Rosulip Plus

Leaflet accompanying the packaging: patient information

Rosulip Plus, 40 mg + 10 mg, hard capsules

Rosuvastatin + Ezetimibe

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed to you specifically. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

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

Rosulip Plus contains two different active substances in one capsule. One of the active substances is rosuvastatin, which belongs to a group of so-called statins, and the other active substance is ezetimibe. Rosulip Plus is a medicine used to reduce blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides. Additionally, it increases the levels of "good" cholesterol (HDL cholesterol). The medicine reduces cholesterol levels by acting in two ways: it reduces the amount of cholesterol absorbed in the gastrointestinal tract and the amount of cholesterol produced in the body. In most people, high cholesterol levels do not affect how they feel, as they do not cause any symptoms. However, if left untreated, fatty deposits can build up in the walls of blood vessels, leading to narrowing of the vessels. Sometimes, these narrowed vessels can become blocked, which can block blood flow to the heart or brain, causing a heart attack or stroke. By reducing cholesterol levels, the risk of heart attack, stroke, or other similar health problems can be reduced. Rosulip Plus is used in patients who have not achieved adequate cholesterol control with diet alone. While taking the medicine, you should continue to follow a low-cholesterol diet. Your doctor may prescribe Rosulip Plus if you are already taking rosuvastatin and ezetimibe in the same doses. Rosulip Plus is used in patients with heart disease. Rosulip Plus reduces the risk of heart attack, stroke, the need for surgical procedures to improve blood flow to the heart, or hospitalization due to chest pain. Rosulip Plus does not help with weight loss.

2. Important information before taking Rosulip Plus

When not to take Rosulip Plus:

• if the patient is allergic to rosuvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6)
• if the patient has liver disease
• if the patient has moderate or severe kidney impairment
• if the patient experiences recurring, unexplained muscle pain or weakness (myopathy)
• if the patient is taking sofosbuvir/velpatasvir/voxilaprevir (medicines used to treat viral hepatitis C infection)
• if the patient has experienced recurring or unexplained muscle pain, if the patient or their family members have had muscle diseases before, or if muscle disorders have occurred while taking other cholesterol-lowering medicines
• if the patient has myasthenia gravis (a disease that causes general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease that causes muscle weakness in the eyes), as statins can sometimes exacerbate symptoms of the disease or lead to myasthenia (see section 4).
• if the patient is taking a medicine called cyclosporine (used, for example, after organ transplantation to prevent rejection of the transplanted organ)
• if the patient is pregnant or breastfeeding. If a woman becomes pregnant while taking Rosulip Plus, she should stop taking the medicine immediately and consult her doctor. Women should avoid becoming pregnant while taking Rosulip Plus by using appropriate methods of contraception.
• if the patient has ever had a severe skin rash or scaling, blisters, or ulcers in the mouth after taking Rosulip Plus or other medicines containing rosuvastatin.
• if the patient has thyroid function disorders (hypothyroidism)
• if the patient regularly consumes large amounts of alcohol
• if the patient is of Asian origin (Japan, China, Philippines, Vietnam, Korea, or India)
• if the patient is taking other medicines called fibrates to lower cholesterol levels (see "Rosulip Plus and other medicines").

If any of the above situations apply to the patient (or if there is any doubt whether such a situation exists), they should consult their doctor.

Warnings and precautions

Before taking Rosulip Plus, the patient should discuss the following with their doctor or pharmacist:

• if the patient has kidney problems
• if the patient has liver problems
• if the patient experiences recurring or unexplained muscle pain or weakness, or if the patient or their family members have had muscle diseases before, or if muscle disorders have occurred while taking other cholesterol-lowering medicines. The patient should consult their doctor immediately if they experience unexplained muscle pain or weakness, especially if accompanied by general malaise or fever. The patient should also report any persistent muscle weakness to their doctor or pharmacist.
• if the patient is of Asian origin (Japan, China, Philippines, Vietnam, Korea, or India). The doctor will determine the appropriate dose of Rosulip Plus for the patient.
• if the patient is taking medicines used to treat infections, including HIV or hepatitis C virus infection, such as lopinavir/ritonavir and/or atazanavir, see "Rosulip Plus and other medicines".
• if the patient has severe respiratory failure
• if the patient is taking other medicines called fibrates to lower cholesterol levels. See "Rosulip Plus and other medicines".
• if the patient regularly consumes large amounts of alcohol
• if the patient has thyroid function disorders (hypothyroidism)
• if the patient is over 70 years old (as the doctor should determine the appropriate dose of Rosulip Plus for the patient).
• if the patient is taking or has taken within the last 7 days an oral or injectable medicine containing fusidic acid (an antibiotic). Taking fusidic acid with Rosulip Plus can lead to severe muscle damage (rhabdomyolysis).

If any of the above situations apply to the patient (or if there is any doubt whether such a situation exists): do not take Rosulip Plus, 40 mg + 10 mg, hard capsules (the highest dose), and consult your doctor or pharmacist again before starting Rosulip Plus.With the use of rosuvastatin, severe skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported. If any of the symptoms described in section 4 occur, stop taking Rosulip Plus and contact your doctor immediately.In a small number of people, statins can affect the liver. To confirm this effect, a simple blood test is performed to detect increased liver enzyme activity in the blood. Therefore, the doctor will regularly order such a blood test (liver function tests) during treatment with Rosulip Plus. It is essential to attend the doctor's appointments for the recommended laboratory tests. If the patient has diabetes or is at risk of developing diabetes, they will be closely monitored by their doctor while taking this medicine. There is a high risk of developing diabetes if the patient has high sugar and fat levels in the blood, is overweight, and has high blood pressure.

Children and adolescents

Rosulip Plus should not be used in children and adolescents under 18 years of age.

Rosulip Plus and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken, or plan to take. The patient should inform their doctor if they are taking any of the following medicines:

• Cyclosporine (used, for example, after organ transplantation to prevent rejection of the transplanted organ. Rosuvastatin's effect is increased when taken with cyclosporine). Do not take Rosulip Plus while taking cyclosporine.
• Blood thinners, such as warfarin, acenocoumarol, or fluindione (their blood-thinning effect and risk of bleeding may be increased when taken with Rosulip Plus), ticagrelor, or clopidogrel.
• Other cholesterol-lowering medicines called fibrates, which also lower triglyceride levels (e.g., gemfibrozil and other fibrates). When taken with these medicines, rosuvastatin's effect is increased. Do not take Rosulip Plus, 40 mg + 10 mg, hard capsules, while taking a fibrate.

40 mg + 10 mg, hard capsules

• Cholestyramine (a medicine also used to lower cholesterol levels), as it affects ezetimibe's action.
• Regorafenib (used to treat cancer).
• Darolutamide (used to treat cancer).
• Any of the following medicines used to treat viral infections, including HIV or hepatitis C virus infection, taken alone or in combination with other medicines (see "Warnings and precautions"): ritonavir, lopinavir, atazanavir, sofosbuvir, velpatasvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.
• Antacids containing aluminum and magnesium (used to neutralize stomach acid; these medicines decrease rosuvastatin's blood levels). This effect can be reduced by taking this type of medicine 2 hours after taking rosuvastatin.
• Erythromycin (an antibiotic). Rosuvastatin's effect is decreased when taken with erythromycin.
• Fusidic acid. If the patient needs to take fusidic acid orally or by injection to treat a bacterial infection, they should temporarily stop taking Rosulip Plus. The doctor will inform the patient when it is safe to restart Rosulip Plus. Taking Rosulip Plus with fusidic acid can rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). More information on rhabdomyolysis can be found in section 4.
• Oral contraceptives (the pill). The levels of sex hormones absorbed from the pill may increase.
• Capmatinib (used to treat cancer).
• Hormone replacement therapy (increased hormone levels in the blood).
• Fostamatinib (used to treat low platelet count).
• Febuxostat (used to treat and prevent high uric acid levels in the blood).
• Teriflunomide (used to treat multiple sclerosis).

If the patient is hospitalized or receives treatment for another condition, they should inform the medical staff that they are taking Rosulip Plus.

Rosulip Plus and alcohol

Do not take Rosulip Plus, 40 mg + 10 mg, hard capsules (the highest dose), if the patient regularly consumes large amounts of alcohol.

Pregnancy and breastfeeding

Rosulip Plus should not be taken if the patient is pregnant, trying to become pregnant, or suspects they may be pregnant. If a woman becomes pregnant while taking Rosulip Plus, she should stop taking the medicine immediately and consult her doctor. While taking Rosulip Plus, women should use appropriate methods of contraception to avoid becoming pregnant. Rosulip Plus should not be taken during breastfeeding, as it is not known whether the medicine passes into breast milk.

Driving and using machines

Rosulip Plus is unlikely to affect the patient's ability to drive or use machines. However, the patient should be aware that some people may experience dizziness after taking Rosulip Plus. If the patient experiences dizziness, they should consult their doctor before driving or using machines.

Rosulip Plus contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per hard capsule, which means it is essentially "sodium-free".

3. How to take Rosulip Plus

Take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist. While taking Rosulip Plus, the patient should continue to follow a low-cholesterol diet and maintain physical activity. The recommended daily dose for adults is one capsule of the given strength once a day.

Rosulip Plus should be taken once a day.

The medicine can be taken at any time of day, with or without food. The capsule should be swallowed whole with water. The medicine should be taken every day at the same time. Rosulip Plus is not suitable for initiating treatment. The initiation of treatment or changes in dosage, if necessary, should only be done using the individual active substances and only after determining the appropriate doses can the patient be switched to Rosulip Plus. The maximum daily dose of rosuvastatin is 40 mg, which is only intended for patients with high cholesterol levels and a high risk of heart attack or stroke, and for whom a 20 mg dose does not provide sufficient cholesterol reduction.

Regular cholesterol checks

It is essential to attend the doctor's appointments for regular cholesterol checks to ensure that cholesterol levels have been reduced and are being maintained at a healthy level.

Taking a higher dose of Rosulip Plus than recommended

The patient should contact their doctor or go to the emergency department of the nearest hospital, as medical attention may be necessary.

Missing a dose of Rosulip Plus

There is no need to worry; the patient should 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 Rosulip Plus treatment

The patient should inform their doctor if they want to stop taking Rosulip Plus. Cholesterol levels may increase again if the patient stops taking Rosulip Plus. If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Rosulip Plus can cause side effects, although not everybody gets them. It is essential to know what side effects can occur.

The patient should stop taking Rosulip Plus and seek medical attention immediately if they experience any of the following symptoms:

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

• Allergic reactions, such as swelling of the face, lips, tongue, and/or throat, which can cause difficulty breathing and swallowing.
• Unusual muscle pain or weakness that persists longer than expected. Rarely, this can lead to a potentially life-threatening muscle injury called rhabdomyolysis, which causes general malaise, fever, and kidney impairment.
• A condition similar to lupus (including rash, joint disorders, and effects on blood cells).
• Muscle rupture.

Frequency not known (cannot be estimated from the available data):

• Red, flat, round, or oval patches on the torso, often with blisters in the center, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. The occurrence of this type of severe skin rash may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
• Widespread rash, high fever, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).
• Polymorphic erythema (life-threatening allergic reactions involving the skin and mucous membranes).

Other possible side effects

Common (may affect up to 1 in 10 people)

• Headache
• Constipation
• Nausea
• Muscle pain
• Feeling weak
• Dizziness
• Protein may be present in the urine - this usually returns to normal on its own without the need to stop rosuvastatin treatment
• Diabetes. This is more likely if the patient has high sugar and fat levels in the blood, is overweight, and has high blood pressure. The doctor will monitor the patient for this while they are taking the medicine.
• Stomach pain (abdominal pain)
• Diarrhea
• Bloating (excessive gas in the intestines)
• Feeling tired
• Increased results of some laboratory blood tests that assess liver function (aminotransferases)

Uncommon (may affect up to 1 in 100 people)

• Rash, itching, hives
• Increased results of some laboratory blood tests that assess muscle function (CK)
• Cough
• Indigestion
• Heartburn
• Joint pain
• Muscle cramps
• Neck pain
• Decreased appetite
• Pain
• Chest pain
• Hot flashes
• High blood pressure
• Feeling of tingling
• Dry mouth
• Gastritis
• Back pain
• Muscle weakness
• Pain in the arms and legs
• Swelling, especially of the hands and feet

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

• Pancreatitis, which can cause severe abdominal pain radiating to the back
• Decreased platelet count

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

• Jaundice (yellowing of the skin and eyes)
• Hepatitis
• Traces of blood in the urine
• Nerve damage in the arms and legs (numbness)
• Memory loss
• Breast enlargement in men (gynecomastia)

Frequency not known (cannot be estimated from the available data):

• Shortness of breath
• Swelling (edema)
• Sleep disorders, including insomnia and nightmares
• Sexual disorders
• Depression
• Breathing problems, including persistent cough and/or shortness of breath or fever
• Tendon injury
• Persistent muscle weakness
• Gallstones or cholecystitis (which can cause abdominal pain, nausea, vomiting)
• Myasthenia gravis (a disease that causes general muscle weakness, including in some cases muscles involved in breathing)
• Ocular myasthenia (a disease that causes muscle weakness in the eyes)

The patient should talk to their doctor if they experience weakness in their arms or legs, worsening after periods of activity, double vision, or drooping eyelids, difficulty swallowing, or shortness of breath.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Phone: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be gathered on the safety of this medicine.

5. How to store Rosulip Plus

Do not store above 30°C. Store in the original packaging to protect 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 and blister. The expiry date refers to the last day of the month. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer need. This will help protect the environment.

6. Contents of the packaging and other information

What Rosulip Plus contains

The active substances of Rosulip Plus are rosuvastatin (in the form of rosuvastatin zinc) and ezetimibe. The capsules contain the zinc salt of rosuvastatin equivalent to 40 mg of rosuvastatin. Each capsule contains 10 mg of ezetimibe. The other ingredients are:

• Core: microcrystalline cellulose (E 460), silicon dioxide (E 551), magnesium stearate (E 572), povidone (E 1201), croscarmellose sodium (E 468), microcrystalline cellulose (E 460), mannitol (E 421), sodium lauryl sulfate (E 514), hydroxypropylcellulose (E 463)

Capsule shell

Cap: red iron oxide (E 172), titanium dioxide (E 171), yellow iron oxide (E 172), gelatin

Body: gelatin, yellow iron oxide (E 172), titanium dioxide (E 171)

What Rosulip Plus looks like and contents of the pack

Rosulip Plus is a self-locking hard gelatin capsule of the Coni Snap type, without markings, with a red cap and a yellow body, filled with three tablets: one white or almost white, round, flat, and beveled tablet of Ezetimibe 10 mg with a stylized "E" on one side and code "612" on the other; two white or almost white, round tablets of Rosuvastatin 20 mg with a logo on one side and no logo on the other. The length of the capsule is approximately 21.7 mm (± 0.5 mm). The packaging contains 10, 28, 30, 56, 60, 84, 90 hard capsules in a cold-formed blister pack with a leaflet in a carton box. In Poland, only packaging of 30, 60, and 90 hard capsules is authorized. Not all pack sizes may be marketed.

Marketing authorization holder

EGIS Pharmaceuticals PLC, Keresztúri út 30-38, 1106 Budapest, Hungary

Manufacturer

EGIS Pharmaceuticals PLC, Bökényföldi út 118-120, 1165 Budapest, Hungary, EGIS Pharmaceuticals PLC, 9900 Körmend, Mátyás király u. 65, Hungary

This medicine is authorized in the Member States of the European Economic Area under the following names:

To obtain more detailed information on this medicine, the patient should contact the local representative of the marketing authorization holder: EGIS Polska Sp. z o.o., ul. Komitetu Obrony Robotników 45D, 02-146 Warsaw, Phone: +48 22 417 92 00. Date of last revision of the leaflet: 22.12.2023