Acebis

Leaflet accompanying the packaging: Patient information

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

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is ACEBIS and what is it 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 packaging and other information

1. What is ACEBIS and what is it used for

ACEBIS contains two active substances - bisoprolol fumarate and ramipril - in one capsule.

• Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. It works by widening the blood vessels, making it easier for the heart to pump blood to the body.
• Bisoprolol fumarate belongs to a group of medicines called beta-blockers (beta-adrenergic blockers). Beta-adrenergic blockers slow the heart rate and increase the efficiency of the heart in pumping blood to the body.

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 not able 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 chronic coronary artery disease (a condition in which blood flow to the heart is reduced or blocked) who have already had a heart attack and/or have undergone a procedure to improve blood flow to the heart by widening the blood vessels that supply it, or have diabetes with at least one other cardiovascular risk factor.

2. Important information before taking ACEBIS

When not to take ACEBIS:

• if you are allergic to bisoprolol or any other beta-adrenergic blocker, ramipril or any other ACE inhibitor, or any of the other ingredients of this medicine (listed in section 6),
• if you have heart failure that has suddenly worsened and may require hospital treatment,
• if you have cardiogenic shock (a serious heart condition caused by very low blood pressure),
• if you have a heart condition characterized by a slow or irregular heart rate (second- or third-degree atrioventricular block, sinoatrial block, sick sinus syndrome),
• if you have a slow heart rate,
• if you have very low blood pressure,
• if you have severe asthma or severe chronic obstructive pulmonary disease (COPD),
• if you have serious blood circulation problems in your limbs (such as Raynaud's syndrome), which may cause tingling, pallor, or cyanosis of the fingers and toes,
• if you have an untreated pheochromocytoma (a rare tumor of the adrenal gland),
• if you have metabolic acidosis, a condition in which the blood contains too much acid,
• if you have had symptoms such as wheezing, facial swelling, tongue or throat swelling, intense itching, or severe skin rash during previous treatment with an ACE inhibitor, or if you or a family member have had such symptoms in any other circumstances (a condition known as angioedema),
• if you are pregnant more than three months (it is also not recommended to take ACEBIS in early pregnancy - see "Pregnancy"),
• if you have diabetes or kidney problems and are taking a blood pressure-lowering medicine containing aliskiren,
• if you are on dialysis or undergoing another type of blood filtration. Depending on the device used, ACEBIS may not be suitable for you.
• if you have kidney problems where blood flow to the kidneys is reduced (renal artery stenosis),
• if you are taking sacubitril/valsartan, a combination medicine containing sacubitril and valsartan, used to treat heart failure (see "Warnings and precautions" and "Other medicines and ACEBIS")

Warnings and precautions

Before starting to take ACEBIS, you should discuss it with your doctor or pharmacist if:

• you have diabetes,
• you have kidney problems (including a transplanted kidney) or are on dialysis,
• you have liver problems,
• you have a narrowing of the aorta and mitral valve (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 the kidney with blood),
• you have abnormally high levels of a hormone called aldosterone in your blood (primary aldosteronism),
• you have heart failure or any other heart problems, such as minor arrhythmias or severe chest pain at rest (Prinzmetal's angina),
• you have a connective tissue disease (such as systemic lupus erythematosus or scleroderma),
• you are on a low-salt diet or taking salt substitutes containing potassium (too much potassium in the blood can cause changes in heart rate),
• you have recently had diarrhea or vomiting or are dehydrated (ACEBIS may cause a drop in blood pressure),
• you are going to have LDL apheresis (a procedure to remove cholesterol from the blood using a special device),
• you are currently undergoing desensitization treatment or plan to undergo desensitization treatment to reduce the effects of an allergy to bee or wasp stings,
• you are on a strict diet or fasting,
• you are going to have anesthesia and/or major surgery,
• you have circulation problems in your limbs,
• you have asthma or COPD,
• you have (or have had) psoriasis,
• you have a pheochromocytoma (adrenal gland tumor),
• you have thyroid disorders (ACEBIS may mask the symptoms of hyperthyroidism),
• you have angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat with difficulty swallowing or breathing). This can occur at any time during treatment. If you experience such symptoms, you should stop taking ACEBIS and contact your doctor immediately.
• you are of black African descent, as you may be at higher risk of angioedema, and this medicine may be less effective in lowering blood pressure than in patients of non-black African descent,
• you are 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), especially in patients with diabetic kidney disease.
• aliskiren. Your doctor may check your kidney function, blood pressure, and electrolyte levels (such as potassium) in your blood at regular intervals. See also the information under "When not to take ACEBIS".
• you are taking any of the following medicines - the risk of angioedema is increased:
• racecadotril (used to treat diarrhea),
• sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of mTOR inhibitors (used to prevent organ rejection),
• sacubitril (available in a fixed-dose combination with valsartan), used to treat chronic heart failure.

Do not stop taking ACEBIS suddenly, as this may cause serious worsening of your heart condition. Do not stop treatment suddenly, especially in patients with coronary artery disease.
A pregnant woman should tell her doctor if she is pregnant (or thinks she may be pregnant). It is not recommended to take ACEBIS in early pregnancy and it must not be taken after the third month of pregnancy, as it may seriously harm the baby (see "Pregnancy").

Children and adolescents

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

Other medicines and ACEBIS

You should tell your doctor or pharmacist about all the medicines you are taking now or have taken recently, as well as any medicines you plan to take.
There are medicines that may change the effect of ACEBIS or whose effect may be changed by ACEBIS. This type of interaction may cause reduced efficacy of one or both medicines. It may also increase the risk or severity of side effects.
You should remember to inform your doctor if you are taking any of the following medicines:

• medicines used to control blood pressure or heart diseases (such as amiodarone, amlodipine, clonidine, digitalis 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 the 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 to treat heart failure: eplerenone and spironolactone at doses of 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 used to treat diarrhea (racecadotril) or to prevent organ rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of mTOR inhibitors). See "Warnings and precautions".
• sacubitril/valsartan (used to treat chronic heart failure). See "When not to take ACEBIS" and "Warnings and precautions".
• lithium used to treat mania or depression,
• certain medicines used to treat depression, such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors),
• certain medicines used to treat schizophrenia (antipsychotic medicines),
• certain medicines used to treat epilepsy (phenytoin, barbiturates such as phenobarbital),
• anesthetics used in surgical procedures,
• vasodilators, including nitrates,
• trimethoprim used to treat infections,
• immunosuppressive medicines (medicines that weaken the body's defense mechanisms), such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after organ transplantation,
• allopurinol used to treat gout,
• parasympathomimetic medicines used to treat diseases such as Alzheimer's disease or glaucoma,
• beta-adrenergic blockers used topically 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 given 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 medicines (NSAIDs), such as ibuprofen or diclofenac, or high doses of 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 you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, you should consult your doctor or pharmacist before taking this medicine.
Pregnancy
A pregnant woman should tell her doctor if she is pregnant (or thinks she may be pregnant).
Usually, the doctor will advise stopping ACEBIS before becoming pregnant or as soon as pregnancy is confirmed and will prescribe another medicine instead of ACEBIS. It is not recommended to take ACEBIS in early pregnancy and it must not be taken after the third month of pregnancy, as it may seriously harm the baby.
Breastfeeding
You should inform your doctor about breastfeeding or intending to breastfeed. ACEBIS is not recommended for breastfeeding mothers, and the doctor may choose another treatment for you if you want to breastfeed, especially if the baby is a newborn or premature.

Driving and using machines

ACEBIS usually does not affect alertness, but some patients may experience dizziness or weakness due to low blood pressure, especially at the beginning of treatment or when changing the medicine, as well as in combination with alcohol. If these changes occur, the ability to drive vehicles or operate machines may be impaired.
Lactose
ACEBIS 2.5 mg + 1.25 mg contains 40.97 mg of lactose (20.49 mg of glucose and 20.49 mg of galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 2.5 mg + 2.5 mg contains 40.97 mg of lactose (20.49 mg of glucose and 20.49 mg of galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 5 mg + 2.5 mg contains 81.94 mg of lactose (40.97 mg of glucose and 40.97 mg of galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 5 mg + 5 mg contains 81.94 mg of lactose (40.97 mg of glucose and 40.97 mg of galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 10 mg + 5 mg contains 163.88 mg of lactose (81.94 mg of glucose and 81.94 mg of galactose) per dose. This should be taken into account in patients with diabetes.
ACEBIS 10 mg + 10 mg contains 163.88 mg of lactose (81.94 mg of glucose and 81.94 mg of galactose) per dose. This should be taken into account in patients with diabetes.
Sodium
ACEBIS contains less than 1 mmol of sodium (23 mg) per capsule, which means the medicine is essentially "sodium-free".

3. How to take ACEBIS

This medicine should always be taken exactly as prescribed by your doctor or pharmacist. If you are unsure, you should consult your doctor or pharmacist.
The recommended dose is one capsule per day. 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 if you have moderate kidney disease. It is not recommended to take ACEBIS if you have severe kidney disease.
Patients with liver function disorders
Your doctor will closely monitor you if you have mild or moderate liver disease when starting treatment with ACEBIS.

Use in children and adolescents

ACEBIS is not recommended for use in children and adolescents.

Taking a higher dose of ACEBIS than prescribed

If you have taken more capsules than prescribed, you should contact your doctor or pharmacist immediately.
The most likely effect of an overdose is low blood pressure, which can cause dizziness or fainting (in such a case, lying down with your legs raised may help), severe breathing difficulties, tremors (due to low blood sugar), and slow heart rate.

Missing a dose of ACEBIS

It is important to take the medicine every day, as regular treatment is more effective. However, if you miss a dose of ACEBIS, you should take the next dose at the usual time. Do not take a double dose to make up for the missed dose.

Stopping ACEBIS treatment

Do not stop taking ACEBIS suddenly or change the dose without consulting your doctor, as this may cause serious worsening of your heart condition. Do not stop treatment suddenly, especially in patients with coronary artery disease.
If you have any further doubts about taking this medicine, you should consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, ACEBIS can cause side effects, although not everybody gets them.
You should stop taking the 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 occur in up to 1 in 10 people),
• worsening of heart failure causing increased shortness of breath and/or fluid retention (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),
• abnormal or irregular heartbeats, chest pain (angina pectoris), or heart attack (uncommon - may occur in up to 1 in 100 people),
• weakness or numbness in the arms or legs or problems with speech, which may be a sign of a possible stroke (frequency not known - cannot be estimated from the available data),
• pancreatitis, which can cause severe abdominal pain radiating to the back, accompanied by a very bad feeling (rare - may occur in up to 1 in 10,000 people),
• yellowing of the skin or eyes (jaundice), which can be a sign of liver inflammation (rare - may occur in up to 1 in 1,000 people),
• a skin rash that often starts with red, itchy patches on the face, hands, or feet (erythema multiforme) (frequency not known - cannot be estimated from the available data).

ACEBIS is usually well-tolerated, but, like all medicines, patients may experience various side effects, especially at the beginning of treatment.

If you notice any of the following side effects or any other side effects not mentioned in this leaflet, you should tell your doctor or pharmacist immediately:

Very common (may occur in more than 1 in 10 people):

• slow heart rate.

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

• headache,
• dizziness,
• fainting, low blood pressure (hypotension), especially when standing up quickly or sitting up,
• numbness in the hands or feet,
• feeling cold in the hands or feet,
• cough,
• shortness of breath,
• sinusitis or bronchitis,
• chest pain,
• gastrointestinal disorders, such as nausea, vomiting, abdominal pain, difficulty swallowing, or indigestion, diarrhea, constipation,
• allergic reactions, such as skin rash, itching,
• muscle cramps, muscle pain (myalgia),
• feeling tired,
• 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 disorders,
• tingling (paresthesia),
• vision disorders,
• ringing in the ears (tinnitus),
• stuffy nose, difficulty breathing, or worsening of asthma,
• inflammation of the nasal mucosa, nasal congestion,
• sudden flushing (especially of the face),
• mood swings,
• sleep disorders,
• depression,
• dry mouth,
• sweating,
• kidney problems,
• increased urine production during the day than usual,
• impotence,
• excessive eosinophils (a type of white blood cell),
• drowsiness,
• palpitations,
• rapid heart rate (tachycardia),
• irregular heart rate (atrioventricular conduction disorders),
• muscle weakness,
• joint pain (arthralgia),
• localized swelling (peripheral edema),
• fever,
• loss of appetite (anorexia),
• changes in laboratory parameters: increased levels of certain white blood cells (eosinophilia), increased urea levels in the blood, increased creatinine levels in the blood, increased liver enzyme activity, increased bilirubin levels in serum,
• increased protein levels in the urine,
• mouth ulcers,
• breast enlargement in men.

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

• nightmares, hallucinations,
• reduced tear secretion (dry eyes),
• redness, itching, swelling, or tearing of the eyes,
• hearing problems,
• liver inflammation, which can cause yellowing of the skin or eyes,
• inflammation of blood vessels,
• changes in laboratory parameters: increased fat levels, decreased red blood cell count, white blood cell count, or hemoglobin levels.

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

• confusion,
• pancreatitis (which can cause severe abdominal pain radiating to the back),
• hair loss,
• appearance or worsening of a scaly skin rash (psoriasis), psoriasis-like rash,
• increased sensitivity of the skin to sunlight (photosensitivity reaction),

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

• discoloration, numbness, and pain in the fingers and toes (Raynaud's phenomenon),
• low sodium levels, very low blood sugar levels (hypoglycemia) in patients with diabetes,
• inflammation of the tongue.

When taking ACE inhibitors, side effects such as concentrated urine (dark color), nausea, or vomiting, muscle cramps, confusion, and seizures may occur, which may be caused by abnormal secretion of antidiuretic hormone (ADH). If you experience these symptoms, you should contact your doctor as soon as possible.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Jerozolimskie Avenue 181C

• 02-222 Warsaw Tel.: +48 22 49 21 301 Fax: +48 22 49 21 309 Website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ACEBIS

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after EXP.
The expiry date refers to the last day of the month stated.
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. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What ACEBIS contains

• The active substances of ACEBIS are ramipril and bisoprolol fumarate.
• The other ingredients are: Contents of the capsule:lactose monohydrate, polyvinyl alcohol, sodium croscarmellose (E468), sodium stearyl fumarate, microcrystalline cellulose, calcium hydrogen phosphate anhydrous, crospovidone type A, colloidal anhydrous silica, magnesium stearate

AquaPolish P yellow :hypromellose (E 464), hydroxypropylcellulose (E463), medium-chain triglycerides, talc (E 553b), titanium dioxide (E 171) ,iron oxide yellow (E 172).
Capsule shell: titanium dioxide (E 171), gelatin, iron oxide red (E 172) – [in capsules 10 mg+10 mg, 10 mg+5 mg, 5 mg+5 mg, 5 mg+2.5 mg], iron oxide yellow (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].
Ink: shellac (E904), iron oxide black (E172), propylene glycol, concentrated ammonia solution, potassium hydroxide.

What ACEBIS looks like and contents of the pack

ACEBIS 2.5 mg + 1.25 mg, hard capsules
The capsule has a yellow cap with black printing "2.5 mg" and a white body with black printing "1.25 mg".
Contents of the 2.5 mg + 1.25 mg capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet
ACEBIS 2.5 mg + 2.5 mg, hard capsules
The capsule has a yellow cap with black printing "2.5 mg" and a yellow body with black printing "2.5 mg".
Contents of the 2.5 mg + 2.5 mg capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet
ACEBIS 5 mg + 2.5 mg, hard capsules
The capsule has an orange cap with black printing "5 mg" and a yellow body with black printing "2.5 mg".
Contents of the 5 mg + 2.5 mg capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet
ACEBIS 5 mg + 5 mg, hard capsules
The capsule has an orange cap with black printing "5 mg" and an orange body with black printing "5 mg".
Contents of the 5 mg + 5 mg capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet
ACEBIS 10 mg + 5 mg, hard capsules
The capsule has a reddish-brown cap with black printing "10 mg" and an orange body with black printing "5 mg".
Contents of the 10 mg + 5 mg capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet
ACEBIS 10 mg + 10 mg, hard capsules
The capsule has a reddish-brown cap with black printing "10 mg" and a reddish-brown body with black printing "10 mg".
Contents of the 10 mg + 10 mg capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of two yellow, biconvex, film-coated, round tablets
BOPA/Aluminum/PVC/Aluminum blisters.
The blisters and patient information leaflet are packaged in a cardboard box.
Capsules are available in packs of:
10, 30, 60, or 100 capsules.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Manufacturer

Adamed Pharma S.A.
Marszałka Józefa Piłsudskiego 5 Street
95-200 Pabianice
Date of last revision of the leaflet:May 2023