Rabada

Leaflet accompanying the packaging: Patient information

RABADA, 2.5 mg + 1.25 mg, hard capsules
RABADA, 2.5 mg + 2.5 mg, hard capsules
RABADA, 5 mg + 2.5 mg, hard capsules

RABADA, 5 mg + 5 mg, hard capsules

RABADA, 10 mg + 5 mg, hard capsules

RABADA, 10 mg + 10 mg, hard capsules

ramipril + bisoprolol fumarate

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• In case of any doubts, 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 the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is RABADA and what is it used for

RABADA 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 blocking agents). Beta-blockers slow the heart rate and increase the efficiency of the heart in pumping blood to the body.

RABADA 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.

2. Important information before taking RABADA

When not to take RABADA:

• 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 that has suddenly worsened and may require hospital treatment,
• if the patient has cardiogenic shock (a serious heart condition caused by very low blood pressure),
• if the patient has a heart condition characterized by a slow or irregular heart rate (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 obstructive pulmonary disease (COPD),
• if the patient has serious circulation problems in the limbs (such as Raynaud's syndrome) that may cause tingling, pallor, or cyanosis of the fingers and toes,
• if the patient has an untreated pheochromocytoma (a rare tumor of the adrenal gland),
• if the patient has metabolic acidosis (a condition in which the blood contains too much acid),
• if the patient has had angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat, and difficulty swallowing or breathing) during previous treatment with an ACE inhibitor, or if the patient or a family member has had angioedema in any other circumstances,
• if the patient is pregnant more than three months (it is also not recommended to take RABADA in early pregnancy - see "Pregnancy"),
• if the patient has diabetes or kidney problems and is taking aliskiren, a medicine used to lower blood pressure,
• if the patient is on dialysis or undergoing another type of blood filtration. Depending on the device used, RABADA may not be suitable for the patient,
• if the patient has kidney problems with reduced blood flow to the kidneys (renal artery stenosis),
• if the patient is taking sacubitril/valsartan, a combination medicine used to treat heart failure (see "Warnings and precautions" and "Other medicines and RABADA")

Warnings and precautions

Before starting to take RABADA, the patient should discuss it with their doctor or pharmacist if:

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

Do not stop taking RABADA suddenly, as this may cause serious worsening of the heart condition. Do not stop treatment suddenly, especially in patients with coronary artery disease.

Children and adolescents

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

Other medicines and RABADA

The patient should tell their doctor or pharmacist about all medicines they are taking or have recently taken, as well as any medicines they plan to take.

• 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 the heading "When not to take RABADA" 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 commonly used to treat diarrhea (racecadotril) or to prevent transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of mTOR inhibitors). See the "Warnings and precautions" section.
• sacubitril/valsartan (used to treat chronic heart failure). See the "When not to take RABADA" and "Warnings and precautions" sections.
• 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 (antipsychotics),
• 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 pressure in the eye),
• 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 RABADA with food, drink, and alcohol

RABADA should be taken before a meal.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor or pharmacist before taking this medicine.

Pregnancy

The patient must tell their doctor if they think they are pregnant (or may become pregnant). The doctor will usually advise stopping RABADA before becoming pregnant or as soon as possible after finding out about the pregnancy, and will prescribe a different medicine instead of RABADA. RABADA should not be taken in early pregnancy and must not be taken after the third month of pregnancy, as it may seriously harm the baby.

Breastfeeding

The patient should inform their doctor about breastfeeding or intending to breastfeed. RABADA is not recommended for breastfeeding mothers, and the doctor may choose a different treatment for the patient if they want to breastfeed, especially if the baby is a newborn or premature.

Driving and using machines

RABADA 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 or operate machinery may be impaired.

Lactose

RABADA 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.

RABADA 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.

RABADA 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.

RABADA 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.

RABADA 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.

RABADA 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

RABADA contains less than 1 mmol of sodium (23 mg) per capsule, which means the medicine is considered "sodium-free".

3. How to take RABADA

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. In case of doubt, the patient should consult their doctor or pharmacist.

The recommended dose is one capsule once a day. The capsule should be swallowed in the morning before a meal, with a glass of water.

Patients with kidney disease

The doctor will adjust the dose of RABADA in patients with moderate kidney disease. RABADA is not recommended in patients with severe kidney disease.

Patients with liver problems

The doctor will closely monitor patients with mild or moderate liver disease when starting treatment with RABADA.

Use in children and adolescents

RABADA is not recommended for use in children and adolescents.

Taking a higher dose of RABADA than recommended

In case of taking more capsules than prescribed, the patient should contact their doctor or pharmacist immediately.

The most likely effect of an overdose is low blood pressure, which may cause dizziness or fainting (in which case lying down with elevated legs may help), severe breathing difficulties, tremors (due to low blood sugar), and slow heart rate.

Missing a dose of RABADA

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

Stopping RABADA treatment

The patient should not stop taking RABADA suddenly or change the dose without consulting their doctor, as this may cause serious worsening of the heart condition. The patient should not stop treatment suddenly, especially if they have coronary artery disease.

In case of any further doubts about taking this medicine, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, RABADA can cause side effects, although not everybody gets them.

The patient should stop taking RABADA and contact their doctor immediately if they 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 increased 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 wheezing, chest pain, shortness of breath, or difficulty breathing (bronchospasm) (uncommon - may affect up to 1 in 100 people),
• abnormal or irregular heartbeats, chest pain (angina pectoris), or heart attack (uncommon - may affect up to 1 in 100 people),
• weakness or numbness in the arms or legs or problems with speech, which may be signs of a possible stroke (frequency not known - cannot be estimated from the available data),
• pancreatitis, which may cause severe abdominal pain radiating to the back, accompanied by a very poor general condition (rare - may affect up to 1 in 10,000 people),
• jaundice (yellowing of the skin or eyes), which may be a sign of liver inflammation (rare - may affect up to 1 in 1,000 people),
• a skin rash, which often starts with red, itchy patches on the face, hands, or feet (erythema multiforme) (frequency not known - cannot be estimated from the available data).

RABADA is usually well-tolerated, but like all medicines, it can cause side effects, especially at the beginning of treatment.

If the patient notices any of the following side effects or any other side effects not mentioned in this leaflet, they should inform their doctor or pharmacist immediately:

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

• slow heart rate.

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

• headache,
• dizziness,
• fainting, low blood pressure, especially when standing up quickly or sitting down,
• 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 weak,
• fatigue,
• blood tests showing high levels of potassium in the blood.

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

• peripheral dizziness,
• taste disorders,
• tingling (paresthesia),
• vision disorders,
• tinnitus (a feeling of ringing in the ears),
• stuffy nose, difficulty breathing, or worsening of asthma,
• sinusitis, 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,
• high levels of eosinophils (a type of white blood cell),
• drowsiness,
• palpitations,
• rapid heart rate (tachycardia),
• irregular heart rhythm (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 levels of urea in the blood, increased levels of creatinine in the blood, increased activity of liver enzymes, increased levels of bilirubin in the serum,
• high levels of protein in the urine,
• mouth ulcers,
• breast enlargement in men.

Rare (may affect 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 may cause yellowing of the skin or eyes,
• inflammation of blood vessels,
• changes in laboratory parameters: increased levels of fat, decreased levels of red blood cells, white blood cells, or platelets, or hemoglobin levels.

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

• confusion,
• pancreatitis (which may 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 levels of sodium, very low levels of sugar in the blood (hypoglycemia) in patients with diabetes,
• tongue inflammation.

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

Reporting side effects

If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse.

Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products

• Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, email: [website URL] Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of this medicine.

5. How to store RABADA

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 pack 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. The patient should ask their 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 RABADA contains

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

Coating: AquaPolish P yellow: hypromellose (E464), hydroxypropyl cellulose (E463), medium-chain triglycerides, talc (E553b), titanium dioxide (E171), yellow iron oxide (E172).

Capsule shell: titanium dioxide (E171), gelatin, red iron oxide (E172) - [in 10 mg+10 mg, 10 mg+5 mg, 5 mg+5 mg, 5 mg+2.5 mg capsules], yellow iron oxide (E172) - [in 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 capsules], quinoline yellow (E104) - [in 5 mg+2.5 mg, 2.5 mg+2.5 mg, 2.5 mg+1.25 mg capsules].

Ink: shellac (E904), black iron oxide (E172), propylene glycol, ammonium hydroxide, concentrated, potassium hydroxide.

What RABADA looks like and contents of the pack

RABADA 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".

RABADA 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".

RABADA 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".

RABADA 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".

RABADA 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".

RABADA 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".

Capsule contents: ramipril as a white or almost white powder and bisoprolol fumarate as a single yellow, biconvex, film-coated, round tablet.

BOPA/Aluminum/PVC/Aluminum blisters.

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

Adamed Pharma S.A.

Pieńków, ul. Mariana Adamkiewicza 6A

05-152 Czosnów

tel.: +48 22 732 77 00

Manufacturer

Adamed Pharma S.A.

ul. Marszałka Józefa Piłsudskiego 5

95-200 Pabianice

Date of last revision of the leaflet