Triplixam

Patient Information Leaflet

Warning! Keep this leaflet! The information on the immediate packaging is in a foreign language.
Triplixam (Covercard Plus)
10 mg + 2.5 mg + 5 mg, film-coated tablets
Perindoprilum argininum + Indapamidum + Amlodipinum
Triplixam and Covercard Plus are different brand names for the same medicine.
Please read this leaflet carefully before taking this medicine, as it contains
important information for the patient.

• 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. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

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

1. What Triplixam is and what it is used for

Triplixam is a combination medicine containing three active substances: perindopril,
indapamide, and amlodipine. It is an antihypertensive medicine used in the treatment of high
blood pressure (arterial hypertension).
Patients already taking perindopril and indapamide in one medicine and amlodipine in another may
instead take a single Triplixam tablet containing these three active substances at the same doses.
Each of the active substances helps lower blood pressure, and together they enable control of the
patient's blood pressure:

• perindopril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors. It works by dilating blood vessels, making it easier for the heart to pump blood through them;
• indapamide is a diuretic (belonging to a group of medicines called sulfonamide derivatives with an indole ring). Diuretics increase the amount of urine produced by the kidneys. However, indapamide differs from other diuretics in that it causes only a slight increase in urine production;
• amlodipine is a calcium antagonist (belonging to a group of medicines called dihydropyridines). It causes relaxation of blood vessels, facilitating blood flow through them.

2. Important information before using Triplixam

When not to use Triplixam:

• if the patient is allergic to perindopril or other ACE inhibitors, indapamide or other sulfonamides, amlodipine or other dihydropyridines, or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has previously experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe rashes during treatment with an ACE inhibitor, or if such symptoms occurred in the patient or a family member under any circumstances (a condition called angioedema);
• if the patient has severe liver disease or a condition known as hepatic encephalopathy (a brain dysfunction caused by liver disease);
• if untreated, uncontrolled heart failure is suspected in the patient (marked fluid retention, breathing difficulties);
• if the patient has aortic valve stenosis (narrowing of the aorta) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body);
• if the patient has heart failure following a heart attack;
• if the patient has very low blood pressure (hypotension);
• if the patient has low potassium levels in the blood;
• if the patient has severe 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 equipment used, Triplixam may not be suitable for the patient;
• if the patient has moderate kidney disease;
• after the 3rd month of pregnancy (it is also advisable to avoid using Triplixam in early pregnancy – see the section on pregnancy);
• if the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medicine containing aliskiren;
• if the patient has taken or is currently taking a combination medicine containing sacubitril and valsartan, used in the treatment of heart failure, as this increases the risk of angioedema (rapid swelling of tissues under the skin, particularly in the throat) (see "Warnings and precautions" and "Triplixam with other medicines").

Warnings and precautions
If any of the following conditions apply to the patient, consult a doctor or pharmacist before using Triplixam:

• if the patient has hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the blood vessel supplying blood to the kidney);
• if the patient has heart failure or any other heart diseases;
• if the patient has severe high blood pressure (hypertensive crisis);
• if the patient has liver disease;
• if the patient has collagenosis (connective tissue disease), such as systemic lupus erythematosus or scleroderma;
• if the patient has atherosclerosis (hardening of the arteries);
• if the patient is undergoing parathyroid function tests;
• if the patient has gout;
• if the patient has diabetes;
• if the patient is on a low-salt diet or using potassium-containing salt substitutes (maintaining appropriate potassium levels in the blood is important);
• if the patient is taking lithium or potassium-sparing diuretics (spironolactone, triamterene), as their use with Triplixam should be avoided (see "Triplixam with other medicines");
• if the patient is elderly and the dose needs to be increased;
• if the patient has previously experienced photosensitivity reactions;
• in black patients, angioedema (swelling of the face, lips, mouth, tongue, or throat, which may cause difficulty swallowing or breathing) may occur more frequently, and the medicine may be less effective in lowering blood pressure;
• if the patient is undergoing dialysis using high-flux membranes;
• if the patient has kidney disease or is on dialysis;
• if the patient experiences worsening vision or eye pain. These may be symptoms of fluid accumulation in the choroidal layer of the eye (choroidal effusion) or increased intraocular pressure, which may occur within hours or weeks of taking Triplixam. Untreated symptoms may lead to permanent vision loss. If the patient previously had an allergy to penicillin or sulfonamides, the risk of these disorders is higher;
• 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 there is excessive acid in the blood, which may cause rapid breathing;
• if the patient has cerebral circulatory insufficiency (low blood pressure in the brain);
• if the patient develops swelling of the face, lips, mouth, tongue, or throat, causing difficulty swallowing or breathing (angioedema), which may occur at any time during treatment. In such case, treatment must be stopped immediately and medical advice sought;
• if the patient is taking any of the following medicines, as they increase the risk of angioedema:
• racecadotril (used to treat diarrhoea);
• sirolimus, everolimus, temsirolimus, and other medicines belonging to the group of so-called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment);
• sacubitril (available in a combination medicine containing sacubitril and valsartan), used in the treatment of chronic heart failure;
• linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the group of drugs called gliptins (used in the treatment of diabetes);
• 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, especially if the patient has kidney dysfunction 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 Triplixam".

The doctor may recommend blood tests to assess whether there is a decrease in sodium or potassium levels or an increase in calcium levels.
Inform your doctor if you are pregnant, planning pregnancy, or suspect pregnancy. Use of Triplixam is not recommended during early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child (see section "Pregnancy and breastfeeding").
When using Triplixam, inform your doctor or healthcare provider if:

• the patient is to undergo anaesthesia and/or surgery;
• the patient has recently experienced diarrhoea or vomiting, or is dehydrated;
• LDL apheresis (mechanical removal of cholesterol from the blood) is to be performed;
• desensitisation treatment to reduce allergic reactions after bee or wasp stings is planned;
• an imaging test requiring iodine-containing contrast agent (a substance allowing visualization of organs such as the kidney or stomach in X-ray examinations) is to be performed.

Athletes should be aware that Triplixam contains an active substance (indapamide) that may lead to a positive result in anti-doping tests.
Children and adolescents
Triplixam must not be given to children or adolescents.
Triplixam with other medicines
Inform your doctor or pharmacist about all medicines currently taken, recently taken, or planned for use.
Patients with diabetes or kidney disease must not take aliskiren (used to treat high blood pressure).
Avoid taking Triplixam with:

• lithium (used to treat certain psychiatric disorders such as mania, bipolar disorder, and recurrent depression);
• potassium-sparing diuretics (triamterene, amiloride), potassium supplements, potassium-containing salt substitutes, or other medicines that may increase potassium levels in the body (such as heparin, a medicine used to thin the blood to prevent clots; trimethoprim and cotrimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole, used to treat bacterial infections);
• dantrolene (intravenous), also used to treat malignant hyperthermia occurring during anaesthesia (symptoms include very high fever and muscle rigidity);
• estramustine (used to treat cancer);
• medicines used to treat diarrhoea (racecadotril) or medicines used to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the group of so-called 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 Triplixam" and "Warnings and precautions";
• other medicines used to treat high blood pressure: ACE inhibitors and angiotensin II receptor antagonists.

Other medicines may affect treatment with Triplixam. The doctor may recommend dose adjustments and/or additional precautions. Inform your doctor if the patient is 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), aliskiren (see also sections "When not to use Triplixam" and "Warnings and precautions"), or diuretics (medicines that increase urine production 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;
• anaesthetics;
• iodine-containing contrast agents;
• bepridil (used to treat angina pectoris);
• methadone (used to treat addiction);
• medicines used to treat heart rhythm disorders (e.g. dofetilide, ibutilide, bretylium, cizapride, difemanil, procainamide, quinidine, hydroquinidine, disopyramide, amiodarone, sotalol);
• verapamil, diltiazem (used in heart diseases);
• digoxin or other cardiac glycosides (used in heart diseases);
• antibiotics used to treat bacterial infections (e.g. rifampicin, intravenous erythromycin, clarithromycin, sparfloxacin, moxifloxacin);
• antifungal medicines (e.g. itraconazole, ketoconazole, intravenous amphotericin B);
• 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, and 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);
• immunosuppressive medicines (given to control immune system responses) used to treat autoimmune diseases or after organ transplantation (e.g. cyclosporine, tacrolimus);
• tetracosactide (used to treat Crohn's disease);
• gold salts, especially when administered intravenously (used to treat symptoms of rheumatoid arthritis);
• halofantrine (used to treat certain types of malaria);
• baclofen used to treat muscle stiffness occurring in diseases such as multiple sclerosis;
• medicines used to treat diabetes, such as insulin or metformin;
• calcium, including calcium supplements;
• stimulant laxatives (e.g. sena);
• medicines used to treat cancer;
• vinpocetine (used to treat symptomatic cognitive disorders in elderly patients, including memory loss);
• medicines used to treat psychiatric disorders such as depression, anxiety, schizophrenia (e.g. tricyclic antidepressants, antipsychotics, imipramine-type antidepressants, neuroleptics such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol);
• pentamidine (used to treat pneumonia);
• ritonavir, indinavir, nelfinavir (so-called protease inhibitors used to treat HIV infections);
• Hypericum perforatum (St. John's wort);
• trimethoprim (used to treat infections);
• medicines used to treat low blood pressure, shock, or asthma (e.g. ephedrine, noradrenaline, or adrenaline);
• nitroglycerin and other nitrates or other vasodilating medicines, as they may further reduce blood pressure.

Triplixam with food and drink
While taking Triplixam, do not consume grapefruit or grapefruit juice, as it may increase the concentration of the active substance – amlodipine – potentially causing an unexpected intensification of the blood pressure-lowering effect of Triplixam.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Pregnancy
Inform your doctor if you are pregnant, suspect pregnancy, or are planning pregnancy. Usually, the doctor will recommend discontinuing Triplixam before a planned pregnancy or immediately after confirmed pregnancy and will advise using an alternative medicine. Use of Triplixam is not recommended during early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child.
Breastfeeding
Inform your doctor if you are breastfeeding or plan to breastfeed. Use of Triplixam is not recommended during breastfeeding, especially when breastfeeding a newborn or premature infant. The doctor may recommend using another medicine.
Driving and operating machinery
Triplixam may affect the ability to drive or operate machinery. If taking the medicine causes nausea, dizziness, fatigue, or headache, do not drive or operate machinery and contact your doctor immediately.
Triplixam contains sodium
Triplixam contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to use Triplixam

This medicine should always be taken exactly as directed by the physician or pharmacist. In case of doubt,
consult the physician or pharmacist.
The tablet should be swallowed with a glass of water, preferably in the morning, before a meal. The physician will determine
the appropriate dose for the patient. The usual recommended dose is one tablet once daily.
Triplixam is available in the following strengths: 5 mg + 1.25 mg + 5 mg, 5 mg + 1.25 mg + 10 mg, 10 mg + 2.5 mg + 5 mg, 10 mg + 2.5 mg + 10 mg.
Taking more Triplixam than prescribed
Taking too many tablets may cause blood pressure to drop, even to a dangerous extent, sometimes accompanied by
nausea, vomiting, cramps, dizziness, drowsiness, disorientation, oliguria (passing less urine than usual), anuria
(absence of urine production or excretion). The patient may feel a "void" in the head, and may experience faintness or weakness.
If the drop in blood pressure is severe, shock may occur, in which the skin becomes cold and clammy and the patient may lose consciousness.
Breathlessness due to excess fluid accumulating in the lungs (pulmonary edema) may occur even 24–48 hours after taking the medicine.
If an overdose of Triplixam is taken, seek immediate medical advice or go to the emergency department of the nearest hospital.
Missing a dose of Triplixam
It is important to take the medicine every day, as regular use ensures more effective treatment. However, if a dose of Triplixam is missed,
take the next dose at the usual time. Do not take a double dose to make up for the missed dose.
Stopping Triplixam
Treatment of high blood pressure is usually long-term; therefore, consult your doctor before stopping this medicine.
If you have any further questions about the use of this medicine, consult your physician or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
If the patient experiences any of the following serious adverse symptoms, the medicine must be discontinued
and medical advice must be sought immediately:

• sudden onset of wheezing, chest pain, shortness of breath or difficulty breathing (uncommon – may affect less than 1 in 100 patients);
• swelling of the eyelids, face or lips (uncommon – may affect less than 1 in 100 patients);
• swelling of the mucous membranes of the mouth, tongue or throat, causing significant difficulty in breathing (uncommon – may affect less than 1 in 100 patients);
• severe skin reactions, including severe rash, urticaria, redness of the entire skin surface, intense itching, blistering, skin peeling and swelling, mucosal inflammation

(Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions (very rare – may affect less than 1 in 10,000 patients);

• severe dizziness or fainting (common – may affect less than 1 in 10 patients);
• myocardial infarction (very rare – may affect less than 1 in 10,000 patients), life-threatening cardiac arrhythmias (frequency not known);
• pancreatitis, which may cause severe upper abdominal pain radiating to the back and severe malaise (very rare – may affect less than 1 in 10,000 patients);
• muscle weakness, cramps, tenderness or muscle pain, particularly when the patient simultaneously feels unwell or has a high temperature, which may be due to abnormal muscle breakdown (frequency not known).

Adverse effects grouped by decreasing frequency of occurrence:

• very common (affects at least 1 in 10 patients): oedema (fluid retention).
• common (affects less than 1 in 10 patients): low blood potassium levels, headache, central dizziness, palpitations (awareness of heartbeat), sudden flushing of the face and neck, labyrinthine dizziness, tingling/numbness, visual disturbance, double vision, tinnitus (sensation of hearing sounds), sensation of "emptiness" in the head due to low blood pressure, cough, shortness of breath, gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, dyspepsia or digestive disturbances, diarrhoea, constipation, changes in bowel rhythm), allergic reactions (such as rashes, itching), muscle cramps, feeling of fatigue, weakness, somnolence, swelling of the ankle area.
• uncommon (affects less than 1 in 100 patients): mood swings, anxiety, depression, sleep disturbances, tremor, urticaria, fainting, pain insensitivity, irregular and/or rapid heartbeat, inflammation of the nasal mucosa (nasal swelling or discharge), hair loss, purpura (small red spots on the skin), skin depigmentation, itching, sweating, chest pain, muscle or joint pain, back pain, pain, malaise, kidney disorders, urinary disorders, nocturia (need to urinate at night), increased frequency of urination, impotence (inability to achieve or maintain erection), fever or elevated body temperature, discomfort or enlargement of the breasts in men, increased or decreased body weight, increased number of a certain type of white blood cells, high blood potassium levels, hypoglycaemia (very low blood sugar levels), low blood sodium levels, which may lead to dehydration and lowered blood pressure, vasculitis, photosensitivity reactions (skin changes) after exposure to sunlight or artificial UVA radiation, clusters of blisters on the skin, swelling of hands or feet, increased blood creatinine and urea levels, falls, dryness of the oral mucosa.
• rare (affects less than 1 in 1,000 patients): disorientation, abnormal laboratory test results: low blood chloride levels, low blood magnesium levels, increased liver enzyme activity, elevated serum bilirubin; exacerbation of psoriasis, reduced or absent urine output, acute kidney failure. Dark-coloured urine, nausea or vomiting, muscle cramps, disorientation and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion).
• very rare (affects less than 1 in 10,000 patients): decreased number of white blood cells, decreased platelet count (leading to easy bruising and nosebleeds), anaemia (reduced number of red blood cells), angina pectoris (chest pain, jaw and back pain, triggered by physical exertion and caused by impaired blood supply to the heart), eosinophilic pneumonia (a rare type of lung inflammation), gingival enlargement, severe skin reactions, including severe rash, redness of the entire skin surface, intense itching, blistering,

skin peeling and swelling, erythema multiforme (rash, often beginning with red, itchy spots on the face, arms or legs), bleeding, tender or enlarged gums, liver function disorders, hepatitis, severe kidney function impairment, jaundice (yellowing of the skin), abdominal distension (gastritis), nerve disorders causing weakness, tingling or numbness, increased muscle tone, hyperglycaemia (very high blood sugar levels), high blood calcium levels, stroke, possibly secondary to significant drop in blood pressure.

• frequency not known (cannot be estimated from available data): hepatic encephalopathy (brain disorder caused by liver disease), abnormal electrocardiogram (ECG) findings; in patients with systemic lupus erythematosus (a type of collagenosis), symptoms may worsen. Myopia, blurred vision, 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). Tremor, postural rigidity, facial masking, bradykinesia and shuffling gait, unsteady gait. Cyanosis, numbness and pain in fingers or toes (Raynaud's phenomenon).

Changes in laboratory test results (blood tests) may occur. Your doctor may recommend blood tests to monitor your health.
If any of these symptoms occur, contact your doctor as soon as possible.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the 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.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Triplixam

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
No special storage conditions are required.
Shelf life after first opening of the container containing 30 coated tablets: 30 days.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Triplixam contains

• The active substances in this medicinal product are: perindopril with arginine, indapamide, and amlodipine.

One coated tablet contains 6.790 mg of perindopril (as 10 mg of perindopril arginine), 2.5 mg of indapamide, and 6.935 mg of amlodipine besylate (equivalent to 5 mg of amlodipine).

• Other components of the tablet:
  • tablet core: calcium carbonate with starch composition: calcium carbonate (90%), pregelatinized starch, corn (10%), microcrystalline cellulose, sodium croscarmellose, magnesium stearate, colloidal anhydrous silica, pregelatinized starch, corn.
  • tablet coating: glycerol, hypromellose 6 mPa·s, macrogol 6000, magnesium stearate, titanium dioxide (E 171).

What Triplixam looks like and contents of the pack
Triplixam 10 mg + 2.5 mg + 5 mg is a white, elongated coated tablet measuring 11.5 mm in length and

6.09 mm in width, with an embossed mark on one side and an embossed mark on the other side.
Tablets are available in cardboard boxes containing 30, 60 (2 containers of 30 tablets each), or 90 tablets (3 containers of 30 tablets each).
The container cap contains a desiccant to absorb moisture.
For further detailed information, please contact the responsible party or the parallel importer.

Marketing Authorisation Holder in Hungary, country of export:
Proterapia Hungary Kft.
1134 Budapest, Lehet utca 11.
Hungary

Manufacturers:
EGIS Gyógyszergyár Zrt.
9900 Körmend, Mátyás király u. 65.
Hungary
Servier (Ireland) Industries Ltd
Gorey Road, Arklow - Co. Wicklow, Ireland
Les Laboratoires Servier Industrie
905 route de Saran, 45520 Gidy, France
Anpharm Przedsiębiorstwo Farmaceutyczne S.A.
Annopol 6B, 03-236 Warsaw, Poland

Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw, Poland

Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw, Poland

Marketing Authorisation Number in Hungary, country of export: OGYI-T-22626/04
Parallel Import Authorisation Number: 441/24

This medicinal product is authorised for sale in the European Economic Area countries under the following names:
Belgium TRIPLIXAM, comprimé pelliculé
Bulgaria TRIPLIXAM, филмирани таблетки
Croatia TRIPLIXAM, filmom obložene tablete
Cyprus TRIPLIXAM, επικαλυμμένα με λεπτό υμένιο δισκία
Czech Republic TRIPLIXAM
Estonia TRIPLIXAM
Finland TRIPLIXAM, kalvopäällysteinen tabletti
France TRIPLIXAM, comprimé pelliculé
Greece TRIPLIXAM, επικαλυμμένα με λεπτό υμένιο δισκία
Ireland COVERDINE film-coated tablets
Italy TRIPLIAM, compresse rivestite con film
Latvia TRIPLIXAM, apvalkotās tabletes
Lithuania TRIPLIXAM, plėvele dengtos tabletės
Luxembourg TRIPLIXAM, comprimé pelliculé
Malta TRIPLIXAM film-coated tablets
Netherlands TRIPLIXAM, filmomhulde tabletten
Poland TRIPLIXAM
Portugal TRIPLIXAM
Romania TRIPLIXAM comprimate filmate
Slovakia TRIPLIXAM, filmom obalené tablety
Slovenia TRIPLIXAM filmsko obložene tablete