Patient Information Leaflet

Bipreterax 4mg/1.25mg Tablets

perindopril terbutilamina/indapamida

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

-Keep this leaflet, as you may need to read it again.

-If you have any questions, ask your doctor or pharmacist.

-This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms, as it may harm them.

-If you experience any side effects, consult your doctor or pharmacist, even

if they are not listed in this leaflet. See section 4.

1.What isBipreterax 4 mg/1.25 mg Tablets and what it is used for

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

3.How to takeBipreterax 4 mg/1.25 mg Tablets

4.Possible side effects

5.Storage ofBipreterax 4 mg/1.25 mg Tablets

6.Contents of the pack and additional information

Bipreterax 4 mg/1,25 mg tablets is an association of two active principles, perindopril and indapamida. It is an antihypertensive and is indicated for the treatment of high blood pressure (hypertension) in adults.

Perindopril belongs to a group of medicines called ACE inhibitors. They act by widening blood vessels, making it easier for the heart to pump blood through them. Indapamida is a diuretic. Diuretics increase the amount of urine produced by the kidneys. However, indapamida is different from other diuretics, as it only produces a slight increase in the amount of urine formed. Each of the active principles lowers blood pressure and acts in conjunction to control blood pressure.

Do not takeBipreterax 4 mg/1.25 mg tablets

• if you are allergic to perindoprilor to any other angiotensin-converting enzyme (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, facial or tongue swelling, intense itching or severe skin eruptions with any previous treatment with ACE inhibitors or if you or a family member has had these symptoms in any other circumstances (a condition called angioedema),
• if you have diabetes or kidney failure and are being treated with a blood pressure-lowering 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 diseasedue to which the blood flow to your kidneys is reduced (renal artery stenosis),
• if you are receiving dialysisor any other type of blood filtration. Depending on the machine used,Bipreterax 4 mg/1.25 mgtabletsmay not be suitable for you,
• if you have low potassium levels in your blood,
• if you suspect that you may have untreated heart failure (severe fluid retention, difficulty breathing),
• if you are more than 3 months pregnant (It is also better 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 heart failure medicine, as it increases the risk of angioedema (rapid swelling under the skin in an area such as the throat) (see “Warnings and precautions” and “Use ofBipreterax 4 mg/1.25 mgtablets 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 leaves the heart) or hypertrophic cardiomyopathy (heart muscle disease) 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 may be symptoms of fluid accumulation in the blood vessels of the eye (choroidal effusion) or increased pressure in your eye and can occur within hours or weeks of taking Bipreterax 4 mg/1.25 mg tablets. If left untreated, this can lead to permanent loss of vision. If you have had a previous 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 following a low-sodium diet or using salt substitutes that contain potassium,
• if you are taking lithium or potassium-sparing diuretics (e.g. spironolactone, triamterene) or potassium supplements, as simultaneous 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 photoallergic 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 (hypertension):

• an angiotensin II receptor antagonist (ARA) (also known as “sartans” - e.g. valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.
• aliskiren.

Your doctor may need to monitor your kidney function, blood pressure, and electrolyte levels (e.g. potassium) at regular intervals.

See also the information under the heading “Do not takeBipreterax 4 mg/1.25 mg tablets”.

• if you are of black ethnicity, as you may be at higher risk of angioedema and this medicine may be less effective in lowering your blood pressure than in patients who are not of black ethnicity,
• if you are a haemodialysis patient with high-flow 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 transplant rejection and for cancer),
• sacubitril (available as a fixed-dose combination with valsartan), used to treat heart failure at a long-term basis,
• linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the class of gliptins (used to treat diabetes).

Angioedema

In patients treated with ACE inhibitors, includingBipreterax4mg/1.25mg tablets, angioedema (severe allergic reactionwith 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 withBipreterax4mg/1.25mg tabletsand seek medical attention immediately. See also Section 4.

You should inform your doctor if you think you are (or could be) pregnant. Bipreterax 4 mg/1.25 mg tablets are not recommended at the beginning of pregnancy, and you should not take them if you are more than 3 months pregnant, as they may cause serious harm to your baby if used during this period (see “Pregnancy and breastfeeding”).

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

• if you are to undergo anesthesia and/or surgery,
• if you have recently had diarrhea or vomiting, or are dehydrated,
• if you are to undergo dialysis or LDL apheresis (removal of cholesterol from your blood using a machine),
• if you are to receive a desensitization treatment to reduce the effects of bee or wasp stings,
• if you are 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 have changes in your vision or eye pain while taking Bipreterax 4 mg/1.25 mg tablets. This may be a sign of 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 thatBipreterax 4 mg/1.25 mg tabletscontain an active ingredient (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 andBipreterax 4 mg/1.25 mg tablets

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

You should avoid takingBipreterax 4 mg/1.25 mg tabletswith:

• lithium (used to treat mania or depression),
• aliskiren (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,other medicines that can increase potassium levels in your body (such as heparin, a medicine used to thin the blood and prevent blood clots; trimethoprim and co-trimoxazole also known as trimethoprim/sulfamethoxazole for bacterial infections),

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

The treatment with Bipreterax 4 mg/1.25 mg tabletsmay be affected by other medicines. Your doctor may need to modify 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 pressureincluding angiotensin II receptor antagonists (ARAs), aliskiren (see also the information under the headings “Do not takeBipreterax 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 diuretics used in the treatment of heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg per day,
• medicines used frequently to treat diarrhea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class called mTor inhibitors). See section “Warnings and precautions”,
• sacubitril/valsartan (used to treat heart failure at a long-term basis). See sections “Do not takeBipreterax 4 mg/1.25 mg tablets” and “Warnings and precautions”,
• anesthetics,
• iodinated contrast agent,
• antibiotics used to treat bacterial infections (e.g. moxifloxacin, ciprofloxacin, intravenous erythromycin),
• methadone (used to treat addiction),
• procainamide (for irregular heart rhythm treatment),
• allopurinol (for gout treatment),
• 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. ciclosporin, tacrolimus),
• halofantrine (used to treat certain types of malaria),
• pentamidine (used to treat pneumonia),
• intravenous 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 used to treat heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide,amiodarone, sotalol, ibutilide, dofetilide, digitals, bretylium),
• cisapride, difemanil (used to treat gastrointestinal problems),
• digoxin or other cardiac glycosides (for heart problems treatment),
• baclofen (for muscle stiffness that occurs in diseases such as multiple sclerosis),
• medicines used to treat diabetes such as insulin, metformin, or gliptins,
• calcium including calcium supplements,
• laxatives (e.g. senna),
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or high doses of salicylates (e.g. aspirin(a substance present in many medicines used to relieve pain and reduce fever, as well as to prevent blood clotting)),
• amphotericin B (used to treat serious fungal infections),
• medicines used to treat mental disorders such as depression, anxiety, schizophrenia... (e.g. tricyclic antidepressants, neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol)),
• tetracosactide (used to treat Crohn's disease),
• trimethoprim (used to treat 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 drink

It is best to takeBipreterax 4 mg/1.25 mg tabletsbefore a meal.

Pregnancy and breastfeeding

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

Pregnancy

You should inform your doctor if youthink you are (or could be) pregnant.

Normally, your doctor will recommend that you stop taking Bipreterax 4 mg/1.25 mg tablets before becoming pregnant or as soon as you know you are pregnant and will recommend that you take another medicine instead of Bipreterax 4 mg/1.25 mg tablets. Bipreterax 4 mg/1.25 mg tablets are not recommended at the beginning of pregnancy, and you should not take them if you are more than 3 months pregnant, as they may cause serious harm to your baby if used during this period.

Breastfeeding

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

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

Go to your doctor immediately.

Driving and operating machines

Bipreterax 4 mg/1.25 mg tablets usuallydo not affect your alertness, but due to the lowering of blood pressure, some patients may experience different reactions such as dizziness or weakness. If this occurs, your ability to drive or operate machinery may be impaired.

Bipreterax 4 mg/1.25 mg tablets contain lactose.

If your doctor has told you that you have a certain sugar intolerance, consult with him before taking this medicine.

Follow exactly the administration instructions for this medication as indicated 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 modify the dose if you have kidney insufficiency. 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 immediately or go to the emergency service of your nearest hospital. In case of overdose or accidental ingestion, consult the Toxicological Information Service, phone (91) 562 04 20.

The most frequent 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 urine production by the kidneys), lying down with legs elevated may help.

If you forgot to takeBipreterax 4 mg/1,25 mg tablets

It is essential to take this medication every day since continuous treatment is more effective. However, if you forgot 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 compensate for the missed dose.

If you interrupt treatment withBipreterax 4 mg/1,25 mg tablets

Since hypertension treatment is usually lifelong, you should talk to your doctor before stopping this medication.

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

Like all medications,this medicationmay cause side effects, although not everyone will experience them.

Stoptreatment with this medication andimmediately consult your doctor if you experience any of the following side effects that may be severe:

• 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 (Infrequent) (may affect up to 1 in 100 people),
• Swelling of the face, lips, mouth, tongue or throat,which causes severe difficulty breathing (angioedema) (See Section 2 "Warnings and precautions") (Infrequent) (may affect up to 1 in 100 people),
• Severe skin reactions that include erythema multiforme (skin rash that often begins with red patches that itch on the face, arms orlegs),or intense skin rash, blisters, skin redness all over the body, intense itching, blister formation, skin peeling and inflammation of the skin and mucous membranes(Stevens-Johnson syndrome) or other allergic reactions) (Very rare - may affect up to 1 in 10,000 people)
• CARDIOVASCULAR DISORDERS (irregular heartbeat, angina (chest pain, jaw pain and back pain, produced by physical exertion), myocardial infarction (Very rare) (may affect up to 1 in 10,000 people).
• Weakness of arms or legs, or speech problems that may 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 sense of discomfort (Very rare) (may affect up to 1 in 10,000 people).
• Yellowing of the skin or eyes (jaundice) that may be a sign of hepatitis (Very rare - may affect up to 1 in 10,000 people),
• Irregular heartbeat with life-threatening risk. (Unknown frequency),
• BRAIN DISEASE CAUSED BY LIVER DISEASE (HEPATIC ENCEPHALOPATHY) (Unknown frequency),
• Muscle weakness, cramps, muscle sensitivity or pain and especially, if you feel unwell or have a high temperature, as they may be caused by abnormal muscle breakdown. (Unknown frequency).

In decreasing order of frequency, side 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 disturbances, tinnitus (sensation of noise in the ears), cough, shortness of breath (dyspnea), gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, indigestion or difficulty digesting, diarrhea, constipation), allergic reactions (such as skin rashes, itching), muscle cramps, feeling tired,low potassium levels in the blood.

• Infrequent (mayaffect up to 1 in 100 people): mood changes, depression, sleep disturbances, urticaria, purpura (red spots on the skin), blister formation, kidney problems, impotence (inability to have or maintain an erection), sweating,an excess of eosinophils (a type of white blood cell), changes in laboratory 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 (rapid heartbeat), hypoglycemia (very low blood sugar) 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 unwell, peripheral edema, fever,elevation ofblood urea, and elevation of blood creatinine, fall.

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

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

• Very rare (may affectup to 1 in 10,000 people): confusion, eosinophilic pneumonia (a rare type of pneumonia), rhinitis (stuffy nose or runny nose), severe kidney problems, changes in blood values such asdecrease in white and red blood cells, decrease in hemoglobin, decrease in platelet count, increase in blood calcium levels,abnormal liver function.

• Unknown frequency (cannot be estimated from available data):abnormal ECG tracing,changes in blood parameters: high levels of uric acid and blood sugar, myopia (nearsightedness), 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 hemorrhage) or acute angle-closure glaucoma),change in color, numbness and pain in the fingers of the hands or feet (Raynaud's disease).If you have systemic lupus erythematosus (a type of collagen disease) it may worsen.

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

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

Reporting of side effects

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

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

Do not usethis medicationafter the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30°C.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and unused medicines at your local SIGRE collection pointat your usual pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and unused medicines. By doing so, you will help protect the environment.

Composition ofBipreterax 4 mg/1.25 mg tablets

-The active ingredients are perindopril terbutilamine and indapamide. Each tablet contains 4mg of perindopril terbutilamine (which corresponds to 3.338 mg of perindopril)and 1.25mg 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 contents of the package

The tablets ofBipreterax 4 mg/1.25 mg tabletsare white, in the form of a rod. A tablet contains 4mg of perindopril terbutilamine and 1.25mg of indapamide.

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

They may only be marketed in some package sizes.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

Les Laboratoires Servier

50, rue Carnot

92284 Suresnes cedex– France

Responsible 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 medicinal product is authorized in the member states of the European Economic Area with the following names:

SloveniaNOLIPREL FORTE4mg/1.25 mg tablets

SpainBipreterax 4mg/1.25mg tablets

FrancePERINDOPRIL /INDAPAMIDE ARROW LAB 4mg/1.25mg

HungaryPRETANIX KOMB

Date of the last review of this leaflet:May 2022

The 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/.