Rabada: detailed information

Package leaflet: Information for the patient

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
Please read this leaflet carefully before taking this medicine, as 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 you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

What RABADA is and what it is used for
What you need to know before taking RABADA
How to take RABADA
Possible side effects
How to store RABADA
Contents of the pack and other information

1. What RABADA is and what it is used for

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

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. It works by relaxing 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.

RABADA is used to treat high blood pressure (hypertension) and/or chronic heart failure with left ventricular dysfunction (a condition in which the heart cannot 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 suffered a myocardial infarction and/or undergone a procedure to improve blood flow to the heart by widening the blood vessels supplying it.
Instead of taking bisoprolol fumarate and ramipril in separate capsules, you take just one RABADA capsule containing both active substances at the same strength.

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 components of this medicine (listed in section 6),
if the patient has heart failure that has suddenly worsened 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 condition characterized 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 an 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, facial, tongue or throat swelling, intense itching, or severe skin rash during treatment with an ACE inhibitor, or if such symptoms occurred in the patient or a family member under any circumstances (a condition called angioedema),
if the patient is pregnant beyond the third month (use of RABADA 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, RABADA may not be suitable for the patient,
if the patient has kidney problems involving reduced blood flow to the kidneys (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 RABADA")

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

the patient has diabetes,
the patient has kidney problems (including a kidney transplant) 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 (RABADA may cause a drop in 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 allergen immunotherapy or plans desensitization therapy to reduce allergic reactions to bee or wasp stings,
the patient is on a strict fast or 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 (RABADA 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 RABADA and contact a doctor immediately.
the patient is of Black race, as such patients may have a higher risk of angioedema, and the 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. The 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 RABADA".
the patient is taking any of the following medicines – the 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 RABADA suddenly, as this may lead to a serious worsening of heart condition. Do not discontinue treatment abruptly, especially in patients with coronary artery disease.
The patient must inform the doctor if she suspects she is pregnant (or may become pregnant). Use of RABADA 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
RABADA is not recommended for use in children and adolescents under 18 years of age.
Other medicines and RABADA
Inform your doctor or pharmacist about all medicines currently taken, recently taken, or planned for use.
Some medicines may alter the effect of RABADA or its effect may be altered by RABADA. 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 treat heart conditions (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 information under "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, or 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 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 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 RABADA" and "Warnings and precautions".
lithium used in the treatment of mania or depression,
certain antidepressants 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),
anaesthetics used during surgical procedures,
vasodilators, including nitrates,
trimethoprim used to treat infections,
immunosuppressive medicines (medicines that suppress the body's immune defences), 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 inflammatory conditions.

Taking RABADA with food, drink and alcohol
It is recommended to take RABADA 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 a doctor or pharmacist before using this medicine.
Pregnancy
The patient must inform the doctor if she suspects she is pregnant (or may become pregnant).
The doctor will usually recommend discontinuing RABADA before pregnancy or immediately after pregnancy is confirmed and will prescribe an alternative medicine. Use of RABADA 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 the doctor if you are breastfeeding or plan to breastfeed. RABADA 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 operating machinery
RABADA 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 change in medication, and especially when combined with alcohol. If such symptoms occur, the ability to drive or operate machinery may be impaired.
Lactose
RABADA 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.
RABADA 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.
RABADA 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.
RABADA 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.
RABADA 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.
RABADA 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
RABADA contains less than 1 mmol sodium (23 mg) per capsule, meaning the medicine is considered "sodium-free".

3. How to take RABADA
Always take this medicine 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 taken 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. Use of RABADA is not recommended in patients with severe kidney disease.
Patients with liver impairment
The doctor will closely monitor patients with mild or moderate liver disease when starting treatment with RABADA.
Use in children and adolescents
Use in children and adolescents is not recommended.
Taking more RABADA than recommended
If more capsules are taken than prescribed, contact a 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 raised may help), severe breathing difficulties, tremor (due to low blood sugar), and slow heart rate.
Missing a dose of RABADA
It is important to take the medicine daily, as regular treatment is more effective. However, if a dose of RABADA is missed, take the next dose at the usual time. Do not take a double dose to make up for a missed dose.
Stopping RABADA
Do not stop taking RABADA suddenly or change the dose without consulting a doctor, as this may lead to a serious worsening of heart condition. Do not discontinue treatment abruptly, especially in patients with coronary artery disease.
If you have any further questions about the use of 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 using 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 rapid or irregular heartbeat, chest pain (angina) or heart attack (uncommon – may occur in up to 1 in 100 people),
weakness in arms or legs or speech problems, which may be signs of a possible stroke (frequency cannot be determined from available data),
pancreatitis, which may cause severe abdominal pain radiating to the back, accompanied by general malaise (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 (uncommon – may occur in up to 1 in 1,000 people),
skin rash, which often begins as red, itchy spots on the face, hands or legs (erythema multiforme) (frequency unknown – frequency cannot be determined from available data).

RABADA 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, you should immediately inform your doctor or pharmacist:
Very common (may occur in more than 1 in 10 people):

slowed heartbeat.

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 of hands or feet,
feeling of cold in hands or feet,
cough,
shortness of breath,
sinusitis or bronchitis,
chest pain,
gastrointestinal disturbances such as nausea, vomiting, abdominal pain, indigestion or dyspepsia, diarrhoea, constipation,
allergic reactions such as skin rash, itching,
muscle cramps, muscle pain (myalgia),
feeling of fatigue,
tiredness,
blood tests showing higher than usual potassium levels in the blood.

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

peripheral dizziness,
taste disturbances,
tingling (paresthesia),
visual disturbances,
tinnitus (ringing in the ears),
nasal congestion, difficulty breathing or worsening of asthma,
nasal mucosal inflammation, nasal obstruction,
sudden flushing (especially of the face),
mood swings,
sleep disturbances,
depression,
dry mouth,
sweating,
kidney problems,
increased urine output during the day compared to usual,
impotence,
eosinophilia (an excess of eosinophils, a type of white blood cell),
drowsiness,
palpitations,
rapid heartbeat (tachycardia),
irregular heart rate (atrioventricular conduction disturbances),
muscle weakness,
arthralgia (joint pain),
localized swelling (peripheral edema),
fever,
loss or decrease of 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,
elevated protein levels in urine,
oral 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,
hepatitis, 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 haemoglobin 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):

skin discoloration, numbness and pain in fingers of hands and feet (Raynaud's phenomenon),
low sodium levels, very low blood sugar levels (hypoglycaemia) in diabetic patients,
inflammation of the tongue.

Adverse reactions such as concentrated urine (dark colour), nausea or vomiting, muscle cramps, confusion and seizures may occur during treatment with ACE inhibitors, 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 Drug Reactions, 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: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store RABADA medicine

Keep this medicine out of the 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 stated month.
Do not store above 30°C. Do not store in the refrigerator or freeze.
Medicines must 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 pack and other information

What the medicine RABADA contains

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

Coating: 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].
Printing ink: Shellac (E904), Iron oxide black (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 printed in black with "2.5 mg" and a white body printed in black with "1.25 mg".
RABADA 2.5 mg + 2.5 mg, hard capsules
The capsule has a yellow cap printed in black with "2.5 mg" and a yellow body printed in black with "2.5 mg".
RABADA 5 mg + 2.5 mg, hard capsules
The capsule has an orange cap printed in black with "5 mg" and a yellow body printed in black with "2.5 mg".
RABADA 5 mg + 5 mg, hard capsules
The capsule has an orange cap printed in black with "5 mg" and an orange body printed in black with "5 mg".
RABADA 10 mg + 5 mg, hard capsules
The capsule has a reddish-brown cap printed in black with "10 mg" and an orange body printed in black with "5 mg".
RABADA 10 mg + 10 mg, hard capsules
The capsule has a reddish-brown cap printed in black with "10 mg" and a reddish-brown body printed in black with "10 mg".
Contents of the capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of a single yellow, biconvex, coated, round tablet.

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

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation 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