Pixoroso: detailed information

Package leaflet: information for the patient

Pixoroso, 10 mg + 4 mg, film-coated tablets
Pixoroso, 10 mg + 8 mg, film-coated tablets
Pixoroso, 20 mg + 4 mg, film-coated tablets
Pixoroso, 20 mg + 8 mg, film-coated tablets
Rosuvastatin + Perindopril tert-butylamine
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 someone else, even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Pixoroso is and what it is used for

Pixoroso contains two active substances, rosuvastatin and perindopril, in one film-coated tablet.
Rosuvastatin helps control high cholesterol levels. Perindopril helps control high blood pressure (hypertension).
Pixoroso is prescribed for the treatment of high blood pressure (arterial hypertension) and concomitant high cholesterol levels in adult patients. Patients who are already taking rosuvastatin and perindopril as separate tablets may instead take one Pixoroso tablet containing both components.

2. Important information before taking Pixoroso

When not to take Pixoroso

if the patient is allergic to rosuvastatin, perindopril, or any other ACE inhibitor, or to any of the other ingredients of this medicine (listed in section 6);
if the patient has previously experienced symptoms such as wheezing, facial, tongue or throat swelling, intense itching, or severe skin rash while being treated with an ACE inhibitor, or if the patient or a family member has had such symptoms under other circumstances (a condition known as angioedema);
if the patient has a liver disease, including any unexplained abnormal blood test results related to liver function;
if the patient has severe kidney disease;
if the patient has kidney disorders causing reduced blood flow to the kidneys (renal artery stenosis);
if the patient is undergoing dialysis or another form of blood filtration. Depending on the device used, Pixoroso may not be suitable for the patient;
if the patient experiences recurrent or unexplained muscle symptoms or pain;
if the patient is taking the combination of sofosbuvir, velpatasvir, and voxilaprevir (used to treat viral hepatitis C);
if the patient is taking a medicine called cyclosporine (used, for example, after organ transplantation);
if the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medicine containing aliskiren;
if the patient has taken or is currently taking a combination medicine containing sacubitril and valsartan, used to treat heart failure, as this increases the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) (see "Warnings and precautions" and "Pixoroso with other medicines");
if the patient is pregnant or breastfeeding. If a woman becomes pregnant while taking Pixoroso, she must stop taking it immediately and inform her doctor. Women should avoid becoming pregnant while taking Pixoroso by using effective contraception.

Warnings and precautions
Before starting Pixoroso, discuss with your doctor or pharmacist:

if the patient has liver disease;
if the patient has recurrent or unexplained muscle pain or discomfort, or if the patient or family members have a history of muscle disorders, or if the patient previously experienced muscle problems while taking other cholesterol-lowering medicines. The patient should contact their doctor immediately if unexplained muscle pain or discomfort occurs, especially if accompanied by general malaise or fever. The doctor should also be informed if persistent muscle weakness develops;
if the patient has or has had myasthenia (a disease causing generalized muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), as statins may sometimes worsen symptoms or trigger myasthenia (see section 4);
if the patient regularly consumes large amounts of alcohol;
if the patient has previously developed severe skin rash, skin peeling, blisters, and/or oral ulcers after taking Pixoroso or similar medicines;
if the patient has been diagnosed with a collagen disease (connective tissue disease), such as systemic lupus erythematosus or scleroderma;
if the patient is of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). In these patients, the doctor will determine the appropriate starting dose of rosuvastatin;
if the patient is of Black race, as there is an increased risk of angioedema and the medicine may be less effective in lowering blood pressure compared to patients of other races;
if the patient is over 70 years of age (as the doctor must determine the appropriate starting dose of rosuvastatin);
if the patient has any other heart conditions;
if the patient has been diagnosed with aortic stenosis (narrowing of the main blood vessel leading from the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of arteries supplying blood to the kidneys);
if the patient has kidney disease or is undergoing dialysis;
if the patient has severe respiratory failure;
if the patient has been diagnosed with diabetes;
if the patient has a thyroid disorder;
if the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
if the patient is taking cholesterol-lowering fibrates. Read the leaflet carefully, even if the patient has previously taken other cholesterol-lowering medicines;
if the patient is taking medicines used to treat HIV infection, such as ritonavir with lopinavir and/or atazanavir, refer to the information under "Pixoroso with other medicines";
if the patient is on a low-salt diet or using potassium-containing salt substitutes;
if the patient is taking any of the following medicines used to treat high blood pressure:
- an angiotensin II receptor antagonist (Angiotensin Receptor Blockers, ARBs), also known as sartans (e.g., valsartan, telmisartan, irbesartan), especially if the patient has kidney problems related to diabetes;
- aliskiren. The treating doctor may monitor kidney function, blood pressure, and blood electrolyte levels (e.g., potassium) at regular intervals. See also information under "When not to take Pixoroso".

If the patient is taking or has taken within the last 7 days, orally or by injection, a medicine containing fusidic acid (used to treat bacterial infections). Concomitant use of fusidic acid with rosuvastatin may lead to severe muscle damage (rhabdomyolysis); see section "Pixoroso with other medicines".
If the patient is taking any of the following medicines, the risk of angioedema increases:

racecadotril (used to treat diarrhoea);
sirolimus, everolimus, temsirolimus, and other medicines belonging to the group of mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment);
sacubitril (available in a combination medicine containing sacubitril and valsartan), used to treat chronic heart failure;
linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the group of gliptins (used to treat diabetes).

Angioedema (a severe allergic reaction; symptoms include swelling of the face, lips, tongue or throat, difficulty swallowing or breathing) has been reported in patients treated with ACE inhibitors, including perindopril. This reaction may occur at any time during treatment. If such symptoms occur, the patient must stop taking Pixoroso and contact a doctor immediately. See also section 4.
While taking Pixoroso, also inform your doctor or healthcare personnel:

if a dry cough develops;
if the patient is to undergo anaesthesia and/or surgery;
if the patient has recently experienced diarrhoea or vomiting, or is dehydrated;
if the patient is to undergo dialysis or LDL apheresis (removal of cholesterol from the blood using a machine);
if the patient is to undergo allergen immunotherapy to reduce allergic reactions to bee or wasp stings.

Serious skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of rosuvastatin. If any of the symptoms described in section 4 occur, stop taking Pixoroso and contact a doctor immediately.
In a small number of patients, statins may affect liver function. To detect this effect, blood tests measuring liver enzyme activity are performed. Usually, the doctor will recommend checking liver enzyme levels in the blood before and during treatment with Pixoroso.
Patients with diabetes or at risk of developing diabetes will be under close medical supervision while taking this medicine. Patients with high blood sugar and fat levels, overweight, and high blood pressure may be at increased risk of developing diabetes.

Children and adolescents
Pixoroso must not be used in children and adolescents.

Pixoroso with other medicines
Tell your doctor or pharmacist about all medicines currently taken, recently taken, or planned for use.
Pixoroso must not be used with:

aliskiren (used to treat high blood pressure) in patients with diabetes or kidney dysfunction;
a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to take Pixoroso" and "Warnings and precautions";
a combination medicine containing sofosbuvir, velpatasvir, and voxilaprevir (used to treat viral hepatitis C);
cyclosporine (used, for example, after organ transplantation).

Other medicines may affect treatment with Pixoroso. The treating doctor may need to adjust the dose and/or take additional precautions with medicines such as:

other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (ARBs), aliskiren (see also information under "When not to take Pixoroso" and "Warnings and precautions"), or diuretics (medicines that increase urine production by the kidneys);
potassium-sparing medicines (e.g., triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes, and other medicines that may increase potassium levels in the body (such as heparin, a blood-thinning medicine used to prevent blood clots; trimethoprim and cotrimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole, used to treat bacterial infections);
potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses of 12.5 mg to 50 mg per day;
lithium, used in the treatment of mania or depression;
non-steroidal anti-inflammatory drugs (e.g., ibuprofen) used for pain relief, or high-dose acetylsalicylic acid (a substance found in many medicines used for pain and fever relief, and to prevent blood clots);
medicines used to treat diabetes (such as insulin, metformin, or gliptins);
baclofen (used to treat muscle stiffness in diseases such as multiple sclerosis);
medicines used to treat psychiatric disorders such as depression, anxiety, schizophrenia, etc. (e.g., tricyclic antidepressants, antipsychotics);
immunosuppressive medicines (reducing the body's immune response) used to treat autoimmune disorders or after organ transplantation (e.g., cyclosporine, tacrolimus);
estramustine (used to treat cancer);
medicines most commonly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other mTOR inhibitors). See section "Warnings and precautions";
allopurinol (used to treat gout);
procainamide (used to treat heart rhythm disorders);
vasodilating medicines, including nitrates;
medicines used to treat low blood pressure, shock, or asthma (e.g., ephedrine, noradrenaline, or adrenaline);
gold salts, especially when administered intravenously (used to treat symptoms of rheumatoid arthritis).

Tell your doctor or pharmacist about all medicines currently taken, recently taken, or planned for use.
Tell your doctor if the patient is taking:

warfarin, clopidogrel, or tikagrelor (or any other blood-thinning medicine);
a fibrate medicine (such as gemfibrozil, fenofibrate) or any other medicine that lowers blood cholesterol (e.g., ezetimibe);
medicines used for indigestion (used to neutralize stomach acid);
erythromycin (an antibiotic), fusidic acid (an antibiotic – see below and section "Warnings and precautions");
oral contraceptives;
regorafenib (used to treat cancer);
darolutamide (used to treat cancer);
capmatinib (used to treat cancer);
tafamidis (used in patients with symptomatic polyneuropathy);
fostamatinib (used to treat low platelet count);
febuxostat (used to treat and prevent high blood uric acid levels);
roxadustat (used to treat anaemia in patients with chronic kidney disease);
eltrombopag (used to treat blood disorders);
dronedarone (used to treat irregular heartbeat);
itraconazole (used to treat fungal infections);
teriflunomide (used to treat multiple sclerosis);
hormone replacement therapy;
any of the following medicines used to treat viral infections, including HIV or hepatitis C virus, used alone or in combination with other medicines (see section: "Warnings and precautions"): ritonavir, lopinavir, atazanavir, ombitasvir, paritaprevir, dasabuvir, simeprevir, grazoprevir, elbasvir, glecaprevir, pibrentasvir, darunavir, tipranavir.

If the patient needs to take fusidic acid orally to treat a bacterial infection, this medicine should be temporarily discontinued. The doctor will inform the patient when it is safe to restart Pixoroso. Taking Pixoroso with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis).
More information about rhabdomyolysis can be found in section 4.

Pixoroso with food and drink
It is recommended to take Pixoroso before a meal.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Do not take Pixoroso if the patient is pregnant or breastfeeding.
If pregnancy occurs while taking Pixoroso, treatment must be stopped immediately and the doctor informed.
Women should avoid becoming pregnant while taking Pixoroso by using appropriate contraception.
Before taking any medicine, consult a doctor or pharmacist.

Driving and operating machinery
Pixoroso does not affect alertness, but dizziness or weakness due to low blood pressure may occur, which could affect the ability to drive or operate machinery. It is recommended not to drive or operate machinery until it is known how Pixoroso affects the patient.

3. How to take Pixoroso

This medicine should always be taken according to the instructions given by your doctor or pharmacist.
If in doubt, consult your doctor or pharmacist.
The recommended dose is one tablet once daily. The tablet should preferably be taken in the morning, before a meal. Swallow the tablet with a glass of water.
Your doctor will decide the appropriate dose for you. Pixoroso is prescribed to patients who are already taking rosuvastatin and perindopril in separate tablets.
Taking more Pixoroso than recommended
If you have taken too many tablets, contact your doctor or the nearest hospital emergency department immediately. The most likely consequence of overdose is low blood pressure. If you experience a significant drop in blood pressure (symptoms such as dizziness or fainting), it may help to lie down with your legs raised.
Missing a dose of Pixoroso
It is important to take this medicine every day, as regular treatment is more effective. However, if you forget to take a dose of Pixoroso, take the next dose at your usual time.
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 will experience them.
You must stop taking this medicine and contact your doctor immediately if any of the following severe adverse reactions occur:

swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema; see section 2 "Warnings and precautions") (uncommon – may occur in up to 1 in 100 patients);
severe dizziness or fainting caused by low blood pressure (common – may occur in up to 1 in 10 patients);
extremely rapid or irregular heartbeat, chest pain (angina) or heart attack (very rare – may occur in up to 1 in 10,000 patients);
weakness in the arms or legs, or difficulty speaking, which may be signs of stroke (very rare – may occur in up to 1 in 10,000 patients);
sudden onset of wheezing, chest pain, shortness of breath or difficulty breathing (bronchospasm) (uncommon – may occur in up to 1 in 100 patients);
inflammation of the pancreas (pancreatitis), which may cause severe upper abdominal pain radiating to the back and general malaise (very rare – may occur in up to 1 in 10,000 patients);
yellowing of the skin or eyes (jaundice), which may be a sign of liver inflammation (very rare – may occur in up to 1 in 10,000 patients);
skin rash, often starting with red, itchy spots on the face, arms or legs (erythema multiforme) (very rare – may occur in up to 1 in 10,000 patients);
red, flat, disc-shaped or circular spots on the trunk, often with blisters in the center, skin peeling, mouth ulcers, throat, nose, genital or eye lesions. Such serious skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome) (very rare – may occur in up to 1 in 10,000 patients);
widespread rash, high fever and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome) (very rare – may occur in up to 1 in 10,000 patients).

You should also stop taking Pixoroso and contact your doctor immediately if you experience unusual muscle pain or other muscle symptoms that persist longer than expected. As with other statins, in a very small number of patients, adverse effects on muscles have been observed. Rarely, these patients developed potentially life-threatening muscle damage (rhabdomyolysis).
Inform your doctor if you experience any of the following adverse reactions:

Frequent adverse reactions (may occur in more than 1 in 100, but less than 1 in 10 patients):

diabetes. The risk of developing diabetes is higher if the patient has high blood sugar and fat levels, overweight and high blood pressure. Your doctor will monitor patients at risk while taking this medicine.
dizziness, headache, tingling sensation, taste disturbances,
visual disturbances, vertigo (dizziness of labyrinthine origin), tinnitus (perception of ringing or other sounds),
dizziness due to low blood pressure,
cough, shortness of breath,
abdominal pain, constipation, loose stools (diarrhea), indigestion or digestive difficulties, nausea, vomiting,
allergic reactions (such as rash, itching),
muscle cramps, muscle pain,
feeling of weakness.

Uncommon adverse reactions (may occur in more than 1 in 1,000, but less than 1 in 100 patients):

increased eosinophil count (a type of white blood cell),
hypoglycemia (very low blood sugar) in diabetic patients, high blood potassium levels (transient after discontinuation of treatment), low sodium levels,
mood changes, sleep disturbances, depression,
drowsiness, fainting,
palpitations, tachycardia,
vasculitis (inflammation of blood vessels),
bronchospasm (chest tightness, wheezing and shortness of breath),
dry mouth,
intense itching (urticaria), angioedema (symptoms such as wheezing, facial or tongue swelling), sweating, photosensitivity reaction (increased skin sensitivity to sunlight), blistering of the skin,
joint pain, muscle pain,
kidney function disorders,
impotence,
chest pain, malaise, peripheral edema, fever,
abnormal laboratory test results: increased blood urea nitrogen, increased serum creatinine,
falls.

Rare adverse reactions (may occur in more than 1 in 10,000, but less than 1 in 1,000 patients):

low platelet count (leading to increased tendency to bleeding or bruising),
severe allergic reactions – symptoms include swelling of the face, lips, tongue and (or) throat, difficulty swallowing and breathing, severe skin itching (with hives). If you suspect an allergic reaction, stop taking Pixoroso immediately and seek medical help.
dark-colored urine, nausea or vomiting, muscle cramps, confusion and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion).
sudden redness of the face and neck,
severe abdominal pain (pancreatitis),
worsening of psoriasis,
muscle damage including muscle rupture. Exercise caution: discontinue use of Pixoroso and contact your doctor immediately if you experience muscle pain or other muscle symptoms that persist longer than expected,
symptoms of lupus-like syndrome (such as rash, joint diseases and hematological changes),
acute kidney failure, reduced or absent urine output,
abnormal laboratory test results: increased liver enzyme activity, elevated serum bilirubin.

Very rare adverse reactions (may occur in less than 1 in 10,000 patients):

inflammation of the nasal mucosa (nasal swelling or discharge),
blood changes such as decreased white blood cell and red blood cell counts,
confusion,
nerve damage in upper and lower limbs (felt as numbness), memory loss,
cardiovascular disorders (irregular heartbeat, angina, heart attack),
eosinophilic pneumonia (a rare type of lung inflammation),
hepatitis (liver inflammation), jaundice (yellowing of skin and eyes),
erythema multiforme (skin rash, often starting with red, itchy spots on the face, arms or legs),
presence of blood in urine,
breast enlargement in men (gynecomastia),
decreased hemoglobin concentration.

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

breathing difficulties,
discoloration, numbness and pain in fingers or toes (Raynaud's phenomenon),
Stevens-Johnson syndrome (a serious blistering disease affecting the skin, mouth, eyes and genitals),
blood, kidney, liver or pancreas disorders and changes in laboratory parameters (blood tests) may occur. Your doctor may order blood tests to monitor your condition,
tendon injury and persistent muscle weakness.

If any of these symptoms occur, contact your doctor as soon as possible.
Reporting of adverse reactions
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, 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 can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Pixoroso

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

6. Contents of the Packaging and Other Information

What Pixoroso contains

The active substances in this medicine are rosuvastatin and perindopril with tert-butylamine.
Pixoroso 10 mg + 4 mg, film-coated tablets: Each film-coated tablet contains 10 mg of rosuvastatin (as rosuvastatin calcium) and 4 mg of perindopril with tert-butylamine.
Pixoroso 10 mg + 8 mg, film-coated tablets: Each film-coated tablet contains 10 mg of rosuvastatin (as rosuvastatin calcium) and 8 mg of perindopril with tert-butylamine.
Pixoroso 20 mg + 4 mg, film-coated tablets: Each film-coated tablet contains 20 mg of rosuvastatin (as rosuvastatin calcium) and 4 mg of perindopril with tert-butylamine.
Pixoroso 20 mg + 8 mg, film-coated tablets: Each film-coated tablet contains 20 mg of rosuvastatin (as rosuvastatin calcium) and 8 mg of perindopril with tert-butylamine.
Other components (excipients):
Tablet core: microcrystalline cellulose, crospovidone (type A), colloidal anhydrous silica, magnesium stearate (E 470b)
Coating:
- Pixoroso 10 mg + 4 mg, film-coated tablets: polyvinyl alcohol, macrogol 3350, titanium dioxide (E 171), talc
- Pixoroso 10 mg + 8 mg, film-coated tablets: polyvinyl alcohol, macrogol 3350, titanium dioxide (E 171), talc, yellow iron oxide (E 172)
- Pixoroso 20 mg + 4 mg, film-coated tablets: polyvinyl alcohol, macrogol 3350, titanium dioxide (E 171), talc, yellow iron oxide (E 172), red iron oxide (E 172)
- Pixoroso 20 mg + 8 mg, film-coated tablets: polyvinyl alcohol, macrogol 3350, titanium dioxide (E 171), talc, yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172)

What Pixoroso looks like and contents of the pack
Pixoroso 10 mg + 4 mg, film-coated tablets: White or almost white, round, biconvex film-coated tablets, marked with "S1" on one side. Dimensions: approximately 9 mm in diameter.
Pixoroso 10 mg + 8 mg, film-coated tablets: Light brownish-yellow, round, biconvex film-coated tablets, marked with "S2" on one side. Dimensions: approximately 11 mm in diameter.
Pixoroso 20 mg + 4 mg, film-coated tablets: Orange-pink, round, biconvex film-coated tablets, marked with "S3" on one side. Dimensions: approximately 11 mm in diameter.
Pixoroso 20 mg + 8 mg, film-coated tablets: Dark pink, round, biconvex film-coated tablets, marked with "S4" on one side. Dimensions: approximately 11 mm in diameter.

Pixoroso is available in cardboard packaging containing:

10, 30, 60, 90 or 100 film-coated tablets in blisters.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
tel. + 48 22 57 37 500