Indix Combi

Package Leaflet: Information for the Patient

Indix Combi, 5 mg + 1.25 mg, Film-Coated Tablets

Perindopril Tosylate + Indapamide

Read the Package Leaflet Carefully Before Taking the Medication, as it Contains Important Information for the Patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medication has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of Contents of the 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 medication containing two active substances: perindopril and indapamide. It is an antihypertensive medication used to treat high blood pressure in adults.

What is Indix Combi used for

Perindopril belongs to a group of medications called angiotensin-converting enzyme inhibitors (ACE inhibitors). These medications work by widening 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 urine production. 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:

Warnings and precautions

If any of the following situations apply to the patient, they should inform their doctor before taking Indix Combi:

• racecadotril, a medication used to treat diarrhea;
• medications used to prevent transplant rejection and treat cancer (e.g., temsirolimus, sirolimus, everolimus) and other medications belonging to the group of mTOR inhibitors;
• linagliptin, saxagliptin, sitagliptin, wildagliptin, and other medications belonging to the group of gliptins (used to treat diabetes);
• sacubitril (available in a combination medication containing sacubitril and valsartan), used to treat chronic heart failure.
• angiotensin receptor blockers (ARBs) (also known as sartans - e.g., valsartan, telmisartan, irbesartan), especially if the patient has kidney problems related to diabetes.
• aliskiren.

Angioedema
Patients treated with ACE inhibitors, including Indix Combi, have reported angioedema (a severe allergic reaction with facial, lip, tongue, or throat swelling, and difficulty swallowing or breathing). This reaction can occur at any time during treatment. If such symptoms occur, the patient should discontinue Indix Combi and seek medical attention immediately. See also section 4.
The patient must inform their doctor if they think they are (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 medication can cause serious harm to the fetus if taken after the third month of pregnancy.
When taking Indix Combi, the patient should inform their doctor or medical staff:

Athletes should be informed that Indix Combi contains an active substance (indapamide) that may result in a positive doping test.

Children and Adolescents

Indix Combi should not be used in children and adolescents.

Other medications and Indix Combi

The patient should inform their doctor or pharmacist about all medications they are currently taking or have recently taken, as well as any medications they plan to take.
Indix Combi should be avoided:

• with lithium (used to treat mania or depression);
• with aliskiren (a medication 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 medications that increase potassium levels in the blood (e.g., trimethoprim and co-trimoxazole, used to treat bacterial infections; cyclosporine, an immunosuppressive medication used to prevent transplant rejection, and heparin, a medication used to thin the blood to prevent clots);
• with estramustine (used to treat cancer);
• with other medications used to treat high blood pressure: ACE inhibitors and angiotensin receptor blockers.

The use of other medications may affect treatment with Indix Combi. The treating doctor may need to change the dose and/or take other precautions when using such medications as:

• other medications used to treat high blood pressure;
• the treating doctor may need to change the dose and/or take other precautions: If the patient is 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 (medications that increase urine production);
• potassium-sparing medications used to treat heart failure: eplerenone and spironolactone in doses of 12.5 mg to 50 mg per day;
• medications commonly used to treat diarrhea (racecadotril) or to prevent transplant rejection (sirolimus, everolimus, temsirolimus, and other medications belonging to the class of mTOR inhibitors). See "Warnings and precautions".
• a combination medication containing sacubitril and valsartan (used to treat chronic heart failure). See "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 (antihistamine medications used to treat hay fever or allergies);
• corticosteroids used to treat various conditions, including severe asthma and rheumatoid arthritis;
• immunosuppressive medications used to treat autoimmune diseases or after transplant surgery to prevent rejection (e.g., cyclosporine, tacrolimus);
• medications used to treat cancer;
• erythromycin administered intravenously (an antibiotic);
• halofantrine (used to treat certain types of malaria);
• pentamidine (used to treat pneumonia);
• gold salts administered intravenously (used to treat rheumatoid arthritis);
• vincamine (used to treat cognitive impairment symptoms in the elderly);
• bepridil (used to treat angina pectoris);
• medications 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 occurring in conditions such as multiple sclerosis);
• medications used to treat diabetes, such as insulin, metformin, or gliptins;
• calcium, including calcium supplements;
• laxatives with a stimulating effect (e.g., senna);
• nonsteroidal anti-inflammatory medications (e.g., ibuprofen) or high doses of salicylates (e.g., acetylsalicylic acid, a substance found in many medications, used as a pain reliever and antipyretic, as well as to prevent blood clots);
• amphotericin B administered intravenously (used to treat severe fungal infections);
• medications 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;
• medications used to treat low blood pressure, shock, or asthma (e.g., ephedrine, noradrenaline, or adrenaline).

Indix Combi with food and drink

It is recommended to take Indix Combi before a meal.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant, breastfeeding, or thinks they may be pregnant, or are planning to have a baby, they should consult their doctor or pharmacist before taking this medication.
Pregnancy
The patient must inform their doctor if they think they are (or may be) pregnant.
Usually, the doctor will advise stopping Indix Combi before becoming pregnant or as soon as the patient finds out they are pregnant, and will recommend another medication 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 medication can cause serious harm to the fetus if taken after the third month of pregnancy.
Breastfeeding
Indix Combi is not recommended during breastfeeding.
The patient should immediately inform their doctor if they are breastfeeding or start breastfeeding.
The patient should immediately consult their doctor.
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 or operate machinery, however, some patients may experience dizziness or fatigue related to low blood pressure. In such cases, the ability to drive or operate machinery may be impaired.

Indix Combi contains lactose

If the patient has been diagnosed with an intolerance to some sugars, they should consult their doctor before taking this medication.

Indix Combi contains sodium

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

3. How to take Indix Combi

This medication should always be taken as directed by the doctor. In case of doubts, the patient should consult their doctor or pharmacist. The recommended dose is usually one tablet per day. The doctor may decide to adjust the dosage in case of kidney problems. The tablet should be taken preferably in the morning, before a meal. The tablet should be swallowed with a glass of water. The tablet can be divided into equal doses.

Overdose of Indix Combi

In case of taking too many tablets, the patient should immediately consult their doctor or go to the nearest emergency department. The most common symptom of overdose is low blood pressure. If the patient experiences significantly low blood pressure (with accompanying nausea, vomiting, cramps, dizziness, drowsiness, disorientation, and changes in urine output), they can be helped by lying down with their legs elevated.

Missing a dose of Indix Combi

It is important to take the medication regularly for it to work best. If a dose of Indix Combi is missed, the next dose should be taken at the usual time. A double dose should not be taken to make up for a missed dose.

Stopping treatment with Indix Combi

Treatment of high blood pressure usually lasts for life, so before stopping treatment with this medication, the patient should consult their doctor. If the patient has any further doubts about taking this medication, they should consult their doctor or pharmacist.

4. Possible side effects

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

If the patient experiences any of the following serious side effects, they should stop taking this medication and immediately consult their doctor:

• severe dizziness or fainting due to low blood pressure (common: may occur in less than 1 in 10 patients),
• bronchospasm (feeling of chest tightness, wheezing, and shortness of breath) (uncommon: may occur in less than 1 in 100 patients),
• facial, lip, mouth, tongue, or throat swelling, difficulty breathing (angioedema, see "Warnings and precautions" in section 2) (uncommon: may occur in less than 1 in 100 patients),
• severe skin reactions, including erythema multiforme (a skin rash often starting with red, itchy patches on the face, arms, or legs) or severe skin rash, hives, redness of the skin, intense itching, blistering, peeling, and skin swelling, mucous membrane inflammation (Stevens-Johnson syndrome) or other allergic reactions (very rare: may occur in less than 1 in 10,000 patients),
• cardiovascular disorders (heart rhythm disorders, angina pectoris, myocardial infarction) (very rare: may occur in less than 1 in 10,000 patients),
• weakness or paralysis of the arms or legs, or speech disorders, which may be symptoms of a stroke (very rare: may occur in less than 1 in 10,000 patients),
• pancreatitis, which can cause severe abdominal pain and very poor general condition (very rare: may occur in less than 1 in 10,000 patients),
• jaundice (yellowing of the skin or eyes), which may be a symptom of liver inflammation (very rare: may occur in less than 1 in 10,000 patients),
• life-threatening heart rhythm disorders (frequency not known),
• hepatic encephalopathy (a brain disease caused by liver disease) (frequency not known),
• muscle weakness, cramps, tenderness, or pain, especially if the patient feels unwell or has a high temperature, which may be caused by abnormal muscle breakdown (frequency not known).

Side effects, grouped by frequency of occurrence:

• common: (may occur in up to 1 in 10 patients)

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, feeling of fatigue;

• uncommon: (may occur in up to 1 in 100 patients) mood changes, depression, sleep disturbances, hives, purpura (red spots on the skin), blistering, kidney function disorders, impotence (erectile dysfunction), increased sweating, elevated eosinophil count (a type of white blood cell), changes in laboratory test results: high potassium levels in the blood that are transient and resolve 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 (rapid heart rate), hypoglycemia (very low blood sugar) in patients with diabetes, vasculitis (inflammation of blood vessels), dryness of the mucous membranes, hypersensitivity to sunlight, joint pain, muscle pain, chest pain, malaise, peripheral edema, fever, elevated urea levels in the blood, elevated creatinine levels in the blood, falls.
• rare: (may occur in up to 1 in 1,000 patients) dark urine, nausea or vomiting, muscle cramps, disorientation, and seizures. These may be symptoms of a condition called SIADH (inappropriate antidiuretic hormone secretion). Sudden reddening 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, elevated liver enzyme activity, high bilirubin levels in serum; fatigue.
• very rare: (may occur in up to 1 in 10,000 patients) disorientation, eosinophilic pneumonia (a rare type of pneumonia), nasal mucosa inflammation (stuffy or runny nose), allergic reaction in the small intestine (angioedema of the 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 available data) abnormal heart function detected on an electrocardiogram, changes in laboratory test results: high uric acid levels and high blood sugar levels, worsening of vision or eye pain due to high pressure (possible symptoms of choroidal effusion or acute glaucoma), cyanosis, numbness, and pain in the fingers of the hands or feet (Raynaud's phenomenon), muscle breakdown leading to kidney damage (rhabdomyolysis). If the patient has 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). The doctor may recommend blood tests to monitor the patient's health.

Reporting side effects

If the patient experiences any side effects, including those not listed in the leaflet, they should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides, Office for Registration of Medicinal Products, Medical Devices, and Biocides, 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, more information can be gathered on the safety of the medication. Side effects can also be reported to the marketing authorization holder.

5. How to store Indix Combi

The medication should be stored out of sight and reach of children. Do not use this medication after the expiry date stated on the packaging and label after the "Expiry Date" or "EXP:" marking. The expiry date refers to the last day of the month stated. After opening, the medication should be used within 100 days. The container should be kept tightly closed to protect from moisture. This medication does not require any special storage conditions. Medications should not be disposed of via wastewater. The patient should ask their pharmacist how to dispose of medications they no longer use. This 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 tosylate and indapamide. Each film-coated tablet contains 5 mg of perindopril tosylate (equivalent to 3.4 mg of perindopril) and 1.25 mg of indapamide.
• Other ingredients of the tablet: lactose monohydrate, cornstarch, sodium bicarbonate, maize starch, 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, 5 mg + 1.25 mg, film-coated tablets are white, biconvex, film-coated tablets in the shape of a capsule with the letter "P", "I", and a dividing line on one side and smooth on the other. The 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