Package leaflet: Information for the patient

Tertensif Bi-Kombi, 10 mg + 2.5 mg, coated tablets
Perindoprilum argininum + Indapamidum
Please read this leaflet carefully before using the medicine, as it contains important information for you.

Keep this leaflet so that you can read it again if necessary.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, 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 of the leaflet:

What Tertensif Bi-Kombi is and what it is used for
Important information before taking Tertensif Bi-Kombi
How to take Tertensif Bi-Kombi
Possible side effects
How to store Tertensif Bi-Kombi
Contents of the pack and other information

1. What Tertensif Bi-Kombi is and what it is used for

Tertensif Bi-Kombi 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). Tertensif Bi-Kombi is prescribed to patients who are already receiving 10 mg of perindopril and 2.5 mg of indapamide as separate tablets; such patients may instead receive one tablet of Tertensif Bi-Kombi containing both components.
Perindopril belongs to a group of medicines called angiotensin-converting enzyme inhibitors (ACE inhibitors). These medicines work by dilating blood vessels, which helps the heart pump blood more easily.
Indapamide is a diuretic medicine. Diuretics increase the amount of urine produced by the kidneys. Indapamide differs from other diuretics in that it only slightly increases urine output.
Both active substances lower blood pressure and work together to help normalize the patient's blood pressure.

2. Important information before using Tertensif Bi-Kombi

When not to use Tertensif Bi-Kombi:

if the patient is 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 the patient has previously experienced symptoms during treatment with an ACE inhibitor such as wheezing, facial or tongue swelling, severe itching, or intense skin rash, 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 dysfunction and is being treated with aliskiren, a blood pressure-lowering medicine;
if the patient has severe liver disease or a condition called hepatic encephalopathy (a brain disorder caused by liver damage);
if the patient has kidney disease causing reduced blood flow to the kidneys (renal artery stenosis);
if the patient is undergoing dialysis or another form of blood filtration. Depending on the equipment used, Tertensif Bi-Kombi may not be suitable for the patient;
if the patient has low potassium levels in the blood;
if the patient is suspected of having untreated, decompensated heart failure (severe fluid retention, breathing difficulties);
if the patient is more than 3 months pregnant (it is also advisable to avoid using Tertensif Bi-Kombi in early pregnancy – see "Pregnancy");
if the patient has taken or is currently taking a combination medicine containing sacubitril and valsartan, used to treat heart failure, because this increases the risk of angioedema (rapid swelling of tissues under the skin, particularly in the throat area) (see "Warnings and precautions" and "Tertensif Bi-Kombi with other medicines").

Warnings and precautions
Before starting Tertensif Bi-Kombi, discuss with your doctor or
pharmacist:

if the patient has aortic valve stenosis (narrowing of the main blood vessel carrying blood from the heart), hypertrophic cardiomyopathy (a heart muscle disorder), or renal artery stenosis (narrowing of the blood vessel supplying blood to the kidney);
if the patient has heart failure or any other heart disease;
if the patient has kidney disease or is undergoing dialysis;
if the patient experiences vision disturbances or eye pain. These may be symptoms of fluid accumulation in the choroid layer of the eye (choroidal effusion) or increased intraocular pressure, which may occur within hours or weeks after taking Tertensif Bi-Kombi. Untreated, these symptoms may lead to permanent vision loss. The risk is higher if the patient previously had an allergy to penicillin or sulfonamides;
if the patient has muscle disorders, including pain, tenderness, weakness, or cramps;
if the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
if the patient has liver disease;
if the patient has collagenosis (a skin disorder) such as systemic lupus erythematosus or scleroderma;
if the patient has atherosclerosis (hardening of the arteries);
if the patient has hyperparathyroidism (overactivity of the parathyroid glands);
if the patient has gout;
if the patient has diabetes;
if the patient is on a low-salt diet or uses potassium-containing salt substitutes;
if the patient is taking lithium or potassium-sparing medicines (spironolactone, triamterene), or potassium supplements – these should be avoided during treatment with Tertensif Bi-Kombi (see "Tertensif Bi-Kombi with other medicines");
if the patient is elderly;
if the patient has previously experienced photosensitivity reactions;
if the patient develops a severe allergic reaction with swelling of the face, lips, mouth, tongue, or throat, causing difficulty in swallowing or breathing (angioedema) – swelling may occur at any time during treatment. If such symptoms occur, treatment must be stopped immediately and medical advice sought without delay;
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 – for example, valsartan, telmisartan, irbesartan, particularly if the patient has kidney problems 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 Tertensif Bi-Kombi".
if the patient is of Black race – in such cases, there may be 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 with high-flux membranes;
if the patient is taking any of the following medicines, which increase the risk of angioedema:
racecadotril (used to treat diarrhoea);
sirolimus, everolimus, temsirolimus, and other medicines belonging to the group known as mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment);
sacubitril (available in a combination medicine containing sacubitril and valsartan), used to treat chronic heart failure;
linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the group known as gliptins (used to treat diabetes).

Angioedema
Angioedema (a severe allergic reaction with swelling of the face, lips,
tongue, or throat, and difficulty in swallowing or breathing) has been reported in patients treated with ACE inhibitors, including Tertensif Bi-Kombi. This reaction may occur at any time during treatment. If such symptoms occur, the patient must stop taking Tertensif Bi-Kombi immediately and contact a doctor without delay. See also section 4.
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Tertensif Bi-Kombi is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the unborn child (see "Pregnancy and breastfeeding").
When taking Tertensif Bi-Kombi, the patient should also inform the doctor or medical staff:

if the patient is to undergo anaesthesia and/or surgery;
if the patient has recently experienced diarrhoea or vomiting, or has been dehydrated;
if dialysis or LDL apheresis (removal of cholesterol from the blood using a special device) is planned;
if desensitisation 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 vision disturbances or pain in one or both eyes occur during treatment with Tertensif Bi-Kombi. These may be symptoms of glaucoma or increased pressure in one or both eyes. The patient should stop taking Tertensif Bi-Kombi and consult a doctor.

Athletes should be aware that Tertensif Bi-Kombi contains an active substance (indapamide) that may lead to a positive result in anti-doping tests.
Children and adolescents
Tertensif Bi-Kombi must not be used in children and adolescents.
Tertensif Bi-Kombi with other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take.
The use of Tertensif Bi-Kombi should be avoided with:

lithium (used to treat mania or depression);
aliskiren (a medicine used to treat high blood pressure) in patients who do not have diabetes or kidney dysfunction;
potassium-sparing diuretics (e.g. triamterene, amiloride), potassium salts, or other medicines that may increase potassium levels in the body (such as heparin, a medicine used to thin the blood to prevent clotting, trimethoprim, and co-trimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole, used to treat bacterial infections);
estramustine (used to treat cancer);
other medicines used to treat high blood pressure: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists.

The use of other medicines may affect treatment with Tertensif Bi-Kombi. The doctor may recommend a dose adjustment and/or additional precautions. Inform your doctor if the patient is taking any of the following medicines, as special precautions may be necessary:

other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (AIIRAs) or aliskiren (see also sections "When not to use Tertensif Bi-Kombi" 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 doses of 12.5 mg to 50 mg per day;
medicines most commonly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the group known as 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 Tertensif Bi-Kombi" and "Warnings and precautions".
anaesthetics;
iodine-containing contrast agents;
antibiotics used to treat bacterial infections (e.g. moxifloxacin, sparfloxacin, intravenous erythromycin);
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 cognitive disorders in the elderly, 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, difemanil (used to treat gastrointestinal disorders);
digoxin or other cardiac 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 (a 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 psychiatric 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, noradrenaline, or adrenaline).

Tertensif Bi-Kombi with food and drink
It is recommended to take Tertensif Bi-Kombi before a meal.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Pregnancy
The doctor will usually advise stopping Tertensif Bi-Kombi before becoming pregnant or as soon as pregnancy is confirmed, and will recommend an alternative medicine. Tertensif Bi-Kombi is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the unborn child.
Breastfeeding
Tertensif Bi-Kombi 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 a doctor immediately.
Driving and operating machinery
Tertensif Bi-Kombi usually does not affect alertness; however, some patients may experience side effects such as dizziness or weakness due to lowered blood pressure. In such cases, the ability to drive or operate machinery may be impaired.
Tertensif Bi-Kombi contains lactose (a type of sugar)
If the patient has been diagnosed with an intolerance to certain sugars, they should consult a doctor before taking this medicine.
Tertensif Bi-Kombi contains sodium
Tertensif Bi-Kombi contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to use Tertensif Bi-Kombi

This medicine should always be taken exactly as directed by your doctor or pharmacist.
If in doubt, consult your doctor or pharmacist.
The recommended dose is one tablet once daily. The tablet should preferably be taken in the morning, before a meal. Swallow the tablet with a glass of water.

Taking more Tertensif Bi-Kombi than recommended
If you take too many tablets, contact your doctor immediately or go to the nearest hospital emergency department. The most common symptom of overdose is low blood pressure. If significantly low blood pressure occurs (accompanied by nausea, vomiting, cramps, dizziness, drowsiness, disorientation, or changes in urine output), lying down with legs raised may help.

If you forget to take Tertensif Bi-Kombi
It is important to take the medicine every day, as regular use is most effective.
However, if you miss a dose of Tertensif Bi-Kombi, take the next dose at your usual time.
Do not take a double dose to make up for a missed dose.

Stopping Tertensif Bi-Kombi
Treatment of high blood pressure is usually long-term; therefore, discuss with your doctor before stopping this medicine.
If you have any further doubts about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following adverse reactions occur in the patient, which may be
serious, treatment with this medicine must be stopped and medical advice must be sought immediately:

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, oral cavity, tongue or throat, difficulty breathing (angioedema, see section "Warnings and precautions" in section 2); uncommon – may occur in less than 1 in 100 patients;
severe skin reactions, including erythema multiforme (skin rash often starting with red, itchy spots on the face, arms or legs) or severe skin rash, urticaria, redness of the entire skin surface, intense 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, caused by physical exertion), myocardial infarction; very rare – may occur in less than 1 in 10,000 patients);
weakness of 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 and general malaise (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 disease 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, grouped by decreasing frequency, may include:

Common (may occur in less than 1 in 10 patients): low blood potassium levels, skin reactions in patients with a tendency to allergic and asthmatic reactions, headache, central dizziness, labyrinthine dizziness, prickling and tingling sensations, visual disturbances, tinnitus (perception of ringing or other sounds), cough, shortness of breath, gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, indigestion or digestive disorders, 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, depression, sleep disturbances, urticaria, purpura (small red spots on the skin), blister clusters, kidney disorders, impotence (inability to achieve or maintain erection), excessive sweating, increased eosinophil count (a type of white blood cell), changes in laboratory test results: high blood potassium levels, which resolve after discontinuation of treatment, low blood sodium levels, which may lead to dehydration and low blood pressure, drowsiness, fainting, palpitations (awareness of heart beating), tachycardia (rapid heart rate), hypoglycaemia (very low blood sugar levels) in diabetic patients, vasculitis (inflammation of blood vessels), 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): worsening of psoriasis, changes in laboratory test results: low blood chloride levels, low blood magnesium levels, increased liver enzyme activity, elevated serum bilirubin levels; fatigue, sudden flushing of the face and neck, reduced or absent urine output, acute kidney failure. 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).
Very rare (may occur in less than 1 in 10,000 patients): confusion, eosinophilic pneumonia (a rare type of lung inflammation), rhinitis (nasal congestion or runny nose), severe kidney diseases, blood parameter changes such as decreased white and red blood cell counts, decreased haemoglobin concentration, decreased platelet count, elevated blood calcium levels; liver function disorders.
Frequency not known (cannot be estimated from available data): abnormal heart function detected on ECG, changes in laboratory test results: elevated blood uric acid levels and elevated blood glucose levels, myopia, blurred vision, visual disturbances, worsening of vision or eye pain due to high pressure (possible symptoms of fluid accumulation in the choroidal layer of the eye (choroidal effusion) or acute angle-closure glaucoma), cyanosis, numbness and pain in fingers or toes (Raynaud's phenomenon). If the patient has systemic lupus erythematosus (a type of collagenosis), disease symptoms may worsen.
Blood, kidney, liver or pancreas disorders may occur, as well as changes in laboratory test results (blood tests). The doctor may recommend blood tests to monitor the patient's health.
If any of these symptoms occur, medical advice should be sought as soon as possible.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, they should be reported to a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Tertensif Bi-Kombi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following the abbreviation
"EXP" (the abbreviation used to describe the expiry date). The expiry date refers to the last day
of the stated month. The word "Lot" on the packaging indicates the batch number of the medicine.
Store in the original packaging, tightly closed, to protect from moisture.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures will help protect
the environment.

6. Contents of the pack and other information

What Tertensif Bi-Kombi contains

The active substances are: perindopril with arginine and indapamide. One coated tablet contains 10 mg of perindopril arginine (equivalent to 6.79 mg of perindopril) and 2.5 mg of indapamide.
Other components of the tablet are: core – lactose monohydrate, magnesium stearate, maltodextrin, colloidal anhydrous silica, sodium carboxymethyl starch (type A); coating – glycerol, hypromellose, polyethylene glycol 6000, magnesium stearate, titanium dioxide (E 171).

What Tertensif Bi-Kombi looks like and contents of the pack
Tertensif Bi-Kombi is a white, round coated tablet with a diameter of 8 mm and curvature radius of 11 mm. One coated tablet contains 10 mg of perindopril arginine and 2.5 mg of indapamide.
Pack sizes: 30, 90, 100 tablets.

Marketing Authorization Holder
ANPHARM Przedsiębiorstwo Farmaceutyczne S.A.
Annopol Street 6B
03-236 Warsaw
Poland

Manufacturer
Les Laboratoires Servier Industrie
905 route de Saran
45520 Gidy
France
Servier (Ireland) Industries Ltd
Gorey Road
Arklow – Co. Wicklow
Ireland
ANPHARM Przedsiębiorstwo Farmaceutyczne S.A.
Annopol Street 6B
03-236 Warsaw
Poland

This medicinal product is authorized in the European Economic Area countries under the following names:
Belgium COVERSYL PLUS 10 mg /2.5 mg
Bulgaria TERTENSIF COMBI 10 mg /2.5 mg
France Perindopril arginine/Indapamide Servier 10mg/2,5mg comprimé pelliculé
Hungary Coverex-AS Komb Forte
Italy TERAXANS (10/2.5)
Latvia Perindopril arginine /Indapamide Servier 10 mg/2.5 mg
Luxembourg COVERSYL PLUS 10 mg /2.5 mg
Poland TERTENSIF BI-KOMBI
Romania NORIPLEX 10 mg /2.5 mg
Slovak Republic PRESTARIUM FORTE COMBI A
Slovenia TertensifKomb 10 mg/2.5 mg filmsko obložene tablete

For detailed information, please contact the representative of the Marketing Authorization Holder:
Servier Polska Sp. z o.o.
Telephone number: (22) 594-90-00