RABIDUX 10 mg/5 mg HARD CAPSULES

Introduction

Patient Information: Summary of Product Characteristics

Rabidux 2.5 mg/1.25 mg hard capsules

Rabidux 2.5 mg/2.5 mg hard capsules

Rabidux 5 mg/2.5 mg hard capsules

Rabidux 5 mg/5 mg hard capsules

Rabidux 10 mg/5 mg hard capsules

Rabidux 10 mg/10 mg hard capsules

ramipril/bisoprolol fumarate

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Rabidux and what is it used for
2. What you need to know before you take Rabidux
3. How to take Rabidux
4. Possible side effects
5. Storage of Rabidux
6. Contents of the pack and other information

1. What is Rabidux and what is it used for

Rabidux contains two active substances, bisoprolol fumarate and ramipril in a single 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 through them.
• Bisoprolol fumarate belongs to a group of medicines called beta-blockers. Beta-blockers slow the heart rate and make the heart pump blood more efficiently throughout the body.

This medicine is used to treat high blood pressure (hypertension) and/or chronic heart failure with left ventricular dysfunction (a condition in which the heart is unable to pump enough blood to meet the body's needs, leading to 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 the blood supply to the heart is reduced or blocked) who have already had a heart attack and/or a procedure to improve blood flow to the heart by dilating the blood vessels that supply it, or diabetes with at least one cardiovascular risk factor.

Instead of taking bisoprolol fumarate and ramipril in separate capsules, you will take a single capsule of this medicine that contains both active substances in the same formulation.

2. What you need to know before you take Rabidux

Do not take Rabidux:

• if you are 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 you have worsening heart failure that 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 lung disease,
• if you have severe blood circulation problems in your limbs (such as Raynaud's syndrome), which can cause tingling in your fingers or toes or pale or blue discoloration,
• if you have an untreated pheochromocytoma, a rare tumor of the adrenal gland (medulla),
• if you have metabolic acidosis, a condition in which your blood contains too much acid,
• if you have experienced symptoms such as wheezing, swelling of the face, tongue, or throat, intense itching, or severe skin rash with previous treatment with an ACE inhibitor or if you or a family member have had these symptoms in any other circumstance (a condition called "angioedema"),
• if you are pregnant for more than 3 months (it is also best to avoid this medicine at the start of pregnancy; see section "Pregnancy and breastfeeding"),
• if you have diabetes or kidney problems and are being treated with a blood pressure-lowering medicine that contains aliskiren,
• if you are undergoing dialysis or any other type of blood filtration. Depending on the machine used, this medicine may not be suitable for you,
• if you have kidney problems where blood supply to the kidneys is reduced (renal artery stenosis),
• if you have taken or are taking sacubitril/valsartan, a medicine used to treat a type of heart failure (see "Warnings and precautions" and "Other medicines and Rabidux").

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medicine, if you:

• have diabetes,
• have kidney problems (including kidney transplant) or are undergoing dialysis,
• have a liver problem,
• have aortic and mitral stenosis (narrowing of the main blood vessel that leaves the heart) or hypertrophic cardiomyopathy (a disease of the heart muscle) or renal artery stenosis (narrowing of the artery that supplies blood to the kidney),
• have abnormally high levels of a hormone called aldosterone in the blood (primary aldosteronism),
• have heart failure or any other heart problem, such as minor changes in heart rhythm or severe chest pain at rest (Prinzmetal's angina),
• suffer from a collagen vascular disease (a disease of the connective tissue) such as systemic lupus erythematosus or scleroderma,
• follow a low-salt diet or use salt substitutes that contain potassium (too much potassium in the blood can cause changes in heart rhythm),
• have recently had diarrhea or vomiting, or are dehydrated (this medicine can cause a drop in blood pressure),
• are going to undergo LDL apheresis (which is the removal of cholesterol from the blood using a machine),
• are receiving allergy treatment or are going to receive desensitization treatment to reduce the effects of an allergy to bee or wasp stings,
• are on a strict fast or diet,
• are going to undergo anesthesia and/or major surgery,
• have circulation problems in your limbs,
• have asthma or chronic lung disease,
• have (or have had) psoriasis,
• have a tumor of the adrenal gland (pheochromocytoma),
• have thyroid disorders (this medicine can mask the symptoms of an overactive thyroid),
• 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 develop such symptoms, you must stop taking this medicine and consult a doctor immediately,
• are of black African or Afro-Caribbean origin, as you may be at higher risk of angioedema and this medicine may be less effective at lowering your blood pressure than in patients who are not of black African or Afro-Caribbean origin,
• are taking any of the following medicines used to treat high blood pressure:

• an "angiotensin II receptor antagonist" (ARA) (also known as "sartans", e.g., valsartan, telmisartan, irbesartan), particularly if you have diabetic kidney problems.
• aliskiren.

Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g., potassium) at regular intervals. See also the information under the heading "Do not take Rabidux".

• are taking any of the following medicines, as they increase the risk of angioedema:

• racecadotril (used to treat diarrhea),
• sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of so-called mTOR inhibitors (used to prevent organ rejection after transplantation),
• sacubitril (available as a fixed-dose combination with valsartan), used to treat long-term heart failure.

Do not stop taking this medicine suddenly, as this can cause a severe worsening of the heart condition. Treatment should not be stopped abruptly, especially in patients with coronary artery disease.

Tell your doctor if you think you are (or might become) pregnant. This medicine is not recommended during the first trimester of pregnancy and must not be taken if you are pregnant for more than 3 months, as it may cause serious harm to your baby if taken after the third month of pregnancy (see section "Pregnancy and breastfeeding").

Children and adolescents

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

Other medicines and Rabidux

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

There are some medicines that may change the effect of this medicine or their effect may be changed by this medicine. This type of interaction could make one or both medicines less effective. It could also increase the risk or severity of side effects.

Make sure to tell your doctor if you are taking any of the following medicines:

• medicines used to control blood pressure or medicines for heart problems (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 (ARAs), aliskiren (see also the information under the headings "Do not take Rabidux" 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 that contain potassium, other medicines that may increase potassium levels in your body (such as heparin and cotrimoxazole, also known as trimethoprim/sulfamethoxazole),
• potassium-sparing medicines used in the treatment of heart failure: eplerenone and spironolactone in doses between 12.5 mg and 50 mg per day,
• sympathomimetic agents for the treatment of clinical shock (adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine),
• estradiol used in cancer therapy,
• medicines that are used more frequently to treat diarrhea (racecadotril) or prevent organ rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of so-called mTOR inhibitors). See section "Warnings and precautions",
• sacubitril/valsartan (used to treat long-term heart failure). See sections "Do not take Rabidux" 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 (antipsychotics),
• certain medicines used to treat epilepsy (phenytoin, barbiturates such as phenobarbital),
• anesthetic agents used for surgery,
• vasodilators, including nitrates (products that make blood vessels widen),
• trimethoprim used to treat infections,
• immunosuppressants (medicines that reduce the body's defense mechanism) such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after transplant surgery,
• allopurinol used to treat gout,
• parasympathomimetic medicines used to treat diseases such as Alzheimer's disease or glaucoma,
• topical beta-blockers used 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 with intravenous administration (used to treat symptoms of rheumatoid arthritis),
• medicines for diabetes such as insulin, metformin, linagliptina, saxagliptina, sitagliptina, vildagliptina,
• non-steroidal anti-inflammatory medicines (NSAIDs) such as ibuprofen or diclofenac or high doses of aspirin to treat arthritis, headache, pain, or inflammation.

Taking Rabidux with food, drinks, and alcohol

It is preferable to take this medicine before a meal.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

You should inform your doctor if you think you are (or might become) pregnant. Your doctor will normally advise you to stop taking this medicine before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of this one. This medicine is not recommended during the first trimester of pregnancy and must not be taken if you are pregnant for more than 3 months, as it may cause serious harm to your baby if taken after the third month of pregnancy.

Breastfeeding

Tell your doctor if you are breastfeeding or plan to breastfeed. This medicine is not recommended for breastfeeding mothers, and your doctor may choose another treatment for you if you want to breastfeed, especially if your baby is a newborn or was born prematurely.

Driving and using machines

This medicine is not expected to affect your ability to drive or use machines. However, some patients may experience dizziness or weakness due to low blood pressure, particularly at the start of treatment or when changing medication, as well as in combination with alcohol. If this happens, do not drive or operate tools or machines.

Rabidux contains lactose

Rabidux 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, which should be taken into account in patients with diabetes mellitus.

Rabidux 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, which should be taken into account in patients with diabetes mellitus.

Rabidux 5 mg/2.5 mg contains 81.94 mg of lactose (40.97 mg of glucose and 40.97 mg of galactose) per dose, which should be taken into account in patients with diabetes mellitus.

Rabidux 5 mg/5 mg contains 81.94 mg of lactose (40.97 mg of glucose and 40.97 mg of galactose) per dose, which should be taken into account in patients with diabetes mellitus.

Rabidux 10 mg/5 mg contains 163.88 mg of lactose (81.94 mg of glucose and 81.94 mg of galactose) per dose, which should be taken into account in patients with diabetes mellitus.

Rabidux 10 mg/10 mg contains 163.88 mg of lactose (81.94 mg of glucose and 81.94 mg of galactose) per dose, which should be taken into account in patients with diabetes mellitus.

Rabidux contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule; this is essentially "sodium-free".

3. How to take Rabidux

Follow the instructions for administration of this medicine exactly as indicated by your doctor or pharmacist. If you are in doubt, consult your doctor or pharmacist again.

The recommended dose is one capsule once a day. Swallow your capsule with a glass of water in the morning before a meal.

Patients with kidney problems

Your doctor will adjust the dose of this medicine if you have moderate kidney disease. This medicine is not recommended if you have severe kidney disease.

Patients with liver problems

Your doctor will closely monitor the start of treatment with this medicine if you have mild or moderate liver disease.

Use in children and adolescents

This medicine is not recommended for use in children and adolescents.

If you take more Rabidux than you should

If you take more capsules than prescribed, contact your doctor or pharmacist immediately.

The most likely effect in case of overdose is low blood pressure, which can make you feel dizzy or faint (if this happens, lying down with your legs raised can help), severe difficulty breathing, tremors (due to low blood sugar), and slow heart rate.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Rabidux

It is important that you take your medicine every day, as regular treatment works best. However, if you forget to take a dose of this medicine, take the next dose at the usual time. Do not take a double dose to make up for forgotten doses.

If you stop taking Rabidux

Do not stop taking this medicine suddenly or change the dose without consulting your doctor, as this can cause a severe worsening of the heart condition. Treatment should not be stopped abruptly, especially in patients with coronary artery disease.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Stop taking this medicine and consult a doctor immediately if you notice any of the following serious side effects:

• severe dizziness or fainting due to low blood pressure (frequent - may affect up to 1 in 10 people),
• worsening of heart failure that causes increased difficulty breathing and/or fluid retention (frequent - 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, difficulty breathing, or shortness of breath (bronchospasm) (uncommon - may affect up to 1 in 100 people),
• abnormally fast or irregular heartbeats, chest pain (angina), or heart attack (uncommon - may affect up to 1 in 100 people),
• weakness in arms or legs, or problems speaking that could be a sign of a possible stroke (frequency cannot be estimated from available data),
• inflamed pancreas that can cause severe abdominal and back pain accompanied by general discomfort (very rare - may affect up to 1 in 10,000 people),
• yellowing of the skin or eyes (jaundice) that could be a sign of hepatitis (rare - may affect up to 1 in 1,000 people),
• skin rash that often starts with red spots that itch on the face, arms, or legs (erythema multiforme) (frequency not known - cannot be estimated from available data).

This medicine is usually well-tolerated, but like any medicine, people may experience different side effects, especially when starting treatment for the first time.

If you notice any of the following side effects or those not mentioned, inform your doctor or pharmacist immediately:

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

• slow heartbeats.

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

• headache,
• dizziness,
• fainting, low blood pressure (hypotension), especially when standing or sitting up quickly,
• numbness of hands or feet,
• feeling of cold in hands or feet,
• cough,
• difficulty breathing,
• inflammation of the paranasal sinuses (sinusitis) or bronchitis,
• chest pain,
• gastrointestinal disorders such as nausea, vomiting, abdominal pain, difficulty digesting, or dyspepsia, diarrhea, constipation,
• allergic reactions such as skin rashes, itching,
• muscle cramps, muscle pain (myalgia),
• feeling of fatigue,
• fatigue,
• blood tests showing higher than normal potassium levels in the blood.

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

• vertigo,
• taste disturbances,
• tingling or numbness (paresthesia),
• vision disturbances,
• tinnitus (ringing in the ears),
• stuffy nose, difficulty breathing, or worsening of asthma,
• rhinitis, nasal congestion,
• flushing,
• mood changes,
• sleep disorders,
• depression,
• dry mouth,
• sweating,
• kidney problems,
• excessive urination, more than usual during the day,
• impotence,
• high levels of eosinophils (a type of white blood cell),
• drowsiness,
• palpitations,
• rapid heartbeat,
• irregular heartbeat (atrioventricular conduction disorders),
• muscle weakness,
• joint pain (arthralgia),
• localized swelling (peripheral edema),
• fever,
• loss or decreased appetite (anorexia),
• changes in laboratory parameters: increased levels of certain white blood cells (eosinophilia), increased urea in blood, increased creatinine in blood, increased liver enzyme levels, high bilirubin levels,
• increased protein levels in urine,
• mouth ulcers,
• breast enlargement in men.

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

• nightmares, hallucinations,
  • reduced tear flow (dry eyes),
  • red, itchy, swollen, or watery eyes,
  • ear problems,
  • inflammation of the liver that can cause yellowing of the skin or eyes,
  • inflammation of blood vessels (vasculitis),
  • changes in laboratory parameters: abnormal fat levels, decreased red blood cells, white blood cells, or platelets, or decreased hemoglobin levels.

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

• confusion,
• inflammation of the pancreas (causing severe abdominal and back pain),
• hair loss,
• appearance or worsening of a scaly skin rash (psoriasis), rash similar to psoriasis,
• increased skin sensitivity to sunlight (photosensitivity reaction).

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

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

Concentrated urine (dark color), feeling or being sick, having muscle cramps, confusion, and seizures that may be due to inadequate ADH (antidiuretic hormone) secretion can occur with ACE inhibitors. If you have these symptoms, contact your doctor as soon as possible.

Reporting of Side Effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Rabidux

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date shown on the blister pack and carton after EXP. The expiration date is the last day of the month indicated.

Do not store above 30°C. Do not refrigerate or freeze.

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicines in the pharmacy's SIGRE collection point. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Rabidux Composition

• The active ingredients are ramipril and bisoprolol fumarate.
• The other ingredients are:

Capsule content: lactose monohydrate, poly(vinyl alcohol), sodium croscarmellose (E468), sodium stearyl fumarate, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, crospovidone type A, colloidal anhydrous silica, and magnesium stearate.

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

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

Printing ink: shellac (E904), black iron oxide (E172), propylene glycol, strong ammonia solution, and potassium hydroxide.

Product Appearance and Package Contents

Rabidux 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: white or almost white ramipril powder and a yellow, round, biconvex bisoprolol fumarate tablet.

Rabidux 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: white or almost white ramipril powder and a yellow, round, biconvex bisoprolol fumarate tablet.

Rabidux 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: white or almost white ramipril powder and a yellow, round, biconvex bisoprolol fumarate tablet.

Rabidux 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: white or almost white ramipril powder and a yellow, round, biconvex bisoprolol fumarate tablet.

Rabidux 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: white or almost white ramipril powder and a yellow, round, biconvex bisoprolol fumarate tablet.

Rabidux 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: white or almost white ramipril powder and two yellow, round, biconvex bisoprolol fumarate tablets.

BOPA/Al/PVC-Aluminum blisters.

The capsules are available in packs of 10, 30, 60, and 100 capsules.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Adamed Laboratorios, S.L.U.

c/ de las Rosas de Aravaca, 31 - 2ª planta

28023 Madrid

Spain

Manufacturer

Adamed Pharma S.A.

ul. Marszalka Józefa Pilsudskiego 5

95-200 Pabianice

Poland

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet: May 2023

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es.