Ramizek Plus

Leaflet accompanying the packaging: Patient information

Ramizek Plus 2.5 mg + 1.25 mg, hard capsules
Ramizek Plus 2.5 mg + 2.5 mg, hard capsules

Ramizek Plus 5 mg + 2.5 mg, hard capsules

Ramizek Plus 5 mg + 5 mg, hard capsules

Ramizek Plus 10 mg + 5 mg, hard capsules

Ramizek Plus 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.
• In case of 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 the patient experiences any side effects, including those not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Ramizek Plus and what is it used for

Ramizek Plus 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-blockers slow the heart rate and increase the efficiency of the heart in pumping blood to the body.

Ramizek Plus 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 undergone a procedure to improve blood flow to the heart by widening the blood vessels that supply it.

Instead of taking bisoprolol fumarate and ramipril in separate capsules, you should take only one Ramizek Plus capsule, which contains both active substances at the same strength.

2. Important information before taking Ramizek Plus

When not to take Ramizek Plus:

• if the patient is 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 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 blood circulation problems in the limbs (such as Raynaud's syndrome), which can 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 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 the patient or a family member has had such symptoms in any other circumstances (a condition known as angioedema),
• if the patient is pregnant more than three months (it is also not recommended to take Ramizek Plus during early pregnancy - see "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 other blood filtration procedures. Depending on the device used, Ramizek Plus 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 to treat heart failure (see "Warnings and precautions" and "Other medicines and Ramizek Plus").

Warnings and precautions

Before starting to take Ramizek Plus, 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 undergoing 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 disease of the heart muscle) or renal artery stenosis (narrowing of the artery supplying the kidneys),
• the patient has abnormally high levels of a hormone called aldosterone in the blood (primary aldosteronism),
• the patient has heart failure or any 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 uses salt substitutes containing potassium (excessive potassium in the blood can cause changes in heart rate),
• the patient has recently had diarrhea or vomiting or is dehydrated (Ramizek Plus can cause low 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 (Ramizek Plus may mask symptoms of hyperthyroidism),
• the patient has 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 such symptoms occur, the patient should stop taking Ramizek Plus 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 races,
• 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 (such as potassium) in the blood at regular intervals. See also the information under "When not to take Ramizek Plus".
• 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 rejection of transplanted organs),
• sacubitril (available in a fixed-dose combination with valsartan), used to treat chronic heart failure.

The patient should not stop taking Ramizek Plus suddenly, as this can cause serious worsening of heart failure. The patient should not stop treatment suddenly, especially if they have coronary artery disease.

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

Children and adolescents

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

Other medicines and Ramizek Plus

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.

There are medicines that can change the effect of Ramizek Plus or whose effect can be changed by Ramizek Plus. This type of interaction can lead to reduced efficacy of one or both medicines. It can also increase the risk or exacerbate side effects.

The patient should remember to inform their doctor if they 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 Ramizek Plus" 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 can 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 rejection of transplanted organs (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 Ramizek Plus" 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,
• nonsteroidal anti-inflammatory medicines (NSAIDs), such as ibuprofen or diclofenac, or high doses of aspirin used to treat arthritis, headache, pain, or inflammation.

Taking Ramizek Plus with food, drinks, and alcohol

Ramizek Plus 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 should tell their doctor if they are pregnant (or think they may be pregnant). The doctor will usually advise stopping Ramizek Plus before becoming pregnant or as soon as pregnancy is confirmed and will prescribe a different medicine instead of Ramizek Plus. Ramizek Plus should not be taken during early pregnancy and must not be taken after the third month of pregnancy, as it can cause serious harm to the baby.

Breastfeeding

The patient should inform their doctor about breastfeeding or intending to breastfeed. Ramizek Plus 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

Ramizek Plus 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 machines may be impaired.

Lactose

Ramizek Plus 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.

Ramizek Plus 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.

Ramizek Plus 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.

Ramizek Plus 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.

Ramizek Plus 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.

Ramizek Plus 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

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

3. How to take Ramizek Plus

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 per 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 Ramizek Plus in patients with moderate kidney disease. Ramizek Plus is not recommended in patients with severe kidney disease.

Patients with liver function disorders

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

Use in children and adolescents

Ramizek Plus is not recommended for use in children and adolescents.

Taking a higher dose of Ramizek Plus than recommended

If the patient has taken more capsules than prescribed, they should contact their doctor or pharmacist immediately.

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

Missing a dose of Ramizek Plus

It is important to take the medicine every day, as regular treatment is more effective. However, if a dose of Ramizek Plus 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 Ramizek Plus treatment

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

If the patient has any further doubts about taking this medicine, they should consult their doctor, pharmacist, or nurse.

4. Possible side effects

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

The patient should stop taking the medicine 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 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 can be a sign of a possible stroke (frequency not known - cannot be estimated from available data),
• pancreatitis, which can cause severe abdominal pain radiating to the back, accompanied by a very poor general condition (rare - may occur in up to 1 in 10,000 people),
• jaundice (yellowing of the skin or eyes), 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 available data).

Ramizek Plus is usually well-tolerated, but like any medicine, patients may experience various side effects, especially at the beginning of treatment.

If the patient notices any of the following side effects or any other side effects not listed, they should tell their doctor or pharmacist:

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, 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 rashes, itching,
• muscle cramps, muscle pain (myalgia),
• feeling tired,
• fatigue,
• blood tests showing high 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,
• passing more urine 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,
• arthralgia (joint pain),
• localized swelling (peripheral edema),
• fever,
• loss of appetite (anorexia),
• laboratory test changes: 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 the serum,
• high 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,
• laboratory test changes: 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 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.

During treatment with ACE inhibitors, side effects such as dark urine (concentrated urine), nausea, or vomiting, muscle cramps, and confusion or seizures, which can be caused by abnormal secretion of antidiuretic hormone (ADH), may occur. If such 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 tell 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, Website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Ramizek Plus

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. 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 Ramizek Plus contains

• The active substances of Ramizek Plus 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.

AquaPolish P yellow coating: hypromellose (E464), hydroxypropylcellulose (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, concentrated ammonia solution, potassium hydroxide.

What Ramizek Plus looks like and contents of the pack

Ramizek Plus 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.

Ramizek Plus 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.

Ramizek Plus 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.

Ramizek Plus 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.

Ramizek Plus 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.

Ramizek Plus 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

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: 04.2023