Co-prenessa 4 mg/1.25 mg tablets

Package leaflet: Information for the patient

Co-Prenessa 4 mg/1.25 mg tablets
tert-butylamine perindopril + indapamide
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, 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 effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Co-Prenessa is and what it is used for
2. What you need to know 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

Co-Prenessa is used to treat high blood pressure (hypertension), in cases where treatment with perindopril alone is not effective.
Co-Prenessa contains a combination of two active substances: perindopril and indapamide.
Perindopril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors.
Indapamide belongs to diuretics, which means medicines that increase the amount of urine produced by the kidneys.

2. Important information before using Co-Prenessa

When not to use Co-Prenessa:

• if the patient is allergic to perindopril or another ACE inhibitor;
• if the patient is allergic to indapamide or other sulfonamides;
• 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 during treatment with ACE inhibitors such as wheezing, facial or tongue swelling, severe itching, or severe skin rash, or if such symptoms occurred in the patient or in the patient's family under other circumstances (a condition called angioedema);
• in patients with severe liver function impairment or with signs of hepatic encephalopathy (degenerative brain disease);
• in patients with severe kidney function impairment or in dialysis patients;
• in patients with abnormally low or high blood potassium levels;
• in patients with suspected untreated, uncompensated heart failure (symptoms may include severe fluid retention and breathing difficulties);
• during pregnancy beyond 3 months (use of Co-Prenessa is also not recommended during early pregnancy – see "Pregnancy and breastfeeding");
• if the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren;
• if the patient has taken or is currently taking sacubitril with valsartan, a medicine used to treat certain types of chronic heart failure in adults, because the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) increases.

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

• if the patient has aortic valve stenosis (narrowing of the main blood vessel carrying blood from the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the blood vessel supplying blood to the kidney);
• if the patient has heart failure or any other heart disease;
• if the patient has kidney disease or is undergoing dialysis;
• if the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• if the patient has liver function disorders;
• if the patient has a collagen disease, such as systemic lupus erythematosus (a type of chronic inflammation) or scleroderma (a connective tissue disease);
• if the patient has atherosclerosis (hardening of the arteries);
• if the patient has hyperparathyroidism (a disorder of the parathyroid glands);
• if the patient has gout;
• if the patient has diabetes;
• if the patient is on a low-salt diet or uses salt substitutes containing potassium;
• if the patient is taking lithium;
• if the patient is taking potassium-sparing diuretics (spironolactone, triamterene), as these medicines should be avoided during treatment with Co-Prenessa (see "Co-Prenessa and other medicines");
• if the patient is elderly;
• if the patient has previously experienced photosensitivity reactions;
• if the patient is taking any of the following medicines used to treat high blood pressure:
• an angiotensin II receptor antagonist (ARB) (also known as sartans – for example, 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 the heading "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 than in patients of other races;
• if the patient is undergoing dialysis with high-flux membranes;
• if the patient is taking any of the following medicines, as the risk of angioedema (rapid swelling of the skin in areas such as the throat) increases:
• 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 the treatment of diabetes).

Angioedema
In patients treated with ACE inhibitors, including Co-Prenessa, cases of angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat, and difficulty swallowing or breathing) have been reported. 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 pregnancy. Use of Co-Prenessa is not recommended during early pregnancy and must not be taken beyond 3 months of pregnancy, as it may have very harmful effects on the unborn child after the third month of pregnancy (see "Pregnancy and breastfeeding").

When taking Co-Prenessa, inform your doctor or healthcare professional:

• if the patient is to undergo anaesthesia and/or surgery;
• if the patient has recently experienced diarrhoea or vomiting, or is dehydrated;
• if dialysis or LDL apheresis (removal of cholesterol from the blood using a special device) is planned;
• if desensitisation treatment is planned to reduce allergic reactions to bee or wasp stings;
• if a diagnostic test requiring an iodine-containing contrast agent (a substance allowing organs such as the kidney or stomach to be visualised in X-ray examinations) is to be performed;
• if vision disturbances or eye pain occur in one or both eyes during treatment with Co-Prenessa. These may be symptoms of fluid accumulation in the avascular membrane surrounding the eye (excessive fluid accumulation between the choroid and sclera) or glaucoma, increased pressure in one or both eyes – which may occur from several hours to several weeks after taking Co-Prenessa. If untreated, these conditions may lead to permanent vision loss. Patients with a previous history of allergy to penicillin or sulfonamides may be at higher risk of such reactions. Stop taking Co-Prenessa and consult your doctor immediately.

Athletes should be informed that Co-Prenessa contains an active substance (indapamide)
that may result in a positive anti-doping test.

Children
Co-Prenessa must not be used in children.

Co-Prenessa and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

Avoid using Co-Prenessa:

• with lithium (used to treat depression);
• with aliskiren (a medicine used to treat high blood pressure) in patients who do not have diabetes or kidney problems;
• with 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);
• with estramustine (used to treat cancer);
• with other medicines used to treat high blood pressure: angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists.

Tell your doctor if any of the following medicines are being taken, as they may interact with Co-Prenessa:

• other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (ARBs) or aliskiren (see also subsections "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 to treat hay fever or allergies);
• corticosteroids used to treat various medical conditions, including severe asthma and rheumatoid arthritis;
• immunosuppressive medicines used to treat autoimmune diseases or to prevent transplant rejection (e.g. cyclosporine, tacrolimus);
• medicines used to treat cancer;
• intravenous erythromycin (an antibiotic);
• halofantrine (used to treat certain types of malaria);
• cisapride or difemanil (used to treat gastrointestinal disorders);
• sparfloxacin or moxifloxacin (antibiotics used to treat infections);
• methadone;
• pentamidine (used to treat pneumonia);
• vincamine (used to treat cognitive symptoms in elderly patients);
• bepridil (used to treat angina pectoris);
• medicines used to treat heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, bretylium);
• digoxin or other cardiac glycosides (used in heart diseases);
• baclofen (used to treat muscle stiffness occurring in diseases such as multiple sclerosis);
• medicines used to treat diabetes, 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 doses of salicylates (e.g. acetylsalicylic acid);
• intravenous amphotericin B (used to treat severe fungal diseases);
• medicines used to treat psychiatric disorders such as depression, anxiety, schizophrenia, including tricyclic antidepressants and neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol);
• tetracosactide (used to treat Crohn's disease);
• vasodilating medicines, including nitrates;
• intravenous gold salts (used to treat rheumatoid arthritis);
• anaesthetics used before or during surgery;
• intravenous contrast agents used before a "special" type of X-ray examination;
• medicines most commonly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus or other medicines belonging to the so-called mTOR inhibitors). See section "Warnings and precautions";
• medicines used to treat low blood pressure, shock or asthma (e.g. ephedrine, noradrenaline or adrenaline).

The treating doctor may need to adjust the dose and/or take additional precautions:

• if the patient is taking an angiotensin II receptor antagonist (ARB) or aliskiren (see also information under the headings "When not to use Co-Prenessa:" and "Warnings and precautions"). If in doubt, consult your doctor.

Co-Prenessa with food and drink
It is recommended to take Co-Prenessa before a meal.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning pregnancy. Your doctor will usually recommend discontinuing Co-Prenessa before planned pregnancy or as soon as possible after pregnancy is confirmed, and will advise taking another medicine instead of Co-Prenessa. Co-Prenessa is not recommended during early pregnancy and must not be taken beyond 3 months of pregnancy, as it may have very harmful effects on the developing child if used after the third month of pregnancy.

Breastfeeding
Inform your doctor if you are breastfeeding or intend to breastfeed. Co-Prenessa is not recommended during breastfeeding. Your doctor may prescribe alternative treatment if you wish to breastfeed, especially if your baby is a newborn or premature.

Driving and operating machinery
Co-Prenessa does not affect the ability to drive or operate machinery. However, some patients may experience dizziness or fatigue related to low blood pressure. In such cases, the ability to drive or operate machinery may be impaired.

Co-Prenessa contains monohydrate lactose and sodium
If the patient has intolerance to certain sugars, they should consult their doctor before starting this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, so it can be considered essentially "sodium-free".

3. How to use Co-Prenessa

This medicine should always be used exactly as directed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
The recommended dose is one tablet daily.
Your doctor may adjust the dose if you have kidney problems.
The tablet should preferably be taken in the morning, before a meal. Swallow the tablet with a
glass of water.
Taking more Co-Prenessa than recommended
If you have taken too many tablets, contact your doctor or go to the nearest hospital emergency department immediately.
The most common symptom of overdose is low blood pressure. If significantly low blood pressure occurs
(associated with nausea, vomiting, cramps, dizziness, drowsiness, disorientation, changes in urine output),
lying down with your legs raised may help.
Missing a dose of Co-Prenessa
It is important to take the medicine regularly for it to be effective. If you miss a dose of Co-Prenessa,
take the next dose at your usual time.
Do not take a double dose to make up for a missed tablet.
Stopping Co-Prenessa
Treatment of high blood pressure is long-term; therefore, you should consult your doctor before stopping
this medicine.
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.
If any of the following adverse reactions occur in the patient, which may be
severe, treatment with this medicine should be discontinued and immediate contact with a doctor is required:

• 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 (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 body, intense itching, blistering, 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 indicate a 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 general 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 liver inflammation (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 if 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 sensation,
• Shortness of breath,
• Cough,
• Gastrointestinal disturbances (nausea and vomiting),
• Abdominal pain,
• Taste disturbances,
• Dyspepsia, 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 (red spots on the skin), clusters of blisters,
• Kidney function disorders,
• Excessive sweating,
• Impotence (inability to achieve or maintain erection),
• Increased number of eosinophils (a type of white blood cells),
• Changes in laboratory test results: high blood potassium levels, which resolve after discontinuation of treatment, low blood sodium levels, which may cause dehydration and low blood pressure,
• Drowsiness, fainting,
• Palpitations (awareness of heartbeat), tachycardia (fast heart rate),
• Hypoglycaemia (very low blood sugar levels) in diabetic patients,
• 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):

• Worsening 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 convulsions. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion),
• Reduced or absent urine output,
• Sudden flushing 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 decreased number of white and red blood cells,
• Decreased haemoglobin levels, decreased 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, decreased vision or eye pain due to increased pressure (possible symptoms of fluid accumulation in the uvea – excessive fluid accumulation between the 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,
• Bluish discoloration, numbness and pain in the 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 Reactions of Medicinal Products at 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 marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Co-Prenessa

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is 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".
Store in the original packaging to protect from moisture.
Store below 30°C.
Medicines must 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 Co-Prenessa contains

• The active substances are: perindopril with tert-butylamine and indapamide. Each tablet contains 4 mg of perindopril with tert-butylamine (equivalent to 3.34 mg of perindopril) and 1.25 mg of indapamide.
• Other ingredients are: microcrystalline cellulose, monohydrate lactose, sodium hydrogen carbonate, colloidal anhydrous silica, magnesium stearate. See section 2 "Co-Prenessa contains monohydrate lactose and sodium".

What Co-Prenessa looks like and contents of the pack
Elongated, white, slightly biconvex tablets with bevelled edges.
Pack: 30 tablets in blisters, 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