Package leaflet: information for the patient

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

Rosuvastatin/ Acetylsalicylic acid
Please read all of 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, as it may 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

What MANASA is and what it is used for
What you need to know before taking MANASA
How to take MANASA
Possible side effects
How to store MANASA
Contents of the pack and other information

1. What MANASA is and what it is used for

MANASA 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 alone have not been effective. Cholesterol is a fatty substance (lipid) that can cause narrowing of the blood vessels of the heart, leading to coronary heart disease. If you are at risk of another heart attack, rosuvastatin may also be used to reduce this risk, even if your cholesterol levels are normal. During treatment, you must continue to follow a standard cholesterol-lowering diet.
Low-dose acetylsalicylic acid belongs to a group of medicines called antiplatelet agents. Platelets are tiny blood cells that cause blood clotting and are involved in thrombosis. When a clot forms in an artery, it blocks blood flow and interrupts the supply of oxygen. 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 already had one or if you suffer from episodes of chest pain (unstable angina pectoris).

MANASA is indicated for patients who are already taking rosuvastatin and acetylsalicylic acid at these dosages. Instead of taking rosuvastatin and acetylsalicylic acid separately, you will receive one capsule of MANASA containing both substances at the same dosages.

2. What you should know before taking MANASA

Do not take MANASA:

if you are allergic to rosuvastatin, acetylsalicylic acid, any 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 allergic to peanuts or soy (see below);
if you are pregnant or breastfeeding. If you become pregnant while being treated with MANASA, stop taking it immediately and contact your doctor. Women must avoid pregnancy during treatment with MANASA by using appropriate contraceptive measures;
if you have liver disease;
if you have moderate or severe kidney impairment;
if you have repeated or unexplained muscle pain or cramps (myalgia);
if you are taking a combination of medicines containing sofosbuvir/velpatasvir/voxilaprevir (used to treat a viral liver infection called hepatitis C);
if you are taking a medicine called cyclosporine (used, for example, after organ transplantation);
if you have previously experienced an asthma attack or swelling of certain body parts, such as face, lips, throat, or tongue (angioedema) after taking salicylates or non-steroidal anti-inflammatory drugs. Symptoms may include itching, hives, red spots on hands, feet, and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing or swallowing;
if you currently suffer or have previously suffered from a stomach or duodenal ulcer or any other type of bleeding, such as cerebrovascular hemorrhage;
if you have ever had problems with blood clotting;
if you suffer from gout;
if you have uncompensated heart failure;
if you are taking a medicine called methotrexate (e.g., 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 rosuvastatin or other related medicines.

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

if you have kidney problems;
if you have liver problems;
if you have had repeated or unexplained muscle pain or cramps, a personal or family history of muscle disorders, or if you previously experienced muscle problems while being treated with other cholesterol-lowering medicines. Inform your doctor immediately if you experience unexplained muscle pain or cramps, especially if you feel unwell or have a 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 medicines called fibrates to lower cholesterol. Read this leaflet carefully, even if you have previously taken other medicines for high cholesterol;
if you are taking medicines used to treat HIV infection, e.g., ritonavir with lopinavir and/or atazanavir; see section “Other medicines and MANASA”;
if you are 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 MANASA can lead to serious muscle problems (rhabdomyolysis). See section “Other medicines and MANASA”;
if you have severe respiratory insufficiency;
if you are over 70 years old: your doctor needs to select the appropriate starting dose for you;
if you are of Asian origin (i.e., Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). Your doctor must choose the correct initial dosage of MANASA suitable for you;
if you have or have had stomach or duodenal problems (ulcers or gastrointestinal bleeding);
if you have high blood pressure;
if you have asthma, hay fever, nasal polyps, or other chronic respiratory diseases; acetylsalicylic acid may trigger an asthma attack;
if you have hypersensitivity (allergy) to other painkillers or anti-inflammatory medicines, or other rheumatism medicines, or other factors that may cause allergies;
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 treatment);
if you have impaired kidney function or reduced cardiac or vascular blood flow (e.g., renal vascular disease, weakened heart muscle, low 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 bleeding;
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 trigger its onset (see section 4).

Severe skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during treatment with MANASA.
Discontinue use of MANASA and seek immediate medical attention if you notice any of the symptoms described in section 4.
Contact your doctor if your symptoms worsen or if you experience serious or unexpected side effects, such as unusual bleeding symptoms, severe skin reactions, or any other signs of severe allergy (see section “Possible side effects”).
Metamizole (a substance used to reduce pain and fever) may reduce the effect of acetylsalicylic acid on platelet aggregation (blood cells that stick together to form a blood clot) when taken simultaneously. Therefore, this combination should be used with caution in patients taking low-dose aspirin for cardioprotection.
In a small number of people, statins may affect liver function. This is detected through a simple blood test monitoring increased levels of liver enzymes. For this reason, your doctor will usually request this blood test (liver function test) before and during treatment with MANASA.
During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing diabetes. You are at increased risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure.
Be careful not to become dehydrated (you may feel thirsty with a dry mouth), as the concomitant use of acetylsalicylic acid may worsen kidney function.
Inform your doctor if you are scheduled for surgery (even minor procedures such as tooth extraction), as acetylsalicylic acid thins the blood and may increase the risk of bleeding.
Acetylsalicylic acid may cause Reye's syndrome when administered to children. Reye's syndrome is a very rare condition affecting the brain and liver and may be life-threatening. For this reason, MANASA must not be given to children and adolescents under 18 years of age.
In patients with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency, acetylsalicylic acid may cause destruction or accelerated destruction of red blood cells or a certain type of anemia. This risk may be increased by factors such as high dosage; fever or acute infections may further increase this risk.
Low-dose acetylsalicylic acid reduces uric acid excretion. This may trigger a gout attack in patients at risk.
If you cut yourself or sustain an injury, bleeding may take longer to stop. This is due to the effect of acetylsalicylic acid. Minor cuts or injuries (e.g., during shaving) usually are not significant. If you experience unusual bleeding (in an unusual location or of unusual duration), contact your doctor.
Children and adolescents
MANASA must not be used in children and adolescents under 18 years of age.
Other medicines and MANASA
Inform your doctor or pharmacist if you are currently taking, have recently taken, or might take any other medicines.
MANASA may interact with or be affected by other medicines such as:

fibrates (e.g., gemfibrozil, fenofibrate) or any other medicine used to lower cholesterol (e.g., ezetimibe);
antacids (used to neutralize stomach acid);
oral contraceptives (the pill);
hormone replacement therapy;
regorafenib (used to treat tumors);
darolutamide (used to treat tumors);
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, simeprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir;
ketoconazole, itraconazole (antifungal medicines);
rifampicin, erythromycin, clarithromycin (antibiotics);
blood-thinning medicines and clot-prevention medicines (e.g., warfarin, heparin, coumarin, ticagrelor, clopidogrel, ticlopidine): acetylsalicylic acid may increase the risk of bleeding when taken before clot removal or blood-thinning treatment; 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). Do not take this medicine concomitantly with cyclosporine, as the effect of rosuvastatin increases;
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 (e.g., NSAIDs such as ibuprofen, naproxen, 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;
antidiabetic medicines (e.g., glibenclamide), which may lower blood sugar levels;
selective serotonin reuptake inhibitors (for treatment of depression), such as sertraline and paroxetine;
corticosteroids used as hormone replacement therapy when adrenal glands or pituitary gland have been destroyed or removed (except for topical corticosteroids or cortisone replacement therapy in Addison’s disease), or to treat inflammation, including rheumatic diseases and intestinal inflammation (corticosteroids). Concomitant use increases the risk of gastrointestinal side effects;
medicines for 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. If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking MANASA. Your doctor will advise you when it is safe to restart MANASA. Taking MANASA with fusidic acid may rarely cause muscle weakness, soreness, or muscle pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.

MANASA may further lower your blood pressure if you are already taking other medicines for high blood pressure.
MANASA with food and drinks
Take MANASA with food.
Do not drink grapefruit juice during treatment with MANASA.
Alcohol consumption may increase the risk of gastrointestinal bleeding and prolong bleeding time.
Pregnancy and breastfeeding
Do not take MANASA if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. If you become pregnant while taking MANASA, stop immediately and inform your doctor.
Women must avoid becoming pregnant during treatment with MANASA by using adequate contraception.
Do not take MANASA if you are breastfeeding.
Driving and using machines
Most people can drive and operate machinery while being treated with MANASA, as it does not affect their abilities.
However, some people may experience dizziness during treatment with MANASA. If the capsules cause you discomfort, dizziness, fatigue, or headaches, do not drive or operate machinery and contact your doctor immediately.
MANASA contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking MANASA.
MANASA contains soybean oil
If you are allergic to peanuts or soy, do not use this medicine.

3. How to take MANASA

Take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.
Taking the medicine

Take this medicine after a meal.
Swallow the capsules whole with a glass of water. Do not take MANASA with grapefruit juice.
Do not open, crush, or chew the capsules.
This medicine should be taken at the same time every day.

Dosage
The recommended dose is one capsule once daily.
Try to take the capsules at approximately the same time each day; this may help you remember to take them.
If you are admitted to hospital or receive treatment for another condition, inform medical staff that you are taking MANASA.
Periodic cholesterol checks
It is important to return to your doctor regularly to monitor your cholesterol levels, to ensure that cholesterol has reached and maintains the correct levels. Your doctor may decide to increase the dose to the amount of MANASA most suitable for you.
Use in elderly patients
There is no need to adjust the dose in elderly patients.
Use in children and adolescents
MANASA must not be used in children and adolescents.
Patients with renal impairment
There is no need to adjust the dose in patients with mild to moderate renal impairment.
The use of MANASA is contraindicated in patients with severe renal impairment.
Patients with hepatic impairment
There is no need to adjust the dose in patients with mild to moderate hepatic impairment.
The use of MANASA is contraindicated in patients with severe hepatic impairment.
If you take more MANASA than you should
Symptoms of severe overdose may include dizziness and ringing in the ears, especially in elderly patients.
Contact your doctor or go immediately to the nearest hospital emergency department. Do not drive yourself to the hospital; ask someone to accompany you or call an ambulance. Bring the medicine packaging with you so the doctor knows what you have taken.
If you forget to take MANASA
Do not worry. If you forget to take a capsule, simply skip that dose. Take the next dose at the usual time. Do not take a double dose to make up for the missed capsule.
If you stop taking MANASA
Your doctor will advise you on how long you should continue taking the medicine. Your cholesterol levels may rise again if you stop taking MANASA. Your condition may return if you stop treatment with the medicine before being told to do so.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Stop taking MANASA and consult your doctor immediately if you experience any of the following very rare and serious side effects after taking this medicine:

Sudden breathlessness, chest pain, shortness of breath or difficulty breathing;
Swelling of the eyelids, face or lips;
Swelling of the tongue and throat causing severe difficulty breathing and/or swallowing;
Severe skin reactions including severe rash, hives, redness of the skin all over the body, intense itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome) or other allergic reactions;
If black stools or blood in vomit occur (signs of severe stomach bleeding);
Flat, non-raised reddish spots, target-shaped or circular rashes 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 rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

In addition, stop taking MANASA and contact your doctor immediately:

if you have any unusual muscle tenderness or pain lasting longer than expected. As with other statins, a very small number of people have experienced unpleasant muscle effects, which rarely progressed to a potentially life-threatening muscle damage known as rhabdomyolysis.
if there is a rupture of a muscle;
if you develop lupus-like syndrome (including skin rash, joint problems and effects on blood cells). The following side effects have been reported. If any of these cause you problems or persist for more than one week, you must 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 already have high levels of sugar and fats in your blood, are overweight and have high blood pressure. Your doctor will monitor you while you are taking this medicine.

Uncommon (may affect up to 1 in 100 people):

Rash, itching, hives or other skin reactions
Increase in the amount of protein in the urine – values usually return to normal spontaneously without needing to stop taking MANASA (only at doses of 5–20 mg).

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

Severe allergic reaction – signs include swelling of the face, lips, tongue and/or throat, difficulty swallowing and breathing, intense itching of the skin (with raised lumps). If you think you are having an allergic reaction, stop taking MANASA and seek immediate medical help.
Muscle damage in adults – as a precaution, stop taking MANASA and contact your doctor immediately if you have unusual muscle tenderness or pain lasting longer than expected
Severe stomach pain (inflammation of the pancreas)
Increase in liver enzymes in the blood
Reduction in platelets in the blood, increasing the risk of bleeding or bruising (thrombocytopenia)
Lupus-like syndrome (includes skin reaction, joint problems and effects on blood cells).

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

Jaundice (yellowing of the skin and eyes)
Hepatitis (inflamed liver)
Blood traces in the urine
Nerve damage in the arms and legs (such as numbness)
Joint pain
Memory loss
Gynaecomastia (enlargement of breast tissue in men)

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

Diarrhoea (watery stools)
Cough
Shortness of breath
Oedema (swelling)
Sleep disorders, including insomnia and nightmares
Sexual problems
Depression
Respiratory problems, including persistent cough and/or breathlessness or fever
Tendon injury
A nerve disorder 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.
Minor bleeding from the gastrointestinal tract (micro-bleeding).
Increased tendency to bleed, e.g. nosebleeds, bleeding gums, skin bleeding or bleeding from the urinary tract and reproductive organs, with possible prolonged bleeding time. This effect may last from 4 to 8 days after taking the medicine.

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 occult blood loss from the stomach or intestine.
Gastric or intestinal ulcers, which very rarely may lead to perforation.
Intracranial bleeding, blood in urine.
Gastrointestinal inflammation.
Skin reactions.

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

Hypersensitivity reactions affecting the skin, respiratory tract, gastrointestinal system and cardiovascular system, especially in asthmatics. The following may occur: drop in blood pressure, breathing difficulties, inflammation of nasal mucosa, nasal congestion, allergic shock, swelling of the face, tongue and larynx (Quincke's oedema).
Severe bleeding, such as bleeding in the brain, especially in patients with uncontrolled hypertension and/or concomitant treatment with anticoagulants (blood-thinning medicines), which in individual cases may be life-threatening.
Confusion
Headache, dizziness
Hearing impairment or ringing in the ears (tinnitus), especially in children and elderly people, which may be signs of overdose (see also “If you take more MANASA than you should”).

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

Increases in liver function test values
Kidney dysfunction and acute kidney failure
Decrease in blood sugar (hypoglycaemia)
Low-dose acetylsalicylic acid reduces the excretion of uric acid. In at-risk patients, this may trigger an attack of gout
Skin rash with fever and involvement of mucous membranes (exudative polymorphic erythema).

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

Accelerated breakdown or destruction of red blood cells in the blood and a specific form of anaemia (low red blood cell count) in patients with severe glucose-6-phosphate-dehydrogenase deficiency.

If any of the side effects worsens, or if you notice any side effect not listed in this leaflet, inform your doctor or pharmacist.
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 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 MANASA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp.". The expiry date refers to the last day of that month.
Store below 30°C. Keep 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 no longer used. This will help protect the environment.

6. Package contents and other information

What MANASA contains
The active substances are rosuvastatin (as rosuvastatin calcium salt) and acetylsalicylic acid.
MANASA hard capsules 5 mg/100 mg contains 5 mg of rosuvastatin (as calcium salt) and 100 mg of
acetylsalicylic acid.
MANASA hard capsules 10 mg/100 mg contains 10 mg of rosuvastatin (as calcium salt) and 100 mg of
acetylsalicylic acid.
MANASA hard capsules 20 mg/100 mg 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 silicon dioxide, magnesium stearate
Film coating: polyvinyl alcohol, titanium dioxide (E171), talc, iron oxide yellow (E172), lecithin (soy), iron oxide red (E172), xanthan gum, iron oxide black (E172)
Tablet containing acetylsalicylic acid:
microcrystalline cellulose, maize starch, anhydrous colloidal silicon dioxide, stearic acid
Gelatin capsule:
gelatin, titanium dioxide (E171), indigotine (E132), iron oxide yellow (E172)
Black ink: shellac, propylene glycol, strong ammonia solution, iron oxide black (E172), potassium hydroxide.

Description of the appearance of MANASA and the contents of the pack
MANASA 5 mg/100 mg: size 2 hard gelatin capsules with an opaque white body and a dark green opaque cap. Each capsule contains one white to almost white, biconvex, oval, uncoated tablet of acetylsalicylic acid and one brown, biconvex, round, film-coated tablet of rosuvastatin 5 mg.
MANASA 10 mg/100 mg: size 1 hard gelatin capsules 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 one white to almost white, biconvex, oval, uncoated tablet of acetylsalicylic acid and one brown, biconvex, round, film-coated tablet of rosuvastatin 10 mg.
MANASA 20 mg/100 mg: size 0 hard gelatin capsules 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 one white to almost white, biconvex, oval, uncoated tablet of acetylsalicylic acid and two brown, biconvex, round, film-coated tablets of rosuvastatin 10 mg.
The hard capsules are available in PA/AL/PVC/AL blisters in packs of 28 capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Errekappa Consumer S.r.l.
Via Ciro Menotti 1/A – 20129 Milano
Italy

Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Poland

Manasa