BIPRETERAX 4 mg/1.25 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Bipreterax 4mg/1.25mg Tablets

perindopril terbutylamine/indapamide

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 or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What Bipreterax 4 mg/1.25 mg Tablets are and what they are used for
2. What you need to know before you take Bipreterax 4 mg/1.25 mg Tablets
3. How to take Bipreterax 4 mg/1.25 mg Tablets
4. Possible side effects
5. Storage of Bipreterax 4 mg/1.25 mg Tablets
6. Contents of the pack and other information

1. What Bipreterax 4 mg/1.25 mg Tablets are and what they are used for

Bipreterax 4 mg/1.25 mg Tablets are a combination of two active substances, perindopril and indapamide. It is an antihypertensive and is indicated for the treatment of high blood pressure in adults.

Perindopril belongs to a group of medicines called ACE inhibitors. They work by widening the blood vessels, which makes it easier for the heart to pump blood through them. Indapamide is a diuretic. Diuretics increase the amount of urine produced by the kidneys. However, indapamide is different from other diuretics, as it only produces a slight increase in the amount of urine formed. Each of the active substances lowers blood pressure and they work together to control your blood pressure.

2. What you need to know before you take Bipreterax 4 mg/1.25 mg Tablets

Do not takeBipreterax 4 mg/1.25 mg Tablets

• if you are allergic to perindopril or any other ACE inhibitor, to indapamide or to any other sulfonamide, or to any of the other ingredients of this medicine (listed in section 6),
• if you have experienced symptoms such as wheezing, swelling of the face or tongue, intense itching or severe skin rashes with previous treatment with ACE inhibitors, or if you or a member of your family have had these symptoms in any other circumstances (a condition called angioedema),
• if you have diabetes or kidney problems and are being treated with a blood pressure medicine that contains aliskiren,
• if you have a severe liver disease or suffer from a condition called hepatic encephalopathy (a degenerative brain disease),
• if you have a severe kidney disease in which the blood flow to your kidneys is reduced (renal artery stenosis),
• if you are undergoing dialysis or any other type of blood filtration. Depending on the machine used, Bipreterax 4 mg/1.25 mg Tablets may not be suitable for you,
• if you have low potassium levels in your blood,
• if you suspect you may have untreated congestive heart failure (severe fluid retention, difficulty breathing),
• if you are pregnant for more than 3 months (It is also best to avoid Bipreterax 4 mg/1.25 mg Tablets at the beginning of pregnancy - see section "Pregnancy"),
• if you have taken or are currently taking sacubitril/valsartan, a medicine for heart failure, as it increases the risk of angioedema (rapid swelling under the skin in an area such as the throat) (see "Warnings and precautions" and "Using Bipreterax 4 mg/1.25 mg Tablets with other medicines").

Warnings and precautions

Consult your doctor or pharmacist before starting to take Bipreterax 4 mg/1.25 mg Tablets:

• if you have aortic stenosis (narrowing of the main blood vessel that comes out of the heart) or hypertrophic cardiomyopathy (a disease of the heart muscle) or renal artery stenosis (narrowing of the artery that carries blood to the kidney),
• if you have heart failure or any other heart problem,
• if you have kidney problems or if you are on dialysis,
• if you experience a decrease in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase in pressure in your eye and can occur within hours to weeks after taking Bipreterax 4 mg/1.25 mg Tablets. If left untreated, this can lead to permanent vision loss. If you have previously had an allergy to penicillin or sulfonamides, you may be at higher risk of developing this,
• if you have muscle disorders, including muscle pain, sensitivity, weakness, or cramps,
• if you have abnormally high levels of a hormone called aldosterone in your blood (primary aldosteronism),
• if you have liver problems,
• if you suffer from a collagen disease (skin disease) such as systemic lupus erythematosus or scleroderma,
• if you have atherosclerosis (hardening of the arteries),
• if you have hyperparathyroidism (overactivity of the parathyroid gland),
• if you have gout,
• if you have diabetes,
• if you are on a low-salt diet or are using salt substitutes that contain potassium,
• if you are taking lithium or potassium-sparing diuretics (e.g., spironolactone, triamterene) or potassium supplements, as concurrent use with Bipreterax 4 mg/1.25 mg Tablets should be avoided (see "Other medicines and Bipreterax 4 mg/1.25 mg Tablets").
• if you are an elderly patient,
• if you have had photosensitivity reactions,
• if you have a severe allergic reaction with facial, lip, mouth, tongue, or throat swelling that can cause difficulty swallowing or breathing (angioedema). This can occur at any time during treatment.

If you develop these symptoms, discontinue treatment and contact your doctor immediately.

• if you 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 nephropathy.
• 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 Bipreterax 4 mg/1.25 mg Tablets".

• if you are of black origin, as you may be at higher risk of angioedema and this medicine may be less effective at lowering your blood pressure than in non-black patients,
• if you are a hemodialysis patient with high-flux membranes.
• if you are 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 called mTor inhibitors (used to prevent organ rejection and to treat cancer),
• sacubitril (available as a fixed-dose combination with valsartan), used to treat long-term heart failure,
• linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the class of gliptins (used to treat diabetes).

Angioedema

In patients treated with ACE inhibitors, including Bipreterax 4 mg/1.25 mg Tablets, angioedema (severe allergic reaction with swelling of the face, lips, tongue, or throat with difficulty swallowing or breathing) has been reported. This can occur at any time during treatment. If you develop these symptoms, discontinue treatment with Bipreterax 4 mg/1.25 mg Tablets and seek medical attention immediately. See also Section 4.

You must inform your doctor if you think you are (or might become) pregnant. Bipreterax 4 mg/1.25 mg Tablets are not recommended at the start of pregnancy, and you should not take them if you are pregnant for more than 3 months, as they may cause serious harm to your baby if taken during this period (see "Pregnancy and breastfeeding").

When taking Bipreterax 4 mg/1.25 mg Tablets, you should inform your doctor or healthcare professional:

• if you are going to have anesthesia and/or surgery,
• if you have recently had diarrhea or vomiting, or are dehydrated,
• if you are going to have dialysis or LDL apheresis (removal of cholesterol from your blood using a machine),
• if you are going to receive desensitization treatment to reduce allergic effects of bee or wasp stings,
• if you are going to undergo any medical test that requires the injection of an iodinated contrast agent (a substance that allows organs such as the kidney or stomach to be visible with X-rays),
• if you experience changes in your vision or pain in one or both eyes while taking Bipreterax 4 mg/1.25 mg Tablets. This may be a sign that you are developing glaucoma, an increase in pressure in your eye(s). You should discontinue treatment with Bipreterax 4 mg/1.25 mg Tablets and seek medical attention.

Athletes should be aware that Bipreterax 4 mg/1.25 mg Tablets contain an active substance (indapamide) that may give a positive result in a doping test.

Children and adolescents

Bipreterax 4 mg/1.25 mg Tablets should not be administered to children or adolescents.

Other medicines and Bipreterax 4 mg/1.25 mg Tablets

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

You should avoid taking Bipreterax 4 mg/1.25 mg Tablets with:

• lithium (used to treat mania or depression),
• aliskiren (a medicine used to treat high blood pressure) if you do not have diabetes or kidney problems,

• potassium-sparing diuretics (e.g., triamterene, amiloride), potassium salts, or other medicines that may increase potassium levels in your body (such as heparin, a medicine used to thin the blood and prevent clots; trimethoprim and cotrimoxazole, also known as trimethoprim/sulfamethoxazole, for bacterial infections),

• estr Mustine (used in cancer treatment),
• other medicines used to treat high blood pressure: ACE inhibitors and angiotensin receptor antagonists.

Treatment with Bipreterax 4 mg/1.25 mg Tablets may be affected by other medicines. Your doctor may need to change your dose and/or take other precautions. Make sure to inform your doctor if you are taking any of the following medicines, as you may need special care:

• other medicines for the treatment of high blood pressure, including angiotensin II receptor antagonists (ARAs), aliskiren (see also the information under the headings "Do not take Bipreterax 4 mg/1.25 mg Tablets" and "Warnings and precautions"), or diuretics (medicines that increase the amount of urine produced by the kidneys),
• potassium-sparing medicines used in the treatment of heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg per day,
• medicines commonly used to treat diarrhea (racecadotril) or to prevent organ rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class called mTor inhibitors). See section "Warnings and precautions",
• sacubitril/valsartan (used to treat long-term heart failure). See sections "Do not take Bipreterax 4 mg/1.25 mg Tablets" and "Warnings and precautions",
• anesthetic medicines,
• iodinated contrast agents,
• antibiotics used to treat bacterial infections (e.g., moxifloxacin, esparfloxacin, erythromycin injection),
• methadone (used to treat addiction),
• procainamide (for the treatment of irregular heartbeat),
• allopurinol (for the treatment of gout),
• antihistamines used to treat allergic reactions, such as hay fever (e.g., mizolastine, terfenadine, astemizole),
• corticosteroids used to treat various disorders, including severe asthma and rheumatoid arthritis,
• immunosuppressants used to treat autoimmune disorders or after a transplant to prevent rejection (e.g., cyclosporine, tacrolimus),
• halofantrine (used to treat some types of malaria),
• pentamidine (used to treat pneumonia),
• injectable gold (used to treat rheumatoid arthritis),
• vincamine (used to treat cognitive disorders in the elderly, including memory loss),
• bepridil (used to treat angina pectoris),
• medicines for heart rhythm disorders (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis, bretylium),
• cisapride, difemanil (used to treat gastrointestinal problems),
• digoxin or other cardiac glycosides (for the treatment of heart problems),
• baclofen (for the treatment of muscle stiffness that occurs in diseases such as multiple sclerosis),
• medicines for the treatment of diabetes, such as insulin, metformin, or gliptins,
• calcium, including calcium supplements,
• stimulant laxatives (e.g., senna),
• non-steroidal anti-inflammatory medicines (e.g., ibuprofen) or high doses of salicylates (e.g., acetylsalicylic acid, a substance present in many medicines used to relieve pain and reduce fever, as well as to prevent blood clotting),
• intravenous amphotericin B (for the treatment of severe fungal diseases),
• medicines used to treat mental problems, such as depression, anxiety, schizophrenia... (e.g., tricyclic antidepressants, neuroleptics, such as amisulpride, sulpiride, sultoprida, tiaprida, haloperidol, droperidol)),
• tetracosactide (for the treatment of Crohn's disease),
• trimethoprim (for the treatment of infections),
• vasodilators, including nitrates (medicines that make blood vessels wider),
• medicines used to treat low blood pressure, shock, or asthma (e.g., ephedrine, noradrenaline, or adrenaline).

Bipreterax 4 mg/1.25 mg Tablets with food and drinks

It is preferable to take Bipreterax 4 mg/1.25 mg Tablets 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.

Normally, your doctor will advise you to stop taking Bipreterax 4 mg/1.25 mg Tablets before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Bipreterax 4 mg/1.25 mg Tablets. Bipreterax 4 mg/1.25 mg Tablets are not recommended at the start of pregnancy, and you should not take them if you are pregnant for more than three months, as they may cause serious harm to your baby if taken after the third month of pregnancy.

Breastfeeding

Bipreterax 4 mg/1.25 mg Tablets are not recommended if you are breastfeeding.

Inform your doctor immediately if you are about to start or are breastfeeding.

Seek medical attention immediately.

Driving and using machines

Bipreterax 4 mg/1.25 mg Tablets usually do not affect alertness, but due to the lowering of blood pressure, some patients may notice different reactions such as dizziness or weakness. If this happens to you, your ability to drive or use machines may be impaired.

Bipreterax 4 mg/1.25 mg Tablets contain lactose.

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Bipreterax 4 mg/1.25 mg Tablets

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is 1 tablet once a day. Your doctor may decide to change the dose if you have kidney problems. Take your tablet preferably in the morning and before breakfast. Swallow the tablet whole with the help of a glass of water.

If you take moreBipreterax 4 mg/1.25 mg Tabletsthan you should

If you ingest too many tablets, contact your doctor or go to the emergency department of your nearest hospital immediately. In case of overdose or accidental ingestion, consult the Toxicology Information Service, telephone (91) 562 04 20.

The most common symptom in case of overdose is a decrease in blood pressure. If a significant decrease in blood pressure occurs (associated with nausea, vomiting, cramps, dizziness, drowsiness, confusion, and changes in the amount of urine produced by the kidneys), it may help to lie down with your legs raised.

If you forget to takeBipreterax 4 mg/1.25 mg Tablets

It is important to take this medicine every day, as continuous treatment is more effective. However, if you forget to take a dose of Bipreterax 4 mg/1.25 mg Tablets, take the next dose at the usual time. Do not take a double dose to make up for the forgotten dose.

If you stop takingBipreterax 4 mg/1.25 mg Tablets

Since the treatment for high blood pressure is usually for life, you should talk to your doctor before stopping this medicine.

If you have any further questions on the use of this medicine, 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.

Stoptreatment with this medicine andgoimmediately to your doctor if you experience any of the following adverse effects that may beserious:

• Severe dizziness or fainting due to low blood pressure, (Frequent - may affect up to 1 in 10 people),
• Bronchospasm (chest tightness, shortness of breath or difficulty breathing (Uncommon) (may affect up to 1 in 100 people),
• Swelling of the face, lips, mouth, tongue or throat, causing great difficulty breathing (angioedema) (See section 2 "Warnings and precautions") (Uncommon) (may affect up to 1 in 100 people),
• Severe skin reactions including erythema multiforme (skin rash that often starts with red spots that itch on the face, arms or legs), or intense skin rash, hives, redness of the skin all over the body, intense itching, blistering, peeling and inflammation of the skin inflammation of the mucous membranes (Stevens-Johnson syndrome) or other allergic reactions) (Very rare - may affect up to 1 in 10,000 people)
• Cardiovascular disorders (irregular heartbeat, chest pain (pain in the chest, jaw and back, caused by physical exertion), myocardial infarction (Very rare) (may affect up to 1 in 10,000 people).
• Weakness in arms or legs, or speech problems that could be a sign of a possible stroke (Very rare - may affect up to 1 in 10,000 people),
• Pancreatitis that can cause severe abdominal and back pain accompanied by a great feeling of 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 (Very rare - may affect up to 1 in 10,000 people),
• Irregular heartbeat with a life-threatening condition. (Frequency not known),
• Brain disease caused by a liver disease (Hepatic encephalopathy) (Frequency not known),
• Muscle weakness, cramps, sensitivity or muscle pain and especially if you feel unwell or have a high temperature, as they may be caused by abnormal muscle breakdown. (Frequency not known).

In decreasing order of frequency, adverse effects may include:

• Frequent (may affect up to 1 in 10 people): skin reactions in people prone to allergic and asthmatic reactions, headache, dizziness, vertigo, tingling, vision changes, tinnitus (feeling of noises in the ears), cough, difficulty breathing (dyspnea), digestive disorders (nausea, vomiting, abdominal pain, taste changes, dyspepsia or difficulty digesting, diarrhea, constipation), allergic reactions (such as skin rashes, itching), muscle cramps, feeling of fatigue, low potassium levels in the blood.

• Uncommon (may affect up to 1 in 100 people): mood changes, depression, sleep disorders, urticaria, purpura (red spots on the skin), blistering, kidney problems, impotence (inability to have or maintain an erection), sweating, excess eosinophils (a type of white blood cell), changes in blood parameters: reversible increase in blood potassium levels when treatment is stopped, decrease in blood sodium levels that can cause dehydration and low blood pressure, somnolence, fainting, palpitations (feeling the heartbeat), tachycardia (fast heartbeat), hypoglycemia (very low blood sugar levels) in diabetic patients, vasculitis (inflammation of blood vessels), dry mouth, photosensitivity reactions (increased skin sensitivity to the sun), arthralgia (joint pain), myalgia (muscle pain), chest pain, feeling of discomfort, peripheral edema, fever, elevated blood urea, and elevated creatinine in blood, fall.

• Rare (may affect up to 1 in 1,000 people): worsening of psoriasis, changes in analytical results: low blood chloride levels, low blood magnesium levels, increased liver enzyme levels, high serum bilirubin levels, fatigue, facial redness, decreased or absent diuresis, acute renal failure.

Concentrated urine, feeling of discomfort (nausea) or being sick (vomiting), muscle cramps, confusion and convulsions. These symptoms may be due to a disease called SIADH (inadequate secretion of antidiuretic hormone).

• Very rare (may affect up to 1 in 10,000 people): confusion, eosinophilic pneumonia (a rare type of pneumonia), rhinitis (congested or runny nose), serious kidney problems, changes in blood values such as decreased white and red blood cell count, decreased hemoglobin, decreased platelet count, increased blood calcium levels, abnormal liver function.

• Frequency not known (cannot be estimated from available data): abnormal cardiac ECG tracing, changes in blood parameters: high uric acid and blood sugar levels, short-sightedness (myopia), blurred vision, visual disturbances, decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma), color change, numbness and pain in the fingers of the hands or feet (Raynaud's disease). If you suffer from systemic lupus erythematosus (a type of collagen disease), it may worsen.

Disorders of the blood, kidney, liver or pancreas and changes in analytical results (blood tests) may appear. Your doctor may need to prescribe blood tests to monitor your condition.

If you experience these symptoms, contact your doctor as soon as possible.

Reporting of Adverse Effects

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

5. Storage of Bipreterax 4 mg/1.25 mg tablets

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date shown on the packaging. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE point of your usual pharmacy. In case of doubt, 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 ofBipreterax 4 mg/1.25 mg tablets

• The active ingredients are perindopril terbutylamine and indapamide. Each tablet contains 4 mg of perindopril terbutylamine (which corresponds to 3.338 mg of perindopril) and 1.25 mg of indapamide.
• The other components of the tablet are: lactose monohydrate, magnesium stearate (E470B), hydrophobic colloidal silica and microcrystalline cellulose.

Appearance of the Product and Package Contents

The Bipreterax 4 mg/1.25 mg tablets are white, stick-shaped. One tablet contains 4 mg of perindopril terbutylamine and 1.25 mg of indapamide.

The tablets are available in blisters of 14, 20, 28, 30, 50, 56, 60, 90, 100 or 500 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Les Laboratoires Servier

50, rue Carnot

92284 Suresnes cedex - France

Manufacturer:

Les Laboratoires Servier Industrie

905 route de Saran

45520 Gidy - France

or

Servier (Ireland) Industries Ltd

Gorey Road

Arklow - Co. Wicklow - Ireland

or

Laboratorios Servier S.L. (only for the Spanish market)

Avda. de los Madroños 33

28043 Madrid - Spain

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

Slovenia NOLIPREL FORTE 4mg/1.25 mg tablets

Spain Bipreterax 4 mg/1.25 mg tablets

France PERINDOPRIL /INDAPAMIDE ARROW LAB 4mg/1.25mg

Hungary PRETANIX KOMB

Date of the last revision of thisprospectus:May 2022

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