BISOPROLOL/HYDROCHLOROTHIAZIDE AUROVITAS 10 mg/25 mg FILM-COATED TABLETS

2. What you need to know before taking Bisoprolol/Hydrochlorothiazide Aurovitas

Do not takeBisoprolol/HydrochlorothiazideAurovitas:

• if you are allergic to bisoprolol, hydrochlorothiazide, other thiazides, sulfonamides (chemically related to hydrochlorothiazide), or any of the other ingredients of this medication, listed in section 6,
• if you have acute weakness of the heart muscle (acute heart failure) or if the weakness of the heart muscle is not under control (uncompensated heart failure),
• if you have shock due to a heart attack (cardiogenic shock),
• if you have significant heart rhythm disorders (second and third degree AV block, sick sinus syndrome, sinoatrial block without pacemaker),
• if your heart rate is very slow (less than 60 beats per minute) before starting treatment,
• if you have severe forms of asthma or any other chronic respiratory problem
• if you have severe circulatory disorders that affect the limbs (such as Raynaud's syndrome, which could cause paleness, bluish discoloration, or tingling in the fingers and toes),
• if you have untreated pheochromocytoma (a rare adrenal tumor),
• if you have metabolic acidosis (an increase in acid concentration in the blood) due to a severe illness,
• if you have severe kidney dysfunction (renal insufficiency) with little or no urine production or liver disease,
• if you have acute kidney inflammation (glomerulonephritis),
• if you have low potassium levels in the blood that do not respond to treatment,
• if you are breastfeeding,
• if you have hyponatremia (low sodium levels),
• if you have hypercalcemia (elevated calcium levels in the blood),
• if you have gout,
• if you are taking floctafenine, used for pain and inflammation (see other medications and Bisoprolol/Hydrochlorothiazide Aurovitas).

Warnings and Precautions

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

• if you have heart failure. Your doctor may adjust your bisoprolol dose before starting bisoprolol/hydrochlorothiazide,
• if you are scheduled to undergo surgery. Heart rate and blood pressure may change when taking anesthetics with bisoprolol/hydrochlorothiazide. Inform the anesthesiologist that you are taking this medication,
• if you have asthma or any other chronic respiratory disorder that may cause difficulty breathing or bronchospasm. In these cases, your doctor may increase the dose of your existing respiratory treatment or add other medications for respiratory problems,
• if you have diabetes, this medication may mask the symptoms caused by low blood sugar levels (hypoglycemia), increased heart rate,
• if you are fasting or engaging in physically strenuous activities,
• if you have an adrenal tumor (pheochromocytoma) and are under treatment: this medication should only be used in combination with certain medications (alpha blockers),
• if you are undergoing treatment for allergic reactions. Bisoprolol/hydrochlorothiazide may increase the severity of your allergic reactions and also may decrease the effectiveness of your treatment,
• if you have a thyroid disorder (bisoprolol may hide the symptoms of hyperthyroidism),
• if you have heart conduction disorders (first degree AV block),
• if you experience chest pressure or pain at rest (Prinzmetal's angina). This medication may increase the number and duration of these attacks,
• if you have a history of recurrent skin disorder with dry, scaly skin rash (psoriasis),
• if you have circulatory problems in your fingers and toes, arms and legs, or cramps with pain in the calves, caused by exercise or walking. These episodes may worsen, especially at the start of treatment,
• if you have reduced blood volume (hypovolemia),
• if you have mild or moderate liver or kidney dysfunction,
• if you have elevated uric acid levels in the blood (hyperuricemia), as this medication may increase the risk of gout attacks,
• if you are elderly,
• if you plan to expose yourself to the sun or artificial ultraviolet light, as certain patients have presented with a skin rash after sun exposure. In that case, you should protect your skin during treatment with this medication,
• treatment should not be stopped abruptly, especially if you have certain heart diseases (e.g., angina). If you need to interrupt treatment, your doctor will gradually decrease the dose over a few days,
• if you have had respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience shortness of breath or severe difficulty breathing after taking bisoprolol/hydrochlorothiazide, seek medical attention immediately,
• if you wear contact lenses, bisoprolol/hydrochlorothiazide may reduce tear production, which may cause irritation,
• this medication affects the body's electrolyte balance. Your doctor will regularly monitor you. These tests are particularly important if you have other diseases that may worsen if the water-electrolyte balance is altered. Your doctor may occasionally check the levels of lipids, potassium, sodium, calcium, uric acid, urea, or glucose in your blood,
• if you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). Protect your skin from sun and UV exposure while taking this medication,
• this medication may cause eye disorders that can start with vision loss or eye pain, such as transient myopia or acute angle-closure glaucoma,
  • cases of acute inflammation of the gallbladder (cholecystitis) should be reported in patients with gallstones,

While taking bisoprolol/hydrochlorothiazide, you should ensure that you drink enough fluids and eat potassium-rich foods (e.g., bananas, vegetables, nuts) to compensate for the increased loss of potassium.

Low potassium levels can cause heart rhythm problems, sometimes fatal.

The benefits of diuretic medications (hydrochlorothiazide) for the treatment of high blood pressure are only obtained when the kidneys function properly. There may be a decrease in kidney function in patients with pre-existing kidney problems.

Other Medications and Bisoprolol/Hydrochlorothiazide Aurovitas

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

Do not take Bisoprolol/Hydrochlorothiazide Aurovitas with:

• floctafenine, used to treat pain or inflammation,
• sultopride, used to treat schizophrenia.

Be cautious if you are taking bisoprolol/hydrochlorothiazide with any of the following medications:

• Certain medications used to treat high blood pressure, angina, or heart rhythm disorders (e.g., verapamil, diltiazem, bepridil, amlodipine, felodipine) that may increase the risk of heart rhythm disorders or low blood pressure.
• Medications for high blood pressure (such as clonidine, moxonidine, amlodipine, methyldopa, reserpine, rilmenidine, and ACE inhibitors).
• Other medications for high blood pressure or that may lower blood pressure (such as barbiturates or phenothiazines).
• Lithium, used to treat psychiatric disorders.
• Antiarrhythmic medications (quinidine, disopyramide, amiodarone, sotalol).
• Digitalis glycosides, used to control heart rate.
• Anti-inflammatory medications, used to treat pain, swelling, or redness.
• Topical beta blockers (e.g., eye drops for glaucoma).
• Insulin or oral treatments for diabetes.
• If you are going to undergo surgery that requires anesthetics, inform your doctor that you are taking bisoprolol/hydrochlorothiazide.
• Tricyclic antidepressants, used to treat depression.
• Rifampicin, an antibiotic: it makes the effect of bisoprolol shorter in duration. Generally, no dose adjustment is necessary.
• Medications that affect the nervous system, e.g., epinephrine, norepinephrine (sympathomimetics).
• Medications that reduce uric acid levels in the blood.
• Medications that affect or may be affected by potassium levels in the blood, such as digoxin, a medication to control heart rate, and certain antipsychotic medications.
• Corticosteroids, carbenoxolone, amphotericin, furosemide, laxatives. These medications may cause potassium deficiency.
• Colestyramine, colestipol, these medications may reduce the effect of this medication.
• Methyldopa, this medication may lead to blood problems.
• Mefloquine, used to prevent malaria: it increases the risk of decreased heart rate.
• Antidepressants (monoamine oxidase inhibitors) may affect blood pressure control.

If you are allergic to penicillin or sulfonamides, the risk of developing an allergy to this medication is higher. Your doctor will inform you if you should stop or change treatment.

Use in Athletes

This medication contains hydrochlorothiazide, which may result in a positive test in anti-doping tests.

Taking Bisoprolol/Hydrochlorothiazide Aurovitas with Food and Drinks

Bisoprolol/Hydrochlorothiazide Aurovitas tablets should be taken in the morning and can be taken with food. They should be swallowed with a sufficient amount of liquid and not chewed.

Pregnancy, Breastfeeding, and Fertility

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

Normally, your doctor will advise you to take another medication instead of Bisoprolol/Hydrochlorothiazide Aurovitas, as this medication is not recommended during pregnancy. This is because it crosses the placenta and its use may cause harmful effects on your baby.

Tell your doctor if you are breastfeeding or plan to start breastfeeding. Bisoprolol/Hydrochlorothiazide should not be used in breastfeeding mothers. Hydrochlorothiazide may affect milk production.

Like other medications, this medication may rarely affect your ability to achieve and maintain an erection.

Driving and Using Machines

This medication usually has no effect on the ability to drive or use machines. However, it may affect your concentration or reaction ability. In that case, do not drive or use machines.

3. How to Take Bisoprolol/Hydrochlorothiazide Aurovitas

Dose

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

The recommended dose is one 5 mg/12.5 mg bisoprolol/hydrochlorothiazide tablet once a day. If the effect is not sufficient, your doctor may decide to increase the dose to one 10 mg/25 mg tablet (or two 5 mg/12.5 mg tablets) once a day.

Use in Children

The use of Bisoprolol/Hydrochlorothiazide Aurovitas is not recommended in children, as there is not enough clinical experience with the use of this medication in children.

Use in Elderly Patients

No dose adjustment is necessary. It is recommended to start treatment with the lowest possible dose.

Renal Insufficiency

In patients with mild or moderate renal insufficiency, the doctor may indicate the use of a lower dose. Bisoprolol/hydrochlorothiazide tablets should not be taken if the patient has severe renal insufficiency (see section 2).

Method of Administration

Bisoprolol/hydrochlorothiazide should be taken orally, in the morning, with or without food. The tablets should be swallowed with some liquid and not chewed.

Frequency of Administration

The tablet(s) should be taken once a day.

Duration of Treatment

The duration of treatment is not limited and will depend on the severity of the disease. The duration of treatment will be determined by your doctor. Do not stop taking the treatment without consulting your doctor first.

If You Take More Bisoprolol/Hydrochlorothiazide Aurovitas Than You Should

If you take more Bisoprolol/Hydrochlorothiazide Aurovitas than you should, contact your doctor or go to the emergency department immediately. Bring the package and any remaining tablets with you. The most common signs of an overdose are dizziness, fainting, discomfort, drowsiness, and slow or irregular heart rate.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately, or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested. It is recommended to bring the package and the package leaflet of the medication to the healthcare professional.

If You Forget to Take Bisoprolol/Hydrochlorothiazide Aurovitas

Do not take a double dose to make up for forgotten doses. Take the next dose at the usual time. If you have forgotten several doses, consult your doctor.

If You Interrupt Treatment with Bisoprolol/Hydrochlorothiazide Aurovitas

Do not interrupt or stop your treatment with bisoprolol/hydrochlorothiazide without consulting your doctor first.

If you interrupt your treatment, you should do so gradually, as abrupt interruption of treatment may lead to acute worsening of the disease.

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

4. Possible Adverse Effects

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

Frequent: may affect more than 1 in 10 people

• abnormal levels of body fluids and electrolytes (increased triglycerides, increased cholesterol, hypokalemia, hypomagnesemia, hyponatremia, hypochloremia, hypercalcemia),
• dizziness*, headaches*,
• feeling of cold or numbness of hands and feet,
• nausea, vomiting, diarrhea or constipation,
• glucose in urine,
• feeling of fatigue or weakness*.

Infrequent: may affect up to 1 in 100 people

• loss of appetite,
• sleep disorders, depression,
• slow heart rate, abnormal heart rhythm, worsening of heart failure,
• feeling of dizziness or lightheadedness when standing up,
• difficulty breathing in people with asthma or respiratory diseases,
• abdominal pain, pancreatitis,
• increased amylase (enzymes involved in digestion),
• muscle weakness and cramps,
• increased levels of creatinine and urea in the blood,
• loss of physical strength.

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

• decrease in the number of white blood cells (leucopenia) or platelets (thrombocytopenia) in blood,
• nightmares, hallucinations,
• fainting,
• decreased tear flow (may have problems if using contact lenses),
• visual disturbances,
• hearing problems,
• rhinorrhea,
• increase in certain liver enzymes in blood tests, liver inflammation (hepatitis), yellowing of the skin and eyes (jaundice),
• allergic reactions such as itching, redness of the face or skin rash, sensitization of the skin to the sun, urticaria, red spots on the skin due to small subcutaneous bleeding (purpura),
• erection disturbances,
• you should consult your doctor immediately if you experience more severe allergic reactions, which may include swelling of the face, neck, tongue, mouth or throat, or difficulty breathing.

Very Rare: may affect up to 1 in 10,000 people

• severe decrease in white blood cells (agranulocytosis),
• increase in blood alkalinity (metabolic alkalosis),
• inflammation of the eye or eyelid (conjunctivitis),
• hair loss,
• appearance or worsening of pre-existing skin rash (psoriasis),
• appearance of hard crusts on the skin (cutaneous lupus erythematosus),
• chest pain,
• acute difficulty breathing (signs include severe difficulty breathing, fever, weakness, and confusion).

Frequency Not Known: cannot be estimated from the available data

• skin and lip cancer (non-melanoma skin cancer),
• interstitial lung disease,
  • sudden decrease in distant vision (acute myopia), decrease in vision or eye pain due to increased eye pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma).

• These symptoms usually appear at the start of treatment. They are usually mild and normally disappear within 1 or 2 weeks.

Reporting of Adverse Effects

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

5. Storage of Bisoprolol/Hydrochlorothiazide Aurovitas

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

Keep it in the original packaging to protect it from light.

Store below 30°C.

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

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the pharmacy's SIGRE point. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition ofBisoprolol/Hydrochlorothiazide Aurovitas

Bisoprolol/Hydrochlorothiazide Aurovitas 10mg/25mg film-coated tablets EFG:

Each film-coated tablet contains 10 mg of bisoprolol fumarate and 25 mg of hydrochlorothiazide.

The other components are:

Core of the tablet:calcium hydrogen phosphate, microcrystalline cellulose (Grade-112), crospovidone (Type-A), anhydrous colloidal silica, and magnesium stearate.

Coating of the tablet:hypromellose 2910 (6 cPs), titanium dioxide (E171), macrogol 400, yellow iron oxide, polysorbate 80, and red iron oxide.

Appearance of the Product and Package Contents

Bisoprolol/Hydrochlorothiazide Aurovitas 10mg/25mg film-coated tablets EFG:

Film-coated tablets of pink color, round (diameter 9.07 mm), biconvex, engraved with 'L and 6' separated by the score line and smooth on the other side.

Bisoprolol/Hydrochlorothiazide Aurovitas film-coated tablets EFG are available in PVC/PE/PVdC - Aluminum blister packs.

Package sizes:

Blister:28, 30, 50, 56, 98, and 100 film-coated tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid,

Spain

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

O

Generis Farmacêutica, S.A.

Rua João de Deus, 19

2700-487 Amadora

Portugal

O

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

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

Germany: Bisoprolol-comp PUREN 10 mg/25 mg Filmtabletten

Spain: Bisoprolol/Hydrochlorothiazide Aurovitas 10 mg/25 mg film-coated tablets EFG

Portugal: Bisoprolol + Hydrochlorothiazide Generis

Date of the Last Revision of this Prospectus:January 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/).