Co-prenessa

Package leaflet: Information for the patient

Co-Prenessa, 8 mg + 2.5 mg, tablets
tert-butylamine perindopril + indapamide
Please read this leaflet carefully before taking this medicine, because it contains
important information for the patient.

• 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 a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Co-Prenessa is and what it is used for
2. Important information before taking Co-Prenessa
3. How to take Co-Prenessa
4. Possible side effects
5. How to store Co-Prenessa
6. Contents of the pack and other information

1. What Co-Prenessa is and what it is used for

What Co-Prenessa is
Co-Prenessa is a combination of two active substances, perindopril and indapamide. Perindopril
belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors.
These medicines work by dilating blood vessels, which helps the heart pump blood more easily.
Indapamide is a diuretic medicine. Diuretics increase the amount of urine produced by the kidneys.
However, indapamide differs from other diuretics in that it causes only a slight increase in urine
production. Each of the active substances lowers blood pressure, and their combined action improves
blood pressure control.

What Co-Prenessa is used for
Co-Prenessa is an antihypertensive medicine used to treat high blood pressure (hypertension).
Co-Prenessa is intended for patients who have previously been treated with perindopril 8 mg and
indapamide 2.5 mg as separate medicines. These patients may now take one tablet of Co-Prenessa
8 mg + 2.5 mg containing both active substances, instead of taking separate tablets.

2. Important information before using Co-Prenessa

When not to use Co-Prenessa:

• if the patient is allergic to perindopril or any other ACE inhibitor;

• if the patient is allergic to indapamide or any other sulphonamide-type medicine;

• if the patient is allergic to any of the other ingredients of this medicine (listed in section 6);

• if the patient has previously experienced symptoms while taking ACE inhibitors such as wheezing, facial or tongue swelling, intense itching or severe skin rashes, or if such symptoms occurred in the patient or a family member under any other circumstances (a condition known as angioedema);

• in patients with severe liver disease or hepatic encephalopathy (a degenerative brain disorder);

• in patients with severe kidney disease or undergoing dialysis;

• in cases of increased or decreased potassium levels in the blood;

• in patients with suspected untreated, uncontrolled heart failure (symptoms may include fluid retention and breathing difficulties);

• after 3 months of pregnancy (use of Co-Prenessa is also advised to be avoided in early pregnancy – see "Pregnancy and breastfeeding");

• if the patient has diabetes or kidney impairment and is being treated with a blood pressure-lowering medicine containing aliskiren;

• if the patient has taken or is currently using sacubitril with valsartan, a medicine used to treat certain types of chronic (long-term) heart failure in adults, as this increases the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat).

Warnings and precautions
Before starting Co-Prenessa, discuss with your doctor or pharmacist if:

• the patient has aortic valve stenosis (narrowing of the main artery valve leaving the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the artery supplying blood to the kidney);
• the patient has heart failure or any other heart conditions;
• the patient has kidney disease or is undergoing dialysis;
• the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• the patient has liver disease;
• the patient has connective tissue diseases such as systemic lupus erythematosus or systemic sclerosis;
• the patient has atherosclerosis (hardening of the arterial walls);
• the patient has hyperparathyroidism (overactivity of the parathyroid glands);
• the patient has gout;
• the patient has diabetes;
• the patient is on a low-salt diet or uses salt substitutes containing potassium;
• the patient is taking lithium;
• the patient is taking potassium-sparing diuretics (e.g. spironolactone, triamterene); their use with Co-Prenessa should be avoided (see "Co-Prenessa with other medicines");
• the patient is elderly;
• the patient has previously experienced photosensitivity reactions;
• the patient is taking any of the following medicines used to treat high blood pressure:
  • an angiotensin II receptor antagonist (AIIRA), also known as a sartan – for example, valsartan, telmisartan, irbesartan, especially if the patient has kidney problems related to diabetes,
  • aliskiren. Your doctor may recommend regular monitoring of kidney function, blood pressure, and blood electrolyte levels (e.g. potassium). See also the section "When not to use Co-Prenessa".
• if the patient is of Black race – in such cases, there may be a higher risk of angioedema and the medicine may be less effective in lowering blood pressure compared to patients of other races;
• if the patient is undergoing dialysis using high-permeability membranes;
• if the patient is taking any of the following medicines, which increase the risk of angioedema (rapid swelling of the skin in areas such as the throat):
  • racecadotril (used to treat diarrhoea),
  • sirolimus, everolimus, temsirolimus and other medicines belonging to the so-called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment),
  • linagliptin, saxagliptin, sitagliptin, vildagliptin and other medicines belonging to the group of drugs called gliptins (used in diabetes treatment).

Angioedema
Angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat, and difficulty swallowing or breathing) has been reported in patients treated with ACE inhibitors, including Co-Prenessa. This reaction may occur at any time during treatment. If such symptoms occur, stop taking Co-Prenessa immediately and contact your doctor without delay. See also section 4.
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Use of Co-Prenessa is not recommended during the first trimester of pregnancy and must not be taken after 3 months of pregnancy, as it may seriously harm the unborn child (see "Pregnancy and breastfeeding").
Inform your doctor or medical staff if you are:

• planning anaesthesia and/or surgery,
• recently had diarrhoea, vomiting or dehydration,
• planning haemodialysis or LDL cholesterol apheresis (a procedure to remove cholesterol from the body using a special device),
• planning immunotherapy for bee or wasp venom,
• planning a diagnostic procedure involving intravenous iodine-containing contrast agents (substances used to visualise organs such as kidneys or stomach on X-ray images),
• experiencing vision disturbances or pain in one or both eyes while taking Co-Prenessa. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive fluid buildup between choroid and sclera) or glaucoma, increased pressure in one or both eyes – which may occur from a few hours to several weeks after taking Co-Prenessa. If untreated, these may lead to permanent vision loss. Patients with a history of penicillin or sulphonamide allergy may be at higher risk of such reactions. Stop taking Co-Prenessa and consult your doctor immediately.

The medicine contains an active substance (indapamide) that may give positive results in doping tests.
Children
Co-Prenessa must not be used in children.
Co-Prenessa with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Avoid taking Co-Prenessa with:

• lithium (used to treat depression),
• aliskiren (a medicine used to treat high blood pressure) in patients who do not have diabetes or kidney impairment;
• potassium-sparing diuretics (e.g. triamterene, amiloride), potassium salts, or other medicines that may increase potassium levels in the body (such as heparin and co-trimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole);
• estramustine (used to treat cancer),
• other medicines used to treat high blood pressure: ACE inhibitors and angiotensin II receptor antagonists.

Inform your doctor if you are taking any of the following medicines, as they may affect the action of Co-Prenessa:

• other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (AIIRAs) or aliskiren (see also sections "When not to use Co-Prenessa" and "Warnings and precautions"), or diuretics (medicines that increase urine output by the kidneys);
• potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses from 12.5 mg to 50 mg per day;
• a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to use Co-Prenessa" and "Warnings and precautions".
• procainamide (used to treat heart rhythm disorders),
• allopurinol (used to treat gout),
• terfenadine, astemizole or mizolastine (antihistamines used for hay fever or allergies),
• corticosteroids used to treat various diseases, including severe asthma and rheumatoid arthritis,
• immunosuppressive medicines used to treat autoimmune diseases or prevent organ transplant rejection (e.g. cyclosporine, tacrolimus),
• anticancer medicines,
• intravenous erythromycin (an antibiotic),
• halofantrine (used for certain types of malaria),
• cisapride or difemanil (used for gastrointestinal disorders),
• sparfloxacin or moxifloxacin (antibiotics used for infections),
• methadone,
• pentamidine (used for pneumonia),
• vincamine (used for memory disorders in the elderly),
• bepridil (used for angina),
• medicines used for heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, bretylium),
• digoxin or other cardiac glycosides (used to treat heart diseases),
• baclofen (used for muscle stiffness in conditions such as multiple sclerosis),
• antidiabetic medicines such as insulin, metformin or gliptins,
• calcium, including calcium supplements,
• stimulant laxatives (e.g. senna),
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or high-dose salicylates (e.g. aspirin),
• intravenous amphotericin B (used for severe fungal infections),
• medicines used for neurological disorders such as depression, anxiety and schizophrenia, including tricyclic antidepressants and neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol),
• tetracosactide (used for Crohn's disease),
• vasodilators, including nitrates,
• intravenous gold (used for arthritis), e.g. sodium aurothiomalate,
• anaesthetics administered before or during surgery,
• intravenous contrast agents used before certain radiological examinations,
• medicines most commonly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus or other mTOR inhibitors). See section "Warnings and precautions",
• medicines used most commonly to treat low blood pressure, shock or asthma (e.g. ephedrine, noradrenaline or adrenaline).

Your doctor may recommend a dose adjustment and/or additional precautions:

• if the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "When not to use Co-Prenessa" and "Warnings and precautions").

Co-Prenessa with food and drink
It is recommended to take Co-Prenessa before a meal.
Pregnancy and breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine.
Pregnancy
Inform your doctor if you are pregnant, suspect pregnancy, or are planning pregnancy. Your doctor will usually advise stopping Co-Prenessa before a planned pregnancy or as soon as possible after pregnancy is confirmed, and will recommend an alternative medicine. Use of Co-Prenessa is not recommended during early pregnancy and must not be taken after 3 months of pregnancy, as it may seriously harm the unborn child if used during this period.
Breastfeeding
Inform your doctor if you are breastfeeding or intend to breastfeed. Co-Prenessa is not recommended during breastfeeding, and your doctor may prescribe an alternative medicine if you wish to breastfeed.
Driving and operating machinery
Co-Prenessa does not affect the ability to drive or operate machinery. However, some patients may experience individual reactions such as dizziness or weakness due to lowered blood pressure. Before driving or operating machinery, ensure that such reactions do not occur in your case.
Co-Prenessa contains lactose and sodium
If you have an intolerance to certain sugars, consult your doctor before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which is considered essentially "sodium-free".
3 How to use Co-Prenessa
Always use this medicine exactly as prescribed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
The recommended dose is one tablet once daily.
Your doctor may decide to adjust the dosage if the patient has concomitant kidney disease.
It is recommended to take the tablet in the morning, before a meal.
Swallow the tablet with a glass of water.
Overdose of Co-Prenessa
If too many tablets are taken, contact your doctor immediately or go to the nearest hospital emergency department. The most likely symptom of overdose is low blood pressure.
If blood pressure drops significantly (accompanied by nausea, vomiting, cramps, dizziness, drowsiness, disorientation, or changes in urine output), lie down flat with legs raised above the level of the body.
Missed dose of Co-Prenessa
It is important to take the medicine daily, as the effectiveness of hypertension treatment depends on regular use. However, if a dose of Co-Prenessa is missed, take the next dose at the usual time. Do not take a double dose to make up for the missed dose.
Stopping Co-Prenessa
Since hypertension treatment usually lasts for life, contact your doctor before stopping treatment.
If you have any further questions about using 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.
If the patient experiences any of the following adverse reactions, which may be
serious, treatment with this medicine must be discontinued and medical advice must be sought immediately:

• Severe dizziness or fainting due to low blood pressure (common – may occur in less than 1 in 10 patients);
• Bronchospasm (feeling of tightness in the chest, wheezing and shortness of breath; uncommon – may occur in less than 1 in 100 patients);
• Swelling of the face, lips, mouth, tongue or throat, difficulty breathing – sudden allergic reaction with breathing difficulties and rash (angioedema, see section “Warnings and precautions” in section 2); uncommon – may occur in less than 1 in 100 patients;
• Severe skin reactions, including erythema multiforme (skin rash often starting with red, itchy spots on the face, arms or legs) or severe skin rash, urticaria, redness of the entire skin surface, intense itching, formation of blisters, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome) or other allergic reactions (very rare – may occur in less than 1 in 10,000 patients);
• Cardiovascular disorders (heart rhythm disturbances, angina pectoris (chest pain radiating to the jaw and back, caused by physical exertion), myocardial infarction; very rare – may occur in less than 1 in 10,000 patients);
• Weakness of the arms or legs, or speech disturbances, which may be signs of stroke (very rare – may occur in less than 1 in 10,000 patients);
• Pancreatitis, which may cause severe upper abdominal pain radiating to the back and severe malaise (very rare – may occur in less than 1 in 10,000 patients);
• Yellowing of the skin or eyes (jaundice), which may be a sign of hepatitis (very rare – may occur in less than 1 in 10,000 patients);
• Life-threatening heart rhythm disturbances (frequency unknown);
• Brain disease caused by liver disease (hepatic encephalopathy; frequency unknown);
• Muscle weakness, cramps, tenderness or pain, particularly when the patient also feels unwell or has a high temperature, which may be due to abnormal muscle breakdown (frequency unknown).

The following adverse reactions have been reported:
Common (may occur in less than 1 in 10 patients):

• Skin reactions in patients with a tendency to allergic and asthmatic reactions,
• Headache,
• Visual disturbances,
• Dizziness,
• Weakness (asthenia),
• Tinnitus,
• Vertigo (spinning sensation),
• Pricking and tingling sensations,
• Dyspnea,
• Cough,
• Gastrointestinal disturbances (nausea and vomiting),
• Abdominal pain,
• Taste disturbances,
• Indigestion, diarrhoea, constipation,
• Muscle cramps,
• Allergic reactions (such as skin rashes, itching),
• Feeling of fatigue,
• Low blood potassium levels.

Uncommon (may occur in less than 1 in 100 patients):

• Mood changes,
• Sleep disturbances,
• Depression,
• Urticaria, purpura (small red spots on the skin), clusters of blisters,
• Kidney function disorders,
• Excessive sweating,
• Impotence (inability to achieve or maintain erection),
• Increased eosinophil count (a type of white blood cells),
• Changes in laboratory test results: high blood potassium levels, which may resolve after discontinuation of treatment, low blood sodium levels, which may lead to dehydration and low blood pressure,
• Drowsiness, fainting,
• Palpitations (awareness of heartbeat), tachycardia (fast heart rate),
• Hypoglycaemia (very low blood sugar levels) in patients with diabetes,
• Vasculitis (inflammation of blood vessels),
• Dryness of the oral mucosa,
• Photosensitivity reactions (increased skin sensitivity to sunlight), joint pain, muscle pain, chest pain, malaise, peripheral oedema, fever, increased blood urea levels, increased blood creatinine levels,
• Falls.

Rare (may occur in less than 1 in 1,000 patients):

• Exacerbation of psoriasis,
• Changes in laboratory test results: increased liver enzyme activity, high serum bilirubin levels, low blood chloride levels, low blood magnesium levels,
• Fatigue,
• Dark urine, nausea or vomiting, muscle cramps, disorientation and seizures. These may be symptoms of a condition known as SIADH (syndrome of inappropriate antidiuretic hormone secretion),
• Reduced or absent urine output,
• Sudden redness of the face and neck,
• Acute kidney failure.

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

• Confusion,
• Nasal congestion or rhinitis (inflammation of the nasal mucosa),
• Eosinophilic pneumonia (a rare form of pneumonia),
• Blood test abnormalities such as reduced number of white and red blood cells,
• Decreased haemoglobin levels, reduced platelet count,
• High blood calcium levels,
• Liver function disorders.

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

• Abnormal heart function detected on ECG,
• Changes in laboratory test results: high blood uric acid levels and high blood glucose levels, myopia, blurred vision, visual disturbances, reduced vision or eye pain due to increased pressure (possible symptoms of fluid accumulation in the uvea surrounding the eye – excessive fluid accumulation between choroid and sclera – or acute angle-closure glaucoma),
• If the patient has systemic lupus erythematosus (a type of collagenosis), symptoms of the disease may worsen,
• Cyanosis, numbness and pain in fingers or toes (Raynaud's phenomenon).

Blood, kidney, liver or pancreas disorders and changes in laboratory test results (blood tests) may occur. The doctor may recommend blood tests to monitor the patient's health.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, the patient should inform their doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 responsible entity.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Co-Prenessa

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the abbreviation
"EXP". The expiry date refers to the last day of the stated month.
The batch number is indicated on the packaging after the abbreviation "Lot".
Do not store above 30°C.
Store in the original packaging to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Proper disposal helps protect the
environment.

6. Contents of the packaging and other information

What Co-Prenessa contains

• The active substances are perindopril tert-butylamine and indapamide. Each tablet contains 8 mg of perindopril tert-butylamine, equivalent to 6.68 mg of perindopril, and 2.5 mg of indapamide.
• The other ingredients are: monohydrate lactose, microcrystalline cellulose, sodium hydrogen carbonate, colloidal anhydrous silica, and magnesium stearate. See section 2 "Co-Prenessa contains monohydrate lactose and sodium".

What Co-Prenessa looks like and contents of the pack
Co-Prenessa is a white, oval, slightly biconvex tablet with a score line on one side. The score line is intended to facilitate breaking the tablet for easier swallowing and does not ensure equal dose division.
Pack sizes: 28, 30, 56, 60 or 100 tablets in blister packs contained in a cardboard box.

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
KRKA-POLSKA Sp. z o.o., Równoległa 5, 02-235 Warsaw, Poland
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For further information about product names in other European Economic Area countries, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5
02-235 Warsaw
Tel. 22 57 37 500