Indix Combi

Package Leaflet: Information for the Patient

Indix Combi, 2.5 mg + 0.625 mg, film-coated tablets
Perindopril tosilate + Indapamide

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Indix Combi and what is it used for
• 2. Important information before taking Indix Combi
• 3. How to take Indix Combi
• 4. Possible side effects
• 5. How to store Indix Combi
• 6. Contents of the pack and other information

1. What is Indix Combi and what is it used for

What is Indix Combi

Indix Combi is a combination medicine that contains two active substances: perindopril and indapamide. It is
an antihypertensive medicine used to treat high blood pressure in adults.

What is Indix Combi used for

Perindopril belongs to a group of medicines called angiotensin-converting enzyme inhibitors (ACE inhibitors). These
medicines work by widening the blood vessels, making it easier for the heart to pump blood.
Indapamide is a diuretic. Diuretics increase the amount of urine produced by the kidneys.
Indapamide differs from other diuretics in that it only slightly increases the amount of urine produced. Both active substances lower blood pressure and work together to normalize blood pressure in the patient.

2. Important information before taking Indix Combi

When not to take Indix Combi:

• if you are allergic to perindopril or other ACE inhibitors, to indapamide or other sulfonamides, or to any of the other ingredients of this medicine (listed in section 6);
• if you have ever had symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin flushing when taking an ACE inhibitor in the past, or if such symptoms have occurred in a family member under any other circumstances (a condition called angioedema);
• if you have severe liver disease or a condition called hepatic encephalopathy (a disease that damages the brain);
• if you have severe kidney disease that reduces blood flow to the kidneys (renal artery stenosis);
• if you are undergoing dialysis or blood filtration using a method other than hemofiltration or ultrafiltration. Depending on the device used, Indix Combi may not be suitable for you.
• if you have low potassium levels in your blood;
• if you have uncontrolled heart failure (excessive fluid retention in the body, difficulty breathing);
• if you are pregnant over 3 months (it is also recommended to avoid taking Indix Combi in early pregnancy - see section "Pregnancy, breastfeeding, and fertility");
• if you have diabetes or kidney problems and are taking a blood pressure-lowering medicine containing aliskiren;
• if you have taken or are currently taking sacubitril with valsartan, a medicine used to treat heart failure, as the risk of angioedema (rapid swelling of tissues under the skin, such as the throat) increases (see "Warnings and precautions" and "Other medicines and Indix Combi").

Warnings and precautions

If any of the following situations apply to you, inform your doctor before taking Indix Combi:

• if you are taking any of the following medicines, the risk of angioedema may increase:
• racecadotril, a medicine used to treat diarrhea;
• medicines used to prevent transplant rejection and treat cancer (e.g., temsirolimus, sirolimus, everolimus) and other medicines belonging to the class of mTOR inhibitors;
• linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the class of gliptins (used to treat diabetes);
• sacubitril (available in a combination medicine containing sacubitril and valsartan), used to treat chronic heart failure.
• if you have aortic stenosis (narrowing of the main blood vessel carrying blood from the heart) or hypertrophic cardiomyopathy (a disease of the heart muscle) or renal artery stenosis (narrowing of the blood vessel supplying the kidney);
• if you have heart failure or any other heart disease;
• if you have kidney disease or are undergoing dialysis;
• if you have muscle disorders, including pain, tenderness, weakness, or cramps;
• if you have an excessive level of a hormone called aldosterone in your blood (primary hyperaldosteronism);
• if you have liver disease;
• if you have collagenosis (a skin disease), such as systemic lupus erythematosus or scleroderma;
• if you have atherosclerosis (hardening of the blood vessels);
• if you have hyperparathyroidism (a disorder of the parathyroid glands);
• if you have gout;
• if you have diabetes;
• if you are on a low-salt diet or using salt substitutes containing potassium;
• if you are taking lithium or potassium-sparing diuretics (spironolactone, triamterene) or potassium supplements; these medicines should be avoided during Indix Combi treatment (see section "Other medicines and Indix Combi");
• if you are elderly;
• if you have had allergic reactions to light;
• if you have had a severe allergic reaction with swelling of the face, lips, mouth, tongue, or throat, which may cause difficulty swallowing or breathing (angioedema) - swelling may occur at any time during treatment. If such symptoms occur, discontinue treatment and consult a doctor immediately;
• if you are taking any of the following medicines used to treat high blood pressure:
• angiotensin receptor blocker (ARB) (also known as sartans - e.g., valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
• aliskiren.
• if you have worsening vision or eye pain. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (exudative detachment) or increased eye pressure, which may occur within a few hours to a few weeks after starting Indix Combi. If left untreated, they can lead to complete loss of vision. In patients allergic to penicillin or sulfonamides, the risk of such disorders is higher.
  Your doctor may monitor kidney function, blood pressure, and electrolyte levels (e.g., potassium) in your blood at regular intervals.
  See also the information under the heading "When not to take Indix Combi".

• if you are black - in this case, there may be a higher risk of angioedema, and the medicine may be less effective in lowering blood pressure than in patients of other races;
• if you are undergoing dialysis using high-flux membranes.

Angioedema
In patients treated with ACE inhibitors, including Indix Combi, angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat, and difficulty swallowing or breathing) has been reported. This reaction may occur at any time during treatment.
If you experience such symptoms, discontinue Indix Combi and consult a doctor immediately. See also section 4.
The patient must inform the doctor if she thinks she is (or may be) pregnant. Indix Combi is not recommended in early pregnancy and should not be taken if the patient is pregnant over 3 months, as the medicine may cause serious harm to the child if taken after the third month of pregnancy.
When taking Indix Combi, inform your doctor or medical 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 the blood using a special device);
• if you are to undergo desensitization treatment to reduce allergic reactions to bee or wasp stings;
• if you are to undergo a test that requires the administration of a contrast agent containing iodine (a substance that allows organs such as the kidney or stomach to be seen on an X-ray);
• if you experience vision disturbances or pain in one or both eyes while taking Indix Combi. These may be symptoms of glaucoma or increased eye pressure. Discontinue Indix Combi and consult a doctor.

Athletes should be informed that Indix Combi contains the active substance indapamide, which may give a positive result in a doping test.

Children and adolescents

Indix Combi should not be used in children and adolescents.

Other medicines and Indix Combi

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Indix Combi should be avoided:

• with lithium (used to treat mania or depression);
• with aliskiren (a medicine used to treat high blood pressure) in patients who do not have diabetes or kidney problems;
• with potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that increase potassium levels in the blood (e.g., trimethoprim and co-trimoxazole, used to treat bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent transplant rejection, and heparin, a medicine used to thin the blood to prevent blood clots);
• with estramustine (used to treat cancer);
• with other medicines used to treat high blood pressure: ACE inhibitors and angiotensin receptor blockers.

Taking other medicines may affect treatment with Indix Combi. Your doctor may need to change the dose and/or take other precautions when taking such medicines as:

• other medicines used to treat high blood pressure;
• your doctor may need to change the dose and/or take other precautions: If you are taking an angiotensin receptor blocker (ARB) or aliskiren (see also the information under the heading "When not to take Indix Combi" and "Warnings and precautions") or diuretics (medicines that increase the amount of urine produced by the kidneys);
• potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone in doses of 12.5 mg to 50 mg per day;
• medicines used to treat diarrhea (racecadotril) or to prevent transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of mTOR inhibitors). See section "Warnings and precautions".
• a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to take Indix Combi" and "Warnings and precautions".
• anesthetics;
• iodine-containing contrast agents;
• moxifloxacin, sparfloxacin (antibiotics used to treat bacterial infections);
• methadone (used to treat addiction);
• procainamide (used to treat heart rhythm disorders);
• allopurinol (used to treat gout);
• mizolastine, terfenadine, or astemizole (antihistamines used to treat hay fever or allergies);
• corticosteroids used to treat various conditions, including severe asthma and rheumatoid arthritis;
• immunosuppressive medicines used to treat autoimmune diseases or after transplant surgery to prevent rejection (e.g., cyclosporine, tacrolimus);
• medicines used to treat cancer;
• intravenous erythromycin (an antibiotic);
• halofantrine (used to treat certain types of malaria);
• pentamidine (used to treat pneumonia);
• intravenous gold salts (used to treat rheumatoid arthritis);
• vincamine (used to treat cognitive disorders in the elderly);
• bepridil (used to treat angina pectoris);
• medicines used to treat heart rhythm disorders (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis preparations, bretylium);
• digoxin or other digitalis glycosides (used to treat heart conditions);
• cisapride, difemanil (used to treat gastrointestinal disorders);
• baclofen (used to treat muscle stiffness in conditions such as multiple sclerosis);
• medicines used to treat diabetes, such as insulin, metformin, or gliptins;
• calcium, including calcium supplements;
• laxatives with a stimulating effect (e.g., senna);
• non-steroidal anti-inflammatory medicines (e.g., ibuprofen) or high doses of salicylates (e.g., acetylsalicylic acid (a substance found in many medicines, used as a pain reliever and antipyretic, as well as to prevent blood clots));
• intravenous amphotericin B (used to treat severe 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 used to treat low blood pressure, shock, or asthma (e.g., ephedrine, norepinephrine, or epinephrine).

Indix Combi with food and drink

It is recommended to take Indix Combi before a meal.

Pregnancy, breastfeeding, and fertility

If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
The patient must inform the doctor if she thinks she is (or may be) pregnant.
Usually, the doctor will advise stopping Indix Combi before becoming pregnant or as soon as the patient knows she is pregnant, and will prescribe another medicine instead of Indix Combi. Indix Combi is not recommended in early pregnancy and should not be taken if the patient is pregnant over 3 months, as the medicine may cause serious harm to the child if taken after the third month of pregnancy.
Breastfeeding
Indix Combi is not recommended during breastfeeding.
Tell your doctor immediately if you are breastfeeding or start breastfeeding.
Consult your doctor immediately.
Fertility
The effect of perindopril or indapamide on human fertility is not known.

Driving and using machines

Indix Combi usually does not affect the ability to drive and use machines, however, some patients may experience dizziness or fatigue related to low blood pressure. In such cases, the ability to drive or operate machines may be impaired.

Indix Combi contains lactose

If you have been told that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Indix Combi contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means it is essentially "sodium-free".

3. How to take Indix Combi

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist. The recommended dose is one tablet per day. Your doctor may decide to increase the dose to two tablets per day if your blood pressure is not well controlled or to modify the dosage in case of kidney problems. Take the tablet preferably in the morning, before a meal. Swallow the tablet with a glass of water.
The score line on the tablet is only to facilitate breaking and not to divide the tablet into equal doses.

What to do if you take more Indix Combi than you should

If you have taken too many tablets, contact your doctor or go to the nearest emergency department immediately. The most common symptom in case of overdose is low blood pressure. If you experience significantly low blood pressure (with accompanying nausea, vomiting, cramps, dizziness, drowsiness, disorientation, and changes in urine output), placing yourself in a reclined position with elevated legs may help.

What to do if you forget to take Indix Combi

It is important to take the medicine regularly for it to work best. However, if you miss a dose, take the next dose at the usual time. Do not take a double dose to make up for the missed dose.

What to do if you stop taking Indix Combi

Treatment of high blood pressure usually lasts for life, so before stopping this medicine, consult your doctor.
If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Indix Combi can cause side effects, although not everybody gets them.

If you experience any of the following serious side effects, stop taking Indix Combi and contact your doctor immediately:

• severe dizziness or fainting due to low blood pressure (common: may affect up to 1 in 10 people),
• bronchospasm (feeling of chest tightness, wheezing, and shortness of breath) (uncommon: may affect up to 1 in 100 people),
• facial, lip, mouth, tongue, or throat swelling, difficulty breathing (angioedema, see section "Warnings and precautions" in section 2) (uncommon: may affect up to 1 in 100 people),
• severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, or other allergic reactions (very rare: may affect up to 1 in 10,000 people),
• cardiovascular disorders (arrhythmias, angina pectoris, chest pain radiating to the jaw and back, caused by exertion), myocardial infarction (very rare: may affect up to 1 in 10,000 people),
• weakness or paralysis of the arms or legs, or speech disorders, which may be symptoms of a stroke (very rare: may affect up to 1 in 10,000 people),
• pancreatitis, which may cause severe abdominal pain and very poor general condition (very rare: may affect up to 1 in 10,000 people),
• jaundice or liver disease (very rare: may affect up to 1 in 10,000 people),
• life-threatening heart rhythm disorders (frequency not known),
• liver disease causing brain damage (hepatic encephalopathy) (frequency not known),
• muscle weakness, cramps, tenderness, or pain, especially if you feel unwell or have a high temperature, which may be caused by abnormal muscle breakdown (frequency not known).

Side effects, grouped by frequency of occurrence:

• common: (may affect up to 1 in 10 people)

low potassium levels in the blood, skin reactions in patients prone to allergic and asthmatic reactions, headache, dizziness, vertigo, tingling, visual disturbances, tinnitus (feeling of hearing sounds), cough, shortness of breath, gastrointestinal disorders (nausea, vomiting, abdominal pain, taste disturbances, indigestion or difficulty digesting, diarrhea, constipation), allergic reactions (such as rashes, itching), painful muscle cramps, fatigue;

• uncommon: (may affect up to 1 in 100 people) mood changes, depression, sleep disturbances, hives, purpura (red spots on the skin), blistering, kidney problems, impotence (inability to achieve or maintain an erection), excessive sweating, increased eosinophil count (a type of white blood cell), changes in laboratory test results: high potassium levels in the blood that are temporary and disappear after treatment is stopped, low sodium levels in the blood that may cause dehydration and low blood pressure, drowsiness, fainting, palpitations (feeling of heartbeat), tachycardia (fast heart rate), hypoglycemia (very low blood sugar) in diabetic patients, vasculitis (inflammation of blood vessels), dry mouth, sensitivity to light, joint pain, muscle pain, chest pain, malaise, peripheral edema, fever, increased urea levels in the blood, increased creatinine levels in the blood, falls.
• rare: (may affect up to 1 in 1,000 people) dark urine, nausea or vomiting, muscle cramps, disorientation, and seizures. These may be symptoms of a condition called SIADH (inappropriate antidiuretic hormone secretion). Sudden flushing of the face and neck, worsening of psoriasis, decreased or absent urine output, acute kidney failure, changes in laboratory test results: low chloride levels in the blood, low magnesium levels in the blood, increased liver enzyme activity, high bilirubin levels in serum; fatigue.
• very rare: (may affect up to 1 in 10,000 people) disorientation, eosinophilic pneumonia (a rare type of pneumonia), rhinitis (stuffy or runny nose), intestinal angioedema (allergic reaction in the small intestine), changes in blood parameters, such as decreased white blood cell count, decreased red blood cell count, decreased platelet count, high calcium levels in the blood; liver function disorders.
• frequency not known: (cannot be estimated from the available data) abnormal heart rhythm detected on an electrocardiogram, changes in laboratory test results: high uric acid levels and high blood sugar levels, worsening vision or eye pain due to high pressure (possible symptoms of fluid accumulation in the vascular layer surrounding the eye or acute glaucoma), cyanosis, numbness, and pain in the fingers or toes (Raynaud's phenomenon), muscle breakdown leading to kidney damage (rhabdomyolysis). If you have systemic lupus erythematosus (a type of collagenosis), the symptoms of the disease may worsen.

There may be blood, kidney, liver, or pancreas disorders, as well as changes in laboratory test results (blood tests). Your doctor may recommend blood tests to monitor your health.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist.
Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products; Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309,
website: https://smz.ezdrowie.gov.pl
By reporting side effects, you can help provide more information on the safety of this medicine.
Side effects can also be reported to the marketing authorization holder.

5. How to store Indix Combi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and label after "Expiry date:" or "EXP:". The expiry date refers to the last day of the month stated.
After opening, use within 100 days.
Keep the container tightly closed to protect from moisture.
This medicine does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Indix Combi contains

• The active substances of Indix Combi are perindopril tosilate and indapamide. Each film-coated tablet contains 2.5 mg of perindopril tosilate (equivalent to 1.7 mg of perindopril) and 0.625 mg of indapamide.
• Other ingredients of the tablet: lactose monohydrate, cornstarch, sodium bicarbonate, pregelatinized cornstarch, povidone K30, magnesium stearate, polyvinyl alcohol, partially hydrolyzed, titanium dioxide (E171), macrogol 3350, talc.

What Indix Combi looks like and contents of the pack

Indix Combi, 2.5 mg + 0.625 mg, film-coated tablets are white, biconvex, film-coated tablets in the shape of a capsule with a score line on one side and smooth on the other.
Tablets are available in packs of 30, 60, 90, 90 (3x30), or 100 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Teva Pharmaceuticals Polska Sp. z o.o.
ul. Emilii Plater 53; 00-113 Warsaw
tel.: (22) 345 93 00

Manufacturer:

TEVA Pharmaceutical Works Private Limited Company
Pallagi út 13, 4042 Debrecen
Hungary
Pharmachemie B.V.
Swensweg 5, 2031 GA Haarlem
Netherlands
Teva Operations Poland Sp. z o.o.
ul. Mogilska 80, 31-546 Kraków

Date of last revision of the leaflet: September 2024