Package leaflet: Information for the patient

Indix Combi, 10 mg + 2.5 mg, film-coated tablets
Perindopril tosylate + Indapamide
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

What Indix Combi is and what it is used for
Important information before taking Indix Combi
How to take Indix Combi
Possible side effects
How to store Indix Combi
Contents of the pack and other information

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

Indix Combi is a combination medicine containing two active substances: perindopril and indapamide.
It is an antihypertensive medicine used in the treatment of high blood pressure (hypertension).
Indix Combi is intended for patients who are already taking perindopril 10 mg and indapamide 2.5 mg as
separate tablets and who may now be switched to a single tablet of Indix Combi containing both components.
Perindopril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors.
These medicines relax blood vessels, making it easier for the heart to pump blood through them. Indapamide
is a diuretic medicine. Diuretics increase the amount of urine excreted by the kidneys. Indapamide differs
from other diuretics in that it increases urine output only to a small extent.
Both active substances lower blood pressure and work together to help normalize it.

2. Important information before using Indix Combi

When not to use Indix Combi

if the patient is allergic to perindopril, indapamide, or to any of the other ingredients of this medicine (listed in section 6);
if the patient is allergic to other ACE inhibitors or to other sulfonamides;
if during previous treatment with an ACE inhibitor the patient experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin rashes, or if such symptoms occurred in the patient or a relative under any other circumstances (a condition known as angioedema);
if the patient has diabetes or kidney function disorders and is being treated with a blood pressure-lowering medicine containing aliskiren;
if the patient has severe liver disease or a condition called hepatic encephalopathy (a liver disease damaging the brain);
if the patient has kidney disease causing reduced blood supply to the kidneys (renal artery stenosis);
if the patient is undergoing dialysis or another form of blood filtration. Depending on the device used, Indix Combi may not be suitable for the patient;
if the patient has low potassium levels in the blood;
if the patient has untreated, uncontrolled heart failure (significant fluid retention, breathing difficulties);
after the 3rd month of pregnancy (it is also advisable to avoid using Indix Combi in early pregnancy – see section "Pregnancy and breastfeeding");
if the patient has taken or is currently taking sacubitril with valsartan, a medicine used to treat certain types of chronic heart failure in adults, because the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) increases.

Warnings and precautions
Before starting treatment with Indix Combi, discuss the following with your doctor or pharmacist:

if there is aortic valve stenosis (narrowing of the main blood vessel carrying blood from the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the blood vessel supplying blood to the kidney);
if there is heart failure or any other heart disease;
if there is kidney disease or the patient is undergoing dialysis;
if the patient has muscle disorders, including pain, tenderness, weakness, or muscle cramps;
if the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
if there is liver disease;
if there is a collagen disease (skin disease), such as systemic lupus erythematosus or scleroderma;
if there is atherosclerosis (hardening of blood vessels);
if there is hyperparathyroidism (a disorder of the parathyroid glands);
if there is gout;
if there is diabetes;
if the patient is on a low-salt diet or uses salt substitutes containing potassium;
if the patient is taking lithium, potassium-sparing diuretics (spironolactone, triamterene), or potassium supplements – these medicines should be avoided while taking Indix Combi (see section "Indix Combi and other medicines");
if the patient is elderly;
if the patient has previously experienced photosensitivity reactions;
if there are severe allergic reactions with swelling of the face, lips, mouth, tongue, or throat, which may cause difficulty in swallowing or breathing (angioedema). Such symptoms may occur at any time during treatment, and if they appear, the patient should stop taking the medicine and contact a doctor immediately.
if the patient is taking any of the following medicines used to treat high blood pressure:
- an angiotensin II receptor antagonist (AIIRA) (also known as a sartan – e.g. valsartan, telmisartan, irbesartan), especially if the patient has kidney disorders related to diabetes,
- aliskiren. The doctor may recommend regular monitoring of kidney function, blood pressure, and blood electrolyte levels (e.g. potassium). See also the section "When not to use Indix Combi".
if the patient is taking any of the following medicines, the risk of angioedema may increase:
- racecadotril, a medicine used to treat diarrhoea,
- medicines used to prevent organ transplant rejection and to treat cancer (e.g. temsirolimus, sirolimus, everolimus),
- linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to a group called gliptins (used to treat diabetes),
sacubitril (available in a combination medicine containing sacubitril and valsartan), used to treat chronic heart failure.
- if the patient is of Black race, because there is a higher risk of angioedema and the medicine may be less effective in lowering blood pressure compared to patients of other races;
- if the patient is undergoing dialysis using highly permeable dialysis membranes;
- if the patient experiences blurred vision or eye pain. These may be symptoms of fluid accumulation in the avascular membrane surrounding the eye (excessive fluid accumulation between the choroid and sclera) or increased intraocular pressure – they may occur from a few hours to weeks after taking Indix Combi. If untreated, they may lead to permanent vision loss. The risk of such disorders is higher in patients allergic to penicillin or sulfonamides.

Angioedema
In patients treated with ACE inhibitors, including Indix Combi, cases of angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat, causing difficulty in swallowing or breathing) have been reported. It may occur at any time during treatment. If such symptoms occur, Indix Combi should be discontinued and the patient should seek immediate medical attention. See also section 4.
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning pregnancy. Use of Indix Combi is not recommended during early pregnancy and must not be taken after the 3rd month of pregnancy, as it may seriously harm the unborn child if used during this period (see section "Pregnancy and breastfeeding").

When using Indix Combi, you should also inform your doctor or healthcare provider:

if the patient is to undergo anaesthesia and/or surgery;
if the patient has recently experienced diarrhoea or vomiting, or is dehydrated;
if dialysis or LDL apheresis (removal of cholesterol from the blood using a special device) is to be performed;
if desensitization treatment is planned to reduce allergic reactions to bee or wasp stings;
if an imaging test requiring iodine-containing contrast agents (substances allowing visualization of organs such as the kidney or stomach in X-ray examinations) is to be performed;
if visual disturbances or eye pain (in one or both eyes) occur while taking Indix Combi. These may be symptoms of glaucoma or increased intraocular pressure. In such cases, treatment with Indix Combi should be stopped and medical advice sought.

Athletes should be informed that Indix Combi contains an active substance (indapamide) that may lead to a positive result in anti-doping tests.

Children and adolescents
Indix Combi should not be used in children and adolescents.

Indix Combi and other medicines
Tell your doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines you plan to use.

Avoid using Indix Combi with:

lithium (used to treat mania or depression);
aliskiren (used to treat high blood pressure) in patients other than those with diabetes or kidney function disorders;
potassium supplements (including salt substitutes), potassium-sparing diuretics (triamterene, amiloride), and other medicines that increase blood potassium levels (e.g. trimethoprim and co-trimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole, used for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots);
estramustine (used to treat cancer);
other medicines used to treat high blood pressure: ACE inhibitors and angiotensin II receptor antagonists.

Other medicines may affect treatment with Indix Combi. Your doctor may recommend dose adjustments and/or additional precautions. Inform your doctor if you are taking any of the following medicines, as special caution may be required:

other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (AIIRAs) or aliskiren (see also sections "When not to use Indix Combi" and "Warnings and precautions"), or diuretics (medicines that increase urine output by the kidneys);
potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at daily doses from 12.5 mg to 50 mg;
anaesthetics;
iodine-containing contrast agents;
antibiotics used to treat bacterial infections (e.g. moxifloxacin, sparfloxacin, erythromycin administered by injection);
methadone (used to treat addiction);
procainamide (used to treat heart rhythm disorders);
allopurinol (used to treat gout);
antihistamines used to treat allergic reactions such as hay fever (e.g. mizolastine, terfenadine, astemizole);
corticosteroids used to treat various diseases, including severe asthma and rheumatoid arthritis;
immunosuppressive medicines used to treat autoimmune diseases or to prevent organ transplant rejection (e.g. cyclosporine, tacrolimus);
halofantrine (used to treat certain types of malaria);
pentamidine (used to treat pneumonia);
injectable gold salts (used to treat rheumatoid arthritis);
vinpocetine (used to treat symptomatic cognitive disorders in elderly patients, 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, digitalis preparations, bretylium);
cisapride, difenamid (medicines used to treat gastrointestinal disorders);
digoxin or other digitalis glycosides (used in heart diseases);
baclofen (used to treat muscle stiffness occurring in diseases such as multiple sclerosis);
medicines used to treat diabetes, such as insulin, metformin, or gliptins;
calcium, including calcium supplements;
stimulant laxatives (e.g. senna);
non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or high doses of salicylates (e.g. acetylsalicylic acid (the substance found in many medicines used for pain relief, fever reduction, and prevention of 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);
vasodilators, including nitrates;
medicines used to treat low blood pressure, shock, or asthma (e.g. ephedrine, noradrenaline, or adrenaline);
medicines most commonly used to treat diarrhoea (racecadotril) or to prevent rejection of transplanted organs (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 use Indix Combi" and "Warnings and precautions".

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.

Pregnancy
Usually, the doctor will recommend discontinuing Indix Combi before becoming pregnant or as soon as pregnancy is confirmed, and will prescribe an alternative medicine. Use of Indix Combi is not recommended during early pregnancy and must not be taken after the 3rd month of pregnancy, as it may seriously harm the unborn child if used after the third month of pregnancy.

Breastfeeding
Use of Indix Combi is not recommended for breastfeeding mothers. The doctor may choose an alternative treatment if the patient intends to breastfeed, especially if the baby is a newborn or was born prematurely.

Contact your doctor immediately.

Driving and operating machinery
Indix Combi usually does not affect attention, but some patients may experience dizziness or fatigue due to low blood pressure. If such symptoms occur, the ability to drive or operate machinery may be impaired.

Indix Combi contains lactose
If the patient has been diagnosed with an intolerance to certain sugars, they should consult a doctor before taking this medicine.

Indix Combi contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Indix Combi

This medicine should always be taken as directed by a physician. In case of doubt, consult a
doctor or pharmacist.
The recommended dose is one tablet per day. The tablet should preferably be taken in the morning, before a meal.
The tablet should be swallowed with a glass of water.
Taking more Indix Combi than recommended
If too many tablets are taken, seek immediate medical advice from a doctor or go to the nearest hospital emergency department.
The most commonly occurring symptom of overdose is low blood pressure. If significantly low blood pressure occurs (with symptoms such as nausea, vomiting, cramps, dizziness, drowsiness, confusion, changes in urine output), lying down with legs elevated may help.
Missing a dose of Indix Combi
It is important to take the medicine every day, as regular use is most effective. However, if a dose of Indix Combi is missed, the next dose should be taken at the usual time. Do not take a double dose to make up for a missed dose.
Stopping Indix Combi treatment
Treatment for high blood pressure usually lasts a lifetime; therefore, consult a doctor before stopping this medicine.
If you have any further questions concerning the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
If the patient experiences any of the following symptoms (which may be severe), the medicine must be discontinued immediately and the doctor should be contacted without delay:

Severe dizziness or fainting due to low blood pressure (common – may occur in less than 1 in 10 patients);
Bronchospasm (feeling of tightness in the chest, wheezing and shortness of breath) (uncommon – may occur in less than 1 in 100 patients);
Swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema, see section 2 "Warnings and precautions") (uncommon – may occur in less than 1 in 100 patients);
Severe skin reactions, including erythema multiforme (skin rash, which often starts with red, itchy spots on the face, hands or feet), or intense skin rash, urticaria, redness of the entire skin, severe itching, blistering, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome), or other allergic reactions (very rare – may occur in less than 1 in 10,000 patients);
Cardiovascular disorders (heart rhythm disturbances, angina pectoris (chest pain radiating to the jaw and back following physical exertion), myocardial infarction) (very rare – may occur in less than 1 in 10,000 patients);
Weakness of the arms or legs, or speech disturbances, which may be signs of stroke (very rare – may occur in less than 1 in 10,000 patients);
Pancreatitis, which may cause severe upper abdominal pain radiating to the back, accompanied by a very poor general condition (very rare – may occur in less than 1 in 10,000 patients);
Yellowing of the skin or eyes (jaundice), which may be a sign of liver inflammation (very rare – may occur in less than 1 in 10,000 patients);
Life-threatening heart rhythm disturbances (frequency not known);
Brain disorder caused by liver disease (hepatic encephalopathy) (frequency not known);
Muscle weakness, cramps, tenderness or pain, particularly when the patient also feels unwell or has a high temperature, which may be due to abnormal muscle breakdown (frequency not known).

Adverse reactions, listed in decreasing order of frequency, are:

Common: (may occur in less than 1 in 10 patients) low blood potassium levels, skin reactions in individuals prone to allergic and asthmatic reactions, headache, central dizziness, labyrinthine dizziness, tingling and pricking sensations, visual disturbances, tinnitus (sensation of hearing sounds), cough, shortness of breath, gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, dyspepsia or indigestion, diarrhoea, constipation), allergic reactions (such as skin rashes, itching), muscle cramps, feeling of fatigue.
Uncommon: (may occur in less than 1 in 100 patients) mood swings, sleep disturbances, depression, urticaria, purpura (small red spots on the skin), formation of clusters of blisters, kidney function disorders, impotence (inability to achieve or maintain erection), excessive sweating, increased number of eosinophils (a type of white blood cells), changes in laboratory test results: high blood potassium levels, which are transient and resolve after discontinuation of treatment, low blood sodium levels, which may lead to dehydration and low blood pressure, drowsiness, fainting, palpitations (awareness of heartbeat), tachycardia (rapid heart rate), hypoglycaemia (very low blood sugar levels) in diabetic patients, vasculitis, dryness of the oral mucosa, photosensitivity reactions (increased skin sensitivity to sunlight), joint pain, muscle pain, chest pain, malaise, peripheral oedema, fever, increased blood urea levels, increased blood creatinine levels, falls.
Rare: (may occur in less than 1 in 1,000 patients) dark urine, nausea or vomiting, muscle cramps, confusion and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion). Sudden redness of the face and neck, worsening of psoriasis, changes in laboratory test results: low blood chloride levels, low blood magnesium levels, increased liver enzyme activity, high serum bilirubin levels, reduced urine output or absence of urine output, acute kidney failure, fatigue.
Very rare: (may occur in less than 1 in 10,000 patients) confusion, eosinophilic pneumonia (a rare type of pneumonia), inflammation of the nasal mucosa (nasal congestion or discharge), allergic reaction in the small intestine (intestinal angioedema), severe kidney function disorders, blood parameter changes such as decreased number of white and red blood cells, decreased haemoglobin concentration, decreased platelet count, high blood calcium levels, liver function disorders.
Frequency not known: (cannot be estimated from available data) abnormal heart function detected in ECG examination, changes in laboratory test results: high blood uric acid levels and high blood glucose levels, worsening of vision and eye pain due to high intraocular pressure (possible symptoms of fluid accumulation in the uvea – excessive fluid accumulation between choroid and sclera – or acute angle-closure glaucoma), myopia, blurred vision, visual disturbance, cyanosis, numbness and pain in fingers or toes (Raynaud's phenomenon). If the patient has systemic lupus erythematosus (a type of collagenosis), symptoms may worsen.

Blood, kidney, liver or pancreas disorders and changes in laboratory test results (blood tests) may occur. The doctor may recommend blood tests to monitor the patient's health.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, the patient should inform their doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, PL-02-222 Warsaw
Tel.: + 48 22 49 21 301, Faks: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Indix Combi

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the container and label, following the abbreviation "EXP:". The expiry date refers to the last day of the specified month.
Store the container tightly closed to protect it from moisture.
This medicine does not require any special storage conditions.
Medicines must not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer in use. Such measures help protect the environment.

6. Contents of the pack and other information

What Indix Combi contains

The active substances are: perindopril tert-butylamine and indapamide. Each coated tablet contains 10 mg of perindopril tert-butylamine (equivalent to 6.816 mg of perindopril) and 2.5 mg of indapamide.
Other components of the tablet: monohydrate lactose, maize starch, sodium bicarbonate, pregelatinized maize starch, povidone, magnesium stearate, partially hydrolysed polyvinyl alcohol, titanium dioxide (E171), macrogol/PEG 3350, talc.

What Indix Combi looks like and contents of the pack
White, round, biconvex coated tablets, approximately 10 mm in diameter, smooth on both sides.
Tablets are available in polypropylene containers with polyethylene caps.
Pack sizes: 30, 50, 60 (2x30), 90 (3x30) or 100 (2 x 50) tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Teva Pharmaceuticals Polska Sp. z o.o.
Emilii Plater 53
00-113 Warsaw
tel.: (22) 345 93 00
Manufacturer
TEVA Gyógyszergyár Zrt.
Debrecen, Pallagi út 13,
H-4042
Hungary
Pharmachemie B.V.
Swensweg 5, Haarlem
2031 GA
The Netherlands
Teva Operations Poland Sp. z o.o
Mogilska 80,
31-546 Kraków