Koleros

Patient Information Leaflet

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

rosuvastatin
Generic medicine

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 others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Koleros is and what it is used for

Koleros belongs to a group of medicines called statins.
You have been prescribed Koleros because:

• your cholesterol level is high. This means you are at risk of heart attack or stroke. Koleros is used in adults, adolescents, and children aged 6 years and older to treat high cholesterol.

You have been prescribed a statin because changes in diet and increased physical activity have not been sufficient to correct your cholesterol levels. While taking Koleros, you must continue your cholesterol-lowering diet and maintain physical activity.
Or

• you have other factors that increase your risk of heart attack, stroke, or related health problems. Heart attack, stroke, and related conditions can be caused by a disease called atherosclerosis. Atherosclerosis is caused by the buildup of fatty deposits inside the arteries.

Why it is important to continue taking Koleros
Koleros 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 "good" cholesterol (HDL-C).

• Koleros 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 not treated, fatty deposits can build up along the walls of blood vessels, causing them to narrow.
Sometimes, these narrowed blood vessels can become blocked, interrupting blood flow to the heart or brain and leading to heart attack or stroke. By lowering cholesterol levels, the risk of having a heart attack, stroke, or related health problems is reduced.
You must continue taking Koleros, even if your cholesterol levels have returned to normal, to prevent them from rising again, which could lead to the formation of fatty deposits. However, you must stop taking Koleros on medical advice or if you become pregnant.

2. What you should know before taking Koleros

Do not take Koleros:

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

If any of the above apply to you (or if you have any doubts), you must return to your doctor and inform them.
Also, do not take Koleros 40 mg (the highest dose):

• if you have moderate kidney problems (if in doubt, ask your doctor);
• if your thyroid gland is not functioning properly;
• if you have repeated or unexplained muscle pain or tenderness, 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 medicines to lower cholesterol, called fibrates.

If any of the above apply to you (or if you have any doubts), you must return to your doctor and inform them.
Warnings and precautions
Talk to your doctor or pharmacist before taking Koleros

• If 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 cause its onset (see section 4).
  • if you have kidney problems;
  • if you have liver problems;
  • if you have had repeated or unexplained muscle pain or tenderness, 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 pain or tenderness, especially if accompanied by malaise or fever. Also, inform your doctor or pharmacist if you have persistent muscle weakness;
  • if serious skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with treatment with Koleros. Stop using Koleros and seek immediate medical help if you notice any of the symptoms described in section 4;
  • if you regularly consume large amounts of alcohol;
  • if your thyroid gland is not functioning properly;
  • if you are taking other cholesterol-lowering medicines called fibrates. Read this leaflet carefully, even if you have previously taken other medicines for high cholesterol;
  • if you are taking medicines used to treat HIV infections, such as ritonavir with lopinavir and/or atazanavir; please read the section “Other medicines and Koleros”;
  • if you are taking or have taken within the last 7 days a medicine called fusidic acid (a medicine used to treat bacterial infections) by mouth or injection. The combination of fusidic acid and Koleros can lead to serious muscle problems (rhabdomyolysis);
  • if you are over 70 years of age (as your doctor needs to select the correct initial dose of Koleros for you);
  • if you have severe respiratory insufficiency;
  • if you are of Asian origin—i.e., Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian. Your doctor needs to select the correct initial dose of Koleros for you.

If any of the above situations apply to you (or if you are unsure):

• Do not take Koleros 40 mg (the highest dose) and consult your doctor or pharmacist before starting to take KOLEROS at any dose.

In a small number of people, statins may affect the liver. This condition is detected by a simple blood test that reveals any increases in liver enzyme levels. For this reason, your doctor will request this blood test (liver function test) before and during treatment with Koleros.
During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing it. You may be at risk of diabetes if you have high levels of sugar and fats in your blood, if you are overweight, or if you have high blood pressure.
Children and adolescents

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

Other medicines and Koleros
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, ticagrelor, or clopidogrel (or any other medicine used to thin the blood),
• fibrates (such as gemfibrozil, fenofibrate), or any other medicine used to lower cholesterol (like ezetimibe),
• antacids (used to neutralize stomach acidity),
• erythromycin (an antibiotic),
• fusidic acid (an antibiotic—please read the section “Warnings and precautions”),
• an oral contraceptive (the pill),
• regorafenib (used to treat cancer),
• darolutamide (used to treat cancer),
• capmatinib (used to treat cancer),
• 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),
• 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.

The effects of these medicines may be altered by Koleros, or the effect of Koleros may be altered by these medicines.
If you need to take fusidic acid orally to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart taking Koleros. Taking Koleros with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). See section 4 for more information on rhabdomyolysis.
Pregnancy and breastfeeding
Do not take Koleros if you are pregnant or breastfeeding. If you become pregnant while being treated with Koleros, you must stop taking the medicine immediately and inform your doctor. Women must avoid pregnancy during treatment with Koleros 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 Koleros, as the treatment does not affect this ability. However, some people may experience dizziness during treatment with Koleros. If you experience dizziness, consult your doctor before driving or operating machinery.
Koleros contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars (lactose or milk sugar), contact them before taking Koleros.
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e., essentially ‘sodium-free’.
Koleros contains Allura Red AC (E129)
It may cause allergic reactions.

3. How to take Koleros

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
Usual dose in adults
If you are taking Koleros for high cholesterol:
Starting dose:
Treatment with Koleros should begin with a dose of 5 mg or 10 mg, even if you have previously taken higher doses with other statins. The choice of starting dose depends on:

• your cholesterol level;
• your risk level for heart attack or stroke;
• the presence of 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 Koleros 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 cramps (myopathy).

Dose increase and maximum daily dose
Your doctor may decide to increase your dose in order to determine the most appropriate Koleros dose for you. If starting at 5 mg, your doctor may, if necessary, decide to double the dose to 10 mg, then to 20 mg, and subsequently to 40 mg. If starting at 10 mg, your doctor may, if necessary, decide to double the dose to 20 mg and then to 40 mg. There must be an interval of 4 weeks between each dose adjustment.
The maximum daily dose of Koleros is 40 mg. This dose is only administered to patients with high cholesterol levels and a high risk of heart attack or stroke, whose cholesterol levels have not been sufficiently reduced with the 20 mg dose.
If you are taking Koleros to reduce the risk of developing 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 usual starting dose is 5 mg. Your doctor may increase the dose to achieve the most appropriate Koleros dosage for you. The maximum daily dose of Koleros is 10 mg for children aged 6 to 9 years and 20 mg for children aged 10 to 17 years. The dose should be taken once daily. Koleros 40 mg tablets must not be used in children.
Administration of tablets
Swallow each tablet whole with a glass of water.
Koleros should be taken once daily. Koleros 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 monitoring
It is important to return to 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 until the most suitable Koleros dose for you is reached.
If you take more Koleros than you should
Contact your doctor or the nearest hospital for advice.
If you go to hospital or receive treatment for other reasons, inform the hospital doctor that you are taking Koleros.
If you forget to take Koleros
Do not panic; take the next dose at your usual time. Do not take a double dose to make up for the missed dose.
If you stop taking Koleros
Inform your doctor if you intend to stop taking Koleros. If you stop taking Koleros, your cholesterol levels may rise again.
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 experiences them.
It is important to be aware of which of these side effects may occur. They are usually mild in nature and disappear after a short time.
Stop taking Koleros 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 in swallowing;
• severe itching of the skin (with raised hives);
• non-raised reddish spots, target-shaped or circular, on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome);
• widespread skin rash, high body temperature, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

Also, stop taking Koleros and contact your doctor immediately:

• if you experience unusual muscle aches or pains lasting longer than expected. 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 fatal, 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 affect up to 1 in 10 people):

• headache, stomach pain, constipation, feeling unwell, muscle pain, feeling weak, dizziness;
• increased amount of protein in the urine – values usually return to normal on their own without needing to stop taking Koleros (only for Koleros 40 mg);
• diabetes. This is more likely if you have high levels of sugar and fats in the blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine.

Possible uncommon side effects (may affect up to 1 in 100 people):

• skin rash, itching, and other skin reactions;
• increased amount of protein in the urine – values usually return to normal on their own without needing to stop taking Koleros (only for Koleros 5 mg, 10 mg, and 20 mg).

Possible rare side effects (may affect up to 1 in 1,000 people):

• severe allergic reactions – signs include swelling of the face, lips, tongue and/or throat, difficulty swallowing and breathing, severe itching of the skin (with raised hives). If you suspect you are having an allergic reaction, stop taking Koleros and seek immediate medical help;
• muscle damage in adults – as a precaution, stop taking Koleros and contact your doctor immediately if you have unusual muscle aches or pains that last 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 levels in the blood;
• lupus-like syndrome (characterized by skin rash, joint problems, and effects on blood cells).

Possible very rare side effects (may affect up to 1 in 10,000 people):

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

Side effects with unknown frequency (frequency cannot be estimated from the available data):

• diarrhea (passing loose stools);
• cough;
• shortness of breath;
• edema (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;
• nerve disorders that may cause weakness, tingling, or numbness (peripheral neuropathy).
  • 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 after periods of activity, double vision or drooping eyelids, difficulty swallowing, or labored breathing.

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 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 Koleros

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 packs, after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Pack contents and other information

What Koleros contains

• The active substance in Koleros is rosuvastatin. Koleros film-coated tablets contain rosuvastatin calcium equivalent to 5 mg, 10 mg, 20 mg or 40 mg of rosuvastatin.
• The other components are: Tablet core: lactose monohydrate, microcrystalline cellulose, crospovidone type A, sodium carbonate monohydrate, sodium lauryl sulfate, magnesium stearate. Tablet coating [5 mg]: Opadry II 85F62533 Yellow; partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), polyethylene glycol, talc, yellow iron oxide (E172). Tablet coating [10 mg, 20 mg, 40 mg]: Opadry II 85F64743 Pink; partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), polyethylene glycol, talc, yellow iron oxide (E172), red iron oxide (E172), Allura Red AC (E129), indigotine (E132).

Description of the appearance of Koleros and pack contents
Koleros is available in 4 dosage strengths:
5 mg tablets: yellow, round, 7 mm, biconvex, with "RU5" engraved on one side and smooth on the other.
10 mg tablets: pink, round, 7 mm, biconvex, with "RU10" engraved on one side and smooth on the other.
20 mg tablets: pink, round, 9 mm, biconvex, with "RU20" engraved on one side and smooth on the other.
40 mg tablets: pink, oval, 15.5 mm x 8 mm, biconvex, with "RU40" engraved on one side and smooth on the other.
Koleros is available in blister packs (Al/Al) containing 28 tablets.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Konpharma s.r.l.
Via Pietro Della Valle n. 1
00193 Rome
Italy

Manufacturer responsible for batch release

1. Actavis Ltd.
   BLB016, Bulebel Industrial Estate
   Zejtun
   ZTN 3000
   Malta
2. Balkanpharma-Dupnitsa AD
   3 Samokovsko Shosse Str.
   Dupnitza 2600
   Bulgaria
3. PharmaPath S.A.
   28is Oktovriou 1,
   Agia Varvara, 123 51,
   Greece