Cholecomb

Patient Information Leaflet

Cholecomb 5 mg/10 mg hard capsules, 10 mg/10 mg hard capsules, 20 mg/10 mg hard capsules

Rosuvastatin and Ezetimibe
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 pass it on to others, even if they have the same symptoms as you, because 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

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

1. What Cholecomb is and what it is used for

Cholecomb contains two different active substances in one capsule.
One of the active substances is rosuvastatin, belonging to the group of medicines known as statins; the other active substance
is ezetimibe.
Cholecomb is a medicine used to lower blood levels of total cholesterol, of so-called "bad" cholesterol (LDL cholesterol), and of other fats known as triglycerides. 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 from the digestive tract and by decreasing the body's own production of cholesterol.
In most people, high cholesterol levels do not affect how they feel, as they produce no symptoms. However, if left untreated, high cholesterol may lead to the buildup of fatty deposits in the walls of blood vessels, causing them to narrow.
Sometimes these narrowed blood vessels can become blocked, interrupting blood flow to the heart and brain and causing a heart attack or stroke. By lowering cholesterol levels, the risk of having a heart attack, stroke, or related health problems can be reduced.
Cholecomb is used in patients whose cholesterol levels cannot be controlled by a cholesterol-lowering diet alone. A cholesterol-lowering diet must always be maintained while taking this medicine.
Your doctor may prescribe Cholecomb to you if you are already taking both rosuvastatin and ezetimibe at the same dosage.
Cholecomb is used in patients with heart disease. Cholecomb reduces the risk of heart attack, stroke, surgical procedures to increase blood flow to the heart, or hospitalization due to chest pain.
Cholecomb does not help with weight loss.

2. What you should know before taking Cholecomb

Do not take Cholecomb 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 impairment.
• you have repeated and unexplained muscle pain (myopathy).
• you are taking a combination of sofosbuvir/velpatasvir/voxilaprevir (a medicine used to treat chronic viral liver infection called hepatitis C).
• you are taking a medicine called cyclosporine (used, for example, after organ transplants).
• you are pregnant or breastfeeding. If you become pregnant while taking Cholecomb, stop the medicine immediately and contact your doctor. Women must avoid pregnancy during treatment with Cholecomb by using adequate contraceptive measures.
• you have ever developed a severe skin rash or skin peeling, blisters, and/or mouth ulcers after taking Cholecomb or other medicines containing rosuvastatin.

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 Cholecomb if:

• you have kidney problems.

• you have liver problems.

• you have experienced repeated or unexplained muscle pain, have a personal or family history of muscle disorders, or have previously experienced muscle problems while taking other cholesterol-lowering medicines. Contact a doctor immediately if you experience repeated and unexplained muscle pain, especially if you feel unwell or have fever. Also consult a doctor or pharmacist if you have persistent muscle fatigue.

• you have or have had myasthenia (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 are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). In such cases, your doctor must choose the appropriate dose of Cholecomb.

• you are taking medicines for infections, including HIV or hepatitis C, such as lopinavir/ritonavir and/or atazanavir. See section “Other medicines and Cholecomb”.

• you have severe respiratory insufficiency.

• you are taking other medicines called fibrates to lower cholesterol levels. See section “Other medicines and Cholecomb” for further information.

• you regularly drink large amounts of alcohol.

• you have an underactive thyroid gland (hypothyroidism).

• you are over 70 years of age (your doctor must determine the appropriate dose of Cholecomb for you).

• you are currently taking or have taken within the last 7 days a medicine called fusidic acid (a medicine for bacterial infections) taken orally or by injection. The combination of fusidic acid and Cholecomb may lead to serious muscle problems (rhabdomyolysis).

If any of the above conditions apply to you (or if you are unsure):
Talk to your doctor or pharmacist before taking any dose of Cholecomb.
Severe skin reactions have been reported during treatment with Cholecomb, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Stop using Cholecomb and seek immediate medical help if you notice any of the symptoms described in section 4.
Statins may cause liver problems in a small number of people. This condition can be easily detected with a simple blood test measuring liver enzyme levels. For this reason, your doctor must regularly perform this blood test (liver function test) during treatment with Cholecomb. It is important to attend all scheduled laboratory tests as advised by your doctor.
While taking this medicine, your doctor will closely monitor you if you have diabetes or are at risk of developing diabetes. The risk of developing diabetes is particularly high if you have high blood sugar and fat levels, are overweight, or have high blood pressure.
Children and adolescents
The use of Cholecomb is not recommended in children and adolescents under 18 years of age.
Other medicines and Cholecomb
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Tell your doctor if you are taking any of the following medicines:

• Cyclosporine (used, for example, after organ transplantation to prevent rejection of transplanted organs). The effect of rosuvastatin is increased when used together with this medicine. Do not take Cholecomb while taking cyclosporine.
• Anticoagulants such as warfarin, acenocoumarol, or phenindione (their anticoagulant effect and risk of bleeding may increase when taken together with Cholecomb), ticagrelor, or clopidogrel.
• Other medicines used to lower cholesterol levels, 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 also used to lower cholesterol levels), as it alters the function of ezetimibe.
• Regorafenib (used to treat tumors).
• Darolutamide (used to treat cancer).
• Any of the following medicines used to treat viral infections, including HIV or hepatitis C, alone or in combination (see section “Warnings and Precautions”): ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.
• Antacids containing aluminium and magnesium (used to neutralize stomach acid; these reduce rosuvastatin levels in the blood). This effect may be minimized by taking such medicines 2 hours after taking rosuvastatin.
• Erythromycin (an antibiotic). Concomitant use of this antibiotic reduces the effects of rosuvastatin.
• Fusidic acid. If you need to take fusidic acid to treat a bacterial infection, you must temporarily stop treatment with this medicine. Your doctor will advise you when it is safe to resume treatment with Cholecomb. The combination of Cholecomb and fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.
• Oral contraceptives (the pill). These increase levels of sex hormones regulated by the pill.
• Capmatinib (used to treat cancer).
• Hormone replacement therapy (increases hormone levels in the blood).
• Fostamatinib (used to treat low platelet count).
• Febuxostat (used to treat and prevent high blood levels of uric acid).
• Teriflunomide (used to treat multiple sclerosis).

If you are hospitalized or receiving treatment for another medical condition, inform the medical staff that you are taking Cholecomb.
Pregnancy and breastfeeding
Do not take Cholecomb if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. If you become pregnant while taking Cholecomb, stop treatment immediately and contact your doctor. Women must always use adequate contraceptive measures during treatment with Cholecomb.
Do not take Cholecomb while breastfeeding, as it is not known whether the medicine passes into breast milk.
Driving and using machines
Cholecomb is not expected to affect your ability to drive or use machines. However, you should consider that some people may experience dizziness after taking Cholecomb. If you experience dizziness, consult your doctor before driving or operating machinery.
Cholecomb contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per hard capsule, i.e., essentially ‘sodium-free’.

3. How to take Cholecomb

Take this medicine exactly as directed 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 regular physical activity while taking
Cholecomb.
The recommended daily dose for adults is one capsule of the prescribed strength.
Take Cholecomb once daily.
Take the capsule at any time of day, with or without food. Swallow the capsule whole with a
glass of water.
Take the medicine at the same time every day.
Cholecomb is not suitable for initiating treatment. The start of treatment, or, if necessary, a dose adjustment,
should only be performed by administering the active substances separately. Once the appropriate dose has been established,
switching to Cholecomb at the corresponding strength may be considered.
Your doctor may decide to prescribe you the lowest dose (5 mg/10 mg) if:

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

Regular cholesterol monitoring
It is important to have your cholesterol levels checked regularly by your doctor to ensure that cholesterol
reaches and maintains the appropriate level.
If you take more Cholecomb than you should
Contact your doctor or the nearest hospital emergency department, as you may require medical attention.
If you forget to take Cholecomb
Do not worry. Skip the missed dose and take the next scheduled dose at the usual time.
Do not take a double dose to make up for the forgotten dose.
If you stop taking Cholecomb
Consult your doctor if you wish to discontinue treatment with Cholecomb. Please note that your
cholesterol levels may rise again if you stop.
If you have any questions about the use of 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 the possible side effects.
Stop treatment with Cholecomb immediately and seek medical help if you experience even one of the following side effects:

Rare (may affect up to 1 in 1,000 people):

• Allergic reactions such as swelling of the face, lips, tongue and/or throat, which may cause difficulty breathing or swallowing.
• Unusual or prolonged muscle pain. These may rarely progress to a potentially fatal muscle damage known as rhabdomyolysis, which leads to malaise, fever and kidney damage.
• Lupus-like syndrome (including skin rashes, joint disorders and effects on blood cells).
• Muscle rupture.

Not known (frequency cannot be estimated from available data):

• Reddish, flat, target-shaped or circular spots on the trunk, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals and eyes. These severe 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).
• Erythema multiforme (life-threatening allergic reactions affecting the skin and mucous membranes).

Other possible side effects
Common (may affect up to 1 in 10 people)

• Headache
• Constipation
• Nausea (feeling unwell)
• Muscle pain
• Feeling weak
• Dizziness
• Diabetes. This is much 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 during treatment.
• Abdominal pain (stomach ache)
• Diarrhoea
• Flatulence (excess gas in the intestinal tract)
• Feeling tired
• Increase in certain laboratory blood tests related to liver function (transaminases)

Uncommon (may affect up to 1 in 100 people)

• Skin rash, itching, hives
• Increased protein content in urine; these usually return to normal levels without discontinuing rosuvastatin.
• Increase 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 in hands and feet

Rare (may affect up to 1 in 1,000 people)

• Inflammation of the pancreas, causing severe stomach pain radiating to the back
• Reduction in platelet count

Very rare (may affect up to 1 in 10,000 people)

• Jaundice (yellowing of the skin and eyes)
• Inflammation of the liver (hepatitis)
• Blood traces in urine
• Nerve damage in arms and legs (such as numbness)
• Memory loss
• Enlargement of the breasts in men (gynecomastia)

Not known (frequency cannot be estimated from available data)

• 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 injuries
• Persistent muscle weakness
• Gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea, vomiting)
• 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). Consult your doctor if you experience weakness in arms or legs that worsens after periods of activity, double vision or drooping eyelids, difficulty swallowing or laboured breathing.

Reporting of side effects
If you experience any side effect, including those 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-avvers.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cholecomb

Store below 30°C.
Keep in the original packaging to protect the medicine from light and moisture.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the carton. 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 no longer required. This will help protect the environment.

6. Package Contents and Other Information

What Cholecomb Contains
The active substances are rosuvastatin (as rosuvastatin zinc) and ezetimibe. The capsules contain rosuvastatin zinc equivalent to 5 mg, 10 mg, or 20 mg of rosuvastatin. Each capsule contains 10 mg of ezetimibe.
The other components are:
Core
Silicified Microcrystalline Cellulose [Microcrystalline Cellulose (E460) and Anhydrous Colloidal Silica (E551)], Anhydrous Colloidal Silica (E551), Magnesium Stearate (E572), Povidone (E1201), Sodium Croscarmellose (E468), Microcrystalline Cellulose (E460), Mannitol (E421), Sodium Lauryl Sulfate (E514), Low-substituted Hydroxypropyl Cellulose (E463).
Capsule Shell
Cholecomb 5mg/10mg hard capsules
Cap: Titanium Dioxide (E171), Yellow Iron Oxide (E172), Gelatin
Body: Titanium Dioxide (E171), Gelatin
Cholecomb 10mg/10mg hard capsules
Cap and body: Yellow Iron Oxide (E172), Titanium Dioxide (E171), Gelatin
Cholecomb 20mg/10mg hard capsules
Cap: Red Iron Oxide (E172), Titanium Dioxide (E171), Yellow Iron Oxide (E172), Gelatin
Body: Yellow Iron Oxide (E172), Titanium Dioxide (E171), Gelatin

Description of the Appearance of Cholecomb and Contents of the Package
Cholecomb 5 mg/10 mg hard capsules: Hard gelatin capsules, unmarked with a Coni Snap-type automatic closure, with a yellow cap and white body, filled with two tablets: one Ezetimibe 10 mg tablet, white or almost white, round, flat, with bevelled edges, bearing a stylized "E" on one side and the code "612" on the other side; one Rosuvastatin 5 mg tablet, white or almost white, round and biconvex, bearing the number "5" on one side and no mark on the other side. The capsule length is approximately 21.7 mm (± 0.5 mm).
Cholecomb 10 mg/10 mg hard capsules: Hard gelatin capsule, unmarked with a Coni Snap-type automatic closure, with yellow cap and yellow body, filled with two tablets: one Ezetimibe 10 mg tablet, white or almost white, round, flat, with bevelled edges, bearing a stylized "E" on one side and the code "612" on the other side; one Rosuvastatin 10 mg tablet, white or almost white, round, bearing a mark on one side and no mark on the other side. The capsule length is approximately 21.7 mm (± 0.5 mm).
Cholecomb 20 mg/10 mg hard capsules: Hard gelatin capsule, unmarked with a Coni Snap-type automatic closure, with caramel-colored cap and yellow body, filled with two tablets: one Ezetimibe 10 mg tablet, white or almost white, round, flat, with bevelled edges, bearing a stylized "E" on one side and the code "612" on the other side; one Rosuvastatin 20 mg tablet, white or almost white, round, bearing a mark on one side and no mark on the other side. The capsule length is approximately 21.7 mm (± 0.5 mm).

5 mg/10 mg: Packs of 28, 30, 60 and 90 hard capsules in cold-form blister packs (OPA/Al/PVC//Al).
10 mg/10 mg and 20 mg/10 mg: Packs of 7, 10, 28, 30, 56, 60, 84, and 90 hard capsules in cold-form blister packs (OPA/Al/PVC//Al), contained in a folding carton with the package leaflet.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Proterapia Hungary Ltd.
1134 Budapest, Lehel utca 11.
Hungary

Marketing Authorization Holder for Distribution
Servier Italia S.p.A.
Via Luca Passi, 85
00166 Rome
Italy

Responsible Manufacturer for Batch Release
Egis Pharmaceuticals PLC
1165 Budapest, Bökényföldi út 118-120.
Hungary
Egis Pharmaceuticals PLC
9900 Körmend, Mátyás király u. 65.
Hungary

This medicinal product is authorized in the European Economic Area member states under the following names:

Patient Information Leaflet

Cholecomb 40 mg/10 mg hard capsules

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

1. What Cholecomb is and what it is used for

Cholecomb contains two different active substances in one capsule.
One of the active substances is rosuvastatin, belonging to the group of medicines known as statins; the other active substance is ezetimibe.
Cholecomb is a medicine used to lower blood levels of total cholesterol, so-called "bad" cholesterol (LDL cholesterol), and other blood fats called triglycerides. It also increases levels of "good" cholesterol (HDL cholesterol). This medicine works in two ways: by reducing the amount of cholesterol absorbed from the digestive tract and by decreasing the body's own production of cholesterol.
For most people, high cholesterol has no effect on how they feel, as it causes no symptoms. However, if left untreated, it can lead to the buildup of fatty deposits in the walls of blood vessels, causing them to narrow.
Sometimes, these narrowed blood vessels may become blocked, interrupting blood flow to the heart and brain, which can result in a heart attack or stroke. By lowering cholesterol levels, it is possible to reduce the risk of having a heart attack, stroke, or other related health problems.
Cholecomb is used in patients whose cholesterol levels cannot be controlled by a cholesterol-lowering diet alone. Such a cholesterol-lowering diet must always be maintained during treatment with this medicine.
Your doctor may prescribe Cholecomb if you are already taking both rosuvastatin and ezetimibe at the same dosage.
Cholecomb is used in patients with heart disease. Cholecomb reduces the risk of heart attack, stroke, surgical procedures to improve blood flow to the heart, or hospitalization due to chest pain.
Cholecomb does not help with weight loss.

2. What you should know before taking Cholecomb

Do not take Cholecomb 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 moderate or severe kidney impairment.
• you have repeated and unexplained muscle pain (myopathy).
• you are taking a combination of sofosbuvir/velpatasvir/voxilaprevir (a medicine used to treat chronic viral liver infection called hepatitis C).
• you have experienced repeated and unexplained muscle pain, have a personal or family history of muscle disorders, or have previously experienced muscle problems while taking other cholesterol-lowering medicines.
• you are taking a medicine called cyclosporine (used, for example, after organ transplants).
• you are pregnant or breastfeeding. If you become pregnant while taking Cholecomb, stop taking it immediately and consult your doctor. Women must avoid pregnancy during treatment with Cholecomb by using adequate contraceptive measures.
• you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking Cholecomb or other medicines containing rosuvastatin.
• you have an underactive thyroid gland (hypothyroidism).
• 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 levels (see section “Other medicines and Cholecomb”).

If any of the above apply to you (or if you are in doubt), contact your doctor.
Warnings and precautions
Talk to your doctor or pharmacist before taking Cholecomb if:

• you have kidney problems.
• you have liver problems.
• you have had repeated or unexplained muscle pain, or have a personal or family history of muscle disorders, or have previously experienced muscle problems while taking other cholesterol-lowering medicines. Contact a doctor immediately if you experience repeated and unexplained muscle pain, especially if you feel unwell or have a fever. Also consult a doctor or pharmacist if you have persistent muscle fatigue.
• 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 are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, and Indian). In such cases, your doctor must choose the appropriate dose of Cholecomb.
• you are taking medicines for infections, including HIV or hepatitis C, such as lopinavir/ritonavir and/or atazanavir. See section “Other medicines and Cholecomb”.
• you have severe respiratory failure.
• you are taking other medicines called fibrates to lower cholesterol. See section “Other medicines and Cholecomb” for further information.
• you regularly drink large amounts of alcohol.
• you have an underactive thyroid gland (hypothyroidism).
• you are over 70 years of age (your doctor must determine the appropriate dose of Cholecomb for you).
• you are taking or have taken within the last 7 days a medicine called fusidic acid (a medicine for bacterial infections) taken orally or by injection. The combination of fusidic acid and Cholecomb can lead to serious muscle problems (rhabdomyolysis).

If any of the above circumstances apply to you (or if you are in doubt):
Do not take Cholecomb 40 mg/10 mg hard capsules (the highest dose) and consult your doctor or
pharmacist before taking any dose of Cholecomb.
Severe skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during treatment with Cholecomb. Discontinue use of Cholecomb and seek immediate medical attention if you notice any of the symptoms described in section 4.
Statins may cause liver problems in a small number of people. This condition can be easily detected with a simple blood test measuring liver enzyme levels. For this reason, your doctor must regularly perform this blood test (liver function test) during treatment with Cholecomb. It is important to attend all scheduled laboratory appointments as advised by your doctor.
While taking this medicine, your doctor will closely monitor you if you have diabetes or are at risk of developing diabetes. The risk of developing diabetes is higher if you have high blood sugar and fat levels, are overweight, or have high blood pressure.
Children and adolescents
The use of Cholecomb is not recommended in children and adolescents under 18 years of age.
Other medicines and Cholecomb
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Tell your doctor if you are taking any of the following medicines:

• Cyclosporine (used, for example, after organ transplantation to prevent organ rejection). The effect of rosuvastatin is increased when taken together with this medicine. Do not take Cholecomb while taking cyclosporine.
• Anticoagulants such as warfarin, acenocoumarol, or phenindione (their anticoagulant effect and risk of bleeding may increase when taken together with Cholecomb), ticagrelor, or clopidogrel.
• Other medicines used to lower cholesterol called fibrates, which also correct triglyceride levels (e.g., gemfibrozil or other fibrates). When taken together with fibrates, the effect of rosuvastatin is increased. Do not take Cholecomb 40 mg/10 mg hard capsules concomitantly with a fibrate.
• Colestipol or cholestyramine (medicines used to lower cholesterol levels), as they may interfere with the action of ezetimibe.
• Regorafenib (used to treat tumors).
• Darolutamide (used to treat cancer).
• Any of the following medicines used to treat viral infections, including HIV or hepatitis C, alone or in combination (see section “Warnings and Precautions”): ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.
• Antacids containing aluminium and magnesium (used to neutralize stomach acid; these 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 effects of rosuvastatin.
• Fusidic acid. If you need to take fusidic acid to treat a bacterial infection, you must temporarily stop treatment with this medicine. Your doctor will advise you when it is safe to restart Cholecomb. The combination of Cholecomb and fusidic acid may rarely cause muscle weakness, pain, or tenderness (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.
• Oral contraceptives (birth control pills). These may increase levels of sex hormones regulated by the pill.
• Capmatinib (used to treat cancer).
• Hormone replacement therapy (increases hormone levels in the blood).
• Fostamatinib (used to treat low platelet count).
• Febuxostat (used to treat and prevent high blood levels of uric acid).
• Teriflunomide (used to treat multiple sclerosis).

If you are hospitalized or receiving treatment for another medical condition, inform the medical staff that you are taking Cholecomb.
Cholecomb and alcohol
Do not take Cholecomb 40 mg/10 mg hard capsules (the highest dose) if you regularly drink large amounts of alcohol.
Pregnancy and breastfeeding
Do not take Cholecomb if you are pregnant, suspect you may be pregnant, or are planning a pregnancy.
If you become pregnant while taking Cholecomb, stop treatment immediately and consult your doctor. Women must always use effective contraceptive measures during treatment with Cholecomb.
Do not take Cholecomb while breastfeeding, as it is not known whether the medicine passes into breast milk.
Driving and using machines
Cholecomb is not expected to affect your ability to drive or use machines. However, you should be aware that some people may experience dizziness after taking Cholecomb.
If you experience dizziness, consult your doctor before driving or operating machinery.
Cholecomb contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per hard capsule, i.e., essentially ‘sodium-free’.

3. How to take Cholecomb

Take this medicine exactly as directed 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 maintain physical activity while taking
Cholecomb.
The recommended daily dose for adults is one capsule of the prescribed strength.
Take Cholecomb once daily.
Take the capsule at any time of day, with or without food. Swallow each capsule whole with a
glass of water.
Take the medicine at the same time every day.
Cholecomb is not suitable for initiating treatment. Treatment initiation or, if necessary, dose adjustment should only be done by administering the active substances separately. Once the appropriate dose has been established, switching to Cholecomb at the corresponding dose may be considered.
The maximum daily dose of rosuvastatin is 40 mg. This medicine is intended only for patients with high
cholesterol and a high risk of heart attack or stroke whose cholesterol levels have not been sufficiently reduced with 20 mg.
Regular Cholesterol Checks
It is important to have your cholesterol levels checked regularly by your doctor to ensure that cholesterol reaches and remains at the target level.
If you take more Cholecomb than you should
Contact your doctor or the nearest hospital emergency department immediately, as you may require medical attention.
If you forget to take Cholecomb
Do not worry. Skip the missed dose and take the next scheduled dose (at the usual time).
Do not take a double dose to make up for the missed dose.
If you stop taking Cholecomb
Consult your doctor if you wish to stop treatment with Cholecomb. Please note that your cholesterol levels may rise again if you stop.
If you have any questions about the use of 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 the possible side effects.
Stop treatment with Cholecomb immediately and seek medical help if you experience even one of the following side effects:

Rare (may affect up to 1 in 1,000 people):

• Allergic reactions such as swelling of the face, lips, tongue and/or throat, which may cause difficulty breathing or swallowing.
• Unusual muscle pain or pain lasting longer than expected. These may rarely progress to potentially fatal muscle damage known as rhabdomyolysis, leading to malaise, fever, and kidney damage.
• Lupus-like syndrome (including skin rashes, joint disorders, and effects on blood cells).
• Muscle rupture.

Not known (frequency cannot be estimated from the available data):

• Flat, red, target-shaped or circular spots on the trunk, often with central blisters, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes. These severe 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).
• Erythema multiforme (life-threatening allergic reactions affecting the skin and mucous membranes).

Other possible side effects
Common (may affect up to 1 in 10 people)

• Headache
• Constipation
• Nausea (feeling unwell)
• Muscle pain
• Feeling weak
• Dizziness
• Increase in protein content in urine; these usually return to normal levels without discontinuing rosuvastatin.
• Diabetes. This is much 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 during treatment.
• Abdominal pain (stomach ache)
• Diarrhea
• Flatulence (excess gas in the intestinal tract)
• Feeling tired
• Increase in certain laboratory blood tests related to liver function (transaminases)

Uncommon (may affect up to 1 in 100 people)

• Skin rash, itching, hives
• Increase 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 in hands and feet

Rare (may affect up to 1 in 1,000 people)

• Inflammation of the pancreas, causing severe stomach pain spreading to the back
• Reduction in platelets

Very rare (may affect up to 1 in 10,000 people)

• Jaundice (yellowing of the skin and eyes)
• Inflammation of the liver (hepatitis)
• Blood traces in urine
• Nerve damage in arms and legs (such as numbness)
• Memory loss
• Enlargement of the breasts in men (gynecomastia)

Not known (frequency cannot be estimated from the available data)

• Shortness of breath
• Edema (swelling)
• Sleep disorders, including insomnia and nightmares
• Sexual difficulties
• Depression
• Respiratory problems, including persistent cough and/or shortness of breath or fever
• Tendon injuries
• Persistent muscle weakness
• Gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea, vomiting)
• Myasthenia gravis (a condition causing generalized 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 arm or leg weakness that worsens with activity, double vision, drooping eyelids, difficulty swallowing, or labored breathing.

Reporting of side effects
If you experience any side effects, including those 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 Cholecomb

Store below 30 °C.
Keep in the original packaging to protect the medicine from light and moisture.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the carton. 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 Cholecomb contains
The active substances are rosuvastatin (as rosuvastatin zinc) and ezetimibe. The capsules contain rosuvastatin zinc
equivalent to 40 mg of rosuvastatin. Each capsule contains 10 mg of ezetimibe.
The other components are:
Core
Silicified Microcrystalline Cellulose [Microcrystalline Cellulose (E460) and Anhydrous Colloidal Silica (E551)], Anhydrous Colloidal Silica (E551), Magnesium Stearate (E572), Povidone (E1201), Sodium Croscarmellose (E468), Microcrystalline Cellulose (E460), Mannitol (E421), Sodium Lauryl Sulfate (E514), Low-substituted Hydroxypropyl Cellulose (E463)
Capsule shell
Cap: Red Iron Oxide (E172), Titanium Dioxide (E171), Yellow Iron Oxide (E172), Gelatin
Body: Gelatin, Yellow Iron Oxide (E172), Titanium Dioxide (E171)

Description of the appearance of Cholecomb and package contents
Hard gelatin capsule, unmarked, type Coni Snap closure, with a red cap and yellow body, filled with three tablets: one Ezetimibe 10 mg tablet, white or almost white, round, flat, with bevelled edges, bearing a stylized "E" on one side and the code "612" on the other side; two Rosuvastatin 20 mg tablets, white or almost white, round, with an imprint on one side and no imprint on the other side. The capsule length is approximately 21.7 mm (± 0.5 mm).

Pack sizes of 7, 10, 28, 30, 56, 60, 84, and 90 hard capsules in cold-form blister packs (OPA/AL/PVC // Al), contained in a folding cardboard box with the package leaflet.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Proterapia Hungary Ltd.
1134 Budapest, Lehel utca 11.
Hungary

Marketing Authorization Holder for distribution
Servier Italia S.p.A.
Via Luca Passi, 85
00166 Rome
Italy

Manufacturer responsible for batch release
Egis Pharmaceuticals PLC
1165 Budapest, Bökényföldi út 118-120.
Hungary
Egis Pharmaceuticals PLC
9900 Körmend, Mátyás király u. 65.
Hungary

This medicinal product is authorized in the European Economic Area member states under the following names: