Cosyrel

Patient Information Leaflet

Cosyrel 5 mg/5 mg, film-coated tablets

bisoprolol fumarate/perindopril arginine
Please read all of this leaflet carefully before you start taking this medicine, as 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, pharmacist or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.
Contents of this leaflet:

1. What Cosyrel is and what it is used for
2. What you need to know before taking Cosyrel
3. How to take Cosyrel
4. Possible side effects
5. How to store Cosyrel
6. Package contents and other information

1. What Cosyrel is and what it is used for

Cosyrel contains two active substances in one tablet: bisoprolol fumarate and perindopril arginine.
Bisoprolol fumarate belongs to a group of medicines called beta-blockers. Beta-blockers slow down the heartbeat and make the heart more efficient at pumping blood throughout the body.
Perindopril arginine is an angiotensin-converting enzyme (ACE) inhibitor. It works by dilating blood vessels, thereby making it easier for the heart to pump blood through them.
Cosyrel is indicated for the treatment of high blood pressure (hypertension) and/or for the treatment of stable chronic heart failure (a condition in which the heart is unable to pump enough blood to meet the body's needs, resulting in shortness of breath and swelling), and/or to reduce the risk of cardiac events such as heart attack in patients with stable coronary artery disease (a condition in which blood supply to the heart is reduced or blocked) who have already had a heart attack and/or undergone a procedure to improve blood supply to the heart by widening the vessels that supply it.
Instead of taking separate tablets containing bisoprolol fumarate and perindopril arginine, you will take a single tablet of Cosyrel containing both active substances at the same dosage.

2. What you need to know before taking Cosyrel

Do not take Cosyrel if: you are allergic to bisoprolol or any other beta-blocker, to perindopril or any other ACE inhibitor, or to any of the other ingredients of this medicine (listed in section 6),
you suffer from heart failure that worsens suddenly and/or may require hospitalization,
you suffer from cardiogenic shock (a serious heart condition caused by very low blood pressure),
you have a heart disease characterized by a slow or irregular heartbeat (second- or third-degree atrioventricular block, sinoatrial block, sick sinus syndrome),
you have a slow heart rate,
you have particularly low blood pressure,
you suffer from severe asthma or severe chronic lung disease,
you suffer from serious circulation problems in the limbs (such as Raynaud's syndrome), which may cause tingling in the fingers of hands and feet, with skin turning pale or blue,
you have untreated phaeochromocytoma, a rare tumor of the adrenal gland (medulla),
you suffer from metabolic acidosis, a condition characterized by excessive accumulation of acids in the blood,
you have experienced symptoms such as shortness of breath, swelling of the face, tongue or throat, intense itching or severe skin rashes related to previous treatment with ACE inhibitors, or if you or a family member has ever experienced such symptoms under any circumstances (a condition called angioedema),
you are more than three months pregnant (it is advisable to avoid Cosyrel even during early pregnancy – see section “Pregnancy”),
you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren,
you are undergoing dialysis or any type of blood filtration. Depending on the equipment used, treatment with Cosyrel may not be suitable for you,
you have kidney problems due to reduced blood flow to the kidneys (renal artery stenosis),
you have taken or are currently taking sacubitril/valsartan, a medicine used to treat heart failure, because of an increased risk of angioedema (rapid swelling under the skin, for example in the throat) (see section “Warnings and precautions” and “Other medicines and Cosyrel”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Cosyrel if:
you have diabetes,
you have kidney problems (including kidney transplant) or are on dialysis,
you have liver problems,
you have aortic or mitral valve stenosis (narrowing of the main artery leaving the heart) or hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidneys),
you have abnormally high levels of a hormone called aldosterone in your blood (primary aldosteronism),
you suffer from heart failure or other heart problems, such as minor heart rhythm disorders or severe chest pain at rest (Prinzmetal's angina),
you have a collagen vascular disease (connective tissue disease) such as systemic lupus erythematosus or scleroderma,
you follow a low-salt diet or use salt substitutes containing potassium (excess potassium in the blood can cause changes in heart rhythm),
you have recently had diarrhea or vomiting, or are dehydrated (Cosyrel may cause a drop in blood pressure),
you are scheduled for LDL apheresis (blood purification from cholesterol using a machine),
you are undergoing allergy treatment or desensitization therapy to reduce the effects of an allergy to bee or wasp stings,
you are on a strict fast or diet,
you are scheduled for anesthesia and/or major surgery,
you have circulation problems in the hands and feet,
you suffer from asthma or chronic lung disease,
you have (or have had) psoriasis,
you have a tumor of the adrenal gland (phaeochromocytoma),
you have thyroid problems (Cosyrel may mask symptoms of overactive thyroid),
you experience symptoms of angioedema (a serious allergic reaction presenting with swelling of the face, lips, tongue or throat, difficulty swallowing or breathing). This may occur at any time during treatment. If you experience such symptoms, stop taking Cosyrel immediately and consult a doctor without delay,
you are of Black ethnicity, as you may have a higher incidence of angioedema and this medicine may be less effective in lowering blood pressure compared to patients of White ethnicity,
you are taking any of the following medicines used to treat high blood pressure:

• an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes,
• aliskiren. Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals. See also section "Do not take Cosyrel". Taking any of the following medicines increases the risk of angioedema:
• racecadotril (used to treat diarrhea),
• sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment),
• sacubitril (available as a fixed-dose combination with valsartan), used for long-term treatment of heart failure,
• linagliptin, saxagliptin, sitagliptin, vildagliptin and other medicines belonging to the class of so-called gliptins (used in the treatment of diabetes).

Do not stop taking Cosyrel suddenly, as this may cause a serious worsening of heart conditions. Treatment should not be stopped abruptly, especially in patients with coronary artery disease.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Cosyrel is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn child if taken during this period (see section “Pregnancy”).
For athletes: using this medicine without medical need constitutes doping and may lead to a positive anti-doping test.

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

Other medicines and Cosyrel
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Some medicines may alter the effect of Cosyrel, or the effect of these medicines may be altered by Cosyrel. Such interactions may reduce the effect of one or both medicines. Alternatively, they may increase the risk or severity of side effects.
Make sure to inform your doctor if you are taking any of the following medicines:
medicines used to control blood pressure or medicines used to treat heart problems (such as amiodarone, amlodipine, clonidine, digitalis glycosides, diltiazem, disopyramide, felodipine, flecainide, lidocaine, methyldopa, moxonidine, procainamide, propafenone, quinidine, rilmenidine, verapamil),
other medicines for treating hypertension, including angiotensin II receptor antagonists (AIIRAs), aliskiren (see also section "Do not take Cosyrel" and "Warnings and precautions"), or diuretics (medicines that increase the amount of urine produced by the kidneys),
potassium-sparing medicines (e.g. triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, other medicines that may increase potassium levels in the blood (such as heparin, a medicine used to thin the blood and prevent clotting; trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole, used to treat bacterial infections),
potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg daily,
sympathomimetic agents used to treat clinical shock (e.g. adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine),
estramustine used in cancer therapy,
medicines used mainly to treat diarrhea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors). See section “Warnings and precautions”,
sacubitril/valsartan (used for long-term treatment of heart failure). See section “Do not take Cosyrel” and “Warnings and precautions”,
lithium used to treat mania or depression,
some medicines used to treat depression, such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors),
medicines for treating schizophrenia (antipsychotics),
medicines for treating epilepsy (phenytoin, barbiturates such as phenobarbital),
anesthetic agents used in surgery,
vasodilators, including nitrates (medicines that dilate blood vessels),
trimethoprim used to treat infections,
immunosuppressants (medicines that suppress the body's defense mechanisms) such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after surgical transplantation,
allopurinol used to treat gout,
parasympathomimetic medicines used to treat conditions such as Alzheimer's disease or glaucoma,
topical beta-blockers used to treat glaucoma (increased eye pressure),
mefloquine used to prevent or treat malaria,
baclofen used to treat muscle stiffness in diseases such as multiple sclerosis,
gold salts, especially administered intravenously (used to treat symptoms of rheumatoid arthritis),
medicines for treating diabetes such as insulin, metformin, linagliptin, saxagliptin, sitagliptin, vildagliptin,
non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac or high doses of acetylsalicylic acid used to treat arthritis, headache, pain or inflammation.

Cosyrel with food, drinks and alcohol
It is preferable to take Cosyrel before meals.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Cosyrel before becoming pregnant or as soon as you know you are pregnant, and will recommend another medicine instead of Cosyrel. Cosyrel is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn child if taken after the third month of pregnancy.
Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. Cosyrel is not recommended for women who are breastfeeding, and your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is a newborn or was born prematurely.

Driving and using machines
Cosyrel usually does not affect alertness, but in some patients side effects such as dizziness or fatigue may occur due to lowered blood pressure, particularly at the start of treatment, when changing dosage, or when taken together with alcohol. If you experience such symptoms, your ability to drive or operate machinery may be impaired.

Cosyrel contains sodium
Cosyrel contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially "sodium-free".

3. How to take Cosyrel

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended dose is one tablet daily. Take the tablet with a glass of
water, in the morning before a meal.
In some cases, your doctor may prescribe half a tablet of Cosyrel once daily, in the morning before
a meal.
Patients with kidney disease
If you have moderate kidney disease, your doctor may prescribe half a tablet of Cosyrel.
Cosyrel is not recommended in cases of severe kidney disease.
Use in children and adolescents
Use in children and adolescents is not recommended.
If you take more Cosyrel than you should
If you have taken more tablets than prescribed, contact your doctor or pharmacist immediately.
The most likely effect in case of overdose is a drop in blood pressure, which may
cause dizziness or weakness (if this occurs, lying down with legs elevated may help),
severe breathing difficulties, tremors (due to low blood sugar), and
slowing of the heartbeat.
If you forget to take Cosyrel
It is important to take the medicine every day, as regular treatment is more effective. However,
if you forget to take a dose of Cosyrel, take the next dose as usual. Do not take a
double dose to make up for the missed dose.
If you stop taking Cosyrel
Do not stop taking Cosyrel suddenly and do not change the dose without first consulting your
doctor, as this may cause a serious worsening of heart conditions. Treatment must not
be stopped abruptly, especially in patients with coronary heart disease.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking this medicine and contact your doctor immediately if you experience any of the
following side effects:
severe dizziness or fainting due to low blood pressure (common – may affect up to 1 in 10 people),
worsening of heart failure causing shortness of breath and/or fluid retention (common – may affect up to 1 in 10 people),
swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (uncommon – may affect up to 1 in 100 people),
sudden breathing difficulty, chest pain, shortness of breath or trouble breathing (bronchospasm) (uncommon – may affect up to 1 in 100 people),
unusually fast or irregular heartbeat, chest pain (angina) or heart attack (very rare – may affect up to 1 in 10,000 people),
weakness in the arms or legs or speech problems which could be signs of a possible stroke (very rare – may affect up to 1 in 10,000 people),
inflamed pancreas which may cause severe abdominal pain and back pain accompanied by a strong feeling of illness (very rare – may affect up to 1 in 10,000 people),
yellowing of the skin or eyes (jaundice) which may be a sign of hepatitis (very rare – may affect up to 1 in 10,000 people),
skin rashes which often begin with red, itchy spots on the face, arms or legs (erythema multiforme) (very rare – may affect up to 1 in 10,000 people).

Cosyrel is generally well tolerated, but as with any medicine, people may experience different side effects, particularly at the beginning of treatment.
If you experience any of the following side effects or any other side effect not listed in this leaflet,
contact your doctor or pharmacist immediately:

Very common (may affect more than 1 in 10 people):
slow heartbeat.

Common (may affect up to 1 in 10 people):
headache,
dizziness,
vertigo,
taste disturbances,
tingling sensation,
tingling or numbness in hands or feet,
vision disturbances,
tinnitus (ringing in the ears),
cold sensation in hands and feet,
cough,
shortness of breath,
gastrointestinal disturbances such as nausea, vomiting, abdominal pain, indigestion or dyspepsia, diarrhoea, constipation,
allergic reactions such as skin rashes, itching,
muscle cramps,
feeling of tiredness,
fatigue.

Uncommon (may affect up to 1 in 100 people):
mood changes,
sleep disorders,
depression,
dry mouth,
intense itching or severe skin rashes,
formation of clusters of blisters on the skin,
increased skin sensitivity to sunlight (photosensitivity reaction),
sweating,
kidney problems,
impotence,
increased eosinophils (a type of white blood cells),
drowsiness,
fainting,
palpitations,
tachycardia,
irregular heart rhythm (AV conduction disturbances), inflammation of blood vessels (vasculitis),
dizziness upon standing,
muscle weakness,
arthralgia (joint pain),
myalgia (muscle pain),
chest pain,
malaise,
localized swelling (peripheral oedema),
fever,
risk of falls,
laboratory test abnormalities: high blood potassium levels (reversible upon discontinuation of treatment), low sodium levels, very low blood sugar levels (hypoglycaemia) in diabetic patients, increased blood urea and increased plasma creatinine.

Rare (may affect up to 1 in 1,000 people):
acute kidney failure,
dark-coloured urine, feeling unwell (nausea) or being unwell (vomiting), muscle cramps, confusion and seizures. These symptoms may be related to a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion),
reduced or absent urine output,
flushing,
nightmares, hallucinations,
reduced tear flow (dry eyes),
hearing problems,
liver inflammation causing yellowing of the skin or whites of the eyes,
runny nose due to allergy, sneezing,
allergic-type reactions such as itching, redness, skin rashes,
worsening of psoriasis,
laboratory test abnormalities: increased liver enzyme levels, high serum bilirubin levels, abnormal fat levels.

Very rare (may affect up to 1 in 10,000 people):
confusion,
eye irritation and redness (conjunctivitis),
eosinophilic pneumonia (a rare type of pneumonia),
inflammation of the pancreas (causing severe abdominal and back pain),
hair loss,
onset or worsening of scaly skin rash (psoriasis), skin rashes resembling psoriasis,
changes in blood values such as decreased white blood cell and red blood cell counts, decreased haemoglobin, decreased platelet count in the blood.

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

• Abnormal colour, numbness and pain in fingers of hands or feet (Raynaud's phenomenon).

If you experience these symptoms, contact your doctor immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cosyrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
After opening, Cosyrel should be used within 20 days for packs containing 10 film-coated tablets, 60 days for packs containing 28 or 30 film-coated tablets, and 100 days for packs containing 100 film-coated tablets.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Cosyrel contains
The active substances are bisoprolol fumarate and perindopril arginine. Each Cosyrel tablet contains
5 mg of bisoprolol fumarate, equivalent to 4.24 mg of bisoprolol, and 5 mg of perindopril arginine,
equivalent to 3.395 mg of perindopril.
The other components are microcrystalline cellulose PH 102 (E460), calcium carbonate (E170), pregelatinized
corn starch, sodium glycolate starch type A (E468), anhydrous colloidal silica (E551),
magnesium stearate (Liga E572), sodium croscarmellose (E468), glycerol (E422), hypromellose (E464),
Macrogol 6000, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and
purified water.
Description of the appearance of Cosyrel and pack contents
Cosyrel is a film-coated, pinkish-beige, oblong, two-layered, scored tablet, with a break line on one side and engraved

with ‘ ’ on one side and ‘5/5’ on the other. The tablet can be divided into two equal parts.
Tablets are available in packs of 10, 28, 30, 84 (3 packs of 28 tablets), 90 (3 packs of 30), 100 and 120 (4 packs of 30) film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes Cedex
France
Manufacturers
Les Laboratoires Servier Industrie (LSI)
905, route de Saran
45520 Gidy
France
Servier (Ireland) Industries Ltd (SII)
Moneylands, Gorey Road
Arklow - Co. Wicklow
Ireland
Anpharm Przedsiebiorstwo Farmaceutyczne S.A.
03-236 Warszawa, ul. Annopol 6b
Poland
EGIS Pharmaceuticals PLC
H- 9900 Körmend, Mátyás király u. 65,
Hungary
This medicinal product is authorised in the European Economic Area countries under the following
names:
Belgium Bipressil 5mg/5mg film-coated tablet
Bulgaria Prestilol 5mg/5mg film-coated tablets
Croatia Prestilol 5mg/5mg film-coated tablets
Cyprus Cosyrel 5mg/5mg film-coated tablets
Czech Republic Cosyrel 5mg/5mg, coated tablets
Estonia Prestilol
Finland Cosyrel 5mg/5mg film-coated tablet
France Cosimprel 5mg/5mg film-coated tablet
Greece Cosyrel 5mg/5mg film-coated tablets
Hungary Cosyrel 5mg/5mg film-coated tablet
Ireland Cosimprel 5mg/5mg film-coated tablet
Italy Cosyrel
Latvia Prestilol 5mg/5mg coated tablets
Lithuania Prestilol 5mg/5mg film-coated tablets
Luxembourg Bipressil 5mg/5mg film-coated tablet
Netherlands Cosimprel 5mg/5mg film-coated tablets
Poland Prestilol
Portugal Cosyrel 5mg/5mg
Romania Cosyrel 5mg/5mg film-coated tablets
Slovakia Prestilol 5mg/5mg film-coated tablets
Slovenia Cosyrel 5mg/5mg film-coated tablets

Package leaflet: Information for the patient

Cosyrel 5 mg/10 mg, film-coated tablets

bisoprolol fumarate/perindopril arginine
Please read this leaflet carefully before taking this medicine as it contains important information for you.
Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
Contents of this leaflet:

1. What Cosyrel is and what it is used for
2. What you need to know before taking Cosyrel
3. How to take Cosyrel
4. Possible side effects
5. How to store Cosyrel
6. Contents of the pack and other information

1. What is Cosyrel and what is it used for?

Cosyrel contains two active substances in one tablet: bisoprolol fumarate and perindopril arginine.
Bisoprolol fumarate belongs to a group of medicines called beta-blockers. Beta-blockers slow down the heartbeat and make the heart more efficient at pumping blood throughout the body.
Perindopril arginine is an angiotensin-converting enzyme (ACE) inhibitor. It works by dilating blood vessels, thereby making it easier for the heart to pump blood through them.
Cosyrel is indicated for the treatment of high blood pressure (hypertension) and/or for reducing the risk of cardiovascular events, such as heart attack, in patients with stable coronary heart disease (a condition in which blood supply to the heart is reduced or blocked) who have previously had a heart attack and/or undergone a procedure to improve blood supply to the heart by widening the vessels that supply it.
Instead of taking separate tablets of bisoprolol fumarate and perindopril arginine, you will take only one tablet of Cosyrel containing both active substances at the same dosage.

2. What you need to know before taking Cosyrel

Do not take Cosyrel if:

you are allergic to bisoprolol or any other beta-blocker, to perindopril or any other ACE inhibitor, or to any of the other ingredients of this medicine (listed in section 6),
you suffer from heart failure that suddenly worsens and/or that may require hospitalization,
you suffer from cardiogenic shock (a serious heart condition caused by very low blood pressure),
you suffer from a heart disease characterized by a slow or irregular heartbeat (second- or third-degree atrioventricular block, sinoatrial block, sick sinus syndrome),
you have a slow heart rate,
you have particularly low blood pressure,
you suffer from severe asthma or severe chronic lung disease,
you suffer from severe circulation problems in the limbs (such as Raynaud's syndrome), which may cause tingling in the fingers of hands and feet, with the skin becoming pale or blue,
you suffer from untreated phaeochromocytoma, a rare tumor of the adrenal gland (medulla),
you suffer from metabolic acidosis, a condition in which there is excessive accumulation of acids in the blood,
you have experienced symptoms such as shortness of breath, swelling of the face, tongue or throat, intense itching or severe skin rashes related to previous treatment with ACE inhibitors, or if you or a family member has experienced such symptoms in any other circumstance (a disorder called angioedema),
you are more than three months pregnant (it is better to avoid Cosyrel even in the early stages of pregnancy – see section “Pregnancy”),
you suffer from diabetes or have impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren,
you are undergoing dialysis or any type of blood filtration. Depending on the equipment used, treatment with Cosyrel may not be suitable for you,
you have kidney problems due to reduced blood flow to the kidneys (renal artery stenosis),
you have taken or are currently taking sacubitril/valsartan, a medicine used to treat heart failure, because of an increased risk of angioedema (rapid swelling under the skin, for example in the throat) (see information under “Warnings and precautions” and “Other medicines and Cosyrel”).

Warnings and precautions

Talk to your doctor or pharmacist before taking Cosyrel if:

you have diabetes,
you have kidney problems (including a kidney transplant) or you are on dialysis,
you have liver problems,
you have aortic or mitral valve stenosis (narrowing of the main artery leaving the heart) or hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidneys),
you have abnormally high levels of a hormone called aldosterone in your blood (primary hyperaldosteronism),
you suffer from heart failure or other heart problems, such as minor heart rhythm disorders or severe chest pain at rest (Prinzmetal's angina),
you have a collagen vascular disease (connective tissue disease) such as systemic lupus erythematosus or scleroderma,
you are on a low-salt diet or use salt substitutes containing potassium (too much potassium in the blood can cause changes in heart rhythm),
you have recently had diarrhea or vomiting, or are dehydrated (Cosyrel can cause a drop in blood pressure),
you are scheduled to undergo LDL apheresis (blood purification from cholesterol using a machine),
you are receiving anti-allergy treatment or are scheduled to undergo desensitization therapy to reduce the effects of an allergy to bee or wasp stings,
you are on a strict fast or diet,
you are scheduled to undergo anesthesia and/or major surgery,
you suffer from circulation problems in the hands and feet,
you suffer from asthma or chronic lung disease,
you have (or have had) psoriasis,
you have a tumor of the adrenal gland (phaeochromocytoma),
you suffer from thyroid problems (Cosyrel may mask symptoms of an overactive thyroid),
you experience symptoms of angioedema (a severe allergic reaction characterized by swelling of the face, lips, tongue or throat, with difficulty swallowing or breathing). This may occur at any time during treatment. If you experience such symptoms, stop taking Cosyrel and consult a doctor immediately,
you are of Black ethnicity, as you may have a higher incidence of angioedema and this medicine may be less effective in lowering blood pressure compared to White patients,
you are taking any of the following medicines used to treat high blood pressure:

• an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans – for example valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.
• aliskiren. Your doctor may monitor your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood at regular intervals. See also information under "Do not take Cosyrel".
• you are taking any of the following medicines, which increase the risk of angioedema:
• racecadotril (used to treat diarrhea),
• sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment),
• sacubitril (available as a fixed-dose combination with valsartan), used in long-term treatment of heart failure,
• linagliptin, saxagliptin, sitagliptin, vildagliptin and other medicines belonging to the class of so-called gliptins (used in the treatment of diabetes).

Do not stop taking Cosyrel suddenly, as this may cause serious worsening of heart conditions. Treatment must not be stopped abruptly, especially in patients with coronary heart disease.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Cosyrel is not recommended during early pregnancy, and must not be taken if you are more than three months pregnant, as it may cause serious harm to the baby if taken during this period (see section “Pregnancy”).
For those engaged in sports: using the drug without therapeutic need constitutes doping and may result in a positive anti-doping test.

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

Other medicines and Cosyrel
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Some medicines may alter the effect of Cosyrel or the effect of these medicines may be altered by Cosyrel. This type of interaction may reduce the effect of one or both medicines. Alternatively, it may increase the risk or severity of side effects.
Make sure to inform your doctor if you are taking any of the following medicines:
medicines used to control blood pressure or medicines used to treat heart problems (such as amiodarone, amlodipine, clonidine, digitalis glycosides, diltiazem, disopyramide, felodipine, flecainide, lidocaine, methyldopa, moxonidine, procainamide, propafenone, quinidine, rilmenidine, verapamil),
other medicines for the treatment of hypertension, including angiotensin II receptor antagonists (AIIRAs), aliskiren (see also information under "Do not take Cosyrel" and "Warnings and precautions"), or diuretics (medicines that increase the amount of urine produced by the kidneys),
potassium-sparing medicines (e.g. triamterene, amiloride), potassium supplements or salt substitutes containing potassium, other drugs that may increase potassium levels in the blood (such as heparin, a medicine used to thin the blood and prevent clot formation; trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole for the treatment of bacterial infections),
potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg per day,
sympathomimetic agents used to treat clinical shock (e.g. adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine),
estramustine used in cancer therapy,
medicines used mainly to treat diarrhea (racecadotril) or to prevent transplant rejection (sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors). See section “Warnings and precautions”,
sacubitril/valsartan (used for long-term treatment of heart failure). See information under “Do not take Cosyrel” and “Warnings and precautions”,
lithium used to treat mania or depression,
some medicines used to treat depression, such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors),
medicines for the treatment of schizophrenia (antipsychotics),
medicines for the treatment of epilepsy (phenytoin, barbiturates such as phenobarbital),
anesthetic agents used in surgery,
vasodilators, including nitrates (medicines that dilate blood vessels),
trimethoprim used to treat infections,
immunosuppressants (medicines capable of suppressing the body's defense mechanisms) such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after surgical transplantation,
allopurinol for the treatment of gout,
parasympathomimetic medicines used to treat conditions such as Alzheimer's disease or glaucoma,
topical beta-blockers used to treat glaucoma (increased eye pressure),
mefloquine used to prevent or treat malaria,
baclofen used to treat muscle stiffness in diseases such as multiple sclerosis,
gold salts, especially when administered intravenously (used to treat symptoms of rheumatoid arthritis),
medicines for the treatment of diabetes such as insulin, metformin, linagliptin, saxagliptin, sitagliptin, vildagliptin,
non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac or high doses of acetylsalicylic acid used to treat arthritis, headache, pain or inflammation.

Cosyrel with food, drinks and alcohol
It is preferable to take Cosyrel before meals.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will normally advise you to stop taking Cosyrel before becoming pregnant or as soon as you know you are pregnant, and will recommend another medicine instead of Cosyrel. Cosyrel is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the baby if taken after the third month of pregnancy.

Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. Cosyrel is not recommended for women who are breastfeeding, and your doctor may choose another treatment if you wish to breastfeed, especially if your baby is a newborn or was born prematurely.

Driving and using machines
Cosyrel usually does not affect alertness, but in some patients side effects such as dizziness or fatigue may occur due to reduced blood pressure, particularly at the beginning of treatment, when the dose is changed, or when combined with alcohol. If you experience such symptoms, your ability to drive or operate machinery may be impaired.

Cosyrel contains sodium
Cosyrel contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially “sodium-free”.

3. How to take Cosyrel

Take this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended dose is one tablet daily. Take the tablet with a glass of
water, in the morning before a meal.
In some cases, your doctor may prescribe half a tablet of Cosyrel once daily, in the morning before
a meal.
Patients with kidney disease
Cosyrel is not recommended in cases of moderate to severe kidney disease.
Use in children and adolescents
Use in children and adolescents is not recommended.
If you take more Cosyrel than you should
If you have taken more tablets than prescribed, contact your doctor or pharmacist immediately.
The most likely effect in case of overdose is a drop in blood pressure which may
cause dizziness or weakness (if this occurs, lying down with your legs raised may be helpful),
severe breathing difficulties, tremors (due to low blood sugar levels), and
slowing of the heartbeat.
If you forget to take Cosyrel
It is important to take the medicine every day, as regular treatment is more effective. If, however,
you forget to take a dose of Cosyrel, take the next dose as usual. Do not take a
double dose to make up for the missed dose.
If you stop taking Cosyrel
Do not stop taking Cosyrel suddenly and do not change the dose without first consulting your
doctor, as this may cause a serious worsening of heart conditions. Treatment must not
be stopped abruptly, especially in patients with coronary heart disease.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop taking this medicine and inform your doctor immediately if you experience any of the
following side effects:
severe dizziness or fainting due to low blood pressure (common – may affect up to 1 in 10 people),
worsening of heart failure causing shortness of breath and/or fluid retention (common – may affect up to 1 in 10 people),
swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (uncommon – may affect up to 1 in 100 people),
sudden breathing difficulty, chest pain, shortness of breath or breathing problems (bronchospasm) (uncommon – may affect up to 1 in 100 people),
unusually fast or irregular heartbeat, chest pain (angina) or heart attack (very rare – may affect up to 1 in 10,000 people),
weakness in the arms or legs or speech problems which could be signs of a possible stroke (very rare – may affect up to 1 in 10,000 people),
inflamed pancreas which may cause severe abdominal pain and back pain accompanied by a feeling of severe illness (very rare – may affect up to 1 in 10,000 people),
yellowing of the skin or eyes (jaundice) which may be a sign of hepatitis (very rare – may affect up to 1 in 10,000 people),
skin rashes that often begin with red, itchy spots on the face, arms or legs (erythema multiforme) (very rare – may affect up to 1 in 10,000 people).

Cosyrel is generally well tolerated, but, as with any medicine, people may experience various side effects, particularly at the beginning of treatment.
If you experience any of the following side effects or any other side effect not listed in this leaflet, inform your doctor or pharmacist immediately:

Very common (may affect more than 1 in 10 people):
slow heartbeat.

Common (may affect up to 1 in 10 people):
headache,
dizziness,
vertigo,
taste disturbances,
tingling sensation,
tingling or numbness in hands or feet,
vision disorders,
tinnitus (ringing or noise in the ears),
cold sensation in hands and feet,
cough,
shortness of breath,
gastrointestinal disturbances such as nausea, vomiting, abdominal pain, indigestion or dyspepsia, diarrhoea,
constipation,
allergic reactions such as skin rashes, itching,
muscle cramps,
feeling of fatigue,
tiredness.

Uncommon (may affect up to 1 in 100 people):
mood changes,
sleep disorders,
depression,
dry mouth,
intense itching or severe skin rashes,
formation of clusters of blisters on the skin,
increased skin sensitivity to sunlight (photosensitivity reaction),
sweating,
kidney problems,
impotence,
elevated eosinophils (a type of white blood cells),
drowsiness,
fainting,
palpitations,
tachycardia,
irregular heartbeat (AV conduction disturbances),
inflammation of blood vessels (vasculitis),
dizziness when standing up,
muscle weakness,
arthralgia (joint pain),
myalgia (muscle pain),
chest pain,
malaise,
localized swelling (peripheral oedema),
fever,
risk of falls,
changes in laboratory parameters: high potassium levels in blood (reversible upon discontinuation of treatment), low sodium levels, very low blood sugar levels (hypoglycaemia) in diabetic patients, increased blood urea and increased plasma creatinine.

Rare (may affect up to 1 in 1,000 people):
acute renal failure,
dark-coloured urine, feeling unwell (nausea) or being unwell (vomiting), muscle cramps, confusion and seizures. These symptoms may be related to a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion),
reduction or absence of urine,
flushing,
nightmares, hallucinations,
reduced tear flow (dry eyes),
hearing problems,
liver inflammation causing yellowing of the skin or whites of the eyes,
allergic runny nose, sneezing,
allergic-type reactions such as itching, redness, skin rashes,
worsening of psoriasis,
changes in laboratory parameters: increased liver enzyme levels, elevated serum bilirubin, abnormal lipid levels.

Very rare (may affect up to 1 in 10,000 people):
confusion,
eye irritation and redness (conjunctivitis),
eosinophilic pneumonia (a rare type of pneumonia),
inflammation of the pancreas (causing severe abdominal and back pain),
hair loss,
appearance or worsening of scaly skin rash (psoriasis), psoriasis-like rashes,
changes in blood values such as reduced numbers of white and red blood cells, reduced haemoglobin, reduced platelet count in blood.

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

• Abnormal colour, numbness and pain in fingers of hands or feet (Raynaud's phenomenon). If you experience these symptoms, consult your doctor immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cosyrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Once opened, Cosyrel must be used within 20 days for packs containing 10 film-coated tablets, 60 days for packs containing 28 or 30 film-coated tablets, and 100 days for packs containing 100 film-coated tablets.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Cosyrel contains
The active substances are bisoprolol fumarate and perindopril arginine. Each tablet of Cosyrel contains
5 mg of bisoprolol fumarate, equivalent to 4.24 mg of bisoprolol, and 10 mg of perindopril arginine,
equivalent to 6.790 mg of perindopril.
The other components are microcrystalline cellulose PH 102 (E460), calcium carbonate (E170),
pregelatinized maize starch, sodium starch glycolate type A (E468), anhydrous colloidal silica (E551),
magnesium stearate (Liga E572), sodium croscarmellose (E468), glycerol (E422), hypromellose (E464),
Macrogol 6000, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and
purified water.
Description of the appearance of Cosyrel and package contents
Cosyrel is a pinkish-beige, oval, film-coated tablet with a double-layered score line, engraved

with ‘ ’ on one side and ‘5/10’ on the other. The tablet can be divided into two equal parts.
Tablets are available in packs of 10, 28, 30, 84 (3 containers of 28 tablets), 90 (3 containers
of 30 tablets), 100 and 120 (4 containers of 30 tablets) film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes Cedex
France
Manufacturers
Les Laboratoires Servier Industrie (LSI)
905, route de Saran
45520 Gidy
France
Servier (Ireland) Industries Ltd (SII)
Moneylands, Gorey Road
Arklow - Co. Wicklow
Ireland
Anpharm Przedsiebiorstwo Farmaceutyczne S.A.
03-236 Warszawa, ul. Annopol 6b
Poland
EGIS Pharmaceuticals PLC
H- 9900 Körmend, Mátyás király u. 65,
Hungary
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Belgium Bipressil 5mg/10mg film-coated tablet
Bulgaria Prestilol 5mg/10mg film-coated tablets
Croatia Prestilol 5mg/10mg film-coated tablets
Cyprus Cosyrel 5mg/10mg film-coated tablets
Czech Republic Cosyrel 5mg/10mg, coated tablets
Estonia Prestilol
Finland Cosyrel 5mg/10mg film-coated tablet
France Cosimprel 5mg/10mg, film-coated tablet
Greece Cosyrel 5mg/10mg film-coated tablets
Hungary Cosyrel 5mg/10mg film-coated tablet
Ireland Cosimprel 5mg/10mg film-coated tablet
Italy Cosyrel
Latvia Prestilol 5mg/10mg film-coated tablets
Lithuania Prestilol 5mg/10mg film-coated tablets
Luxembourg Bipressil 5mg/10mg film-coated tablet
Netherlands Cosimprel 5mg/10mg film-coated tablets
Poland Prestilol
Portugal Cosyrel 5mg/10mg
Romania Cosyrel 5mg/10mg film-coated tablets
Slovakia Prestilol 5mg/10mg film-coated tablets
Slovenia Cosyrel 5mg/10mg film-coated tablets

Patient Information Leaflet

Cosyrel 10 mg/5 mg, film-coated tablets

bisoprolol fumarate/perindopril arginine
Please read this entire leaflet carefully before taking this medicine, because it contains important information for you.
Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
Contents of this leaflet:

1. What Cosyrel is and what it is used for
2. What you need to know before taking Cosyrel
3. How to take Cosyrel
4. Possible side effects
5. How to store Cosyrel
6. Contents of the pack and other information

1. What Cosyrel is and what it is used for

Cosyrel contains two active substances in one tablet: bisoprolol fumarate and perindopril arginine.
Bisoprolol fumarate belongs to a group of medicines called beta-blockers. Beta-blockers slow down the heartbeat and make the heart more efficient at pumping blood throughout the body.
Perindopril arginine is an angiotensin-converting enzyme (ACE) inhibitor. It works by dilating blood vessels, making it easier for the heart to pump blood through them.
Cosyrel is indicated for the treatment of high blood pressure (hypertension) and/or for the treatment of stable chronic heart failure (a condition in which the heart is unable to pump enough blood to meet the body's needs, resulting in shortness of breath and swelling), and/or to reduce the risk of cardiac events, such as heart attack, in patients with stable coronary artery disease (a condition in which blood supply to the heart is reduced or blocked) who have already had a heart attack and/or undergone a procedure to improve blood supply to the heart by widening the vessels that supply it.
Instead of taking separate tablets of bisoprolol fumarate and perindopril arginine, you will take a single tablet of Cosyrel containing both active substances at the same dosage.

2. What you need to know before taking Cosyrel

Do not take Cosyrel if:
you are allergic to bisoprolol or any other beta-blocker, to perindopril or any other ACE inhibitor, or to any of the other ingredients of this medicine (listed in section 6),
you suffer from heart failure that suddenly worsens and/or may require hospitalization,
you suffer from cardiogenic shock (a serious heart condition caused by very low blood pressure),
you have a heart disease characterized by a slow or irregular heartbeat (second or third degree atrioventricular block, sinoatrial block, sick sinus syndrome),
you have a slow heart rate,
you have particularly low blood pressure,
you suffer from severe asthma or severe chronic lung disease,
you suffer from severe circulation problems in the limbs (such as Raynaud's syndrome), which may cause tingling in the fingers of hands and feet, with the skin becoming pale or blue,
you have untreated phaeochromocytoma, a rare tumor of the adrenal gland (medulla),
you have metabolic acidosis, a condition in which there is excessive accumulation of acids in the blood,
you have previously experienced symptoms such as shortness of breath, swelling of the face, tongue or throat, intense itching or severe skin rashes related to prior treatment with ACE inhibitors, or if you or a family member has ever experienced such symptoms under any circumstances (a disorder called angioedema),
you are more than three months pregnant (it is better to avoid Cosyrel even in the early stages of pregnancy – see section “Pregnancy”),
you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren,
you are undergoing dialysis or any type of blood filtration. Depending on the equipment used, treatment with Cosyrel may not be suitable for you,
you have kidney problems due to reduced blood flow to the kidneys (renal artery stenosis),
you have taken or are currently taking sacubitril/valsartan, a medicine used to treat heart failure, because of an increased risk of angioedema (rapid swelling under the skin, for example in the throat) (see information under “Warnings and precautions” and “Other medicines and Cosyrel”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Cosyrel if:
you have diabetes,
you have kidney problems (including kidney transplant) or are on dialysis,
you have liver problems,
you have aortic or mitral valve stenosis (narrowing of the main artery leaving the heart) or hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidneys),
you have abnormally high levels of a hormone called aldosterone in the blood (primary aldosteronism),
you suffer from heart failure or other heart problems, such as minor heart rhythm disorders or severe chest pain at rest (Prinzmetal's angina),
you have a collagen vascular disease (connective tissue disease) such as systemic lupus erythematosus or scleroderma,
you are on a diet that restricts salt intake or use potassium-containing salt substitutes (too much potassium in the blood can cause changes in heart rhythm),
you have recently had diarrhea or vomiting, or are dehydrated (Cosyrel may cause a drop in blood pressure),
you are scheduled to undergo LDL apheresis (blood purification from cholesterol using a machine),
you are receiving allergy treatment or are scheduled for desensitization therapy to reduce the effects of an allergy to bee or wasp stings,
you are following a strict fast or diet,
you are scheduled for anesthesia and/or major surgery,
you have circulation problems in your hands and feet,
you suffer from asthma or chronic lung disease,
you have (or have had) psoriasis,
you have a tumor of the adrenal gland (phaeochromocytoma),
you have thyroid problems (Cosyrel may mask symptoms of overactive thyroid),
you experience symptoms of angioedema (a severe allergic reaction presenting with swelling of the face, lips, tongue or throat, difficulty swallowing or breathing). This may occur at any time during treatment. If you experience such symptoms, stop taking Cosyrel and consult a doctor immediately,
you are of black ethnicity, as you may have a higher incidence of angioedema and this medicine may be less effective in lowering blood pressure compared to white patients,
you are taking any of the following medicines used to treat high blood pressure:

• an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans – for example valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
• aliskiren. Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals. See also information under "Do not take Cosyrel".
• you are taking any of the following medicines, which increase the risk of angioedema:
• racecadotril (used to treat diarrhea)
• sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors (used to prevent organ transplant rejection or in cancer treatment)
• sacubitril (available as a fixed-dose combination with valsartan), used in long-term treatment of heart failure
• linagliptin, saxagliptin, sitagliptin, vildagliptin and other medicines belonging to the class of so-called gliptins (used in diabetes treatment).

Do not stop taking Cosyrel suddenly, as this may cause serious worsening of heart conditions. Treatment should not be stopped abruptly, especially in patients with coronary artery disease.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Cosyrel is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn child if taken during this period (see section “Pregnancy”).
For athletes: using this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.

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

Other medicines and Cosyrel
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Some medicines may alter the effect of Cosyrel or the effect of these medicines may be altered by Cosyrel. Such interactions may reduce the effect of one or both medicines. Alternatively, they may increase the risk or severity of side effects.
Make sure to inform your doctor if you are taking any of the following medicines:
medicines used to control blood pressure or medicines used to treat heart problems (such as amiodarone, amlodipine, clonidine, digitalis glycosides, diltiazem, disopyramide, felodipine, flecainide, lidocaine, methyldopa, moxonidine, procainamide, propafenone, quinidine, rilmenidine, verapamil),
other medicines for treating hypertension, including angiotensin II receptor antagonists (AIIRAs), aliskiren (see also information under “Do not take Cosyrel” and “Warnings and precautions”), or diuretics (medicines that increase the amount of urine produced by the kidneys),
potassium-sparing medicines (e.g. triamterene, amiloride), potassium supplements or potassium-containing salt substitutes, other medicines that may increase potassium levels in the blood (such as heparin, a medicine used to thin the blood and prevent clotting; trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole for treating bacterial infections),
potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg per day,
sympathomimetic agents used to treat clinical shock (e.g. adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine),
estramustine used in cancer therapy,
medicines mainly used to treat diarrhea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors). See section “Warnings and precautions”,
sacubitril/valsartan (used for long-term treatment of heart failure). See information under “Do not take Cosyrel” and “Warnings and precautions”,
lithium used to treat mania or depression,
some medicines used to treat depression, such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors),
medicines for treating schizophrenia (antipsychotics),
medicines for treating epilepsy (phenytoin, barbiturates such as phenobarbital),
anaesthetic agents used in surgery,
vasodilators, including nitrates (medicines that dilate blood vessels),
trimethoprim used to treat infections,
immunosuppressants (medicines that suppress the body's defense mechanisms) such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after surgical transplantation,
allopurinol for treating gout,
parasympathomimetic medicines used to treat conditions such as Alzheimer's disease or glaucoma,
topical beta-blockers used to treat glaucoma (increased eye pressure),
mefloquine used to prevent or treat malaria,
baclofen used to treat muscle stiffness in diseases such as multiple sclerosis,
gold salts, especially when administered intravenously (used to treat symptoms of rheumatoid arthritis),
medicines for treating diabetes such as insulin, metformin, linagliptin, saxagliptin, sitagliptin, vildagliptin,
non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac or high doses of acetylsalicylic acid used to treat arthritis, headache, pain or inflammation.

Cosyrel with food, drinks and alcohol
It is preferable to take Cosyrel before meals.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Cosyrel before becoming pregnant or as soon as you know you are pregnant and will recommend an alternative medicine instead of Cosyrel. Cosyrel is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn child if taken after the third month of pregnancy.
Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. Cosyrel is not recommended for women who are breastfeeding, and your doctor may choose another treatment if you wish to breastfeed, especially if your baby is a newborn or was born prematurely.

Driving and using machines
Cosyrel usually does not affect alertness, but in some patients, side effects such as dizziness or fatigue may occur due to lowering of blood pressure, particularly at the start of treatment, when dosage is changed, or when taken together with alcohol. If you experience such symptoms, your ability to drive or operate machinery may be impaired.

Cosyrel contains sodium
Cosyrel contains less than 1 mmol of sodium (23 mg) per tablet, thus is practically "sodium-free".

3. How to take Cosyrel

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

The recommended dose is one tablet daily. Swallow the tablet with a glass of water in the morning before a meal.

Patients with kidney disease
Cosyrel is not recommended in cases of moderate to severe kidney disease.

Use in children and adolescents
The use of Cosyrel is not recommended in children and adolescents.

If you take more Cosyrel than you should
If you have taken more tablets than prescribed, contact your doctor or pharmacist immediately.
The most likely effect of an overdose is low blood pressure, which may cause dizziness or weakness (if this occurs, lying down with your legs raised may help), severe breathing difficulties, tremors (due to low blood sugar), and slowed heart rate.

If you forget to take Cosyrel
It is important to take the medicine every day, as regular treatment is more effective. If you forget to take a dose of Cosyrel, take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

If you stop taking Cosyrel
Do not stop taking Cosyrel suddenly and do not change the dose without first consulting your doctor, as this may cause a serious worsening of heart conditions. Treatment should not be stopped abruptly, especially in patients with coronary heart disease.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking this medicine and contact your doctor immediately if you experience any of the
following side effects:
severe dizziness or fainting due to low blood pressure (common – may affect up to 1 in 10 people),
worsening heart failure causing shortness of breath and/or fluid retention (common – may affect up to 1 in 10 people),
swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (uncommon – may affect up to 1 in 100 people),
sudden breathing difficulty, chest pain, shortness of breath or difficulty breathing (bronchospasm) (uncommon – may affect up to 1 in 100 people),
unusually fast or irregular heartbeat, chest pain (angina) or heart attack (very rare – may affect up to 1 in 10,000 people),
weakness in arms or legs or speech problems which may be signs of a possible stroke (very rare – may affect up to 1 in 10,000 people),
inflamed pancreas which may cause severe abdominal pain and back pain accompanied by a general feeling of severe illness (very rare – may affect up to 1 in 10,000 people),
yellowing of the skin or eyes (jaundice) which may be a sign of hepatitis (very rare – may affect up to 1 in 10,000 people),
skin rashes which often begin as red, itchy spots on the face, arms or legs (erythema multiforme) (very rare – may affect up to 1 in 10,000 people).

Cosyrel is generally well tolerated, but, as with any medicine, people may experience different side effects, particularly at the beginning of treatment.
If you experience any of the following side effects or any other side effect not listed in this leaflet,
contact your doctor or pharmacist immediately:

Very common (may affect more than 1 in 10 people):
slow heartbeat.

Common (may affect up to 1 in 10 people):
headache,
dizziness,
vertigo,
altered taste,
tingling sensation,
tingling or numbness in hands or feet,
vision disturbances,
tinnitus (ringing in the ears),
cold sensation in hands and feet,
cough,
shortness of breath,
gastrointestinal disturbances such as nausea, vomiting, abdominal pain, indigestion or dyspepsia, diarrhoea,
constipation,
allergic reactions such as skin rashes, itching,
muscle cramps,
feeling of tiredness,
fatigue.

Uncommon (may affect up to 1 in 100 people):
mood changes,
sleep disorders,
depression,
dry mouth,
intense itching or severe skin rashes,
formation of blisters on the skin,
increased sensitivity of the skin to sunlight (photosensitivity reaction),
sweating,
kidney problems,
impotence,
elevated eosinophil count (a type of white blood cells),
drowsiness,
fainting,
palpitations,
tachycardia,
irregular heartbeat (AV conduction disturbances),
inflammation of blood vessels (vasculitis),
dizziness when standing up,
muscle weakness,
arthralgia (joint pain),
myalgia (muscle pain),
chest pain,
malaise,
localized swelling (peripheral oedema),
fever,
risk of falls,
changes in laboratory parameters: high potassium levels in the blood (reversible upon discontinuation of treatment), low sodium levels, very low blood sugar levels (hypoglycaemia) in diabetic patients, increased blood urea and increased plasma creatinine.

Rare (may affect up to 1 in 1,000 people):
acute kidney failure,
dark-coloured urine, feeling unwell (nausea) or unwell state (vomiting), muscle cramps, confusion and seizures. These symptoms may be related to a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion),
reduced or absent urine output,
flushing,
nightmares, hallucinations,
reduced tear flow (dry eyes),
hearing problems,
liver inflammation causing yellowing of the skin or whites of the eyes,
runny nose due to allergy, sneezing,
allergic-type reactions such as itching, redness, skin rashes,
worsening of psoriasis,
changes in laboratory parameters: increased liver enzyme levels, elevated serum bilirubin, abnormal lipid levels.

Very rare (may affect up to 1 in 10,000 people):
confusion,
eye irritation and redness (conjunctivitis),
eosinophilic pneumonia (a rare type of pneumonia),
pancreatic inflammation (causing severe abdominal and back pain),
hair loss,
appearance or worsening of scaly skin rash (psoriasis), psoriasis-like rashes,
changes in blood values such as decreased white blood cell and red blood cell counts, decreased haemoglobin, decreased platelet count in the blood.

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

• Abnormal colour, numbness and pain in fingers of hands or feet (Raynaud's phenomenon).

If you experience these symptoms, contact your doctor immediately.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cosyrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
After opening, Cosyrel should be used within 20 days for packs containing 10 film-coated tablets, 60 days for packs containing 28 or 30 film-coated tablets, and 100 days for packs containing 100 film-coated tablets.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Cosyrel contains
The active substances are bisoprolol fumarate and perindopril arginine. Each Cosyrel tablet contains
10 mg of bisoprolol fumarate, equivalent to 8.49 mg of bisoprolol, and 5 mg of perindopril arginine,
equivalent to 3.395 mg of perindopril.
The other components are microcrystalline cellulose PH 102 (E460), calcium carbonate (E170), pregelatinized
corn starch, sodium glycolate starch type A (E468), anhydrous colloidal silica (E551),
magnesium stearate (Liga E572), sodium croscarmellose (E468), glycerol (E422), hypromellose (E464),
Macrogol 6000, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and
purified water.
Description of the appearance of Cosyrel and contents of the pack

Cosyrel is a pink-beige, round, bilayer, film-coated tablet, marked with ‘ ’ on one side and ‘10/5’ on the other.
The tablets are available in packs of 10, 28, 30, 84 (3 containers of 28 tablets), 90 (3 containers of 30), 100 and 120 (4 containers of 30) film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes Cedex
France
Manufacturers
Les Laboratoires Servier Industrie (LSI)
905, route de Saran
45520 Gidy
France
Servier (Ireland) Industries Ltd (SII)
Moneylands, Gorey Road
Arklow - Co. Wicklow
Ireland
Anpharm Przedsiebiorstwo Farmaceutyczne S.A.
03-236 Warszawa, ul. Annopol 6b
Poland
EGIS Pharmaceuticals PLC
H- 9900 Körmend, Mátyás király u. 65,
Hungary
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Belgium Bipressil 10mg/5mg film-coated tablet
Bulgaria Prestilol 10mg/5mg film-coated tablets
Croatia Prestilol 10mg/5mg film-coated tablets
Cyprus Cosyrel 10mg/5mg film-coated tablets
Czech Republic Cosyrel 10mg/5mg, coated tablets
Estonia Prestilol
Finland Cosyrel 10mg/5mg film-coated tablet
France Cosimprel 10mg/5mg, film-coated tablet
Greece Cosyrel 10mg/5mg film-coated tablets
Hungary Cosyrel 10mg/5mg film-coated tablet
Ireland Cosimprel 10mg/5mg film-coated tablet
Italy Cosyrel
Latvia Prestilol 10mg/5mg coated tablets
Lithuania Prestilol 10mg/5mg film-coated tablets
Luxembourg Bipressil 10mg/5mg film-coated tablet
Netherlands Cosimprel 10mg/5 mg film-coated tablet
Poland Prestilol
Portugal Cosyrel 10mg/5mg
Romania Cosyrel 10mg/5mg film-coated tablets
Slovakia Prestilol 10mg/5mg film-coated tablets
Slovenia Cosyrel 10mg/5mg film-coated tablets

Patient information leaflet

Cosyrel 10 mg/10 mg, film-coated tablets

bisoprolol fumarate/perindopril arginine
Please read this leaflet carefully before taking this medicine because it contains important information for you.
Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
Contents of this leaflet:

1. What Cosyrel is and what it is used for
2. What you need to know before taking Cosyrel
3. How to take Cosyrel
4. Possible side effects
5. How to store Cosyrel
6. Contents of the pack and other information

1. What Cosyrel is and what it is used for

Cosyrel contains two active substances in one tablet: bisoprolol fumarate and perindopril arginine.
Bisoprolol fumarate belongs to a group of medicines called beta-blockers. Beta-blockers slow down the heartbeat and make the heart more efficient at pumping blood throughout the body.
Perindopril arginine is an angiotensin-converting enzyme (ACE) inhibitor. It works by dilating blood vessels, making it easier for the heart to pump blood through them.
Cosyrel is indicated for the treatment of high blood pressure (hypertension) and/or for reducing the risk of cardiovascular events, such as heart attack, in patients with stable coronary artery disease (a condition in which blood supply to the heart is reduced or blocked) who have already had a heart attack and/or undergone a procedure to improve blood supply to the heart by widening the vessels that supply it.
Instead of taking separate tablets of bisoprolol fumarate and perindopril arginine, you will take just one tablet of Cosyrel containing both active substances at the same dosage.

2. What you should know before taking Cosyrel

Do not take Cosyrel if:
you are allergic to bisoprolol or any other beta-blocker, perindopril or any other
ACE inhibitor, or to any of the other ingredients of this medicine (listed in section 6),
you suffer from heart failure that worsens suddenly and/or may require hospitalization,
you suffer from cardiogenic shock (a serious heart condition caused by very low blood pressure),
you suffer from a heart disease characterized by a slow or irregular heartbeat (second- or third-degree
atrioventricular block, sinoatrial block, sick sinus syndrome),
you have a slow heart rate,
you have particularly low blood pressure,
you suffer from severe asthma or severe chronic lung disease,
you suffer from serious circulation problems in the limbs (such as Raynaud's syndrome), which
can cause tingling in the fingers and toes, with skin turning pale or blue,
you suffer from untreated phaeochromocytoma, a rare tumor of the adrenal gland (medulla),
you suffer from metabolic acidosis, a condition in which there is excessive accumulation of acid in the
blood,
you have previously experienced symptoms such as shortness of breath, swelling of the face, tongue or throat, intense itching or severe skin rashes related to prior treatment with ACE inhibitors, or if you or a family member has experienced such symptoms under any circumstances (a condition called
angioedema),
you are more than three months pregnant (it is best to avoid Cosyrel even in the early stages of
pregnancy – see section “Pregnancy”),
you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren,
you are undergoing dialysis or any type of blood filtration. Depending on the equipment used, treatment with Cosyrel may not be suitable for you,
you have kidney problems due to reduced blood flow to the kidneys (renal artery stenosis),
you have taken or are currently taking sacubitril/valsartan, a medicine used to treat heart failure, as there is an increased risk of angioedema (rapid swelling under the skin, for example in the throat) (see information under “Warnings and precautions” and “Other medicines and Cosyrel”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Cosyrel if:
you have diabetes,
you have kidney problems (including a kidney transplant) or you are on dialysis,
you have liver problems,
you have aortic or mitral valve stenosis (narrowing of the main artery leaving the heart) or hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidneys),
you have abnormally high levels of a hormone called aldosterone in your blood (primary aldosteronism),
you suffer from heart failure or other heart problems, such as minor heart rhythm disorders or severe chest pain at rest (Prinzmetal's angina),
you have a collagen vascular disease (connective tissue disease) such as systemic lupus erythematosus or scleroderma,
you are on a salt-restricted diet or use potassium-containing salt substitutes (too much potassium in the blood can cause changes in heart rhythm),
you have recently had diarrhea or vomiting, or are dehydrated (Cosyrel can cause a drop in blood pressure),
you are scheduled to undergo LDL apheresis (blood purification from cholesterol using a machine),
you are receiving allergy treatment or are scheduled to undergo desensitization therapy to reduce the effects of an allergy to bee or wasp stings,
you are following a strict fast or diet,
you are scheduled to undergo anesthesia and/or major surgery,
you suffer from circulation problems in the hands and feet,
you suffer from asthma or chronic lung disease,
you have (or have had) psoriasis,
you have a tumor of the adrenal gland (phaeochromocytoma),
you suffer from thyroid problems (Cosyrel may mask symptoms of an overactive thyroid),
you experience symptoms of angioedema (a severe allergic reaction presenting with swelling of the face, lips, tongue or throat, difficulty swallowing or breathing). This may occur at any time during treatment. If you experience such symptoms, stop taking Cosyrel and consult a doctor immediately,
you are of Black ethnicity, as you may have a higher incidence of angioedema and this medicine may be less effective in lowering blood pressure compared to White patients,
you are taking any of the following medicines used to treat high blood pressure:

• an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans – for example valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
• aliskiren. Your doctor may monitor your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood at regular intervals. See also information under "Do not take Cosyrel".
• you are taking any of the following medicines, which increase the risk of angioedema:
• racecadotril (used to treat diarrhea),
• sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment),
• sacubitril (available as a fixed-dose combination with valsartan), used in long-term treatment of heart failure,
• linagliptin, saxagliptin, sitagliptin, vildagliptin and other medicines belonging to the class of so-called gliptins (used in diabetes treatment).

Do not stop taking Cosyrel suddenly, as this may cause a serious worsening of heart conditions. Treatment must not be stopped abruptly, especially in patients with coronary heart disease.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Cosyrel is not recommended during early pregnancy, and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn child if taken during this period (see section “Pregnancy”).
For athletes: using the drug without therapeutic need constitutes doping and may lead to a positive anti-doping test.

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

Other medicines and Cosyrel
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Some medicines may alter the effect of Cosyrel, or the effect of these medicines may be altered by Cosyrel. This type of interaction may reduce the effect of one or both medicines. Alternatively, it may increase the risk or severity of side effects.
Make sure to inform your doctor if you are taking any of the following medicines:
medicines used to control blood pressure or medicines used to treat heart problems (such as amiodarone, amlodipine, clonidine, digitalis glycosides, diltiazem, disopyramide, felodipine, flecainide, lidocaine, methyldopa, moxonidine, procainamide, propafenone, quinidine, rilmenidine, verapamil),
other medicines for the treatment of hypertension, including angiotensin II receptor antagonists (AIIRAs), aliskiren (see also information under "Do not take Cosyrel" and "Warnings and precautions"), or diuretics (medicines that increase the amount of urine produced by the kidneys),
potassium-sparing medicines (e.g. triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, other drugs that may increase potassium levels in the blood (such as heparin, a medicine used to thin the blood and prevent clotting; trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole, used to treat bacterial infections),
potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg daily,
sympathomimetic agents used to treat clinical shock (e.g. adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine),
estramustine used in cancer therapy,
medicines used mainly to treat diarrhea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors). See section “Warnings and precautions”,
sacubitril/valsartan (used in long-term treatment of heart failure). See information under “Do not take Cosyrel” and “Warnings and precautions”,
lithium used to treat mania or depression,
some medicines used to treat depression, such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors),
medicines for the treatment of schizophrenia (antipsychotics),
medicines for the treatment of epilepsy (phenytoin, barbiturates such as phenobarbital),
anesthetic agents used in surgery,
vasodilators, including nitrates (medicines that dilate blood vessels),
trimethoprim used to treat infections,
immunosuppressants (medicines that can suppress the body's defense mechanisms) such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after surgical transplantation,
allopurinol for the treatment of gout,
parasympathomimetic medicines used to treat conditions such as Alzheimer's disease or glaucoma,
topical beta-blockers used to treat glaucoma (increased eye pressure),
mefloquine used to prevent or treat malaria,
baclofen used to treat muscle stiffness in diseases such as multiple sclerosis,
gold salts, especially when administered intravenously (used to treat symptoms of rheumatoid arthritis),
medicines for the treatment of diabetes such as insulin, metformin, linagliptin, saxagliptin, sitagliptin, vildagliptin,
non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac or high doses of acetylsalicylic acid used to treat arthritis, headache, pain or inflammation.

Cosyrel with food, drinks and alcohol
It is preferable to take Cosyrel before meals.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Cosyrel before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine instead of Cosyrel. Cosyrel is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn child if taken after the third month of pregnancy.

Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed.
Cosyrel is not recommended for women who are breastfeeding, and your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is a newborn or was born prematurely.

Driving and using machines
Cosyrel usually does not affect alertness, but in some patients, side effects such as dizziness or fatigue may occur due to lowered blood pressure, particularly at the start of treatment, when dosage is changed, or when taken together with alcohol. If you experience such symptoms, your ability to drive or operate machinery may be impaired.

Cosyrel contains sodium
Cosyrel contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially “sodium-free”.

3. How to take Cosyrel

Take this medicine exactly as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.
The recommended dose is one tablet daily. Take the tablet with a glass of water, in the morning before a meal.

Patients with kidney disease
Cosyrel is not recommended in cases of moderate to severe kidney disease.

Use in children and adolescents
Use in children and adolescents is not recommended.

If you take more Cosyrel than you should
If you have taken more tablets than prescribed, contact your doctor or pharmacist immediately.
The most likely effect of an overdose is low blood pressure, which may cause dizziness or weakness (if this occurs, lying down with your legs raised may help), severe breathing difficulties, tremors (due to low blood sugar), and slowed heart rate.

If you forget to take Cosyrel
It is important to take the medicine every day, as regular treatment is more effective. However, if you forget to take a dose of Cosyrel, take the next dose as usual. Do not take a double dose to make up for the missed dose.

If you stop taking Cosyrel
Do not stop taking Cosyrel suddenly and do not change the dose without first consulting your doctor, as this may cause a serious worsening of heart conditions. Treatment should not be stopped abruptly, especially in patients with coronary heart disease.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking this medicine and inform your doctor immediately if you experience any of the
following side effects:
severe dizziness or fainting due to low blood pressure (common – may affect up to 1 in 10 people),
worsening of heart failure causing shortness of breath and/or fluid retention (common – may affect up to 1 in 10 people),
swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (uncommon – may affect up to 1 in 100 people),
sudden breathing difficulty, chest pain, shortness of breath or difficulty breathing (bronchospasm) (uncommon – may affect up to 1 in 100 people),
unusually fast or irregular heartbeat, chest pain (angina) or heart attack (very rare – may affect up to 1 in 10,000 people),
weakness in the arms or legs or speech problems which may be signs of a possible stroke (very rare – may affect up to 1 in 10,000 people),
inflamed pancreas which may cause severe abdominal pain and back pain accompanied by a strong feeling of being unwell (very rare – may affect up to 1 in 10,000 people),
yellowing of the skin or eyes (jaundice), which may be a sign of hepatitis (very rare – may affect up to 1 in 10,000 people),
skin rashes which often begin as red, itchy spots on the face, arms or legs (erythema multiforme) (very rare – may affect up to 1 in 10,000 people).

Cosyrel is generally well tolerated, but as with any medicine, people may experience different side effects, particularly at the beginning of treatment.
If you experience any of the following side effects or any other side effect not listed in this leaflet,
inform your doctor or pharmacist immediately:

Very common (may affect more than 1 in 10 people):
slowed heartbeat.

Common (may affect up to 1 in 10 people):
headache,
dizziness,
vertigo,
taste disturbances,
tingling sensation,
tingling or numbness in hands or feet,
vision disorders,
tinnitus (ringing or noise in the ears),
cold sensation in hands and feet,
cough,
shortness of breath,
gastrointestinal disturbances such as nausea, vomiting, abdominal pain, indigestion or dyspepsia, diarrhoea,
constipation,
allergic reactions such as skin rashes, itching,
muscle cramps,
feeling of tiredness,
fatigue.

Uncommon (may affect up to 1 in 100 people):
mood changes,
sleep disorders,
depression,
dry mouth,
intense itching or severe skin rashes,
formation of clusters of blisters on the skin,
increased sensitivity of the skin to sunlight (photosensitivity reaction),
sweating,
kidney problems,
impotence,
elevated eosinophil count (a type of white blood cells),
drowsiness,
fainting,
palpitations,
tachycardia,
irregular heartbeat (AV conduction disturbances),
inflammation of blood vessels (vasculitis),
dizziness when standing up,
muscle weakness,
arthralgia (joint pain),
myalgia (muscle pain),
chest pain,
malaise,
localized swelling (peripheral oedema),
fever,
risk of falls,
changes in laboratory parameters: high potassium levels in blood (reversible upon discontinuation of treatment), low sodium levels, very low blood sugar levels (hypoglycaemia) in diabetic patients, increased blood urea and increased plasma creatinine.

Rare (may affect up to 1 in 1,000 people):
acute renal failure,
dark-coloured urine, feeling unwell (nausea) or being unwell (vomiting), muscle cramps, confusion and seizures. These symptoms may be related to a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion),
reduced or absent urine output,
flushing,
nightmares, hallucinations,
reduced tear flow (dry eyes),
hearing problems,
liver inflammation causing yellowing of the skin or whites of the eyes,
allergic runny nose, sneezing,
allergic-type reactions such as itching, redness, skin rashes,
worsening of psoriasis,
changes in laboratory parameters: increased liver enzyme levels, high serum bilirubin levels, abnormal lipid levels.

Very rare (may affect up to 1 in 10,000 people):
confusion,
eye irritation and redness (conjunctivitis),
eosinophilic pneumonia (a rare type of pneumonia),
inflammation of the pancreas (causing severe abdominal and back pain),
hair loss,
onset or worsening of scaly skin rash (psoriasis), skin rashes resembling psoriasis,
changes in blood values such as decreased white blood cell and red blood cell counts, decreased haemoglobin, decreased platelet count in blood.

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

• Unusual colour, numbness and pain in fingers of hands or feet (Raynaud's phenomenon).

If you experience these symptoms, contact your doctor immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cosyrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
After opening, Cosyrel must be used within 20 days for packs containing 10 film-coated tablets, 60 days for packs containing 28 or 30 film-coated tablets, and 100 days for packs containing 100 film-coated tablets.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Cosyrel contains
The active substances are bisoprolol fumarate and perindopril arginine. Each Cosyrel tablet contains
10 mg of bisoprolol fumarate, equivalent to 8.49 mg of bisoprolol, and 10 mg of perindopril arginine,
equivalent to 6.790 mg of perindopril.
The other components are microcrystalline cellulose PH 102 (E460), calcium carbonate (E170), pregelatinized
corn starch, sodium glycolate starch type A (E468), anhydrous colloidal silica (E551),
magnesium stearate (Liga E572), sodium croscarmellose (E468), glycerol (E422), hypromellose (E464),
Macrogol 6000, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and
purified water.
Description of the appearance of Cosyrel and contents of the pack

Cosyrel is a film-coated, pinkish-beige, elongated, bilayer tablet, engraved with ‘ ’ on one side and ‘10/10’ on the other.
Tablets are available in packs containing 10, 28, 30, 84 (3 containers of 28 tablets), 90 (3 containers of
30 tablets), 100 and 120 (4 containers of 30 tablets) film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes Cedex
France
Manufacturers
Les Laboratoires Servier Industrie (LSI)
905, route de Saran
45520 Gidy
France
Servier (Ireland) Industries Ltd (SII)
Moneylands, Gorey Road
Arklow - Co. Wicklow
Ireland
Anpharm Przedsiebiorstwo Farmaceutyczne S.A.
03-236 Warszawa, ul. Annopol 6b
Poland
EGIS Pharmaceuticals PLC
H- 9900 Körmend, Mátyás király u. 65,
Hungary
This medicinal product is authorized in the Member States of the European Economic Area under the following
names:
Belgium Bipressil 10mg/10mg film-coated tablet
Bulgaria Prestilol 10mg/10mg film-coated tablets
Croatia Prestilol 10mg/10mg film-coated tablets
Cyprus Cosyrel 10mg/10mg film-coated tablets
Czech Republic Cosyrel 10mg/10mg, coated tablets
Estonia Prestilol
Finland Cosyrel 10mg/10mg Tabletti, kalvopäällysteinen
France Cosimprel 10mg/10mg, film-coated tablet
Greece Cosyrel 10mg/10mg film-coated tablets
Hungary Cosyrel 10mg/10mg filmtabletta
Ireland Cosimprel 10mg/10mg film-coated tablet
Italy Cosyrel
Latvia Prestilol 10mg/10mg film-coated tablets
Lithuania Prestilol 10mg/10mg plėvele dengtos tabletės
Luxembourg Bipressil 10mg/10mg comprimé pelliculé
Netherlands Cosimprel 10mg/10mg filmomhulde tabletten
Poland Prestilol
Portugal Cosyrel 10mg/10mg
Romania Cosyrel 10mg/10mg film-coated tablets
Slovakia Prestilol 10mg/10mg filmom obalené tablety
Slovenia Cosyrel 10mg/10mg filmsko obložene tablete