Package leaflet: Information for the user

Kastel, 10 mg + 5 mg, hard capsules
Kastel, 10 mg + 10 mg, hard capsules
Kastel, 20 mg + 5 mg, hard capsules
Kastel, 20 mg + 10 mg, hard capsules
Rosuvastatin + Ramipril
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 further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Kastel is and what it is used for

Kastel contains two different active substances in one capsule: rosuvastatin and ramipril.
Rosuvastatin belongs to a group of medicines called statins, which regulate lipid (fat) levels in the body.
Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. In patients with high blood pressure, this medicine widens blood vessels, making it easier for the heart to pump blood.

Kastel is used to treat high blood pressure (hypertension) in adults who also have one of the following conditions:

Elevated cholesterol levels (primary hypercholesterolemia), or
Elevated levels of cholesterol and another fat (triglycerides) (mixed hyperlipidemia), and/or
Increased risk of heart attack, stroke, or other related diseases, which can be reduced with Kastel.

Kastel is intended for patients who are already taking rosuvastatin and ramipril as separate tablets. Instead of taking two separate tablets of rosuvastatin and ramipril, one Kastel capsule containing both active substances at the same strengths can be taken.
You should continue to follow a cholesterol-lowering diet while taking this medicine.
Kastel is not a weight-loss medicine.

2. What you need to know before taking Kastel

Do not take Kastel:

If you are allergic to ramipril, any other ACE inhibitor, rosuvastatin, or any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction may include: rash, difficulty swallowing or breathing, swelling of the lips, face, throat, or tongue;
If you have ever had a serious allergic reaction called "angioedema." Symptoms include: itching, hives, red patches on hands, feet, and throat, swelling of the throat and tongue, puffiness around the eyes and mouth, difficulty breathing or swallowing;
If you have recently taken (within the last 36 hours) or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure;
If you are undergoing dialysis or another type of blood filtration. Depending on the equipment used, treatment with Kastel may not be appropriate;
If you have kidney diseases involving reduced blood flow to the kidneys (renal artery stenosis) or if you have severe kidney dysfunction;
If you are pregnant or breastfeeding. If you become pregnant while taking Kastel, stop taking it immediately and inform your doctor. Women of childbearing potential should use appropriate contraception during treatment with Kastel (see below under "Pregnancy and breastfeeding");
If you have abnormally low or unstable blood pressure. This requires medical evaluation;
If you have diabetes or kidney dysfunction and are taking a blood pressure-lowering medicine containing aliskiren;
If you have liver disease;
If you have recurrent muscle pain of unknown cause (myopathy);
If you are taking the combination of sofosbuvir/velpatasvir/voxilaprevir (medicines used to treat viral hepatitis C);
If you are taking cyclosporine (used, for example, after organ transplantation);
If you have ever experienced severe skin rash, skin peeling, blistering, and/or mouth ulcers after taking Kastel or other medicines containing rosuvastatin.

If any of the above apply, do not take Kastel. If in doubt, talk to your doctor before taking Kastel.

Warnings and precautions:

Before starting Kastel, consult your doctor or pharmacist:

If you have heart, liver, or kidney disease;
If you have lost a large amount of salt or fluid (due to vomiting, diarrhoea, excessive sweating, a low-salt diet, long-term use of diuretics, or dialysis);
If you are planning to undergo treatment to reduce allergy to bee or wasp stings (desensitisation);
If you are scheduled for anaesthesia, including for surgery or dental procedures. You may need to stop taking Kastel one day before anaesthesia; consult your doctor;
If you have high potassium levels in your blood (detected in a blood test);
If you are taking medicines or have conditions that may reduce sodium levels in your blood. Your doctor may recommend regular blood tests to monitor sodium levels, especially in elderly patients;
If you are taking medicines that may increase the risk of a serious allergic reaction called angioedema, such as mTOR inhibitors (e.g. temsirolimus, everolimus, sirolimus), vildagliptin, neprilysin inhibitors (NEP) (e.g. racecadotril) or sacubitril/valsartan. For information on sacubitril/valsartan, see section 2 "Do not take Kastel";
If you have a collagen disease such as scleroderma or systemic lupus erythematosus;
If you are taking any of the following medicines for high blood pressure:
- An angiotensin II receptor antagonist (ARB) (also known as sartans, including valsartan, telmisartan, irbesartan), especially if you also have kidney disease related to diabetes;
- Aliskiren. Your doctor may recommend regular monitoring of kidney function, blood pressure, and blood electrolyte levels (e.g. potassium). See also information under "Do not take Kastel";
If you have recurrent or unexplained muscle pain, if you or your family have a history of muscle disorders, or if you previously had muscle problems while taking other cholesterol-lowering medicines. If you experience unexplained muscle pain, especially with malaise or fever, inform your doctor immediately. Also inform your doctor if you have persistent muscle weakness;
If you have or have had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), as statins may sometimes worsen symptoms or trigger myasthenia (see section 4);
If you regularly drink large amounts of alcohol;
If you have thyroid dysfunction (hypothyroidism);
If you are taking other cholesterol-lowering medicines called fibrates (see section "Kastel with other medicines");
If you are taking medicines for HIV infection, e.g. ritonavir with lopinavir and/or atazanavir (see section "Kastel with other medicines");
If you are taking or have taken within the last 7 days, orally or by injection, a medicine containing fusidic acid (used to treat bacterial infections). Taking fusidic acid together with Kastel may lead to serious muscle problems (rhabdomyolysis). See section "Kastel with other medicines";
If you are over 70 years of age (as your doctor will need to select an appropriate dose of Kastel);
If you have severe respiratory insufficiency;
If you are of Asian origin (Japan, China, Philippines, Vietnam, Korea, or India). Your doctor must select an appropriate dose of Kastel.

If any of the above apply (or if you have any doubts), talk to your doctor or pharmacist before starting Kastel.

Serious skin reactions such as Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with rosuvastatin use. If you notice any symptoms described in section 4, stop taking Kastel immediately and contact your doctor.

In a small number of patients, statins may damage the liver. This can be detected by a simple blood test measuring liver enzymes. Therefore, during treatment with Kastel, your doctor will regularly order blood tests (liver function tests). It is important that you undergo the blood tests prescribed by your doctor.

During treatment with this medicine, your doctor will carefully monitor patients who have diabetes or are at risk of developing diabetes. Increased risk of diabetes applies to people with high blood sugar and fat levels, overweight, or high blood pressure.

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

Kastel with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken. This is necessary because Kastel may affect the action of other medicines, and other medicines may affect the action of Kastel.

Tell your doctor if you are taking any of the following medicines:

Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs such as ibuprofen, indomethacin, or acetylsalicylic acid);
Medicines used to treat low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, or adrenaline. Your doctor will monitor your blood pressure;
Sacubitril/valsartan – used to treat certain types of chronic heart failure in adults (see section 2 "Do not take Kastel");
Cyclosporine (used, for example, after transplants to prevent organ rejection). Do not take Kastel during treatment with cyclosporine;
Anticancer medicines (used in chemotherapy, such as regorafenib, darolutamide);
Diuretics, such as furosemide;
Medicines that may increase potassium levels in blood, such as spironolactone, triamterene, amiloride, potassium salts, trimethoprim alone or in combination with sulfamethoxazole (used to treat infections), and heparin (used to thin the blood);
Anti-inflammatory steroid medicines, such as prednisolone;
Allopurinol (a medicine that lowers uric acid levels in blood);
Procainamide (used for heart rhythm disorders);
Temsirolimus (used to treat cancers);
Sirolimus, everolimus (medicines to prevent transplant rejection);
Vildagliptin (used to treat type 2 diabetes);
Racecadotril (a medicine for diarrhoea);
Your doctor may need to adjust the dose and/or take other precautions if you are taking an angiotensin receptor antagonist (ARB) or aliskiren (see also information under "Do not take Kastel" and "Warnings and precautions");
Medicines used to treat diabetes, such as oral hypoglycaemics and insulin. Kastel may lower blood sugar levels. Blood sugar levels should be carefully monitored during treatment with Kastel;
Lithium (used in psychiatric disorders). Kastel may increase lithium levels in blood. Close monitoring of lithium levels by your doctor will be required;
Warfarin, ticagrelor, or clopidogrel, or other blood-thinning medicines (concurrent use with Kastel may enhance their anticoagulant effect and increase the risk of bleeding);
Fibrates (such as gemfibrozil, fenofibrate) or another cholesterol-lowering medicine (such as ezetimibe). Concurrent use may enhance the effect of rosuvastatin;
Antacids containing aluminium and magnesium (used to neutralise stomach acid; they reduce rosuvastatin plasma concentrations). This effect can be minimised by taking such antacids 2 hours apart from rosuvastatin;
Erythromycin (an antibiotic). Concurrent use may weaken the effect of rosuvastatin;
Fusidic acid (an antibiotic). If treatment with fusidic acid is required for a bacterial infection, you will need to temporarily stop taking Kastel. Your doctor will advise when it is safe to resume Kastel. Taking Kastel with fusidic acid may rarely lead to weakness, tenderness, and muscle pain (rhabdomyolysis). More information on rhabdomyolysis can be found in section 4;
Oral contraceptives (the pill). Absorption of sex hormones from the pill may increase;
Capmatinib (used to treat cancers);
Hormone replacement therapy (increased hormone activity in blood);
Fostamatinib (used to treat thrombocytopenia);
Febuxostat (used to prevent and treat high uric acid levels in blood);
Teriflunomide (used to treat multiple sclerosis);
Antiviral medicines such as ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir (used to treat infections, including HIV and hepatitis C virus infection). See sections: "Do not take Kastel" and "Warnings and precautions".

If any of the above apply (or if you have any doubts), talk to your doctor before taking Kastel.
If you go to hospital or receive treatment for another illness, inform the medical staff that you are taking Kastel.

Kastel and alcohol
Drinking alcohol while taking Kastel may cause dizziness. If in doubt about how much alcohol you can drink while being treated with Kastel, talk to your doctor, as blood pressure-lowering medicines may have additive effects with alcohol.

Pregnancy and breastfeeding
Pregnancy
Do not take Kastel during pregnancy, when planning pregnancy, or if pregnancy is suspected, as it may harm the unborn child. If you become pregnant while taking Kastel, stop taking it immediately and inform your doctor. Women of childbearing potential should use appropriate contraception during treatment with Kastel.

Breastfeeding
Do not take Kastel while breastfeeding, as it is not known whether the medicine passes into breast milk.

Driving and using machines
Some people may experience dizziness while being treated with Kastel. If you experience dizziness, consult your doctor before driving or operating machinery.

Kastel contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. it is considered "sodium-free".

3. How to take Kastel

This medicine should always be taken exactly as directed by the physician or pharmacist. If in doubt,
contact a physician or pharmacist.
During treatment with Kastel, a low-cholesterol diet should be continued.
The recommended daily dose is one capsule of the specified strength.
Kastel should be taken once daily.
The medicine should be taken every day at the same time, with or without food.
The capsule should be swallowed whole and taken with water.
Use in children and adolescents
Kastel is not recommended for use in children and adolescents under 18 years of age.
Taking more Kastel than recommended
Seek immediate medical advice from a doctor or go to the nearest hospital, as medical assistance may be required. Do not drive yourself to the hospital; ask someone to drive you or call an ambulance. Take the medicine packaging with you.
This will allow the doctor to know which medicine has been taken.
Missed dose of Kastel
There is no cause for concern; simply take the next dose at the usual time. Do not take a double dose to make up for a missed dose.
Stopping Kastel
If the patient wishes to stop taking Kastel, this should be discussed with the doctor.
If there are any further doubts about the use of this medicine, consult a doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.
It is important to know which adverse symptoms may occur.
If any of the following severe adverse symptoms occur, stop taking Kastel immediately and seek medical advice without delay – urgent medical assistance may be required:

Swelling of the face, lips, tongue and (or) throat causing difficulty in breathing or swallowing, together with skin itching and rash. This may be a sign of a severe allergic reaction to Kastel.
Severe skin reactions, such as red, flat, disc-shaped or circular spots on the trunk, often with central blistering and 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), or worsening of a pre-existing skin disease (such as Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme).
Widespread rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
Unusual muscle pain lasting longer than expected. In rare cases, potentially life-threatening muscle damage, known as rhabdomyolysis, may occur, leading to general breakdown, fever and impaired kidney function.
Lupus-like syndrome (rash, joint disorders and blood cell disorders).
Muscle rupture.

Contact your doctor immediately if any of the following occur:

Rapid heartbeat, irregular or forceful heartbeat (palpitations), chest pain, feeling of pressure in the chest, or more serious problems such as heart attack or stroke.
Shortness of breath or cough. These may be symptoms of lung disease.
Easy bruising, prolonged bleeding compared to usual, various types of bleeding (e.g. bleeding gums), red spotted petechiae on the skin, or increased susceptibility to infections, sore throat and fever, feeling of fatigue, fainting, dizziness or pale skin. These may be symptoms of blood or bone marrow disorders.
Severe abdominal pain radiating to the back. This may be a sign of pancreatitis.
Fever, chills, fatigue, loss of appetite, abdominal pain, nausea, yellowing of the skin or eyes (jaundice). These may be symptoms of liver problems, such as hepatitis or liver damage.

Other adverse effects:
If any of the following adverse effects worsen or persist for more than a few days, inform your doctor:
Common (may occur in up to 1 in 10 patients)

Headache or feeling of fatigue, feeling of weakness
Dizziness
Fainting, hypotension (abnormally low blood pressure), especially when standing up or sitting up quickly from a lying position
Dry, persistent cough, sinusitis or bronchitis, shortness of breath
Abdominal pain, constipation, diarrhoea, indigestion, nausea
Rash with raised skin lesions or without
Chest pain
Muscle cramps or muscle pain
Increased potassium levels in blood tests
Diabetes. The risk of developing diabetes is higher in patients with high blood sugar and fat levels, overweight and high blood pressure. Patients will be under close medical supervision during treatment.

Uncommon (may occur in up to 1 in 100 patients)

Balance disorders (dizziness)
Itching or unusual sensory sensations such as tingling, numbness, pricking, burning or stinging of the skin (paraesthesia)
Loss or disturbance of taste
Sleep disturbances, including excessive drowsiness
Feeling of depression, anxiety, increased nervousness or restlessness
Nasal congestion, difficulty breathing or worsening of asthma
Severe abdominal pain (pancreatitis)
Intestinal swelling called "intestinal angioedema" presenting with abdominal pain, vomiting and diarrhoea
Heartburn, dry mouth
Passing more urine than usual during the day
Sweating more than usual
Loss or decrease of appetite (anorexia)
Rapid or irregular heartbeat
Swelling of hands or feet. This may be a sign of increased fluid retention in the body
Hot flushes
Blurred vision
Joint pain
Fever
Impotence in men, decreased libido in men or women
Increased number of certain types of white blood cells (eosinophilia) detected in laboratory blood tests
Laboratory blood test results indicating impaired liver, pancreas or kidney function
Rash, itching or other skin reactions
Increased protein in urine – usually resolves spontaneously without the need to discontinue Kastel

Rare (may occur in up to 1 in 1,000 patients)

Feeling of trembling or confusion
Vasoconstriction, reduced blood flow (hypoperfusion), inflammation of blood vessels (vasculitis)
Redness and swelling of the tongue
Severe skin peeling or detachment of skin sheets, itchy nodular rash
Nail problems (e.g. loosening or separation of the nail plate from the nail bed)
Skin rash or bruising
Skin spots and cold extremities
Redness, itching, swelling or watering of the eyes
Hearing disturbances or ringing in the ears (tinnitus)
Laboratory blood test results indicating reduced number of red blood cells, white blood cells or platelets, or reduced haemoglobin levels

Very rare (may occur in up to 1 in 10,000 patients)

Increased sensitivity to sunlight
Jaundice (yellowing of the skin and whites of the eyes), hepatitis, blood in urine, nerve damage in hands or feet (numbness), joint pain, memory loss and breast enlargement in men (gynaecomastia)

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

Concentration difficulties
Swelling of the lips
Laboratory blood test results indicating too low a number of blood cells (all types)
Laboratory blood test results indicating reduced sodium levels in blood
Concentrated (dark) urine, nausea or vomiting, muscle cramps, confusion and seizures, which may be caused by inappropriate antidiuretic hormone secretion. If such symptoms occur, contact your doctor as soon as possible
Depression
Change in colour of fingers of hands and feet after cold exposure, followed by tingling or pain upon warming (Raynaud's phenomenon)
Slowed or blunted reactions
Burning sensation
Change in smell perception
Hair loss
Cough
Sleep disturbances, including insomnia and nightmares
Tendon damage and persistent muscle weakness
Myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing)
Ocular myasthenia (a disease causing weakness of eye muscles). Talk to your doctor if the patient experiences weakness of hands or feet worsening after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring 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 effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Kastel

Keep out of the reach and sight of children.
Store below 25 °C in the original packaging, protected from light and moisture.
Do not use this medicine after the expiry date stated on the carton and blister after EXP: The expiry date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Kastel contains
The active substances in this medicine are rosuvastatin and ramipril.
Kastel 10 mg + 5 mg hard capsules:
The capsules contain calcium salt of rosuvastatin equivalent to 10 mg of rosuvastatin and 5 mg of ramipril.
Kastel 10 mg + 10 mg hard capsules:
The capsules contain calcium salt of rosuvastatin equivalent to 10 mg of rosuvastatin and 10 mg of ramipril.
Kastel 20 mg + 5 mg hard capsules:
The capsules contain calcium salt of rosuvastatin equivalent to 20 mg of rosuvastatin and 5 mg of ramipril.
Kastel 20 mg + 10 mg hard capsules:
The capsules contain calcium salt of rosuvastatin equivalent to 20 mg of rosuvastatin and 10 mg of ramipril.

Other components are:
Capsule contents: silicified microcrystalline cellulose [microcrystalline cellulose (E460), colloidal anhydrous silica (E551)], magnesium stearate (E572), colloidal anhydrous silica (E551), microcrystalline cellulose (E460), crospovidone type B, hypromellose, sodium stearyl fumarate, colloidal hydrophobic silica, iron oxide yellow (E172).

Capsule shell:
Kastel 10 mg + 5 mg hard capsules:
Body: titanium dioxide (E171), iron oxide black (E172), gelatin
Cap: titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172), gelatin

Kastel 10 mg + 10 mg hard capsules:
Body: titanium dioxide (E171), iron oxide red (E172), gelatin
Cap: titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172), gelatin

Kastel 20 mg + 5 mg hard capsules:
Body: titanium dioxide (E171), iron oxide black (E172), gelatin
Cap: titanium dioxide (E171), iron oxide red (E172), gelatin

Kastel 20 mg + 10 mg hard capsules:
Body: titanium dioxide (E171), iron oxide red (E172), gelatin
Cap: titanium dioxide (E171), iron oxide red (E172), gelatin

What Kastel looks like and contents of the pack
Kastel 10 mg + 5 mg hard capsules:
Unmarked, self-closing hard gelatin capsules of Coni Snap type, size 2, with a whitish body and brick-red cap, filled with 2 tablets.

Kastel 10 mg + 10 mg hard capsules:
Unmarked, self-closing hard gelatin capsules of Coni Snap type, size 0, with a pink body and brick-red cap, filled with 2 tablets.

Kastel 20 mg + 5 mg hard capsules:
Unmarked, self-closing hard gelatin capsules of Coni Snap type, size 0, with a whitish body and rust-brown cap, filled with 2 tablets.

Kastel 20 mg + 10 mg hard capsules:
Unmarked, self-closing hard gelatin capsules of Coni Snap type, size 0, with a pink body and rust-brown cap, filled with 2 tablets.

Packaging: 30, 60, 90 or 100 hard capsules in OPA/Aluminium/PVC//Aluminium blister packs contained in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Egis Pharmaceuticals PLC
1106 Budapest, Keresztúri út 30-38.
Hungary

Manufacturer(s)
Egis Pharmaceuticals PLC
1165 Budapest, Bökényföldi út 118-120.
Hungary
Egis Pharmaceuticals PLC
9900 Körmend, Mátyás Király u. 65.
Hungary

The medicinal product is registered in the following names in the European Economic Area countries:
Hungary Romus 10 mg/5 mg, 10 mg/10 mg, 20 mg/5 mg, 20 mg/10 mg hard capsule
Bulgaria Rozuramlon 10 mg/5 mg, 10 mg/10 mg, 20 mg/5 mg, 20 mg/10 mg твърда капсула / Rosuramlon 10 mg/5 mg, 10 mg/10 mg, 20 mg/5 mg, 20 mg/10 mg hard capsules
Czech Republic Kastel
Lithuania Ramostin 10 mg/5 mg, 10 mg/10 mg, 20 mg/5 mg, 20 mg/10 mg kietosios kapsulės
Latvia Ramostin 10 mg/5 mg, 10 mg/10 mg, 20 mg/5 mg, 20 mg/10 mg cietās kapsulas
Poland Kastel
Slovakia Rosuramlon 10 mg/5 mg, 10 mg/10 mg, 20 mg/5 mg, 20 mg/10 mg tvrdé kapsuly

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
EGIS Polska Sp. z o.o.
ul. Komitetu Obrony Robotników 45D
02-146 Warsaw
Tel.: +48 22 417 92 00