Package leaflet: Information for the user

Simestat 5 mg film-coated tablets, 10 mg film-coated tablets, 20 mg film-coated tablets, 40 mg film-coated tablets

rosuvastatin
Please read this leaflet carefully before 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 other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Simestat is and what it is used for
What you need to know before taking Simestat
How to take Simestat
Possible side effects
How to store Simestat
Contents of the pack and other information

1. What Simestat is and what it is used for

Simestat belongs to a group of medicines called statins.
Your doctor has prescribed Simestat because:

Your cholesterol level is high. This means you are at risk of heart attack or stroke. Simestat is used in adults, adolescents and children aged 6 years and older to treat high cholesterol.
A statin has been prescribed for you because changes in diet and increased physical activity have not been sufficient to correct your cholesterol levels. While taking Simestat, you must continue your cholesterol-lowering diet and maintain regular physical activity.

You have other risk factors that increase your likelihood of developing heart attack, stroke or related health problems.

Heart attack, stroke and related health problems can be caused by a disease called atherosclerosis. Atherosclerosis is due to the buildup of fatty deposits inside the arteries.
Why it is important to continue taking Simestat
Simestat is used to correct levels of fatty substances in the blood called lipids, the most common of which is cholesterol.
There are different types of cholesterol in the blood: so-called "bad" cholesterol (LDL-C) and so-called "good" cholesterol (HDL-C).

Simestat can reduce "bad" cholesterol and increase "good" cholesterol.
It works by helping to block the body's production of "bad" cholesterol and also improves the body’s ability to remove "bad" cholesterol from the blood.

For many people, high cholesterol does not affect how they feel, as it causes no symptoms. However, if high cholesterol is left untreated, fatty deposits can accumulate in the walls of blood vessels, leading to narrowing.
Sometimes, these narrowed blood vessels can become blocked, interrupting blood flow to the heart or brain and causing a heart attack or stroke. By lowering cholesterol levels, the risk of heart attack, stroke or related health problems is reduced.
You must continue taking Simestat, even if your cholesterol levels have returned to normal, to prevent them from rising again and causing fatty deposits to form. However, you must stop taking Simestat on medical advice or if you become pregnant.
2. What you need to know before taking Simestat
Do not take Simestat:

if you have previously had an allergic reaction to Simestat or to any of the ingredients of this medicine;
if you are pregnant or breastfeeding. If you become pregnant while taking Simestat, stop taking it immediately and inform your doctor. Women must avoid pregnancy while taking Simestat by using appropriate contraceptive measures;
if you have liver disease;
if you have severe kidney problems;
if you have repeated or unexplained muscle aches or pains;
if you are taking the combination medicine sofosbuvir/velpatasvir/voxilaprevir (used to treat a viral liver infection called hepatitis C);
if you are taking a medicine called cyclosporine (used, for example, after organ transplantation). If you fall into any of the above categories (or have any doubts), you must consult your doctor and inform them.

In addition, do not take Simestat 40 mg (the highest dose):

if you have moderate kidney problems (ask your doctor if you are unsure);
if your thyroid gland is not functioning properly;
if you have repeated or unexplained muscle aches or pains, a personal or family history of muscle problems, or have previously experienced muscle problems while taking other cholesterol-lowering medicines;
if you regularly consume large amounts of alcohol;
if you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean or Indian);
if you are taking other cholesterol-lowering medicines called fibrates.

If you fall into any of the above categories (or have any doubts), you must consult your doctor and inform them.
Warnings and precautions
Talk to your doctor or pharmacist before taking Simestat if:

you have kidney problems;
you have liver problems;
you have had repeated or unexplained muscle aches or pains, a personal or family history of muscle problems, or have previously experienced muscle problems while taking other cholesterol-lowering medicines. Inform your doctor immediately if you experience unexplained muscle aches or pains, especially if accompanied by malaise or fever. Also, inform your doctor or pharmacist if you have persistent muscle weakness;
you have or have had myasthenia gravis (a disease characterized by generalized muscle weakness, including in some cases the 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);
you have ever developed a severe skin rash, skin peeling, blisters and/or mouth ulcers after taking Simestat or other related medicines;
you regularly consume large amounts of alcohol;
your thyroid gland is not functioning properly;
you are taking other cholesterol-lowering medicines called fibrates. Read this leaflet carefully, even if you have previously taken other medicines for high cholesterol;
you are taking medicines used to treat HIV infections, such as ritonavir with lopinavir and/or atazanavir; please read the section “Other medicines and Simestat”;
you are currently taking or have taken within the last 7 days, orally or by injection, a medicine called fusidic acid (a medicine used to treat bacterial infections). The combination of fusidic acid and Simestat can lead to serious muscle problems (rhabdomyolysis); please read the section “Other medicines and Simestat”;
you are over 70 years of age (your doctor needs to select the appropriate starting dose of Simestat for you);
you have severe respiratory failure;
you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean or Indian). Your doctor needs to select the appropriate starting dose of Simestat for you.

If you fall into any of the above categories (or are unsure):

do not take Simestat 40 mg (the highest dose) and check with your doctor or pharmacist before starting Simestat at any dosage.

Severe skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with Simestat treatment. Stop taking Simestat and seek immediate medical attention if you notice any of the symptoms described in section 4.
In a small number of people, statins may have a negative effect on the liver, which can be detected by a simple blood test showing elevated liver enzyme levels.
For this reason, your doctor will request this test (liver function test) before and during treatment with Simestat.
During treatment with this medicine, your doctor will carefully monitor whether you have diabetes or are at risk of developing diabetes. You are at risk of developing diabetes if you have high levels of sugar and fat in your blood, are overweight, and have high blood pressure.
Children and adolescents

If the patient is under 6 years of age: Simestat must not be given to children under 6 years of age.
If the patient is under 18 years of age: Simestat 40 mg tablets are not suitable for use in children and adolescents under 18 years of age.

Other medicines and Simestat
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Inform your doctor if you are taking any of the following medicines:

cyclosporine (used, for example, after organ transplantation),
warfarin, clopidogrel or ticagrelor (or any other medicine used to thin the blood),
fibrates (such as gemfibrozil, fenofibrate) or any other medicine used to lower cholesterol (such as ezetimibe),
antacids (used to neutralize stomach acid),
erythromycin (an antibiotic),
fusidic acid (an antibiotic – please read the section “Warnings and precautions”),
an oral contraceptive (the pill),
regorafenib (used to treat tumours),
darolutamide (used to treat tumours),
capmatinib (used to treat tumours),
hormone replacement therapy,
fostamatinib (used to treat low platelet count),
febuxostat (used to treat and prevent high levels of uric acid in the blood),
teriflunomide (used to treat multiple sclerosis),
leflunomide (used to treat rheumatoid arthritis),
any of the following medicines used to treat viral infections, including HIV or hepatitis C, alone or in combination (see Warnings and Precautions): ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.
roxadustat or vadadustat (used to treat anaemia in patients with chronic kidney disease)
tafamidis (used to treat a disease called transthyretin amyloidosis)
momelotinib (used to treat myelofibrosis in adults with anaemia)

The effects of these medicines may be altered by Simestat, or the effect of Simestat may be altered by these medicines.
If you need to take oral fusidic acid to treat a bacterial infection, you will need to temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart Simestat. Taking Simestat with fusidic acid may rarely cause muscle weakness, tenderness or pain (rhabdomyolysis). For more information about rhabdomyolysis, see section 4.
Pregnancy and breastfeeding
Do not take Simestat if you are pregnant or breastfeeding. If you become pregnant while taking Simestat, you must stop taking it immediately and inform your doctor.
Women must avoid pregnancy during treatment with Simestat by using appropriate contraceptive measures.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Most people can drive and operate machinery while taking Simestat – it does not affect their ability to drive or use machines. However, some people may experience dizziness during treatment with Simestat. If you experience dizziness, consult your doctor before driving or operating machinery.
Simestat contains lactose.
If your doctor has diagnosed you with an intolerance to certain sugars (lactose or milk sugar), contact them before taking Simestat.
For a complete list of other ingredients, see section “Contents of the pack and other information”.

3. How to take Simestat

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.

Usual dosage in adults

If you are taking Simestat for high cholesterol:

Starting dose
Treatment with Simestat should begin at a dose of 5 mg or 10 mg, even if you have previously taken higher doses of other statins. The choice of starting dose depends on:

your cholesterol level;
your risk of having a heart attack or stroke;
any factors that may make you more sensitive to possible side effects.

Check with your doctor or pharmacist to determine the most appropriate starting dose of Simestat for you.
Your doctor may decide to prescribe the lowest dose (5 mg) if you:

are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian);
are over 70 years old;
have moderate kidney problems;
are at risk of muscle pain or spasms (myopathy).

Dose increase and maximum daily dose
Your doctor may decide to increase your dose to determine the most suitable dose for you.
If you start with a 5 mg dose, your doctor may, if necessary, decide to double the dose to 10 mg, then to 20 mg, and subsequently to 40 mg.
If you start with 10 mg, your doctor may, if necessary, decide to double the dose to 20 mg and then to 40 mg.
There should be an interval of 4 weeks between each dose adjustment.
The maximum daily dose of Simestat is 40 mg. This dose is given only to patients with high cholesterol levels and a high risk of heart attack or stroke whose cholesterol levels have not been sufficiently lowered with the 20 mg dose.

If you are taking Simestat to reduce the risk of heart attack, stroke, or related health problems:
The recommended dose is 20 mg daily. However, your doctor may decide to use a lower dose if you have any of the risk factors listed above.

Use in children aged 6 to 17 years
The dosage range for children and adolescents aged 6 to 17 years is 5 mg to 20 mg once daily. The usual starting dose is 5 mg daily, and your doctor may gradually increase the dose until reaching the most appropriate Simestat dosage for the patient. The maximum daily dose of Simestat is 10 mg or 20 mg for children aged 6 to 17 years, depending on the underlying condition being treated. The dose should be taken once daily. Simestat 40 mg tablets must not be used in children.

Administration of tablets
Swallow each tablet whole with a glass of water.
Simestat should be taken once daily. Simestat can be taken at any time of day, with or without food.
Try to take the tablets at approximately the same time each day; this may help you remember to take them.

Periodic cholesterol checks
It is important to visit your doctor regularly to monitor your cholesterol levels, to ensure that cholesterol has reached and remains at the appropriate levels. Your doctor may decide to increase your dose to achieve the amount of Simestat most suitable for you.

If you take more Simestat than you should
Contact your doctor or the nearest hospital for advice.
If you go to hospital or receive treatment for another condition, inform the hospital doctor that you are taking Simestat.

If you forget to take Simestat
Do not panic. Take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Simestat
Inform your doctor if you intend to stop taking Simestat. If you stop taking Simestat, your cholesterol levels may rise again.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
It is important to be aware of which of these side effects may occur. They are usually mild and disappear within a short time.

Stop taking Simestat and seek immediate medical help if you experience any of the following allergic reactions:

Difficulty breathing, with or without swelling of the face, lips, tongue and/or throat;
Swelling of the face, lips, tongue and/or throat that may cause difficulty swallowing;
Severe itching of the skin (with raised hives);
Reddish, non-raised spots, target-shaped or circular, on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These serious 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).

Also, stop taking Simestat and contact your doctor immediately:

If you experience unusual muscle aches or pains lasting longer than expected. Muscle-related symptoms are more common in children and adolescents than in adults. As with other statins, a very small number of people have experienced muscle-related side effects, and rarely these have progressed to a condition causing muscle damage, potentially life-threatening, known as rhabdomyolysis.
If you experience muscle tearing.
If you develop lupus-like syndrome (characterized by skin rash, joint problems and effects on blood cells).

Possible common side effects (may occur in 1 out of 10 to 1 out of 100
patients):

Headache, stomach pain, constipation, feeling unwell, muscle pain, feeling of weakness, dizziness.
Increased amount of protein in the urine – values usually return to normal on their own without needing to stop Simestat (only for Simestat 40 mg).
Diabetes. This is 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.

Possible uncommon side effects (may occur in 1 out of 100 to 1 out of
1,000 patients):

Skin rash, itching and other skin reactions.
Increased amount of protein in the urine – these usually return to normal on their own without needing to stop treatment with Simestat (only for Simestat 5 mg, 10 mg and 20 mg).

Possible rare side effects (may occur in 1 out of 1,000 to 1 out of 10,000
patients):

Severe allergic reactions – signs include swelling of the face, lips, tongue and/or throat, difficulty swallowing or breathing, severe itching of the skin (with raised hives). If you suspect you are having an allergic reaction, stop taking Simestat and seek immediate medical help.
Muscle damage in adults – as a precaution, stop taking Simestat and contact your doctor immediately if you have unusual muscle aches or pains lasting longer than expected.
Severe stomach pain (inflamed pancreas).
Increased liver enzymes in the blood.
Bleeding or bruising more easily than normal due to low platelet count in the blood.
Lupus-like syndrome (characterized by skin rash, joint problems and effects on blood cells).

Possible very rare side effects (may occur in fewer than 1 out of
10,000 patients):

Jaundice (yellowing of the skin and eyes), hepatitis (liver inflammation), blood traces in the urine, nerve damage in arms and legs (numbness), joint pain, memory loss and breast enlargement in men (gynecomastia).

Side effects of unknown frequency may include:

Diarrhoea (passing of loose stools), cough, shortness of breath, oedema (swelling), sleep disorders including insomnia and nightmares, sexual problems, depression, breathing problems including persistent cough and/or shortness of breath or fever, tendon injury and persistent muscle weakness;
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 weakness in the arms or legs that worsens with activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may 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 Simestat

Blister: store below 30°C. Keep in the original packaging to protect the medicine from moisture.
Containers: store below 30°C. Keep the bottle tightly closed to protect the medicine from moisture.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton/blister pack/labelling, following "Exp". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Simestat contains
The active substance in Simestat is rosuvastatin. Simestat film-coated tablets contain
rosuvastatin calcium salt equivalent to 5 mg, 10 mg, 20 mg or 40 mg of rosuvastatin.
The other components are: lactose monohydrate, microcrystalline cellulose, calcium phosphate,
crospovidone, magnesium stearate, hypromellose, triacetin, titanium dioxide (E171). Simestat 10 mg,
20 mg and 40 mg film-coated tablets also contain red iron oxide (E172).
Simestat 5 mg film-coated tablets also contain yellow iron oxide (E172).

Description of the appearance of Simestat and contents of the pack
Simestat is supplied in blister packs containing 7, 14, 15, 20, 28, 30, 42, 50, 56, 60, 84, 90, 98
and 100 tablets, and plastic containers containing 30 and 100 tablets.
(Not all pack sizes may be marketed in all countries.)
Simestat is available as tablets in four dosage strengths:
Simestat 5 mg film-coated tablets, yellow, round, marked with “ZD4522” and “5” on one side
and smooth on the other side.
Simestat 10 mg film-coated tablets, pink, round, marked with “ZD4522” and “10” on one
side and smooth on the other side.
Simestat 20 mg film-coated tablets, pink, round, marked with “ZD4522” and “20” on one
side and smooth on the other side.
Simestat 40 mg film-coated tablets, pink, oval, marked with “ZD4522” on one side and “40”
on the other side.

Marketing Authorisation Holder
GRÜNENTHAL ITALIA S.r.l.
Via Vittor Pisani 16 - 20124 Milano, Italy

Manufacturers
AstraZeneca AB, S-152 57, Södertälje, Sweden
Tel.: +46 8 55326000
Grünenthal GmbH, Zieglerstraße 6, 52078 Aachen, Germany
Tel.: +49 (0) 241 569 0
Farmaceutici Formenti S.p.A.
Via Di Vittorio, 2
21040 Origgio (VA), Italy

This medicinal product is authorised in the European Economic Area countries under the
following names:
Simestat 5 mg, 10 mg, 20 mg and 40 mg (Italy)
Rosuvastatin Grünenthal 5 mg, 10 mg, 20 mg and 40 mg (Netherlands)