Acebis

Package leaflet: Information for the patient

ACEBIS, 2.5 mg + 1.25 mg, hard capsules
ACEBIS, 2.5 mg + 2.5 mg, hard capsules
ACEBIS, 5 mg + 2.5 mg, hard capsules
ACEBIS, 5 mg + 5 mg, hard capsules
ACEBIS, 10 mg + 5 mg, hard capsules
ACEBIS, 10 mg + 10 mg, hard capsules
ramipril + bisoprolol fumarate
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What ACEBIS is and what it is used for

ACEBIS contains two active substances – bisoprolol fumarate and ramipril – in a single capsule.

• Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. It works by dilating blood vessels, which helps the heart pump blood through the body more easily.
• Bisoprolol fumarate belongs to a group of medicines called beta-blockers (beta-adrenolytics). Beta-adrenolytics slow down the heart rate and improve the heart's efficiency in pumping blood.

ACEBIS is used to treat high blood pressure (hypertension) and/or chronic heart failure with left ventricular dysfunction (a condition in which the heart is unable to pump enough blood to meet the body's needs, resulting in breathlessness and swelling), and/or to reduce the risk of cardiovascular events such as myocardial infarction in patients with chronic coronary artery disease (a condition in which blood flow to the heart is reduced or blocked), who have previously experienced a myocardial infarction and/or undergone a procedure to improve blood supply to the heart by widening the blood vessels supplying it, or in patients with diabetes and at least one cardiovascular risk factor.
Instead of taking bisoprolol fumarate and ramipril in separate capsules, you take only one ACEBIS capsule containing both active substances at the same strength.

2. Important information before taking ACEBIS

When not to take ACEBIS:

• if the patient is allergic to bisoprolol or any other beta-blocker, ramipril or any other ACE inhibitor, or any of the other ingredients of this medicine (listed in section 6),
• if the patient has heart failure which is suddenly worsening and (or) may require hospital treatment,
• if the patient has cardiogenic shock (a severe heart condition caused by very low blood pressure),
• if the patient has a heart disease characterised by slow or irregular heartbeat (second- or third-degree atrioventricular block, sinoatrial block, sick sinus syndrome),
• if the patient has a slow heart rate,
• if the patient has very low blood pressure,
• if the patient has severe asthma or severe chronic lung disease,
• if the patient has serious circulation problems in the limbs (such as Raynaud's syndrome), which may cause tingling, paleness or blueness of the fingers and toes,
• if the patient has untreated phaeochromocytoma, a rare tumour of the adrenal gland (medulla),
• if the patient has metabolic acidosis, a condition in which the blood contains too much acid,
• if the patient previously experienced symptoms such as wheezing, swelling of the face, tongue or throat, intense itching, or severe skin rash during earlier treatment with an ACE inhibitor, or if such symptoms occurred in the patient or a family member under any other circumstances (a condition called angioedema),
• if the patient is pregnant beyond the third month (ACEBIS is also not recommended during early pregnancy – see section "Pregnancy"),
• if the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren,
• if the patient is undergoing dialysis or another type of blood filtration. Depending on the device used, ACEBIS may not be suitable for the patient.
• if the patient has kidney problems in which blood flow to the kidneys is reduced (renal artery stenosis),
• if the patient is being treated with sacubitril/valsartan, a combination medicine containing sacubitril and valsartan, used in heart failure (see "Warnings and precautions" and "Other medicines and ACEBIS")

Warnings and precautions
Before starting ACEBIS, consult your doctor or pharmacist if:

• the patient has diabetes,
• the patient has kidney problems (including a transplanted kidney) or is undergoing dialysis,
• the patient has liver problems,
• the patient has aortic or mitral valve stenosis (narrowing of the main blood vessel leaving the heart) or hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidneys),
• the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism),
• the patient has heart failure or any other heart problems, such as minor heart rhythm disturbances or severe chest pain at rest (Prinzmetal's angina),
• the patient has a collagen vascular disease (connective tissue disease) such as systemic lupus erythematosus or scleroderma,
• the patient is on a low-salt diet or uses salt substitutes containing potassium (excess potassium in the blood may cause changes in heart rate),
• the patient has recently had diarrhoea or vomiting or is dehydrated (ACEBIS may cause low blood pressure),
• the patient is due to undergo LDL apheresis (removal of cholesterol from the blood using a special device),
• the patient is currently undergoing allergy immunotherapy or plans allergen desensitisation treatment to reduce the effects of allergy to bee or wasp stings,
• the patient is currently fasting or on a strict diet,
• the patient is due to undergo anaesthesia and (or) major surgery,
• the patient has circulation problems in the limbs,
• the patient has asthma or chronic lung disease,
• the patient has (or has had) psoriasis,
• the patient has an adrenal gland tumour (phaeochromocytoma),
• the patient has thyroid disorders (ACEBIS may mask symptoms of hyperthyroidism),
• the patient has angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat, causing difficulty in swallowing or breathing). This may occur at any time during treatment. If such symptoms occur, stop taking ACEBIS and contact your doctor immediately.
• the patient is of Black race, as such patients may have a higher risk of angioedema, and this medicine may be less effective in lowering blood pressure compared to patients of non-Black race,
• the patient is taking any of the following medicines used to treat high blood pressure:
  • angiotensin II receptor antagonists (ARBs) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), particularly in patients with kidney problems related to diabetes.
  • aliskiren. Your doctor may check kidney function, blood pressure and blood electrolyte levels (e.g. potassium) at regular intervals. See also information under the heading "When not to take ACEBIS".
• the patient is taking any of the following medicines – risk of angioedema increases:
  • racecadotril (used to treat diarrhoea),
  • sirolimus, everolimus, temsirolimus and other medicines belonging to the class of mTOR inhibitors (used to prevent rejection of transplanted organs),
  • sacubitril (available in fixed-dose combination with valsartan), used in the treatment of chronic heart failure.

Do not stop taking ACEBIS suddenly, as this may lead to a serious worsening of heart condition. Do not abruptly discontinue treatment, especially in patients with coronary artery disease.
The patient must inform the doctor if she suspects she is pregnant (or might become pregnant). ACEBIS is not recommended during early pregnancy and must not be used after the third month of pregnancy, as it may seriously harm the unborn child (see section "Pregnancy").
Children and adolescents
ACEBIS is not recommended for use in children and adolescents under 18 years of age.
Other medicines and ACEBIS
Inform your doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines the patient plans to take.
Some medicines may alter the effect of ACEBIS or their effect may be altered by ACEBIS. This type of interaction may reduce the effectiveness of one or both medicines. It may also increase the risk or severity of adverse effects.
Remember to inform your doctor if the patient is taking any of the following medicines:

• medicines used to control blood pressure or medicines used for heart conditions (such as amiodarone, amlodipine, clonidine, cardiac glycosides, diltiazem, disopyramide, felodipine, flecainide, lidocaine, methyldopa, moxonidine, procainamide, propafenone, quinidine, rilmenidine, verapamil),
• other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (ARBs), aliskiren (see also information under "When not to take ACEBIS" 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 body (such as heparin and cotrimoxazole, also known as trimethoprim/sulfamethoxazole),
• potassium-sparing medicines used in heart failure: eplerenone and spironolactone at doses from 12.5 mg to 50 mg per day,
• sympathomimetic medicines used to treat shock (adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine),
• estramustine used in cancer therapy,
• medicines most commonly used to treat diarrhoea (racecadotril) or to prevent rejection of transplanted organs (sirolimus, everolimus, temsirolimus and other medicines belonging to the class of mTOR inhibitors). See section "Warnings and precautions".
• sacubitril/valsartan (used in the treatment of chronic heart failure). See section "When not to take ACEBIS" and "Warnings and precautions".
• lithium used to treat mania or depression,
• certain antidepressants such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors),
• certain antipsychotic medicines used to treat schizophrenia,
• certain medicines used to treat epilepsy (phenytoin, barbiturates such as phenobarbital),
• anaesthetics used during surgical procedures,
• vasodilators, including nitrates,
• trimethoprim used to treat infections,
• immunosuppressive medicines (medicines that suppress the body's immune system), such as cyclosporine, tacrolimus, used in autoimmune disorders or after organ transplantation,
• allopurinol used to treat gout,
• parasympathomimetic medicines used to treat conditions such as Alzheimer's disease or glaucoma,
• beta-blockers used locally to treat glaucoma (may increase intraocular pressure),
• mefloquine used to prevent or treat malaria,
• baclofen used to treat muscle stiffness in conditions such as multiple sclerosis,
• gold salts, especially when administered intravenously (used to treat symptoms of rheumatoid arthritis),
• medicines used to treat diabetes, such as insulin, metformin, linagliptin, saxagliptin, sitagliptin, vildagliptin,
• non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or diclofenac or high-dose aspirin used to treat arthritis, headache, pain or inflammation.

Taking ACEBIS with food, drink and alcohol
It is recommended to take ACEBIS before a meal.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
The patient must inform the doctor if she suspects she is pregnant (or might become pregnant). The doctor will usually advise stopping ACEBIS before becoming pregnant or immediately after pregnancy is confirmed and will recommend an alternative medicine. ACEBIS is not recommended during early pregnancy and must not be used after the third month of pregnancy, as it may seriously harm the unborn child.
Breastfeeding
Inform your doctor if you are breastfeeding or plan to breastfeed. ACEBIS is not recommended for breastfeeding mothers, and the doctor may choose an alternative treatment if the patient wishes to breastfeed, especially if the baby is a newborn or was born prematurely.
Driving and using machines
ACEBIS usually does not affect alertness, but some patients may experience central dizziness or weakness due to low blood pressure, particularly at the beginning of treatment or after a dose change, and especially when combined with alcohol. If these symptoms occur, the ability to drive or operate machinery may be impaired.
Lactose
ACEBIS 2.5 mg + 1.25 mg contains 40.97 mg lactose (20.49 mg glucose and 20.49 mg galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 2.5 mg + 2.5 mg contains 40.97 mg lactose (20.49 mg glucose and 20.49 mg galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 5 mg + 2.5 mg contains 81.94 mg lactose (40.97 mg glucose and 40.97 mg galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 5 mg + 5 mg contains 81.94 mg lactose (40.97 mg glucose and 40.97 mg galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 10 mg + 5 mg contains 163.88 mg lactose (81.94 mg glucose and 81.94 mg galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 10 mg + 10 mg contains 163.88 mg lactose (81.94 mg glucose and 81.94 mg galactose) per dose. This should be taken into account in patients with diabetes.
Sodium
ACEBIS contains less than 1 mmol sodium (23 mg) per capsule, meaning the medicine is considered "sodium-free".
3. How to take ACEBIS
This medicine should always be taken exactly as prescribed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
The recommended dose is one capsule once daily. The capsule should be swallowed in the morning before a meal, with a glass of water.
Patients with kidney disease
Your doctor will adjust the dose of ACEBIS in patients with moderate kidney disease. ACEBIS is not recommended in severe kidney disease.
Patients with liver impairment
Your doctor will closely monitor patients with mild or moderate liver disease when starting treatment with ACEBIS.
Use in children and adolescents
Not recommended for use in children and adolescents.
Taking more ACEBIS than prescribed
If more capsules are taken than prescribed, contact your doctor or pharmacist immediately.
The most likely consequence of overdose is low blood pressure, which may cause dizziness or fainting (in such cases, lying down with legs elevated may help), severe breathing difficulties, tremors (due to low blood sugar levels), and slow heart rate.
Missing a dose of ACEBIS
It is important to take the medicine daily, as regular treatment is more effective. However, if a dose of ACEBIS is missed, take the next dose at the usual time. Do not take a double dose to make up for a missed dose.
Stopping ACEBIS
Do not stop taking ACEBIS suddenly or change the dose without consulting your doctor, as this may lead to a serious worsening of heart condition. Do not abruptly discontinue treatment, especially in patients with coronary artery disease.
If you have any further questions about using this medicine, consult your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should stop taking the medicine and contact your doctor immediately if any of the following adverse reactions occur:

• Severe central dizziness or fainting caused by low blood pressure (common – may occur in up to 1 in 10 people),
• Worsening of heart failure causing severe shortness of breath and/or fluid retention in the body (common – may occur in up to 1 in 10 people),
• Swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (uncommon – may occur in up to 1 in 100 people),
• Sudden wheezing, chest pain, shortness of breath or difficulty breathing (bronchospasm) (uncommon – may occur in up to 1 in 100 people),
• Unusual fast or irregular heartbeats, chest pain (angina) or heart attack (uncommon – may occur in up to 1 in 100 people),
• Weakness in arms or legs or problems with speech, which may be signs of a possible stroke (frequency cannot be determined from available data),
• Inflammation of the pancreas, which may cause severe abdominal pain radiating to the back, accompanied by a very poor general condition (very rare – may occur in up to 1 in 10,000 people),
• Yellowing of the skin or eyes (jaundice), which may be a sign of liver inflammation (rare – may occur in up to 1 in 1,000 people),
• Skin rash, often starting as red, itchy spots on the face, hands or legs (erythema multiforme) (frequency unknown – frequency cannot be determined from available data).

ACEBIS is generally well tolerated, but, as with any medicine, patients may experience various adverse reactions, particularly at the beginning of treatment.
If you notice any of the adverse reactions listed below or not listed, inform your doctor or pharmacist immediately:
Very common (may occur in more than 1 in 10 people):

• Slowed heart rate.

Common (may occur in up to 1 in 10 people):

• Headache,
• Central dizziness,
• Fainting, hypotension (abnormally low blood pressure), especially when standing up or sitting down quickly,
• Numbness in hands or feet,
• Cold sensation in hands or feet,
• Cough,
• Shortness of breath,
• Sinusitis or bronchitis,
• Chest pain,
• Gastrointestinal disturbances such as nausea, vomiting, abdominal pain, indigestion or dyspepsia, diarrhea, constipation,
• Allergic reactions such as skin rashes, itching,
• Muscle cramps, muscle pain (myalgia),
• Feeling of fatigue,
• Fatigue,
• Blood tests showing higher than normal potassium levels in the blood.

Uncommon (may occur in up to 1 in 100 people):

• Peripheral dizziness,
• Taste disturbances,
• Tingling sensations (paresthesia),
• Visual disturbances,
• Tinnitus (ringing in the ears),
• Nasal congestion, difficulty breathing or worsening of asthma,
• Inflammation of the nasal mucosa, nasal obstruction,
• Sudden flushing (especially of the face),
• Mood swings,
• Sleep disturbances,
• Depression,
• Dry mouth,
• Sweating,
• Kidney problems,
• Passing larger amounts of urine during the day than usual,
• Impotence,
• Eosinophilia (increased number of eosinophils – a type of white blood cell),
• Drowsiness,
• Palpitations,
• Fast heartbeat (tachycardia),
• Irregular heart rate (atrioventricular conduction disturbances),
• Muscle weakness,
• Arthralgia (joint pain),
• Localized swelling (peripheral edema),
• Fever,
• Loss of appetite or reduced appetite (anorexia),
• Changes in laboratory parameters: increased number of certain white blood cells (eosinophilia), increased blood urea levels, increased blood creatinine levels, increased liver enzyme activity, increased serum bilirubin levels,
• Increased protein in urine,
• Mouth ulcers,
• Breast enlargement in men.

Rare (may occur in up to 1 in 1,000 people):

• Nightmares, hallucinations,
• Reduced tear production (dry eyes),
• Redness, itching, swelling or watering of the eyes,
• Hearing problems,
• Liver inflammation, which may cause yellowing of the skin or whites of the eyes,
• Vasculitis (inflammation of blood vessels),
• Changes in laboratory parameters: increased fat levels, decreased number of red blood cells, white blood cells or platelets, or decreased hemoglobin levels.

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

• Confusion,
• Pancreatitis (causing severe upper abdominal pain radiating to the back),
• Hair loss,
• New onset or worsening of scaly skin rash (psoriasis), psoriasiform rash,
• Increased skin sensitivity to sunlight (photosensitivity reaction).

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

• Discoloration, numbness and pain in fingers of hands and feet (Raynaud's phenomenon),
• Low sodium levels, very low blood sugar levels (hypoglycemia) in diabetic patients,
• Inflammation of the tongue.

When taking ACE inhibitors, adverse reactions such as concentrated urine (dark color), nausea or vomiting, muscle cramps, confusion and seizures may occur, which may be caused by abnormal ADH (antidiuretic hormone) secretion. If any of these symptoms occur, contact your doctor as soon as possible.
Reporting of adverse reactions
If any adverse reactions occur in patients, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store ACEBIS

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton following EXP.
The expiry date refers to the last day of the stated month.
Do not store above 30°C. Do not store in the refrigerator or freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What ACEBIS contains

• The active substances are ramipril and bisoprolol fumarate.
• Other ingredients are:
  Capsule contents: Monohydrate lactose, Polyvinyl alcohol, Sodium croscarmellose (E468), Sodium stearyl fumarate, Microcrystalline cellulose, Anhydrous calcium hydrogen phosphate, Crospovidone type A, Anhydrous colloidal silica, Magnesium stearate

AquaPolish P yellow coating: Hypromellose (E 464), Hydroxypropylcellulose (E463), Medium-chain triglycerides, Talc (E 553b), Titanium dioxide (E 171), Yellow iron oxide (E 172).
Capsule shell: Titanium dioxide (E 171), Gelatin, Red iron oxide (E 172) – [in capsules 10 mg+10 mg, 10 mg+5 mg, 5 mg+5 mg, 5 mg+2.5 mg], Yellow iron oxide (E 172) – [in capsules 10 mg+5 mg, 5 mg+5 mg, 5 mg+2.5 mg, 2.5 mg+2.5 mg, 2.5 mg+1.25 mg], Quinoline yellow (E 104) – [in capsules 5 mg+2.5 mg, 2.5 mg+2.5 mg, 2.5 mg+1.25 mg].
Printing ink: Shellac (E904), Black iron oxide (E172), Propylene glycol, Ammonium hydroxide concentrated, Potassium hydroxide.

What ACEBIS looks like and contents of the packaging

ACEBIS 2.5 mg + 1.25 mg, hard capsules
The capsule has a yellow cap with black print "2.5 mg" and a white body with black print "1.25 mg".
Contents of the 2.5 mg + 1.25 mg capsule: ramipril as a white or almost white powder and bisoprolol fumarate as one yellow, biconvex, coated, round tablet.

ACEBIS 2.5 mg + 2.5 mg, hard capsules
The capsule has a yellow cap with black print "2.5 mg" and a yellow body with black print "2.5 mg".
Contents of the 2.5 mg + 2.5 mg capsule: ramipril as a white or almost white powder and bisoprolol fumarate as one yellow, biconvex, coated, round tablet.

ACEBIS 5 mg + 2.5 mg, hard capsules
The capsule has an orange cap with black print "5 mg" and a yellow body with black print "2.5 mg".
Contents of the 5 mg + 2.5 mg capsule: ramipril as a white or almost white powder and bisoprolol fumarate as one yellow, biconvex, coated, round tablet.

ACEBIS 5 mg + 5 mg, hard capsules
The capsule has an orange cap with black print "5 mg" and an orange body with black print "5 mg".
Contents of the 5 mg + 5 mg capsule: ramipril as a white or almost white powder and bisoprolol fumarate as one yellow, biconvex, coated, round tablet.

ACEBIS 10 mg + 5 mg, hard capsules
The capsule has a reddish-brown cap with black print "10 mg" and an orange body with black print "5 mg".
Contents of the 10 mg + 5 mg capsule: ramipril as a white or almost white powder and bisoprolol fumarate as one yellow, biconvex, coated, round tablet.

ACEBIS 10 mg + 10 mg, hard capsules
The capsule has a reddish-brown cap with black print "10 mg" and a reddish-brown body with black print "10 mg".
Contents of the 10 mg + 10 mg capsule: ramipril as a white or almost white powder and bisoprolol fumarate as two yellow, biconvex, coated, round tablets.

Blister packs: BOPA/Aluminium/PVC/Aluminium.
The blisters and the patient leaflet are packed in a cardboard box.
Capsules are available in pack sizes of:
10, 30, 60 or 100 capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice