Package Insert: Information for the Patient

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 this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert.See section 4.

Rabidux contains two active principles, bisoprolol fumarate and ramipril in a single capsule:

• Ramipril is aninhibitor ofangiotensin-converting enzyme (ACE). It acts by dilating blood vessels, making it easier for the heart to pump blood through them.
• Bisoprolol fumarate belongs to a group of medications called beta-blockers. Beta-blockersslow the heart rate andmake the heart pump blood more efficiently throughout the body.

This medication is used to treat high blood pressure (hypertension) and/or chronic heart failure with left ventricular dysfunction (a disease in which the heart cannot pump enough blood to meet the body's needs, causing dyspnea (difficulty breathing)and edema) and/or to reduce the risk of cardiac events, such as myocardial infarction, in patients with chronic coronary artery disease (a disease in which blood flow to the heart is reduced or blocked) who have already experienced a myocardial infarction and/or undergone a procedure to improve blood flow to the heart by dilating the vessels that irrigate 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 medication that contains both active principles in the same presentation.

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 components of this medication (listed in section 6),
• if you have heart failure that worsens suddenly and/or 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 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 chronic lung disease,
• if you have severe circulatory problems in your limbs (such as Raynaud's syndrome), which can cause tingling in your fingers and toes or paleness or blueness,
• if you have an untreated phaeochromocytoma, 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, lips, 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 more than 3 months pregnant (it is also best to avoid this medication at the beginning of pregnancy; see section "Pregnancy and breastfeeding"),
• if you have diabetes or kidney failure and are being treated with a blood pressure-lowering medication that contains aliskiren,
• if you are undergoing dialysis or any other type of blood filtration.
• Depending on the machine used, this medication may not be suitable for you,
• if you have kidney problems where the blood supply to the kidneys is reduced (renal artery stenosis),
• if you have taken or are taking sacubitrilo/valsartan, a medication used to treat a type of heart failure (see "Warnings and precautions" and "Other medications and Rabidux").

Warnings and precautions

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

• have diabetes,
• have kidney problems (including kidney transplant) or are receiving dialysis,
• have liver problems,
• have aortic and mitral stenosis (narrowing of the main blood vessel that leaves the heart) or hypertrophic cardiomyopathy (heart muscle disease) 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 alterations in heart rhythm or intense chest pain at rest (Prinzmetal's angina),
• have a disease of the collagen vascular tissue (connective tissue disease) such as systemic lupus erythematosus or scleroderma,
• are following a low-sodium diet or using sodium substitutes that contain potassium (excessive potassium in the blood can cause changes in heart rate),
• have recently had diarrhea or vomiting, or are dehydrated (this medication can cause a drop in blood pressure),
• are undergoing LDL apheresis (removal of cholesterol from the blood using a machine),
• are taking current allergy treatment or are about to have desensitization treatment to reduce the effects of an allergy to bee or wasp stings,
• are on a strict fast or diet,
• are about to undergo anesthesia and/or major surgery,
• have any problem with circulation 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 medication can mask symptoms of an overactive thyroid),
• have angioedema (severe allergic reaction with swelling of the face, lips, tongue, or throat, difficulty swallowing or breathing). This can occur at any time during treatment. If you develop such symptoms, stop taking this medication and consult a doctor immediately,
• are of black race, as you may have a higher risk of angioedema and this medication may be less effective in reducing blood pressure than in patients who are not of black race,
• are taking any of the following medications used to treat high blood pressure:

• a "angiotensin II receptor antagonist" (ARA) (also known as "sartanes", for example, valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.
• aliskirén.

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

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

• racecadotrilo (used to treat diarrhea),
• sirolimus, everolimus, temsirolimus, and other medications belonging to the class of so-called mTOR inhibitors (used to prevent rejection of transplanted organs),
• sacubitrilo (available as a fixed-dose combination with valsartan), used to treat chronic heart failure.

Do not stop taking this medication 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.

Inform your doctor if you think you are (or may be) pregnant. This medication is not recommended at the beginning of pregnancy and should not be taken if you are more than 3 months pregnant, as it can cause serious harm to your baby if taken after the third month of pregnancy (see section "Pregnancy and breastfeeding").

Children and adolescents

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

Other medications and Rabidux

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

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

Make sure to inform your doctor if you are taking any of the following medications:

• medications used to control blood pressure or medications for heart problems (such as amiodarone, amlodipine, clonidine, digitalis glycosides, diltiazem, disopyramide, felodipine, flecainide, lidocaine, methyldopa, moxonidine, procainamide, propafenone, quinidine, rilmenidine, verapamil),
• other medications used to treat high blood pressure, including angiotensin II receptor antagonists (ARAs), aliskirén (see also the information under the headings "Do not take Rabidux" and "Warnings and precautions") or diuretics (medications that increase the amount of urine produced by the kidneys),
• potassium-sparing medications (e.g., triamterene, amiloride), potassium supplements or sodium substitutes that contain potassium, other medications that can increase potassium in your body (such as heparin and co-trimoxazole, also known as trimethoprim/sulfamethoxazole),
• potassium-sparing medications used in the treatment of heart failure: eplerenone and spironolactone in doses between 12.5 mg and 50 mg per day,
• sympathomimetic agents used to treat shock (adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine),
• estramustine used in cancer therapy,
• medications, which are used more frequently to treat diarrhea (racecadotril) or prevent rejection of transplanted organs (sirolimus, everolimus, temsirolimus, and other medications belonging to the class of so-called mTOR inhibitors).See section "Warnings and precautions",
• sacubitrilo/valsartan (used to treat chronic heart failure). See sections "Do not take Rabidux" and "Warnings and precautions",
• litium used to treat mania or depression,
• some medications used to treat depression, such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors),
• some medications used to treat schizophrenia (antipsychotics),
• some medications used to treat epilepsy (phenytoin, barbiturates such as phenobarbital),
• anesthetic agents used for surgery,
• vasodilators, including nitrates (substances that cause blood vessels to dilate),
• trimethoprim used to treat infections,
• immunosuppressants (medications that reduce the body's defense mechanism) such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after organ transplantation,
• allopurinol used to treat gout,
• parasympathomimetic agents 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 intravenous administration (used to treat symptoms of rheumatoid arthritis),
• medications used to treat diabetes such as insulin, metformin, linagliptin, saxagliptin, sitagliptin, vildagliptin,
• nonsteroidal anti-inflammatory drugs (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 best to take this medication before a meal.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

You should inform your doctor if you think you are (or may be) pregnant. Your doctor will usually recommend that you stop taking this medication before becoming pregnant or as soon as you know you are pregnant and recommend that you take another medication instead of this medication. This medication is not recommended at the beginning of pregnancy and should not be taken if you are more than 3 months pregnant, as it can cause serious harm to your baby if taken after the third month of pregnancy.

Breastfeeding

Inform your doctor if you are breastfeeding or are about to start breastfeeding. This medication 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 premature.

Driving and operating machines

This medication usually does not affect alertness, but some patients may experience dizziness or weakness due to low blood pressure, particularly at the beginning of treatment or when changing medications, as well as with alcohol. If this occurs, 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 medication contains less than 1 mmol of sodium (23 mg) per capsule; that is, it is essentially "sodium-free".

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If 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 renal insufficiency

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

Patients with hepatic insufficiency

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

Use in children and adolescents

This medication 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 that may make you feel dizzy or faint (if this happens, lying down with your legs elevated may help), severe difficulty breathing, tremors (due to decreased blood sugar) and slow heart rate.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take Rabidux

It is essential to take your medication every day since regular treatment works better. However, if you forget to take a dose of this medication, take the next dose at the usual time. Do not take a double dose to compensate for the missed doses.

If you interrupt the treatment with Rabidux

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

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

• intense dizziness or fainting due to low blood pressure (frequent - may affect up to 1 in 10 people),
• worsening of heart failure that causes 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) (infrequent - may affect up to 1 in 100 people),
• sudden wheezing, chest pain, difficulty breathing, or difficulty breathing (bronchospasm) (infrequent: may affect up to 1 in 100 people),
• unusually rapid or irregular heartbeats, chest pain (angina) or heart attack (infrequent - may affect up to 1 in 100 people),
• weakness in arms or legs, or difficulty speaking that may 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 begins with red, itchy patches on the face, arms, or legs (erythema multiforme) (frequency unknown (frequency 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 side effects listed below or not mentioned, inform your doctor or pharmacist immediately:

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

• slow heartbeats.

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

• headache,
• dizziness,
• fainting, hypotension (abnormally low blood pressure), especially when standing up or sitting quickly,
• numbness in hands or feet,
• sensation 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 indigestion, diarrhea, constipation,
• allergic reactions such as skin rashes, itching,
• muscle cramps, muscle pain (myalgia),
• sensation of fatigue,
• fatigue,
• blood tests showing higher-than-normal potassium levels in the blood.

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

• dizziness,
• alterations in taste,
• needles and pins (paresthesia),
• vision changes,
• tinnitus (sensation of sounds in the ears),
• stuffy nose, difficulty breathing, or worsening of asthma,
• rhinitis, nasal congestion,
• redness,
• mood changes,
• sleep disorders,
• depression,
• dry mouth,
• sweating,
• kidney problems,
• excessive urination, more than normal during the day,
• impotence,
• excess eosinophils (a type of white blood cell),
• drowsiness,
• palpitations,
• tachycardia,
• irregular heart rhythm (conduction disorders of the auriculoventricular (AV) node),
• muscle weakness,
• arthralgia (joint pain),
• localized swelling (peripheral edema),
• fever,
• loss or decrease of appetite (anorexia),
• changes in blood test parameters: increased number of certain white blood cells (eosinophilia), increased urea in the blood, increased creatinine in the blood, increased levels of liver enzymes, high bilirubin levels in the blood,
• increased protein levels in the urine,
• mouth ulcers,
• enlargement of the breasts 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,
• hearing problems,
• inflammation of the liver that can cause yellowing of the skin or white of the eyes,
• inflammation of the blood vessels (vasculitis),
• changes in blood test parameters: abnormal fat levels, decreased number of 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 (which causes severe abdominal and back pain),
• hair loss,
• appearance or worsening of a scaly skin rash (psoriasis), rash similar to psoriasis,
• increased sensitivity of the skin to the sun (photosensitivity reaction).

Frequency unknown (frequency cannot be estimated from available data):

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

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

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the blister pack and on the outer packaging after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 86°F (30°C). Do not refrigerate or freeze.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and unused medications at the SIGRE collection pointat the pharmacy. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Composition of Rabidux

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

Content of the capsule: lactose monohydrate, poly (vinyl alcohol), sodium croscarmellose (E468), stearate of fumaric acid and sodium, microcrystalline cellulose, anhydrous calcium phosphate, crospovidone type A, anhydrous colloidal silica, and magnesium stearate.

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

Capsule coating: 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.

Appearance of the product and contents of the package

Rabidux 2.5 mg/1.25 mg hard capsules: the capsule has a yellow-colored cap with black printing "2.5 mg" and a white-colored body with black printing "1.25 mg". Contents of the capsule of 2.5 mg/1.25 mg: ramipril powder white or almost white and a yellow-colored, round, biconvex tablet of bisoprolol fumarate.

Rabidux 2.5 mg/2.5 mg hard capsules: the capsule has a yellow-colored cap with black printing "2.5 mg" and a yellow-colored body with black printing "2.5 mg". Contents of the capsule of 2.5 mg/2.5 mg: ramipril powder white or almost white and a yellow-colored, round, biconvex tablet of bisoprolol fumarate.

Rabidux 5 mg/2.5 mg hard capsules: the capsule has an orange-colored cap with black printing "5 mg" and a yellow-colored body with black printing "2.5 mg".

Contents of the capsule of 5 mg/2.5 mg: ramipril powder white or almost white and a yellow-colored, round, biconvex tablet of bisoprolol fumarate.

Rabidux 5 mg/5 mg hard capsules: the capsule has an orange-colored cap with black printing "5 mg" and an orange-colored body with black printing "5 mg".

Contents of the capsule of 5 mg/5 mg: ramipril powder white or almost white and a yellow-colored, round, biconvex tablet of bisoprolol fumarate.

Rabidux 10 mg/5 mg hard capsules: the capsule has a reddish-brown-colored cap with black printing "10 mg" and an orange-colored body with black printing "5 mg". Contents of the capsule of 10 mg/5 mg: ramipril powder white or almost white and a yellow-colored, round, biconvex tablet of bisoprolol fumarate.

Rabidux 10 mg/10 mg hard capsules: the capsule has a reddish-brown-colored cap with black printing "10 mg" and a reddish-brown-colored body with black printing "10 mg".

Contents of the capsule of 10 mg/10 mg: ramipril powder white or almost white and two yellow-colored, round, biconvex tablets of bisoprolol fumarate.

Blister packs of BOPA/Al/PVC-Aluminum.

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

Only some package sizes may be marketed.

Marketing authorization holder

Adamed Laboratorios, S.L.U.

c/ de las Rosas de Aravaca, 31 - 2nd floor

28023 Madrid

Spain

Responsible for manufacturing

Adamed Pharma S.A.

ul. Marszalka Józefa Pilsudskiego 5

95-200 Pabianice

Poland

This medicinal product is authorized inthe member states of the European Economic Area with the following names:

Last revision date of this leaflet: May 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es.