PERINDOPRIL/INDAPAMIDE COMBIX 4 mg/1.25 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Perindopril/Indapamide Combix4 mg/1.25 mg Tablets EFG

perindopril tert-butylamine/indapamide

Read all of 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 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 experience 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 Package Leaflet

1. What is Perindopril/Indapamide Combix and what is it used for
2. What you need to know before you take Perindopril/Indapamide Combix
3. How to take Perindopril/Indapamide Combix
4. Possible side effects
5. Storing Perindopril/Indapamide Combix
6. Package Contents and Further Information

1. What is Perindopril/Indapamide Combix and what is it used for

Perindopril/Indapamide is a combination of two active substances, perindopril and indapamide. This medicine is used to treat high blood pressure (hypertension).

• Perindopril belongs to a group of medicines called ACE inhibitors. They work by widening the blood vessels, making it easier for your 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 causes 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 Perindopril/Indapamide Combix

Do not take Perindopril/Indapamida Combix

• if you are allergicto perindopril or any other ACE inhibitor, to indapamide or other sulfonamides, 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 has had these symptoms in any other circumstance (a disorder known as 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 diseaseor if you are receiving dialysis,
• if you have low or high potassium levels in your blood,
• if you suspect you may have untreated heart failure(severe fluid retention, difficulty breathing),
• if you are pregnant for more than 3 months(also, it is best to avoid perindopril/indapamide at the beginning of pregnancy - see "Pregnancy and Breastfeeding"),
• if you are breastfeeding(see Breastfeeding).

Children and Adolescents

DO NOT give this medicine to children.

Warnings and Precautions

Consult your doctor or pharmacist before starting to take Perindopril/Indapamida Combix if:

• you have narrowing of the main blood vesselthat comes out of the heart (aortic stenosis),
• you have narrowing of the left valve of the heart(mitral valve stenosis),
• you have heart muscle disease(cardiomyopathy)
• you have narrowing of the artery that supplies blood to the kidney(renal artery stenosis),
• you suffer from any other heart or kidney problems,
• you have liver problems,
• you suffer from a collagen disease(skin disease) such as systemic lupus erythematosus or scleroderma,
• you suffer from atherosclerosis(hardening of the arteries),
• you suffer from hyperparathyroidism(overactivity of the parathyroid gland),
• you have gout,
• you have diabetes,
• you are on a low-salt dietor are using salt substitutes that contain potassium,
• you are taking lithium or potassium-sparing diuretics (spironolactone, triamterene), as concurrent use with perindopril/indapamide should be avoided (see "Using other medicines"),
• you are taking any of the following medicines used to treat high blood pressure(hypertension):
• • an angiotensin II receptor antagonist (ARA II) (also known as "sartans", e.g., valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
  • 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 Perindopril/Indapamida Combix".

• you are over 70 years old,
• you think you are (or might become) pregnant. Perindopril/indapamide is not recommended at the beginning of pregnancy, and must not be taken if you are pregnant for more than three months, as it may cause serious harm to your baby if used after the third month of pregnancy (see section on pregnancy).

You should also inform your doctor if you are taking this medicine and:

• are going to have anesthesiaand/or surgery,
• have recently suffered from diarrhea, vomiting, or are dehydrated,
• have noticed an increased sensitivity of your skin to sunlight,
• have a dry coughthat persists,
• have abdominal pain with or without nausea or vomiting; these could be symptoms of a serious allergic reaction called intestinal angioedema,
• are going to have dialysis or LDL apheresis(removal of cholesterol from the blood by a machine),
• are going to receive desensitization treatmentto reduce the effects of an allergy to bees or wasps,
• are going to have a medical examination that requires the injection of an iodinated contrast agent(a substance that makes organs such as the kidney or stomach visible with X-rays).
• Perindopril/indapamide may be less effective in people of black race.

Using Perindopril/Indapamida Combix with other medicines

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

Avoid taking this medicine with:

• lithium (used to treat depression),
• potassium-sparing diuretics (spironolactone, triamterene),
• potassium salts.

In particular, consult your doctor before taking this medicine if you are taking any of the following, as your doctor may need to change your dose and/or take other precautions:

• other medicines for treating high blood pressure, including angiotensin II receptor antagonists (ARA II), aliskiren (see also the information under the headings "Do not take Perindopril/Indapamida Combix" and "Warnings and Precautions").
• other medicines for treating heart rhythm problems(e.g., procainamide, digoxin, hydroquinidine, disopyramide, quinidine, amiodarone, sotalol, difemanil),
• antihistaminesfor hay fever or allergies, such as terfenadine, astemizole, mizolastine,
• bepridil(for angina pectoris),
• benzamides(for psychotic disorders, e.g., sultopride),
• butyrophenones(for psychiatric disorders, e.g., haloperidol),
• cisapride(intestinal medicine),
• erythromycinfor injection (an antibiotic),
• moxifloxacinor esparfloxacino(antibiotics),
• methadone(anti-addictive medicine),
• allopurinol(for gout),
• corticosteroidsused to treat various disorders, including severe asthma and rheumatoid arthritis,
• immunosuppressantsused to treat autoimmune disorders or after a transplant to prevent rejection (e.g., cyclosporine),
• medicines for treating cancer,
• halofantrine(for malaria),
• pentamidine(for pneumonia),
• vincamine(for cognitive disorders in elderly patients),
• baclofen(for muscle stiffness that occurs in diseases such as multiple sclerosis),
• medicines for treating diabetes, such as insulin, metformin, or glimepiride,
• calcium,
• stimulant laxatives(e.g., senna),
• non-steroidal anti-inflammatory drugs (NSAIDs) for pain reliefor high doses of salicylates (e.g., aspirin),
• amphotericin Binjectable (for severe fungal infections),
• medicines for treating mental disorders, such as depression, anxiety, schizophrenia (e.g., tricyclic antidepressants, neuroleptics),
• tetracosactide(for Crohn's disease),
• gold(sodium aurothiomalate) injectable (medicine for rheumatic disorders).

Consult your doctor if you are not sure what these medicines are.

Taking Perindopril/Indapamida Combix with food, drinks, and alcohol

Take the tablets with a glass of water, preferably in the morning and before meals. Be careful if you are on a low-salt diet. Consult your doctor before taking the tablets.

Pregnancy, Breastfeeding, and Fertility

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

Ask your doctor or pharmacist for advice before taking any medicine.

Ask your doctor if you are (or think you may be) pregnant. Your doctor will normally advise you to stop taking perindopril/indapamide before you become pregnant or as soon as possible if you are pregnant, and will recommend an alternative medicine. Perindopril/indapamide is not recommended during the first few months of pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breastfeeding

Do not take perindopril/indapamide if you are breastfeeding. Consult your doctor immediately if you are breastfeeding or about to start breastfeeding.

Driving and using machines

This medicine does not affect alertness, but due to the lowering of blood pressure, you may feel dizzy or weak, especially at the beginning of treatment or when increasing the dose. If this happens, your ability to drive or operate machinery may be affected.

Perindopril/Indapamida Combix contains lactoseIf your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Perindopril/Indapamida Combix

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.

The recommended dose is one tablet per day.

Take the tablets with a glass of water, preferably in the morning and before meals.

Adults

The normal dose is one tablet once a day.

Elderly patients

Your doctor will decide what dose is best for you.

Patients with kidney problems

Your doctor may decide to adjust the dose if you have kidney problems.

Use in children and adolescents

This medicine is not suitable for children.

If you take more Perindopril/Indapamida Combix than you should

If you have taken too many tablets, contact your doctor or go to the casualty department of your nearest hospital immediately. The most common symptom in case of overdose is low blood pressure. If you experience a significant drop in blood pressure (symptoms such as dizziness or fainting), it may help to lie down with your legs raised.

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

If you forget to take Perindopril/Indapamida Combix

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

If you stop taking Perindopril/Indapamida Combix

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

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

4. Possible Adverse Effects

Like all medicines, Perindopril/Indapamida Combix can cause adverse effects, although not all people suffer from them.

If you experience any of the following symptoms, STOP treatment with this medication and contact your doctor immediately.These are symptoms of a severe allergic reactionand should be treated immediately, usually in a hospital.

inflammation of the face, lips, mouth, tongue, eyes, or throat,

• difficulty breathing,
• severe dizziness or fainting,
• blistering of the skin, mouth, eyes, and genitals.

Also, contact your doctor immediatelyif you experience any of the following adverse effects:

• abnormally fast or irregular heartbeats,
• chest pain

Other Adverse Effects

Frequent(may affect up to 1 in 10 people)

• constipation,
• dry mouth,
• nausea,
• vomiting,
• stomach discomfort after eating (dyspepsia),
• abdominal pain,
• epigastric pain,
• anorexia,
• diarrhea,
• taste disorders,
• dry cough,
• breathing difficulties,
• vision disorders,
• ringing or buzzing in the ears,
• muscle cramps,
• feeling of weakness (asthenia),
• low blood pressure and dizziness or fainting when standing up,
• headache,
• feeling of dizziness,
• tingling, itching, or numbness without apparent cause (paresthesia),
• feeling of dizziness (vertigo),
• skin reactions (rash, hives, itching),
• low potassium levels in the blood

Uncommon(may affect up to 1 in 100 people)

• red spots on the skin (purpura),
• itchy skin rash (urticaria),
• mood changes and/or sleep disorders,
• difficulty breathing with coughing or wheezing (bronchospasm),
• swelling of the face, lips, mouth, tongue, eyes, or throat,
• kidney disorders (renal failure),
• impotence (inability to have or maintain an erection),
• sweating,
• depression,
• low sodium levels in the blood, which can cause dehydration and low blood pressure.

If you have systemic lupus erythematosus (a collagen disease), it may worsen.

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

• high calcium levels in the blood,
• intestinal angioedema (presenting with abdominal pain or with or without nausea or vomiting),
• worsening of psoriasis,
• 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),
• decreased or absent diuresis,
• facial flushing,
• acute kidney failure,
• low chloride levels in the blood,
• low magnesium levels in the blood.

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

• pancreatitis (inflammation of the pancreas),
• reduced platelet count,
• reduced white blood cell count, making infections more likely,
• reduced red blood cell count, which can cause paleness of the skin and produce weakness or shortness of breath (anemia in patients who have received a kidney transplant or in patients undergoing hemodialysis, aplastic anemia, or hemolytic anemia),
• hepatitis (inflammation of the liver),
• pneumonia,
• nasal congestion or nasal discharge,
• heart disorders (slow or abnormally fast heartbeat, chest pain, or heart attack),
• severe skin reactions (manifested as a rash, skin redness, swelling of the lips, eyes, or mouth, skin peeling with or without fever),
• increased skin sensitivity to sunlight,
• confusion.

Unknown(frequency cannot be estimated from available data)

• changes in laboratory parameters studied in blood tests.
• color change, numbness, and pain in the fingers of the hands or feet (Raynaud's disease)

Reporting 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: https//: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Perindopril/Indapamida Combix

Keep this medication out of sight and reach of children.

No special storage conditions are required.

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

Do not use this medication if you observe any visible signs of deterioration.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and unused medications at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Perindopril/Indapamida Combix

• The active ingredients are perindopril terbutylamine and indapamide. Each tablet contains 3.338 mg of perindopril, corresponding to 4 mg of perindopril terbutylamine and 1.25 mg of indapamide.
• The other components (excipients) are lactose monohydrate, microcrystalline cellulose (E460i), anhydrous colloidal silica (E551), and magnesium stearate (E470b).

Appearance of the Product and Package Contents

White to off-white, elongated, biconvex tablets with smooth surfaces on both sides.

OPA/AL/PVC-Aluminum blister packs in packages of 30 tablets.

PVC/PVDC-Aluminum blister packs in packages of 30 tablets

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Specialites Pharmaceutiques

ZAC des Suzots

35 Rue de la Chapelle

63450 Saint Amant Tallende

France

Date of the Last Revision of this Prospectus: November 2021

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