Crosuvo plus

Package leaflet: Information for the patient

Crosuvo Plus, 5 mg + 10 mg, film-coated tablets
Crosuvo Plus, 10 mg + 10 mg, film-coated tablets
Crosuvo Plus, 20 mg + 10 mg, film-coated tablets
Crosuvo Plus, 40 mg + 10 mg, film-coated tablets
Rosuvastatin + Ezetimibe
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Crosuvo Plus is and what it is used for

Crosuvo Plus contains two different active substances in one film-coated tablet. One of the active substances is rosuvastatin calcium, belonging to a group of medicines called statins, and the other is ezetimibe.
Crosuvo Plus is a medicine used to lower blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides. Additionally, this medicine increases levels of "good" cholesterol (HDL cholesterol).
This medicine lowers cholesterol by acting in two ways: it reduces the amount of cholesterol absorbed from the gastrointestinal tract and the amount of cholesterol produced in the body.
In most people, high cholesterol does not affect well-being, as it causes no symptoms. However, if left untreated, fatty deposits may build up in the walls of blood vessels, leading to their narrowing.
Sometimes these narrowed vessels may become blocked, cutting off blood flow to the heart or brain, which may result in a heart attack or stroke. Lowering cholesterol levels may help reduce the risk of heart attack, stroke, or other related health problems.
Crosuvo Plus is used in patients in whom diet alone is not sufficient to maintain normal cholesterol levels. While taking this medicine, you should continue to follow a cholesterol-lowering diet.
Your doctor may prescribe Crosuvo Plus if you are already taking rosuvastatin and ezetimibe at the same doses.
Crosuvo Plus is used in cases of:

• elevated blood cholesterol levels (primary hypercholesterolemia).

Crosuvo Plus does not affect body weight reduction.

2. Important information before taking Crosuvo Plus

When not to take Crosuvo Plus:

• if the patient is allergic to ezetimibe, rosuvastatin, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has liver disease;
• if the patient has severe kidney function impairment;
• if the patient has recurrent, unexplained muscle pain or symptoms (myopathy);
• if the patient is taking a medicine called cyclosporine (used, for example, after organ transplantation);
• if the patient is taking the combination of medicines sofosbuvir/velpatasvir/voxilaprevir (used to treat viral hepatitis C infection);
• if the patient is pregnant or breastfeeding. If the patient becomes pregnant while taking Crosuvo Plus, she must stop treatment immediately and consult her doctor. Women of childbearing potential should avoid becoming pregnant while being treated with Crosuvo Plus by using effective contraceptive methods. Additionally, rosuvastatin 40 mg (the highest dose) should not be used:
  • if the patient has moderate kidney function impairment (in case of doubt, consult a doctor);
  • if the patient has thyroid disorders (hypothyroidism);
  • if the patient regularly consumes large amounts of alcohol;
  • if the patient is of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian);
  • if the patient is taking other lipid-lowering medicines known as fibrates (see section "Crosuvo Plus and other medicines");
  • if the patient has ever experienced severe skin rash, skin peeling, blisters, and/or oral ulcers after taking Crosuvo Plus or other similar medicines. If any of the above apply to the patient (or in case of doubt), consult a doctor.

Warnings and precautions
Before starting to take Crosuvo Plus, discuss with your doctor or pharmacist:

• if the patient has kidney disease;
• if the patient has liver disease;
• if the patient has recurrent or unexplained muscle symptoms or pain, has muscle problems, or if such problems occurred in the family, or if muscle-related side effects occurred previously during treatment with other cholesterol-lowering medicines. Contact your doctor immediately if unexplained muscle symptoms or pain occur, especially if accompanied by general malaise or fever. Inform your doctor or pharmacist if persistent muscle weakness occurs;
• if the patient has or has had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), because statins may sometimes worsen symptoms or trigger myasthenia (see section 4);
• if the patient is of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). The doctor will determine the appropriate dose of Crosuvo Plus for the patient;
• if the patient is taking medicines used to treat infections, including HIV infection or viral hepatitis C, e.g. lopinavir/ritonavir and/or atazanavir or symeprevir; see section "Crosuvo Plus and other medicines";
• if the patient has severe respiratory insufficiency;
• if the patient is taking other cholesterol-lowering medicines known as fibrates. See section "Crosuvo Plus and other medicines";
• if the patient regularly consumes large amounts of alcohol;
• if the patient has thyroid disorders (hypothyroidism);
• if the patient is over 70 years of age (as the doctor should determine the appropriate starting dose of Crosuvo Plus);
• if the patient is currently taking or has taken within the last 7 days the medicine fusidic acid (used to treat bacterial infections) orally or by injection. The combination of fusidic acid and Crosuvo Plus may cause serious muscle problems (rhabdomyolysis).

Serious skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during treatment with Crosuvo Plus. If any of the symptoms described in section 4 occur, stop taking Crosuvo Plus immediately and contact your doctor without delay.
If any of the above apply to the patient (or in case of doubt), consult a doctor or pharmacist before taking Crosuvo Plus.
In a small number of patients, statins may affect liver function. To detect such effects, a simple blood test is performed to identify increased liver enzyme activity in the blood. Therefore, your doctor will regularly order such blood tests (liver function tests) during treatment with Crosuvo Plus. It is important to visit your doctor, who will arrange for the necessary laboratory tests.
Patients with diabetes or those at risk of developing diabetes will be under close medical supervision during treatment with this medicine. Patients with high blood sugar and lipid levels, obesity, and high blood pressure may be at increased risk of developing diabetes.

Children and adolescents
Crosuvo Plus is not recommended for use in children and adolescents under 18 years of age.

Crosuvo Plus and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take, including over-the-counter medicines.
Inform your doctor if the patient is taking any of the following medicines:

• cyclosporine (used, for example, after organ transplantation to prevent organ rejection. Concomitant use increases the effect of rosuvastatin). Crosuvo Plus must not be taken during treatment with cyclosporine;
• anticoagulant medicines, e.g. warfarin, acenocoumarol, or fluindione (their effect and risk of bleeding may be increased when taken together with Crosuvo Plus, ticagrelor, or clopidogrel);
• darolutamide (used in cancer treatment);
• other cholesterol-lowering medicines known as fibrates, which also reduce triglyceride levels in blood (e.g. gemfibrozil and other fibrates). Concomitant use increases the effect of rosuvastatin;
• cholestyramine (a cholesterol-lowering medicine), as it affects the way ezetimibe works;
• any of the following medicines used to treat viral infections, including HIV infection or viral hepatitis C, administered alone or in combination with other medicines (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; they reduce rosuvastatin plasma concentration). This interaction can be avoided by taking these antacids at least 2 hours after taking rosuvastatin;
• erythromycin (an antibiotic). Concomitant use reduces the effect of rosuvastatin;
• fusidic acid. If the patient needs to take fusidic acid to treat a bacterial infection, they should temporarily stop taking Crosuvo Plus. The doctor will advise when it is safe to resume taking Crosuvo Plus. Concomitant use of Crosuvo Plus with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). For additional information on rhabdomyolysis, refer to section 4;
• oral contraceptives ("the pill"). Increased absorption of sex hormones from the pill occurs;
• hormone replacement therapy (increased blood levels of sex hormones);
• regorafenib (used in cancer treatment). If the patient is admitted to hospital or treated for another illness, they should inform healthcare staff that they are taking Crosuvo Plus.

Crosuvo Plus and alcohol
Do not take Crosuvo Plus in the 40 mg + 10 mg dose (the highest dose) if the patient regularly consumes large amounts of alcohol.

Pregnancy and breastfeeding
Do not take Crosuvo Plus if the patient is pregnant, planning to become pregnant, or suspects she may be pregnant. If the patient becomes pregnant while taking Crosuvo Plus, she must stop taking the medicine immediately and inform her doctor without delay. Women should use effective contraception methods during treatment with Crosuvo Plus.
Do not take Crosuvo Plus during breastfeeding, as it is not known whether the medicine passes into breast milk.

Driving and operating machinery
Crosuvo Plus is not expected to affect the ability to drive or operate machinery.
However, bear in mind that dizziness may occur in some patients after taking Crosuvo Plus. If dizziness occurs after taking this medicine, consult your doctor before driving or operating machinery.

Crosuvo Plus contains lactose
Crosuvo Plus tablets contain a sugar called lactose. If the patient has been previously diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.

3. How to use Crosuvo Plus

This medicine should always be taken as instructed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
While taking Crosuvo Plus, you should follow a diet aimed at lowering cholesterol levels
and maintain regular physical activity.
The recommended daily dose for adults is one tablet of a given strength.
Crosuvo Plus should be taken once daily.
The medicine can be taken at any time of day, regardless of meals. Each tablet should be
swallowed whole with water.
The medicine should be taken at the same time each day.
Crosuvo Plus is not intended for initiating treatment. Starting therapy or adjusting doses, if
necessary, should be done using the active substances as separate medicines.
Only after the appropriate doses have been established can Crosuvo Plus be used at the
corresponding dose.
The maximum daily dose of rosuvastatin is 40 mg. This dose is used only in patients with high
cholesterol levels and high risk of heart attack or stroke, in whom a 20 mg dose was insufficient
to reduce cholesterol levels.
Regular cholesterol monitoring
To ensure that cholesterol levels have decreased and remain at the desired level, regular check-ups
with your doctor and blood tests are necessary.
Taking more than the recommended dose of Crosuvo Plus
Contact your doctor or go to the nearest hospital emergency department, as medical assistance
may be required.
Missing a dose of Crosuvo Plus
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.
Stopping Crosuvo Plus
If you wish to stop taking Crosuvo Plus, you should consult your doctor. After stopping the
medicine, cholesterol levels may rise again.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
It is important for the patient to be aware of which adverse reactions may occur.
Treatment with Crosuvo Plus must be discontinued and immediate medical advice sought if any of the following symptoms occur:

• swelling of the face, lips, tongue, and (or) throat, which may cause difficulty in breathing and swallowing;
• drug-induced lupus-like syndrome (including rash, joint disorders, and effects on blood cells);
• muscle rupture;
• red, flat, target-shaped or circular spots on the trunk, often with blisters in the center, skin peeling, mucosal ulcers in the mouth, throat, nose, genital organs, and eyes. Such potentially life-threatening skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome);
• widespread rash, high body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome). If an unusual muscle pain persists longer than expected, immediate medical advice should be sought. In rare cases, these symptoms may lead to potentially life-threatening muscle damage known as rhabdomyolysis, which manifests as malaise, fever, and impaired kidney function.

The following terms are used to define the frequency of adverse reactions:

• very common (may occur in more than 1 in 10 people);
• common (may occur in up to 1 in 10 people);
• uncommon (may occur in up to 1 in 100 people);
• rare (may occur in up to 1 in 1,000 people);
• very rare (may occur in up to 1 in 10,000 people, including single reports).

Common adverse reactions:

• headache;
• constipation;
• nausea;
• muscle pain;
• weakness;
• dizziness;
• diabetes. The occurrence of diabetes is more likely if the patient has high levels of blood sugar and lipids, overweight, and high blood pressure. The doctor will monitor the patient's condition during treatment with this medicine;
• abdominal pain;
• diarrhoea;
• flatulence (excess gas in the gastrointestinal tract);
• fatigue;
• increased laboratory test results indicating the activity of certain liver enzymes (aminotransferases).

Uncommon adverse reactions:

• rash, itching, urticaria;
• increased protein in urine – usually resolves spontaneously without the need to discontinue rosuvastatin;
• elevated laboratory test results related to muscle function (CK);
• cough;
• indigestion;
• heartburn;
• joint pain;
• muscle cramps;
• 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 hands and feet;
• swelling, particularly of hands and feet.

Rare adverse reactions:
inflammation of the pancreas causing severe abdominal pain radiating to the back,
reduction in platelet count.

Very rare adverse reactions:
jaundice (yellowing of the skin and eyes), inflammation of the liver (hepatitis), presence of trace amounts of blood in urine, nerve damage in arms and legs (e.g. numbness), memory loss, enlargement of breasts in men (gynaecomastia).

Frequency not known:
dyspnoea, oedema, sleep disorders including insomnia and nightmares, sexual dysfunction, depression, breathing problems including persistent cough and (or) dyspnoea or fever, tendon injury, persistent muscle weakness, gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea, vomiting), myasthenia (a disease causing generalised muscle weakness, including in some cases muscles involved in breathing), ocular myasthenia (a disease causing weakness of eye muscles).

Patients should consult a doctor if they experience weakness in arms or legs worsening with activity, double vision or drooping eyelids, difficulty swallowing, or dyspnoea.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, patients should inform their doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301 Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions may also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Crosuvo Plus

Keep the medicine in its original packaging to protect it from moisture and light.
There are no special storage temperature requirements for this medicine.
The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after the
abbreviation "EXP". The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Crosuvo Plus contains

• The active substances are rosuvastatin (as rosuvastatin calcium) and ezetimibe.
  Crosuvo Plus 5 mg + 10 mg: Each tablet contains 5.20 mg of rosuvastatin calcium (equivalent to 5 mg of rosuvastatin) and 10 mg of ezetimibe.
  Crosuvo Plus 10 mg + 10 mg: Each tablet contains 10.40 mg of rosuvastatin calcium (equivalent to 10 mg of rosuvastatin) and 10 mg of ezetimibe.
  Crosuvo Plus 20 mg + 10 mg: Each tablet contains 20.80 mg of rosuvastatin calcium (equivalent to 20 mg of rosuvastatin) and 10 mg of ezetimibe.
  Crosuvo Plus 40 mg + 10 mg: Each tablet contains 41.60 mg of rosuvastatin calcium (equivalent to 40 mg of rosuvastatin) and 10 mg of ezetimibe.
• Other ingredients:
  Tablet core (same for all strengths): microcrystalline cellulose (E460), colloidal anhydrous silica (E551), magnesium stearate (E572), povidone K30 (E1201), sodium croscarmellose (E468), sodium lauryl sulfate (E487), lactose monohydrate, hypromellose 2910 (E464).
  Film-coating composition:
  Crosuvo Plus 5 mg + 10 mg: Opadry Yellow, hypromellose 2910 (E464), titanium dioxide (E171), macrogol 4000 (E1521), yellow iron oxide (E172), talc (E553b), red iron oxide (E171).
  Crosuvo Plus 10 mg + 10 mg: Opadry Beige, hypromellose 2910 (E464), titanium dioxide (E171), macrogol 4000 (E1521), yellow iron oxide (E172), talc (E553b).
  Crosuvo Plus 20 mg + 10 mg: Vivacoat Yellow, hypromellose 2910 (E464), titanium dioxide (E171), macrogol 4000 (E1521), yellow iron oxide (E172), talc (E553b).
  Crosuvo Plus 40 mg + 10 mg: Opadry White, lactose monohydrate, hypromellose 2910 (E464), titanium dioxide (E171), macrogol 4000 (E1521).

What Crosuvo Plus looks like and contents of the pack
Crosuvo Plus 5 mg + 10 mg: light yellow, round, biconvex film-coated tablets, approximately 10 mm in diameter, with the imprint "EL5" on one side.
Crosuvo Plus 10 mg + 10 mg: beige, round, biconvex film-coated tablets, approximately 10 mm in diameter, with the imprint "EL4" on one side.
Crosuvo Plus 20 mg + 10 mg: yellow, round, biconvex film-coated tablets, approximately 10 mm in diameter, with the imprint "EL3" on one side.
Crosuvo Plus 40 mg + 10 mg: white, round, biconvex film-coated tablets, approximately 10 mm in diameter, with the imprint "EL2" on one side.
Crosuvo Plus is available in packs containing 30, 60, and 90 film-coated tablets in blisters made of OPA/Aluminum/PVC/Aluminum, packed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus
Dublin 24, D24PPT3
Ireland
Manufacturer:
ELPEN Pharmaceutical Co. Inc.
95, Marathonos Ave., Pikermi 19009
Attica, Greece

This medicinal product is authorised in the European Economic Area countries under the following names:
Slovakia/Czech Republic: Horime
Netherlands: Rosuvastatine/ezetimibe Bausch Health Ireland Limited