Package Insert: Information for the Patient

Perindopril/Indapamida Combix 4 mg/1.25 mg Tablets EFG

perindopril terbutilamine/indapamide

Read this package insert carefully before starting to take this medication,because 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 or pharmacist.
• This medication 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 adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Perindopril/Indapamida is an association of two active principles, perindopril and indapamida. This medicationis used for the treatment of high blood pressure (hypertension).

• Perindopril belongs to a group of medications called angiotensin-converting enzyme (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 urine formation.

Each of the active principles reduces blood pressure and acts in conjunction to control blood pressure.

Do not take Perindopril/Indapamida Combix

• if you areallergicto perindopril or any other angiotensin-converting enzyme (ACE) inhibitor, to indapamida or other sulfonamides, or to any of the other components of this medication (listed in section 6),
• if you have experienced symptoms such asbreathing with wheezing, facial or tongue swelling, intense itching, or severe skin eruptionswith any previous treatment with ACE inhibitors or if you or a family member has had these symptoms in any other circumstance (a condition known as angioedema),
• if you have diabetes or kidney insufficiency and are being treated with a medication to lower blood pressure that contains aliskirén.
• if you have a severe liver disease or suffer from a condition calledhepatic encephalopathy(a degenerative brain disease),
• if you have asevere kidney diseaseor if you are receiving dialysis,
• if you havelow or high potassium levels in your blood,
• if you suspect that you may have untreatedheart failure(severe fluid retention, difficulty breathing),
• if you aremore than 3 months pregnant(equally, it is best to avoid perindopril/indapamida at the beginning of pregnancy - see "Pregnancy and breastfeeding"),
• if you are inlactation(see lactation).

Children and adolescents

DO NOT give this medication tochildren.

Warnings and precautions

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

• you haveaortic stenosis(narrowing of the main blood vessel that leaves the heart),
• you havemitral stenosis(narrowing of the left heart valve),
• you havehypertrophic cardiomyopathy(heart muscle disease),
• you haverenal artery stenosis(narrowing of the artery that carries blood to the kidney),
• you have any otherheart or kidney problems,
• you haveliver problems,
• you suffer from acollagen disease(skin disease) such as systemic lupus erythematosus or scleroderma,
• you haveatherosclerosis(hardening of the arteries),
• you havehyperparathyroidism(overactivity of the parathyroid gland),
• you havegout,
• you havediabetes,
• you are following alow-sodium dietor using salt substitutes that contain potassium,
• you are takinglitioordiuretics that spare potassium(espironolactona, triamtereno), as simultaneous use with perindopril/indapamida should be avoided (see "Use of other medications"),
• you are takingany of the following medications used to treathigh blood pressure(hypertension):
• • an angiotensin II receptor antagonist (ARA II) (also known as "sartanes" for example, valsartán, telmisartán, irbesartán),in particular if you have kidney problems related to diabetes.
  • aliskirén

You may need to have your kidney function, blood pressure, and electrolyte levels (such as potassium) checked regularly by your doctor.

See also the information under the heading "Do not take Perindopril/Indapamida Combix".

• you are over70 years old,
• you think you may be (or could become)pregnant. Perindopril/indapamida is not recommended at the beginning of pregnancy, and should not be taken if you are more than three months pregnant, as it may cause serious harm to your baby if used in this stage of pregnancy (see pregnancy section).

You should also inform your doctor that you are taking this medication if:

• you are toundergo anesthesiaand/orsurgery,
• you have recently haddiarrhea,vomiting, or aredehydrated,
• you have noticed an increase in skin sensitivity tosunlight,
• you havedry coughpersisting,
• you haveabdominal pain with or without nausea or vomiting; these may be symptoms of a serious allergic reaction called angioedema intestinal,
• you are to undergodialysis or LDL apheresis(removal of cholesterol from the blood by a machine),
• you are to receiveallergy desensitization treatmentto reduce the effects of an allergy to bees or wasps,
• you are to undergo a medical examination that requires the injection of acontrast agent containing iodine(a substance that makes organs such as the kidney or stomach visible with X-rays).
• Perindopril/indapamida may be less effective in people ofblack race.

Use of Perindopril/Indapamida Combix with other medications

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

Avoid taking this medication with:

• litio (used to treat depression),
• diuretics that spare potassium (espironolactona, triamtereno),
• salt substitutes that contain potassium.

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

• other medications for the treatment ofhigh blood pressure, including angiotensin II receptor antagonists (ARA II), aliskirén (see also the information under the headings "Do not take Perindopril/Indapamida Combix" and "Warnings and precautions").
• other medications to treatheart rhythm problems(for example, procainamide, digoxin, hydroquinidine, disopyramide, quinidine, amiodarone, sotalol, difemanil),
• antihistaminesfor hay fever or allergies such as terfenadine, astemizol, mizolastina,
• bepridil(for angina pectoris),
• benzamidas(for psychotic disorders such as sultoprida),
• butyrophenones(for psychiatric disorders such as haloperidol),
• cisaprida(intestinal medication),
• erythromycinfor injection (an antibiotic),
• moxifloxacinooresparfloxacino(antibiotics),
• metadona(anti-addictive medication),
• alopurinol(for gout),
• corticoesteroidesused to treat various disorders including severe asthma and rheumatoid arthritis,
• immunosuppressantsused to treat autoimmune disorders or after a transplant to prevent rejection (for example: ciclosporina),
• medications for the treatment ofcancer,
• halofantrina(for malaria),
• pentamidina(for pneumonia),
• vincamina(for cognitive disorders in elderly patients),
• baclofeno(for muscle stiffness that occurs in diseases such as multiple sclerosis),
• medications fordiabetessuch as insulin, metformin, or glimepirida,
• calcio,
• laxatives that stimulate(for example: sena),
• nonsteroidal anti-inflammatory drugs (NSAIDs) forpain reliefor high doses of salicylates (for example:aspirina),
• anfotericina Binjectable (for severe fungal diseases),
• medications to treat mental disorders such as depression, anxiety, schizophrenia (for example:tricyclic antidepressants,neuroleptics),
• tetracosactida(for the treatment of Crohn's disease),
• oro(aurotiomalato sódico) injectable (medication for rheumatic disorders).

Consult your doctor if you are unsure about these medications.

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 especially careful if you are on a low-sodium diet. Consult your doctor before taking the tablets.

Pregnancy, lactation, and fertility

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

Pregnancy

Consult your doctor or pharmacist before using any medication.

Consult your doctor if you are (or think you may be) pregnant. Generally, your doctor will advise you to stop taking perindopril/indapamida before becoming pregnant or as soon as possible if you are pregnant and will recommend taking another medication instead of perindopril/indapamida. Perindopril/indapamida is not recommended in the first months of pregnancy and should not be taken after the third month of pregnancy, as it may cause serious harm to your baby if used in this stage of pregnancy.

Lactation

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

Driving and operating machinery

This medication does not affect your 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 occurs, it may affect your ability to drive and operate machinery.

Perindopril/Indapamida Combix contains lactose
If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

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

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 usual dose is one tablet once a day.

Senior patients

Your doctor will decide on the best dose for you.

Patients with renal insufficiency

Your doctor may decide to modify the dosing regimen if you suffer from renal insufficiency.

Use in children and adolescents

This medication is not suitable for use in children.

If you take more Perindopril/Indapamida Combix than you should

If you ingest too many tablets, contact your doctor immediately or go to the nearest hospital emergency department. The most common symptom of overdose is a decrease in blood pressure. If a significant decrease in blood pressure occurs (symptoms such as dizziness or fainting), lying down with legs elevated may help.

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 Perindopril/Indapamida Combix

It is essential to take this medication every day, as continuous treatment is more effective. However, if you forgot to take a dose of perindopril/indapamida, take the next dose at the usual time. Do not take a double dose to compensate for the missed dose.

If you interrupt treatment with Perindopril/Indapamida Combix

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

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

Like all medicines, Perindopril/Indapamida Combix may cause side effects, although not everyone will experience them.

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

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

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

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

• abnormally rapid or irregular heartbeat,
• chest pain

Other side effects

Common(may affect up to 1 in 10 people)

• constipation,
• dry mouth,
• nausea,
• vomiting,
• indigestion after eating (dyspepsia),
• abdominal pain,
• epigastric pain,
• loss of appetite,
• diarrhea,
• disturbances of taste,
• dry cough,
• difficulty breathing,
• vision disturbances,
• ringing or buzzing in the ears,
• muscle cramps,
• sensation of weakness (asthenia),
• low blood pressure and dizziness or fainting when standing up,
• headache,
• sensation of dizziness,
• sensation of tingling, itching, or numbness without apparent cause (paresthesia),
• sensation of dizziness (vertigo),
• skin reactions (rash, urticaria, itching),
• low potassium levels in the blood

Uncommon(may affect up to 1 in 100 people)

• red patches on the skin (purpura),
• skin eruption with itching (urticaria),
• changes in mood and/or sleep disturbances,
• difficulty breathing with cough or wheezing (bronchospasm),
• swelling of the face, lips, mouth, tongue, eyes, or throat,
• renal disturbances (renal insufficiency),
• impotence (inability to achieve or maintain an erection),
• sweating,
• depression,
• low sodium levels in the blood that may 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)

• elevated calcium levels in the blood,
• intestinal angioedema (presented with abdominal pain or with or without nausea or vomiting).
• exacerbation of psoriasis,
• concentrated urine, feeling unwell (nausea) or vomiting, muscle cramps, confusion, and convulsions. These symptoms may be a disease called SIADH (inadequate secretion of antidiuretic hormone),
• decreased or absent diuresis,
• facial flushing,
• acute renal insufficiency,
• low chloride levels in the blood,
• low magnesium levels in the blood.

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

• inflammation of the pancreas (pancreatitis),
• reduction in the number of platelets,
• reduction in the number of white blood cells in the blood, making infections more likely,
• reduction in the number of red blood cells that may cause pale 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),
• hepatic inflammation (hepatitis),
• pneumonia,
• nasal congestion or nasal discharge,
• cardiac disturbances (abnormally slow or irregular heartbeat, chest pain, or heart attack),
• severe skin reactions (manifested as rash, skin redness, swelling of the lips, eyes, or mouth, skin peeling with or without fever),
• sensitivity to sunlight,
• confusion.

Unknown(the frequency cannot be estimated from the available data)

• in the case of liver failure (liver problems), there is a possibility of brain disturbances (change of personality, confusion, stupor, tremors, convulsions, confusion, disturbances of consciousness),
• changes in laboratory parameters studied in blood tests.
• change in color, numbness, and pain in the fingers of the hands or feet (Raynaud's disease)

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 does not appear 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 adverse 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.

No special storage conditions are required.

Do not use this medication after the expiration date that appears 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.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Perindopril/Indapamida Combix

-The active principles are perindopril terbutilamine and indapamida. Each tablet contains 3.338 mg of perindopril corresponding to 4 mg of perindopril terbutilamine and 1.25 mg of indapamida.

-The other components (excipients) are lactose monohydrate, microcrystalline cellulose (E460i), anhydrous colloidal silica (E551), and magnesium stearate (E470b).

Appearance of the product and content of the packaging

White to off-white, elongated, biconvex, smooth tablets on both faces.

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

PVC/PVDC-Aluminium blister in packs of 30 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Combix Laboratories, S.L.U.

C/ Badajoz 2, Building 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

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

Last review date of this leaflet: November 2021

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.