Rosumibe

Patient Information Leaflet: Information for the Patient

ROSUMIBE 20 mg/10 mg tablets, 10 mg/10 mg tablets, 5 mg/10 mg tablets

rosuvastatin and ezetimibe
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, consult 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, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ROSUMIBE tablets are and what they are used for

ROSUMIBE tablets contain two different active substances in a single tablet. One of the active substances is rosuvastatin, belonging to the family of drugs known as statins; the other is ezetimibe.
ROSUMIBE tablets are a medicine used to lower total cholesterol levels, "bad" cholesterol (LDL cholesterol), and fat levels in the blood called triglycerides. In addition, it increases levels of "good" cholesterol (HDL cholesterol). This medicine reduces cholesterol in two ways: by reducing the amount absorbed from the digestive tract and by decreasing the body's own production of cholesterol.
In most people, high cholesterol levels do not cause any symptoms. However, if left untreated, fatty deposits can build up in the walls of blood vessels, causing them to narrow. Sometimes, this narrowing of blood vessels can block blood flow to the heart or brain, leading to heart attack or stroke. Lowering cholesterol levels can reduce the risk of heart attack, stroke, or other related health problems.
ROSUMIBE tablets are used for patients whose cholesterol levels cannot be controlled by a low-cholesterol diet alone. You must continue to follow a cholesterol-lowering diet during treatment with this medicine. Your doctor may prescribe ROSUMIBE tablets if you are already taking rosuvastatin and ezetimibe at the same doses.
ROSUMIBE tablets are used if you have:

• increased cholesterol levels in the blood (primary hypercholesterolemia)
• heart disease; Rosuvastatin and Ezetimibe reduce the risk of heart attack, stroke, surgical procedures to improve blood flow to the heart, or hospitalization due to chest pain

ROSUMIBE tablets do not help with weight loss.

2. What you should know before taking ROSUMIBE tablets

Do not take ROSUMIBE tablets if:

• you are allergic to rosuvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6);
• you have liver disease;
• you have severe kidney problems;
• you have unexplained repeated muscle pain or tenderness (myopathy);
• you are taking a combination of medicines containing sofosbuvir/velpatasvir/voxilaprevir (used for a viral liver infection called hepatitis C);
• you are taking a medicine called cyclosporine (used, for example, after organ transplant);
• you are pregnant or breastfeeding. If you become pregnant while taking ROSUMIBE tablets, stop taking it immediately and inform your doctor. Women must avoid pregnancy during treatment with ROSUMIBE tablets by using appropriate contraceptive measures (see below: Pregnancy and breastfeeding);
• you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking ROSUMIBE or other related medicines.

If any of these apply to you (or if you are unsure), consult your doctor.
Warnings and precautions
Talk to your doctor or pharmacist before taking ROSUMIBE tablets if:

• you have kidney problems;
• you have liver problems;
• you have experienced unexplained repeated muscle pain or tenderness, have a personal or family history of muscle disorders, or have previously had muscle problems during treatment with other cholesterol-lowering medicines. Inform your doctor or pharmacist immediately if you experience unexplained muscle pain or tenderness, especially if you feel unwell or have a fever. Also inform your doctor or pharmacist if you have persistent muscle weakness;
• you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). Your doctor must choose the correct dosage of ROSUMIBE tablets suitable for you;
• you are taking medicines used to treat infections, including HIV or hepatitis C infection, e.g. lopinavir/ritonavir and/or atazanavir or simeprevir; see “Other medicines and ROSUMIBE tablets”;
• you have severe respiratory failure;
• you are taking other medicines called fibrates to lower cholesterol. See “Other medicines and ROSUMIBE tablets”;
• you regularly consume large amounts of alcohol;
• you have an underactive thyroid gland (hypothyroidism);
• you are over 70 years old (your doctor must determine the correct dosage of ROSUMIBE tablets suitable for you);
• you are currently taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine used for bacterial infections). The combination of fusidic acid and ROSUMIBE tablets can lead to serious muscle problems (rhabdomyolysis).

If any of these apply to you (or if you have doubts): consult your doctor or pharmacist before
starting to take any dose of ROSUMIBE tablets.
Statins may affect liver function in a small number of people. This is detected by a simple blood test that monitors increases in liver enzyme levels. For this reason, your doctor will usually request this blood test (liver function test) during treatment with ROSUMIBE tablets. It is important to attend your doctor’s appointments for prescribed laboratory tests.
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 fats in your blood, are overweight, and have high blood pressure.
Serious skin reactions have been reported with the use of ROSUMIBE, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS).
Stop using ROSUMIBE and seek immediate medical attention if you notice any of the symptoms described in section 4.
Children and adolescents
The use of ROSUMIBE tablets is not recommended in children and adolescents under 18 years of age.
Other medicines and ROSUMIBE tablets
Talk to your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Talk to your doctor if you are taking any of the following medicines:

• Cyclosporine (used, for example, after organ transplant to prevent organ rejection). The effect of rosuvastatin increases when used together with this medicine. Do not take ROSUMIBE tablets concomitantly with cyclosporine;
• Anticoagulants such as warfarin, acenocoumarol, fluindione, or ticagrelor (their anticoagulant effect and risk of bleeding may increase if taken together with ROSUMIBE tablets), or clopidogrel;
• Other cholesterol-lowering medicines called fibrates, which also correct triglyceride levels (e.g. gemfibrozil or other fibrates). When used concomitantly with fibrates, the effect of rosuvastatin is increased;
• Colestiramine (a medicine to lower cholesterol levels), as it interferes with the action of ezetimibe;
• Darolutamide, Regorafenib (used to treat tumours);
• 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, simeprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir;
• Antacids containing aluminium and magnesium (used to neutralize stomach acid; these metals reduce rosuvastatin levels in the blood). This effect may be minimized by taking this type of medicine 2 hours after taking rosuvastatin;
• Erythromycin (an antibiotic). Concomitant use of this antibiotic reduces the effect of rosuvastatin;
• 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 advise you when it is safe to restart taking ROSUMIBE tablets. Taking ROSUMIBE tablets with fusidic acid may rarely cause muscle weakness, fatigue, or muscle pain (rhabdomyolysis). See further information on rhabdomyolysis in section 4;
• An oral contraceptive (the pill). These increase the absorbed hormone levels from the pill;
• Hormone replacement therapy (increases hormone levels in the blood).

If you are hospitalized or receiving treatment for another medical condition, inform the medical staff that you are taking ROSUMIBE tablets.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take ROSUMIBE tablets if you are pregnant, suspect you may be pregnant, or are planning to become pregnant. If you become pregnant while taking ROSUMIBE tablets, stop taking it immediately and inform your doctor. Women must always use effective contraception during treatment with ROSUMIBE tablets.
Breastfeeding
Do not take ROSUMIBE tablets during breastfeeding, as it is not known whether the medicine is excreted in breast milk.
Driving and using machines
ROSUMIBE tablets should not affect your ability to drive or operate machinery. However, you should consider that some people may experience dizziness after taking ROSUMIBE tablets. If you experience dizziness, consult your doctor before driving or operating machinery.
ROSUMIBE contains lactose monohydrate
If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.
ROSUMIBE contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., “essentially sodium-free”.

3. How to take ROSUMIBE tablets

Take this medicine exactly as directed by your doctor. 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
ROSUMIBE tablets.
The recommended daily dose for adults is one tablet of the specific strength.
Take ROSUMIBE tablets once daily.
It can be taken 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.
ROSUMIBE tablets are not suitable for initial therapy.
Initiation of treatment or dose adjustment, if necessary, must only be performed by administering the active substances separately; once the appropriate doses have been established, switching to ROSUMIBE tablets is possible.
Regular cholesterol monitoring
It is important to return to your doctor regularly to monitor your cholesterol levels and ensure they have reached and remain within the normal target range.
If you take more ROSUMIBE tablets than you should
Contact your doctor or the nearest hospital emergency department, as you may require medical attention.
If you forget to take ROSUMIBE tablets
Do not worry. Skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the forgotten dose.
If you stop taking ROSUMIBE tablets
Talk to your doctor if you wish to discontinue treatment with ROSUMIBE tablets. Your cholesterol levels may rise again if you stop taking ROSUMIBE tablets.
If you have further questions about the use of this medicine, you may contact 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 the possible side effects.
Stop taking ROSUMIBE tablets and go to a doctor immediately if you experience any of the following side effects:

• swelling of the face, lips, tongue and/or throat, which may cause difficulty breathing and swallowing;
• symptoms of a lupus-like illness (including skin rash, joint problems and effects on blood cells);
• muscle breakdown;
• flat, reddish, target-shaped or circular spots on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital and eye ulcers. These serious skin reactions 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 have unusual muscle tenderness or pain lasting longer than expected. These symptoms may rarely progress to fatal muscle damage known as rhabdomyolysis, which leads to malaise, fever and kidney dysfunction.
The following terms are used to describe how often 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. You are at risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight and have high blood pressure. Your doctor will monitor you while you are taking this medicine.
• Stomach pain;
• Diarrhoea;
• Flatulence (excess gas in the intestinal tract);
• Feeling tired;
• Increased levels in certain laboratory blood tests related to liver function (transaminases).

Uncommon side effects

• Rash, itching, hives;
• Increase in the amount of protein in the urine – this usually returns to normal without stopping rosuvastatin;
• Increases in certain laboratory blood tests related to 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 of hands and feet.

Rare side effects
Inflammation of the pancreas, causing severe stomach pain spreading to the back, reduction in platelets.
Very rare side effects
Jaundice (yellowing of the skin and eyes), liver inflammation (hepatitis), blood in the urine, nerve damage in arms and legs (such as numbness), memory loss, breast enlargement in men (gynaecomastia).
Not known
Shortness of breath, oedema (swelling), sleep disorders, including difficulty sleeping and nightmares, sexual problems, depression, breathing problems, including persistent cough and/or shortness of breath or fever, tendon disorders, persistent muscle weakness, gallstones or inflammation of the gallbladder (which may cause stomach pain, nausea, vomiting).
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at 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 ROSUMIBE tablets

Keep in the original packaging to protect the medicine from light.
This medicine does not require any special storage temperature.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister. 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 in use. This will help protect the environment.

6. Package contents and other information

What ROSUMIBE tablets contain
The active substances are rosuvastatin (as rosuvastatin calcium) and ezetimibe. The tablets contain rosuvastatin calcium equivalent to 5 mg, 10 mg or 20 mg of rosuvastatin. Each tablet contains 10 mg of ezetimibe.
The other components are: Monohydrate lactose, Microcrystalline cellulose, Sodium croscarmellose,
Crosspovidone type A, Povidone K-30, Sodium lauryl sulfate and Magnesium stearate.

Description of the appearance of ROSUMIBE tablets and pack contents
ROSUMIBE 20 mg/10 mg tablets: white to off-white, round, biconvex, uncoated tablet. The tablet diameter is 11 mm.
ROSUMIBE 10 mg/10 mg tablets: white to off-white, oval, biconvex, uncoated tablet, with "E1" engraved on one side and "1" on the other side. The tablet dimensions are 15 mm x 7 mm.
ROSUMIBE 5 mg/10 mg tablets: white to off-white, round, flat, uncoated tablet, with "E2" engraved on one side and "2" on the other side. The tablet diameter is 10 mm.
Pack sizes of 7, 10, 14, 28, 30, 56, 60, 84, 90, 98 and 100 tablets in blisters (PA/AL/PVC//Al), packed in cardboard boxes with the leaflet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Piam Farmaceutici S.p.A.
Via Fieschi, 8/7
16121 - Genoa
Italy

Manufacturer
Pabianickie Zakłady Farmaceutyczne Polfa S.A.
Marszałka J. Piłsudskiego Street 5,
95-200 Pabianice
Poland
Adamed Pharma S.A.
ul. Marszalka Józefa Pilsudskiego 5,
95-200 Pabianice
Poland

Patient Information Leaflet

ROSUMIBE 15 mg/10 mg, tablets, 30 mg/10 mg, tablets, 40 mg/10 mg, tablets

rosuvastatin and ezetimibe
Please read this entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult 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, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ROSUMIBE tablets are and what they are used for

ROSUMIBE tablets contain two different active substances in a single tablet. One active substance is rosuvastatin, belonging to the family of drugs known as statins; the other active substance is ezetimibe.
ROSUMIBE tablets are a medicine used to lower total cholesterol levels, "bad" cholesterol (LDL cholesterol), and blood fats known as triglycerides. Additionally, this medicine increases levels of "good" cholesterol (HDL cholesterol). This medicine reduces cholesterol in two ways: by decreasing the amount absorbed from the digestive tract and by reducing the body's own production of cholesterol.

For most people, high cholesterol levels do not cause any symptoms. However, if left untreated, fatty deposits can build up in the walls of blood vessels, causing them to narrow. In some cases, this narrowing of blood vessels can block blood flow to the heart or brain, leading to a heart attack or stroke. Lowering cholesterol levels can reduce the risk of heart attack, stroke, or other health-related complications.

ROSUMIBE tablets are used for patients whose cholesterol levels cannot be controlled by a low-cholesterol diet alone. You must continue to follow a cholesterol-lowering diet during treatment with this medicine.

Your doctor may prescribe ROSUMIBE tablets if you are already taking rosuvastatin and ezetimibe at the same doses.

ROSUMIBE tablets are used if you have:

• increased cholesterol levels in the blood (primary hypercholesterolemia)
• heart disease; ROSUMIBE reduces the risk of heart attack, stroke, surgical procedures to improve blood flow to the heart, or hospitalization due to chest pain.

ROSUMIBE tablets do not help with weight loss.

2. What you should know before taking ROSUMIBE tablets

Do not take ROSUMIBE tablets if:

• you are allergic to rosuvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6);
• you have liver disease;
• you have severe kidney problems;
• you have unexplained repeated muscle pain or tenderness (myopathy);
• you are taking a combination of medicines containing sofosbuvir/velpatasvir/voxilaprevir (used to treat a viral liver infection called hepatitis C);
• you are taking a medicine called cyclosporine (used, for example, after organ transplant);
• you are pregnant or breastfeeding. If you become pregnant while taking ROSUMIBE tablets, stop taking them immediately and inform your doctor. Women must avoid pregnancy during treatment with ROSUMIBE tablets by using appropriate contraceptive measures (see below: Pregnancy and breastfeeding);
• you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking ROSUMIBE or other related medicines.

If any of these apply to you (or if you are unsure), consult your doctor.
Also, do not take ROSUMIBE 40 mg/10 mg (the highest dose) if:

• you have moderate kidney problems (if in doubt, ask your doctor);
• your thyroid gland is not working properly (hypothyroidism);
• you have had repeated or unexplained muscle pain, a personal or family history of muscle problems, or a previous history of muscle problems while taking other cholesterol-lowering medicines;
• you regularly drink large amounts of alcohol;
• you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, and Indian);
• you are taking other medicines called fibrates to lower cholesterol (see section “Other medicines and ROSUMIBE tablets”).

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

• you have kidney problems;
• you have liver problems;
• you have had unexplained repeated muscle pain or tenderness, a personal or family history of muscle problems, or if you previously experienced muscle problems while taking other cholesterol-lowering medicines. Inform your doctor immediately if you experience unexplained muscle pain or tenderness, especially if you feel unwell or have a fever. Also inform your doctor or pharmacist if you have persistent muscle weakness;
• you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, and Indian). Your doctor must choose the correct dosage of ROSUMIBE tablets suitable for you;
• you are taking medicines used to treat infections, including HIV or hepatitis C, e.g. lopinavir/ritonavir and/or atazanavir; see “Other medicines and ROSUMIBE tablets”;
• you have severe respiratory failure;
• you are taking other medicines called fibrates to lower cholesterol. Please read this leaflet carefully, even if you have previously taken other medicines for high cholesterol. See “Other medicines and ROSUMIBE tablets”;
• you regularly consume large amounts of alcohol;
• your thyroid gland is not working properly (hypothyroidism);
• you are over 70 years old (your doctor must determine the appropriate dosage of ROSUMIBE tablets for you);
• you are currently taking or have taken within the last 7 days a medicine called fusidic acid (a medicine used for bacterial infections), taken orally or by injection. The combination of fusidic acid and ROSUMIBE tablets may lead to serious muscle problems (rhabdomyolysis);
• you have or have had myasthenia (a disease causing general muscle weakness, sometimes including muscles used for breathing), or ocular myasthenia (a disease causing weakness of the eye muscles), as statins may occasionally worsen the condition or trigger the onset of myasthenia (see section 4);
• you have ever developed a severe skin rash, skin peeling, blistering, and/or mouth ulcers after taking rosuvastatin or other related medicines.

If any of these apply to you (or if you have any doubts): do not take ROSUMIBE 40 mg/10 mg (the highest dose) and consult your doctor or pharmacist before starting any dose of ROSUMIBE tablets.
Statins may affect liver function in a small number of people. This is detected by a simple blood test that monitors increases in liver enzyme levels. For this reason, your doctor will usually request this blood test (liver function test) during treatment with ROSUMIBE tablets. It is important to attend all scheduled laboratory appointments with your doctor.
During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing diabetes. You are at increased risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure.
Serious skin reactions have been reported with ROSUMIBE, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Stop taking ROSUMIBE and seek immediate medical attention if you notice any of the symptoms described in section 4.

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

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

• Cyclosporine (used, for example, after organ transplant to prevent organ rejection. The effect of rosuvastatin increases when used together with this medicine). Do not take ROSUMIBE tablets together with cyclosporine;
• Anticoagulants such as warfarin, acenocoumarol, fluindione, ticagrelor, or clopidogrel (their anticoagulant effect and risk of bleeding may increase when taken together with ROSUMIBE tablets);
• Other cholesterol-lowering medicines called fibrates, which also correct triglyceride levels (e.g. gemfibrozil or other fibrates). When used together with fibrates, the effect of rosuvastatin increases. Do not take ROSUMIBE 40 mg/10 mg tablets together with a fibrate.
• Colestyramine (a medicine used to lower cholesterol levels), as it alters the function of ezetimibe;
• Darolutamide, regorafenib, capmatinib (used to treat cancer);
• Any of the following medicines used to treat viral infections, including HIV or hepatitis C, either alone or in combination (see Warnings and precautions): ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir. See section Warnings and precautions;
• Antacids containing aluminium and magnesium (used to neutralize stomach acids; these metals reduce rosuvastatin levels in the blood). This effect may be minimized by taking these medicines 2 hours after taking rosuvastatin;
• Erythromycin (an antibiotic). Concomitant use of this antibiotic reduces the effect of rosuvastatin;
• 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 advise you when it is safe to restart ROSUMIBE tablets. Taking ROSUMIBE tablets with fusidic acid may rarely cause muscle weakness, pain, or tenderness (rhabdomyolysis).
  See further information on rhabdomyolysis in section 4;
• An oral contraceptive (the pill). These increase the absorbed hormone levels from the pill;
• Hormone replacement therapy (increases hormone levels in the blood);
• 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).

If you are admitted to hospital or are being treated for another medical condition, inform the medical staff that you are taking ROSUMIBE tablets.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
Do not take ROSUMIBE tablets if you are pregnant, think you may be pregnant, or are planning to become pregnant. If you become pregnant while taking ROSUMIBE tablets, stop taking them immediately and inform your doctor. Women must always use effective contraceptive measures during treatment with ROSUMIBE tablets.

Breastfeeding
Do not take ROSUMIBE tablets while breastfeeding, as it is not known whether the medicine passes into breast milk.

Driving and using machines
ROSUMIBE tablets should not affect your ability to drive or use machinery. However, you should consider that some people may experience dizziness after taking ROSUMIBE tablets. If you experience dizziness, consult your doctor before driving or operating machinery.

ROSUMIBE tablets contain lactose monohydrate
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

ROSUMIBE tablets contain sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which essentially means it is “sodium-free”.

3. How to take ROSUMIBE tablets

Take this medicine exactly as prescribed by your doctor. 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 ROSUMIBE tablets.
The recommended daily dose for adults is one tablet of the prescribed strength.
Take ROSUMIBE tablets once daily.
It can be taken 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.
ROSUMIBE tablets are not suitable for initial therapy.
The initiation of treatment or dose adjustment, if necessary, must only be performed by administering the active substances separately; once the appropriate doses have been established, switching to ROSUMIBE tablets is possible.
The maximum daily dose of rosuvastatin is 40 mg. This dose is indicated only for patients with high cholesterol levels and at high risk of heart attack or stroke whose cholesterol levels are not sufficiently lowered with 30 mg.
Regular cholesterol checks
It is important to return to your doctor regularly to monitor your cholesterol levels and ensure they have reached and remain within the target range.
If you take more ROSUMIBE tablets than you should
Contact your doctor or the nearest hospital emergency department, as you may require medical assistance.
If you forget to take ROSUMIBE tablets
Do not worry. Skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the forgotten dose.
If you stop taking ROSUMIBE tablets
Talk to your doctor if you wish to stop treatment with ROSUMIBE tablets. Your cholesterol levels may rise again if you stop taking ROSUMIBE tablets.
If you have any further questions about the use of this medicine, you can contact 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 the possible side effects.
Stop taking ROSUMIBE tablets and seek immediate medical attention if you experience any of the following:

• allergic reactions: swelling of the face, lips, tongue and/or throat, which may cause difficulty in breathing and swallowing, severe itching of the skin (with raised lumps). These are rare possible side effects;
• lupus-like disease syndrome (including skin rash, joint disorders and effects on blood cells). This is a rare possible side effect;
• muscle breakdown. This is a rare possible side effect;
• flat, red, target-shaped or circular spots on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital and eye ulcers. These serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome). The frequency of this possible side effect is unknown;
• widespread rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome). The frequency of this possible side effect is unknown.

Contact your doctor immediately if you have unusual muscle tenderness or muscle pain lasting longer than expected. These may rarely progress to a fatal muscle damage known as rhabdomyolysis, which leads to malaise, fever and kidney dysfunction.

The following terms are used to describe how often 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;
• muscle tenderness;
• feeling of weakness;
• dizziness;
• increased amount of protein in the urine – these usually return to normal on their own without discontinuing ROSUMIBE (only with rosuvastatin 40 mg);
• diabetes. You are at risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine;
• stomach pain;
• diarrhoea;
• flatulence (excess gas in the intestinal tract);
• feeling of tiredness;
• increase in certain laboratory blood tests related to liver function (transaminases).

Uncommon side effects:

• skin rash, itching, urticaria;
• increased amount of protein in the urine – which usually returns to normal without discontinuing rosuvastatin (only with rosuvastatin 10 mg and 20 mg);
• increases in certain laboratory blood tests related to muscle function (CK);
• cough;
• indigestion;
• heartburn;
• nausea;
• muscle spasms;
• neck pain;
• decreased 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 of hands and feet.

Rare side effects:

• inflammation of the pancreas, causing severe stomach pain radiating to the back;
• bleeding or bruising more easily than normal due to low platelet levels.

Very rare side effects:
Jaundice (yellowing of the skin and eyes), liver inflammation (hepatitis), blood in the urine, nerve damage in the arms and legs (such as numbness), memory loss, breast enlargement in men (gynaecomastia).
Side effects not known:
Shortness of breath, oedema (swelling), sleep disorders, including difficulty sleeping and nightmares, sexual problems, depression, respiratory problems including persistent cough and/or shortness of breath or fever, tendon disorders, persistent muscle weakness, raised red skin rash, sometimes with target-shaped lesions (erythema multiforme), muscle tenderness, gallstones or inflammation of the gallbladder (which may cause stomach pain, nausea, vomiting).
Myasthenia gravis (a condition causing general muscle weakness, including in some cases the muscles used for breathing), ocular myasthenia (a condition causing weakness of the eye muscles). Consult your doctor if you experience worsening weakness in arms or legs after periods of 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 can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ROSUMIBE tablets

Keep in the original packaging to protect the medicine from light.
This medicine does not require any special storage temperature.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month.
Do not dispose of medicines 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 ROSUMIBE tablets contain
The active substances are rosuvastatin (as rosuvastatin calcium salt) and ezetimibe. The tablets contain rosuvastatin calcium equivalent to 15 mg, 30 mg or 40 mg of rosuvastatin. Each tablet contains 10 mg of ezetimibe.
The other components are: Monohydrate lactose, Microcrystalline cellulose, Sodium croscarmellose,
Crosspovidone type A, Povidone K-30, Sodium lauryl sulfate and Magnesium stearate.

Description of the appearance of ROSUMIBE tablets and package contents
ROSUMIBE 15mg/10mg tablets: Uncoated tablet, hexagonal, biconvex, white to off-white in colour, approximately 9 x 8 mm in size, with "E3" engraved on both sides.
ROSUMIBE 30mg/10mg tablets: Uncoated tablet, biconvex, white to off-white in colour, rectangular in shape, 12 x 6 mm in size, with "X" engraved on both sides.
ROSUMIBE 40mg/10mg tablets: Uncoated tablet, elliptical, biconvex, white to off-white in colour, approximately 13 x 6 mm in size, with "E6" engraved on both sides.
Pack sizes of 28, 30, 56, 60, 90 and 100 tablets in blisters (PA/AL/PVC//Al) contained in cardboard boxes with the package leaflet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Piam Farmaceutici S.p.A.
Via Fieschi, 8/7
16121 - Genova
Italy

Manufacturer
Adamed Pharma S.A.
ul. Marszalka Józefa Pilsudskiego 5,
95-200 Pabianice
Poland