcohol.
• if you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian).
• if you are taking other medicines called fibrates to lower cholesterol (see section "Other medicines and Stezerol").
• if you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking Stezerol or other related medicines.

If any of the above apply to you (or if you are unsure), contact your doctor.

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

• you have kidney problems.
• you have liver problems.
• you have had recurrent or unexplained muscle pain, a personal or family history of muscle disorders, or previous muscle problems while taking other cholesterol-lowering medicines. Contact your doctor immediately if you experience unexplained muscle pain, especially if you feel unwell or have a fever. Also, consult your doctor or pharmacist if you have persistent muscle weakness.
• you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). Your doctor will need to choose the correct dose of Stezerol for you.
• you are taking medicines used to treat infections, including those for HIV or hepatitis C infection, such as lopinavir/ritonavir and/or atazanavir or simeprevir; see section "Other medicines and Stezerol".
• you have severe respiratory failure.
• you are taking other medicines called fibrates to lower cholesterol. See section "Other medicines and Stezerol".
• you regularly drink large amounts of alcohol.
• you have an underactive thyroid gland (hypothyroidism).
• you are over 70 years old (as your doctor needs to select the appropriate dose of Stezerol).
• you are currently taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (used to treat bacterial infections). The combination of fusidic acid and Stezerol can cause serious muscle problems (rhabdomyolysis).
• you have or have had myasthenia (a disease causing general muscle weakness, including in some cases the muscles used for breathing), or ocular myasthenia (a condition causing weakness in the eye muscles), as statins may sometimes worsen the condition or trigger the onset of myasthenia (see section 4).

If any of the above apply to you (or if you are unsure), consult your doctor or pharmacist before starting any dose of Stezerol.

In a small number of people, statins can affect the liver. This can be detected by a simple blood test measuring elevated levels of liver enzymes. For this reason, your doctor will regularly perform this blood test (liver function test) during treatment with Stezerol. It is important to attend all scheduled laboratory check-ups.

Serious skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with Stezerol treatment.

Stop taking Stezerol and seek immediate medical attention if you notice any of the symptoms described in section 4.

During treatment with this medicine, your doctor will monitor you closely if you have diabetes or are at risk of developing it. You are likely at risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure.

Children and adolescents
The use of Stezerol is not recommended in children and adolescents under 18 years of age.

Other medicines and Stezerol
Inform your doctor if you are currently taking, have recently taken, or might take any other medicines, including those without a prescription.

Tell your doctor if you are taking any of the following medicines:

• Cyclosporine (used, for example, after organ transplants to prevent organ rejection). The effect of rosuvastatin increases when taken together. Do not take Stezerol while taking cyclosporine.
• Anticoagulants, such as warfarin, acenocoumarol, or fluindione (their anticoagulant effect and risk of bleeding may increase when taken with Stezerol), or clopidogrel.
• Other cholesterol-lowering medicines called fibrates, which also correct triglyceride levels in the blood (e.g., gemfibrozil and other fibrates). The effect of rosuvastatin increases during concomitant use.
• Colestiramine (a medicine to lower cholesterol), as it affects how ezetimibe works.
• Antiviral medicines such as ritonavir with lopinavir and/or atazanavir or simeprevir (used to treat infections, including HIV or hepatitis C infection). See section "Warnings and precautions".
• Indigestion remedies containing aluminium and magnesium (used to neutralize stomach acid; they reduce the plasma level of rosuvastatin). This effect can be minimized by taking these medicines 2 hours after rosuvastatin.
• Erythromycin (an antibiotic). The effect of rosuvastatin decreases when taken together.
• Fusidic acid. 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 Stezerol. Taking Stezerol with fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.
• Oral contraceptive (the pill). Levels of sex hormones absorbed from the pill increase.
• Hormone replacement therapy (increased levels of hormones in the blood).
• Regorafenib (used to treat cancer).
• Simeprevir (used to treat chronic hepatitis C infection).
• Anticoagulants, such as warfarin, acenocoumarol, or fluindione (their anticoagulant effect and risk of bleeding may increase when taken with this medicine), ticagrelor, or clopidogrel.
• Any of the following medicines used to treat viral infections, including HIV or chronic hepatitis C infection, alone or in combination (see section "Warnings and precautions"): ritonavir, lopinavir, atazanavir, simeprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.

If you go to hospital or receive treatment for another condition, inform the medical staff that you are taking Stezerol.

Stezerol and alcohol
Do not take Stezerol 40 mg/10 mg (the highest dose) if you regularly drink large amounts of alcohol.

Pregnancy and breastfeeding
Do not take Stezerol if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. If you become pregnant while taking Stezerol, stop immediately and contact your doctor. Women must use contraceptive measures during treatment with Stezerol.

Do not take Stezerol if you are breastfeeding, as it is not known whether the medicine passes into breast milk.

Driving and using machines
Stezerol 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 Stezerol. If you experience dizziness, consult your doctor before driving or using machinery.

Stezerol contains lactose
Stezerol tablets contain a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to use Stezerol

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
You must continue to follow a low-cholesterol diet and engage in physical activity while taking Stezerol.
The recommended daily dose for adults is one tablet of the prescribed strength.
Take Stezerol once daily.
You may take it at any time of day, with or without food. Swallow each tablet whole with a glass of water.
Take the medicine at the same time every day.
Stezerol is not suitable for initiating treatment. The start of treatment or dose adjustment, if necessary, should be carried out by administering the active substances separately. Once the appropriate doses have been established, you may switch to Stezerol by selecting the appropriate strength.
The maximum daily dose of rosuvastatin is 40 mg. This dose is intended only for patients with high cholesterol levels and a high risk of heart attack or stroke, whose cholesterol levels are not sufficiently reduced with 20 mg.
Regular cholesterol checks
It is important to visit your doctor regularly for cholesterol monitoring, to ensure that your cholesterol has reached and remains at the correct levels.
If you take more Stezerol than you should
Contact your doctor or the nearest hospital emergency department, as you may require medical attention.
If you forget to take Stezerol
Do not worry. Skip the missed dose and take the next dose at the scheduled time. Do not take a double dose to make up for the missed one.
If you stop taking Stezerol
Talk to your doctor if you wish to stop taking Stezerol. Your cholesterol levels may rise again if you stop taking Stezerol.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause unwanted side effects, although not everybody gets them.
It is important to be aware of the possible side effects.
Stop taking Stezerol and seek immediate medical help if you experience any of the following symptoms:

• swelling of the face, lips, tongue and/or throat, which may cause difficulty breathing and swallowing;
• lupus-like disease syndrome (including skin rash, joint disorders and effects on blood cells);
• muscle breakdown;
• red, flat, target-shaped or circular spots on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome);
• widespread rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

Contact your doctor immediately if you experience unusual muscle pain or tenderness that lasts longer than expected. Rarely, this may progress to potentially life-threatening muscle damage known as rhabdomyolysis, which leads to malaise, fever and kidney impairment.

The following terms are used to describe how often the side effects have been reported:

• Very common (may affect more than 1 in 10 people)
• Common (may affect up to 1 in 10 people)
• Uncommon (may affect up to 1 in 100 people)
• Rare (may affect up to 1 in 1,000 people)
• Very rare (may affect up to 1 in 10,000 people, including isolated cases)

Common side effects:

• Headache
• Constipation
• Feeling unwell
• Muscle pain
• Feeling weak
• Dizziness
• Diabetes. This is more likely if you have high levels of sugar and fats in your blood, are overweight and have high blood pressure. Your doctor should monitor you while you are taking this medicine.
• Abdominal pain
• Diarrhoea
• Flatulence (excess gas in the intestinal tract)
• Feeling tired
• Increased levels in certain liver function laboratory tests (transaminases)

Uncommon side effects:

• Rash, itching, hives
• Increased amount of protein in the urine may occur – this usually returns to normal on its own without stopping rosuvastatin
• Increases in certain laboratory tests of muscle function (CK)
• Cough
• Indigestion
• Heartburn
• Joint pain
• Muscle spasms
• Neck pain
• Loss of appetite
• Pain
• Chest pain
• Hot flushes
• High blood pressure
• Tingling sensation
• Dry mouth
• Inflammation of the stomach
• Back pain
• Muscle weakness
• Pain in arms and legs
• Swelling, especially in hands and feet

Rare side effects:

• Inflammation of the pancreas, causing severe abdominal pain that may spread to the back
• Reduction in platelets in the blood

Very rare side effects:

• Jaundice (yellowing of the skin and eyes), inflammation of the liver (hepatitis), blood in the urine, nerve damage in arms and legs (such as numbness), memory loss, breast enlargement in men (gynaecomastia)

Not known:

• Breathing difficulties, oedema (swelling), sleep disorders including insomnia and nightmares, sexual problems, depression, respiratory problems including persistent cough and/or breathing difficulties or fever, tendon damage, persistent muscle weakness, gallstones or inflammation of the gallbladder (which may cause stomach pain, nausea, vomiting), myasthenia gravis (a disease causing general muscle weakness, including muscles used for breathing), ocular myasthenia (a disease causing weakness in eye muscles).

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

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Stezerol

Store in the original packaging to protect the medicinal product from moisture and light. This medicinal
product does not require any special storage temperature conditions.
Keep this medicinal product out of the sight and reach of children.
Do not use this medicinal product after the expiry date stated on the carton and bottle after EXP. The expiry
date refers to the last day of the month indicated.
Do not dispose of any medicinal product via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer used. This will help protect the environment.

6. Contents of the pack and other information

What Stezerol contains
The active substances are rosuvastatin (as rosuvastatin calcium salt) and ezetimibe.
Stezerol 5 mg/10 mg:
Each tablet contains 5.20 mg of rosuvastatin calcium (equivalent to 5 mg of rosuvastatin) and 10 mg of ezetimibe.
Stezerol 10 mg/10 mg:
Each tablet contains 10.40 mg of rosuvastatin calcium (equivalent to 10 mg of rosuvastatin) and 10 mg of ezetimibe.
Stezerol 20 mg/10 mg:
Each tablet contains 20.80 mg of rosuvastatin calcium (equivalent to 20 mg of rosuvastatin) and 10 mg of ezetimibe.
Stezerol 40 mg/10 mg:
Each tablet contains 41.60 mg of rosuvastatin calcium (equivalent to 40 mg of rosuvastatin) and 10 mg of ezetimibe.

Other excipients are:
Tablet core (same for all strengths): Microcrystalline cellulose (E460), colloidal anhydrous silica (E551), magnesium stearate (E572), povidone (E1201), sodium croscarmellose (E468), sodium lauryl sulfate (E487), lactose monohydrate, hypromellose (E464).

Coating:
Opadry yellow (5 mg/10 mg): Hypromellose (E464), titanium dioxide (E171), macrogol (E1521), yellow iron oxide (E172), talc (E553b), red iron oxide (E171).
Opadry beige (10 mg/10 mg): Hypromellose (E464), titanium dioxide (E171), macrogol (E1521), yellow iron oxide (E172), talc (E553b).
Vivacoat yellow (20 mg/10 mg): Hypromellose (E464), titanium dioxide (E171), macrogol (E1521), yellow iron oxide (E172), talc (E553b).
Opadry white (40 mg/10 mg): Lactose monohydrate, hypromellose (E464), titanium dioxide (E171), macrogol (E1521).

Description of the appearance of Stezerol and contents of the pack
Rosuvastatin / Ezetimibe 5 mg / 10 mg film-coated tablets: Round, biconvex, film-coated, light yellow tablets, approximately 10 mm in diameter, with "MR 5" engraved on one side.
Rosuvastatin / Ezetimibe 10 mg / 10 mg film-coated tablets: Round, biconvex, film-coated, beige tablets, approximately 10 mm in diameter, with "MR 4" engraved on one side.
Rosuvastatin / Ezetimibe 20 mg / 10 mg film-coated tablets: Round, biconvex, film-coated, yellow tablets, approximately 10 mm in diameter, with "MR 3" engraved on one side.
Rosuvastatin / Ezetimibe 40 mg / 10 mg film-coated tablets: Round, biconvex, film-coated, white tablets, approximately 10 mm in diameter, with "MR 2" engraved on one side.

Packs of 30 and 100 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
PharmExtracta S.p.A.
Via G. Natta 28
29010 Pontenure (PC)
Italy

Manufacturer 1:
Elpen Pharmaceutical Co.Inc.
Marathonos 95
190 09 Pikermi
Greece

Manufacturer 2:
MEDICAIR BIOSCIENCE LABORATORIES S.A.
61° Km National Road Athinon-Lamias, Schimatari
Greece

This leaflet was last revised on