Rosuasa

Package leaflet: Information for the user

ROSUASA 5 mg/100 mg hard capsules, 10 mg/100 mg hard capsules, 20 mg/100 mg hard capsules

rosuvastatin and acetylsalicylic acid
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 effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ROSUASA is and what it is used for

ROSUASA contains two active substances – rosuvastatin and acetylsalicylic acid.
Rosuvastatin belongs to a group of substances called statins, medicines that regulate lipids (fats), which are used to reduce levels of lipids known as cholesterol and triglycerides in the blood when a low-fat diet and lifestyle changes have not been effective. Cholesterol is a fatty substance (lipid) that can cause narrowing of the blood vessels in the heart, leading to coronary heart disease. If you are at risk of having a heart attack, rosuvastatin may also be used to reduce this risk even if your cholesterol levels are normal. You must maintain a standard cholesterol-lowering diet during treatment.

• Acetylsalicylic acid at low dose belongs to a group of medicines called platelet anti-aggregation agents. Platelets are small cells in the blood that cause blood clotting and are involved in thrombosis. When a blood clot forms in an artery, blood flow is blocked and oxygen supply is interrupted. When this occurs in the heart, it can cause a heart attack or angina. These two active substances, taken together, reduce the likelihood of having another heart attack if you have previously had a heart attack or suffer from episodes of chest pain (unstable angina pectoris).

ROSUASA is indicated for patients who are already taking rosuvastatin and acetylsalicylic acid at these doses. Instead of taking rosuvastatin and acetylsalicylic acid separately, you will receive one capsule of ROSUASA containing both ingredients at the same dosage as before.

2. What you need to know before taking ROSUASA

Do not take ROSUASA

• If you are allergic to rosuvastatin, acetylsalicylic acid, other salicylates, or non-steroidal anti-inflammatory drugs (NSAIDs), 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 ROSUASA, stop taking it immediately and inform your doctor. Women must avoid pregnancy while taking ROSUASA by using appropriate contraceptive measures.
• If you have liver disease
• If you have severe kidney problems
• If you have repeated or unexplained muscle cramps or muscle pain (myalgia)
• If you are taking a medicine called cyclosporine (used, for example, after organ transplantation)
• If you have previously experienced asthma attacks or swelling of certain body parts, e.g., face, lips, throat, or tongue (angioedema), after taking salicylates or non-steroidal anti-inflammatory drugs.
• If you currently have or have ever had a peptic ulcer or other type of bleeding, such as a stroke.
• If you have ever had problems with proper blood clotting.
• If you suffer from gout
• If you suffer from uncompensated heart failure
• If you are taking a medicine called methotrexate (used for cancer or rheumatoid arthritis) at doses
• exceeding 15 mg per week;
• if you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking ROSUASA or other related medicines.

Warnings and precautions
Talk to your doctor or pharmacist before taking ROSUASA

• If you have kidney problems
• If you have liver problems
• If you have experienced repeated or unexplained muscle cramps or pain, personal or family history of muscle problems, or have previously had muscle problems while taking other cholesterol-lowering medicines. Inform your doctor immediately if you experience unexplained muscle cramps or pain, especially if accompanied by malaise or fever. Also, inform your doctor or pharmacist if you have persistent muscle weakness.
• 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, read section “Other medicines and ROSUASA”.
• If you are currently taking or have taken within the last 7 days an oral or injectable medicine containing fusidic acid (used to treat bacterial infections). The combination of fusidic acid and ROSUASA may cause serious muscle problems (rhabdomyolysis); see section “Other medicines and ROSUASA”.
• If you have severe respiratory insufficiency
• If you are over 70 years old
• If you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). Your doctor will need to choose an appropriate starting dose for you.
• If you have previously had stomach or intestinal ulcers or bleeding (gastrointestinal ulcers or bleeding)
• If your blood pressure is high
• If you suffer from bronchial asthma, hay fever, nasal polyps, or other chronic respiratory diseases, acetylsalicylic acid may trigger an asthma attack.
• In case of hypersensitivity (allergy) to other painkillers and anti-inflammatory medicines, other medicines for rheumatism, or other allergy triggers.
• If you have other allergies (e.g., skin reactions, itching).
• If you are taking other medicines called anticoagulants (e.g., coumarin derivatives, heparin – except for low-dose heparin treatments).
• With impaired kidney function or reduced cardiac and vascular blood flow (e.g., renal vascular disease, weakened heart muscle, reduced blood volume, major surgery, blood poisoning, or increased bleeding): acetylsalicylic acid may further increase the risk of kidney dysfunction and acute kidney failure.
• If you have heavy menstrual periods.
• 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), since statins may sometimes worsen myasthenia or cause its onset (see section 4).

Contact your doctor if your symptoms worsen or if you experience serious or unexpected side effects such as
signs of bleeding, severe skin reactions, or any other serious allergic manifestations (read section “Possible side effects”).
In a small number of people, statins may affect the liver, which can be detected by a simple blood test showing increased liver enzyme levels. For this reason, your doctor will request this test (liver function test) before and during treatment with
ROSUASA.
During treatment with this medicine, your doctor will carefully monitor whether you have diabetes or are at risk of developing diabetes. You are at risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure.
You should be careful not to become dehydrated (you may feel thirsty and have a dry mouth), as taking
acetylsalicylic acid at the same time may worsen kidney function.
Inform your doctor before any surgical procedures (even minor ones, such as a tooth extraction), because acetylsalicylic acid may increase the tendency to bleed.
Acetylsalicylic acid may cause Reye's syndrome if given to children. Reye's syndrome is a very rare condition affecting the brain and liver and can be fatal. For this reason, ROSUASA must not be taken by children and adolescents under 18 years of age.
In patients with severe glucose-6-phosphate dehydrogenase deficiency: acetylsalicylic acid may cause accelerated breakdown or destruction of red blood cells or a certain form of anemia. This risk may be increased by factors such as high dosage, fever, or acute infections.
Acetylsalicylic acid reduces uric acid excretion at low doses. This may trigger a gout attack in patients at risk.
If you cut or injure yourself, it may take longer than usual to stop bleeding. This is related to the effect of acetylsalicylic acid. Minor cuts and injuries (e.g., during shaving) usually are not significant. In case of unusual bleeding (in an unusual location or of unusual duration), contact your doctor.
Serious skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with rosuvastatin treatment.
Discontinue use of ROSUASA and seek immediate medical attention if you notice any of the symptoms described in section 4.

Children and adolescents
ROSUASA must not be taken by children and adolescents.

Other medicines and ROSUASA
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
ROSUASA may affect or be affected by other medicines, such as:

• Fibrates (such as gemfibrozil, fenofibrate) or any other drug used to lower cholesterol (such as ezetimibe);

• Remedies for indigestion (used to neutralize stomach acids);

• An oral contraceptive (the pill);

• Hormone replacement therapy;

• Regorafenib (used to treat cancer);

• Any of the following drugs used to treat viral infections, including HIV or hepatitis C infection, alone or in combination (see Warnings and precautions): ritonavir, lopinavir, atazanavir, simeprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.

• Ketoconazole, itraconazole (antifungal medicines)

• Rifampicin, erythromycin, clarithromycin (antibiotics)

• Medicines to thin the blood and prevent clots (warfarin, heparin, clopidogrel, ticagrelor, ticlopidine): acetylsalicylic acid may increase the risk of bleeding when taken before clot removal or blood thinning. Therefore, if you are undergoing such treatment, be alert for signs of external or internal bleeding (e.g., bruising).

• Cyclosporine, tacrolimus (used, for example, after organ transplantation);

• Medicines for high blood pressure (e.g., diuretics and ACE inhibitors)

• Medicines to regulate heart rhythm (digoxin)

• Medicines for manic-depressive disorders (lithium)

• Medicines for pain and inflammation (non-steroidal analgesics, such as ibuprofen, or steroids)

• Medicines for gout (e.g., probenecid, benzbromarone)

• Medicines for glaucoma (acetazolamide)

• Methotrexate (for treatment of cancer and rheumatoid arthritis) at doses below 15 mg per week

• Medicines to lower blood sugar (antidiabetics) (e.g., glibenclamide) – blood sugar levels may decrease

• Selective serotonin reuptake inhibitors (for treatment of depression), such as sertraline and paroxetine

• Corticosteroids used as hormone replacement therapy when adrenal glands or pituitary have been destroyed or removed (except for products applied to the skin or cortisone replacement therapy for Addison's disease) or to treat inflammation, including rheumatic diseases and intestinal inflammation

• Concomitant use increases the risk of gastrointestinal side effects.

• Cerebral seizures [epilepsy] (valproic acid)

• Medicines that increase urinary excretion (diuretics: so-called aldosterone antagonists such as spironolactone and canrenoate, loop diuretics, e.g., furosemide)

• Alcohol: increases the risk of gastrointestinal ulcers and bleeding.

Metamizole (a substance used to reduce pain and fever) may reduce the effect of acetylsalicylic acid on platelet aggregation (blood cells that clump together to form a clot) when taken simultaneously. Therefore, this combination should be used with caution in patients taking low-dose aspirin for cardioprotection.
If you need to take oral fusidic acid to treat a bacterial infection, you will need to temporarily stop taking ROSUASA. Your doctor will tell you when it is safe to restart ROSUASA. Taking ROSUASA with fusidic acid may rarely cause weakness, soreness, or muscle pain (rhabdomyolysis). See section 4 for more information on rhabdomyolysis.
ROSUASA may further lower your blood pressure if you are already taking other medicines to treat high blood pressure.

ROSUASA with food, drinks, and alcohol
ROSUASA should be taken with food. Do not drink grapefruit juice during treatment with ROSUASA.
Drinking alcohol may potentially increase the risk of gastrointestinal bleeding and prolong bleeding time.

Pregnancy and breastfeeding
Do not take ROSUASA if you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding.
If you become pregnant while taking ROSUASA, stop taking it immediately and inform your doctor.
Women must avoid pregnancy during treatment with ROSUASA by using appropriate contraceptive measures.

Driving and using machines
Most people can drive and operate machinery while taking ROSUASA – it does not affect their ability to drive or operate machinery. However, some people may experience dizziness during treatment with ROSUASA. If you experience dizziness, fatigue, or headache, do not drive or operate machinery and contact your doctor immediately.

ROSUASA contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars (lactose or milk sugar), contact him before taking this medicine.

3. How to take ROSUASA

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Adults
Your doctor will determine the appropriate dosage for you, based on your condition, current treatment, and personal risk factors.
This medicine is not suitable for initiating treatment. Treatment initiation must be done only by taking the active substances separately; once the appropriate doses have been established, switching to ROSUASA at the appropriate dosage may be considered.
The recommended dose is one capsule daily.
This medicine should be taken with food. Take the medicine at the same time each day. Swallow the capsules whole with plenty of fluid; do not crush or chew them.
Do not take ROSUASA with grapefruit juice.
If you are admitted to hospital or receiving treatment for another condition, inform medical staff that you are taking ROSUASA.

Use in elderly patients
Dosage adjustment is not required in elderly patients.

Use in children and adolescents
ROSUASA must not be used in children and adolescents.

Patients with renal impairment
Dosage adjustment is not required in patients with mild or moderate renal impairment. The use of ROSUASA is contraindicated in patients with severe renal impairment.

Patients with hepatic impairment
Dosage adjustment is not required in patients with mild or moderate hepatic impairment. The use of ROSUASA is contraindicated in patients with severe hepatic impairment.

If you take more ROSUASA than you should
Contact your doctor or go immediately to the nearest hospital emergency department.

If you forget to take ROSUASA
If you forget to take a capsule, do not panic. Do not take an extra dose. Take the next dose at your usual time. Do not take a double dose to make up for the missed capsule.

If you stop taking ROSUASA
Your doctor will advise you on how long to take the medicine. Your cholesterol levels may rise again if you stop taking ROSUASA. Your condition may return if you discontinue the medicine before advised to do so.

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 everybody gets them.
Stop taking ROSUASA and seek immediate medical help if you experience any of the following allergic reactions:

• Sudden shortness of breath, abdominal pain, breathlessness or difficulty breathing
• Swelling of the eyelids, face or lips
• Swelling of the tongue and/or throat which may cause difficulty breathing and/or swallowing
• Severe skin reactions including intense rash, hives, redness all over the body, itching, blistering, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson Syndrome) or other allergic reactions
• If you pass black stools or notice blood in your vomit (signs of severe stomach bleeding)
• Flat red spots, target-shaped or circular rashes on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These serious skin rashes 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)

Also, stop taking ROSUASA and contact your doctor immediately

• if you have 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 tears
• if you develop a lupus-like syndrome (including skin rash, joint problems and effects on blood cells)

The following side effects have been reported. If any of these trouble you or last longer than one week, you should contact your doctor.

ROSUVASTATIN
Common (may affect up to 1 in 10 people)

• Headache
• Stomach pain
• Constipation
• Feeling unwell
• Muscle pain
• Feeling weak
• Dizziness
• Diabetes. This is more likely if you have high levels of sugar and fats in your blood, are overweight and have high blood pressure. Your doctor will monitor you during treatment with this medicine.

Uncommon (may affect up to 1 in 100 people)

• Skin rash, itching, hives and other skin reactions
• Increased protein in urine – usually resolves without stopping treatment with ROSUASA (only at doses of 5 and 20 mg).

Rare (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 (with raised lumps). If you think you are having an allergic reaction, stop taking ROSUASA and contact your doctor immediately.
• Muscle damage in adults – as a precaution, stop taking ROSUASA and contact your doctor immediately if you have unusual muscle aches or pains lasting longer than expected.
• Severe stomach pain (inflammation of the pancreas)
• Increased liver enzymes in the blood
• Reduced blood platelets, increasing the risk of bleeding or bruising (thrombocytopenia)
• Lupus-like disease syndrome (including skin rash, joint disorders and effects on blood cells)

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

• Jaundice (yellowing of the skin and eyes)
• Hepatitis (liver inflammation)
• Blood in urine
• Nerve damage in arms and legs (numbness)
• Joint pain
• Memory loss
• Gynecomastia (breast enlargement in men)

Not known (frequency cannot be estimated from available data)

• Diarrhoea (watery stools)
• Cough
• Shortness of breath
• Oedema (swelling)
• Sleep disorders, including insomnia and nightmares
• Sexual dysfunction
• Depression
• Breathing problems, including persistent cough and/or breathlessness or fever
• Tendon injury
• Nerve disorders that may cause weakness, tingling or numbness
• Persistent muscle weakness
• 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 worsening weakness in arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing or breathlessness.

ACETYLSALICYLIC ACID
Common (may affect up to 1 in 10 people)

• Gastrointestinal disorders such as heartburn, nausea, vomiting, abdominal pain and diarrhoea
• Mild bleeding from the gastrointestinal tract (micro-bleeding)
• Bleeding such as nosebleeds, bleeding gums, skin bleeding or bleeding from the urinary tract and genital organs, possibly with prolonged bleeding time. This effect may last from 4 to 8 days after ingestion.

Uncommon (may affect up to 1 in 100 people)

• Bleeding from the stomach or intestine. After long-term use of acetylsalicylic acid, anaemia (iron deficiency anaemia) may occur due to hidden blood loss from the stomach or intestine.
• Intracranial bleeding, blood in urine
• Gastric or intestinal ulcers, which very rarely may lead to perforation
• Gastrointestinal inflammation
• Skin reactions

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

• Hypersensitivity reactions affecting the skin, respiratory tract, gastrointestinal area and cardiovascular system, particularly in asthmatics. The following symptoms may occur: drop in blood pressure, shortness of breath attacks, nasal mucosa inflammation, nasal congestion, allergic shock, swelling of the face, tongue and larynx (Quincke’s oedema)
• Severe bleeding such as bleeding from the brain, especially in patients with uncontrolled hypertension and/or concomitant treatment with anticoagulants (blood thinners), which may be potentially fatal in individual cases
• Confusion
• Headache, dizziness
• Impaired hearing or ringing in the ears (tinnitus), especially in children and elderly people, which may be signs of overdose (see also section "If you take more ROSUASA than you should")

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

• Increased liver function tests
• Kidney dysfunction and acute kidney failure
• Decreased blood sugar (hypoglycaemia)
• Acetylsalicylic acid reduces uric acid excretion at low doses. This may trigger a gout attack in at-risk patients
• Feverish skin rashes with mucosal involvement (erythema multiforme)

Not known (frequency cannot be estimated from available data)

• Accelerated breakdown or destruction of red blood cells and a specific form of anaemia in patients with severe glucose-6-phosphate dehydrogenase deficiency.

If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store ROSUASA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and blister after Exp.
The expiry date refers to the last day of that month.
Store below 30°C in the original packaging to protect the medicine from moisture.
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. Package contents and other information What ROSUASA contains

The active substances are rosuvastatin (as calcium salt) and acetylsalicylic acid.
ROSUASA 5 mg/100 mg hard capsules: each hard capsule contains 5 mg of rosuvastatin (as calcium salt) and 100 mg of acetylsalicylic acid.
ROSUASA 10 mg/100 mg hard capsules: each hard capsule contains 10 mg of rosuvastatin (as calcium salt) and 100 mg of acetylsalicylic acid.
ROSUASA 20 mg/100 mg hard capsules: each hard capsule contains 20 mg of rosuvastatin (as calcium salt) and 100 mg of acetylsalicylic acid.

The other components are:
Film-coated tablet containing rosuvastatin:
Tablet core: monohydrate lactose, microcrystalline cellulose, heavy magnesium oxide, crospovidone (type A), anhydrous colloidal silica, magnesium stearate.
Film coating: polyvinyl alcohol, titanium dioxide (E 171), talc, iron oxide yellow (E 172), lecithin (soy), iron oxide red (E 172), xanthan gum, iron oxide black (E 172).
Tablet containing acetylsalicylic acid: microcrystalline cellulose, maize starch, anhydrous colloidal silica, stearic acid.
Gelatin capsule: Gelatin, titanium dioxide (E171), indigotine (E 132), iron oxide yellow (E172).
Black ink: Shellac gum, propylene glycol, concentrated ammonia solution, iron oxide black (E 172), potassium hydroxide.

Description of the appearance of ROSUASA and the contents of the pack
ROSUASA 5 mg/100 mg: hard gelatin capsules, size 2, with an opaque white body and an opaque dark green cap. Each capsule contains an uncoated tablet, white or almost white, biconvex, oval-shaped tablet of acetylsalicylic acid and a brown, biconvex, round film-coated tablet of rosuvastatin 5 mg.
ROSUASA 10 mg/100 mg: hard gelatin capsules, size 1, with an opaque white body printed in black with “ASA 100” and an opaque light green cap printed in black with “RSV 10 mg”. Each capsule contains an uncoated tablet, white or almost white, biconvex, oval-shaped tablet of acetylsalicylic acid and a brown, biconvex, round film-coated tablet of rosuvastatin 10 mg.
ROSUASA 20 mg/100 mg: hard gelatin capsules, size 0, with an opaque white body printed in black with “ASA 100” and an opaque green cap printed in black with “RSV 20 mg”. Each capsule contains an uncoated tablet, white or almost white, biconvex, oval-shaped tablet of acetylsalicylic acid and two brown, biconvex, round film-coated tablets of rosuvastatin 10 mg.

ROSUASA is available in blisters containing 28 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder
PIAM Farmaceutici S.p.A.
Via Fieschi 8
16121 Genoa (Italy)

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