Triplixam

Package leaflet: Information for the patient

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Triplixam, 5 mg + 1.25 mg + 5 mg, coated tablets
Perindoprilum argininum + Indapamidum + Amlodipinum
Please read the entire leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, so that you can read it again if necessary.
• 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. This medicine may harm other people, even if their symptoms are identical.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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 to treat high
blood pressure (hypertension).
Patients already taking perindopril and indapamide in one medicine and amlodipine in another may instead take one Triplixam tablet containing these three active substances in the same doses.
Each of the active substances lowers blood pressure, and together they help control the patient's blood pressure:

• perindopril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors. It works by widening 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 blood vessels to relax, making it easier for blood to 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, severe itching, or intense skin rash during prior treatment with an ACE inhibitor,

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or if such symptoms occurred in the patient or a family member under any other circumstances (a condition known as angioedema);

• if the patient has severe liver disease or a condition called hepatic encephalopathy (a brain disorder caused by liver disease);
• if untreated, decompensated heart failure is suspected in the patient (marked fluid retention, difficulty breathing);
• if the patient has aortic valve stenosis (narrowing of the aorta) or cardiogenic shock (a condition in which the heart cannot supply enough 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 flow to the kidneys (renal artery stenosis);
• if the patient is undergoing dialysis or another form of blood filtration. Depending on the device used, Triplixam may not be suitable for the patient;
• after the 3rd month of pregnancy (it is also advisable to avoid using Triplixam in early pregnancy –
• see 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 to treat heart failure, as this increases the risk of angioedema (rapid swelling of tissues under the skin, particularly in the throat area) (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 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 severe high blood pressure (hypertensive crisis);
• if the patient has liver disease;
• if the patient has a collagen vascular 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 blood is important);
• if the patient is taking lithium or potassium-sparing diuretics (spironolactone, triamterene), as these should not be used with Triplixam (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;
• angioedema (swelling of the face, lips, mouth, tongue, or throat, possibly causing difficulty in swallowing or breathing) occurs more frequently in black patients, 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 choroid layer of the eye (choroidal effusion) or increased intraocular pressure, which may occur within hours or weeks of taking Triplixam. Untreated, these 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.

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• 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, possibly causing difficulty in swallowing or breathing (angioedema), which may occur at any time during treatment; 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 class of 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 class of drugs known as gliptins (used to treat 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 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 Triplixam”. The doctor may recommend blood tests to assess whether sodium or potassium levels have decreased or calcium levels have increased.

Inform the doctor if the patient is pregnant, planning pregnancy, or suspects 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 the doctor or medical staff if:

• the patient is to undergo anaesthesia and/or surgery;
• the patient has recently experienced diarrhoea or vomiting, or is dehydrated;
• an LDL apheresis procedure (mechanical removal of cholesterol from the blood) is planned;
• desensitisation treatment is planned to reduce allergic reactions following bee or wasp stings;
• 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.

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
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Inform the doctor or pharmacist about all medicines currently or recently taken by the patient,
as well as any medicines the patient plans to 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 medicines (triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes, and 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 (administered intravenously), 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 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
a dose adjustment and/or additional precautions. Inform the doctor if the patient
is taking any of the following medicines, as special precautions 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 from 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, cisapride, 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);

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• immunosuppressive medicines (administered 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. senna);
• 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 (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 this may increase blood levels of the active substance – amlodipine – potentially causing
unexpectedly intensified blood pressure-lowering effects of Triplixam.
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
Inform the doctor about pregnancy, suspected pregnancy, or planned pregnancy. Usually, the doctor will recommend
discontinuing Triplixam before planned pregnancy or immediately after pregnancy is confirmed, and will recommend
an alternative medicine instead of Triplixam. 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 the doctor if the patient is breastfeeding or intends to breastfeed. Use of Triplixam is not recommended
during breastfeeding, especially when nursing a newborn or premature infant. The doctor may recommend an alternative 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, the patient should not drive or operate machinery and should contact the doctor immediately.
Triplixam contains sodium
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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 as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
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.
The tablet should be swallowed with a glass of water, preferably in the morning before a meal. The doctor will determine
the appropriate dose for the patient. The usual recommended dose is one tablet once daily.

Taking more Triplixam than prescribed
Taking too many tablets may cause blood pressure to drop, even to a dangerous extent, which may sometimes
be 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, experience faintness or weakness.
If the drop in blood pressure is severe, shock may occur, characterized by cold and clammy skin and loss of consciousness.
Breathlessness due to fluid accumulation in the lungs (pulmonary edema) may occur even 24–48 hours after taking the medicine.
If too many Triplixam tablets have been taken, seek immediate medical attention by contacting a doctor
or going to the nearest hospital emergency department.

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, the next dose should be taken at the usual time. Do not take a double dose to make up for a missed dose.

Stopping Triplixam treatment
Treatment of high blood pressure is usually long-term; therefore, consult a doctor before stopping this medicine.
If there are any further doubts about the use of this medicine, consult a doctor or pharmacist.

4. Possible adverse effects

Like any medicine, 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 immediately and medical advice must be sought without delay:

• sudden onset of wheezing, chest pain, shortness of breath or difficulty breathing (uncommon – may occur in less than 1 in 100 patients);

• swelling of the eyelids, face or lips (uncommon – may occur in less than 1 in 100 patients);

• swelling of the mucous membranes of the mouth, tongue or throat causing significant breathing difficulties (uncommon – may occur in less than 1 in 100 patients);

• severe skin reactions, including severe rash, urticaria, redness of the entire skin surface, intense itching, blistering, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions (very rare – may occur in less than 1 in 10,000 patients);

• severe dizziness or fainting (common – may occur in less than 1 in 10 patients);

• myocardial infarction (very rare – may occur in less than 1 in 10,000 patients), life-threatening cardiac arrhythmias (frequency unknown);

• pancreatitis, which may cause severe upper abdominal pain radiating to the back and severe malaise (very rare – may occur in less than 1 in 10,000 patients);

• muscle weakness, cramps, tenderness or pain, particularly when accompanied by general malaise or fever, which may be due to abnormal muscle breakdown (frequency unknown).

Adverse effects grouped by decreasing frequency of occurrence:

• very common (occurring in at least 1 in 10 patients): oedema (fluid retention).

• common (occurring in 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 disturbances, double vision, tinnitus (sensation of hearing sounds), feeling of "emptiness" in the head due to low blood pressure, cough, dyspnoea, gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, indigestion or digestive disorders, diarrhoea, constipation, changes in bowel rhythm), allergic reactions (such as rashes, itching), muscle cramps, fatigue, weakness, somnolence, swelling around the ankles.

• uncommon (occurring in less than 1 in 100 patients): mood swings, anxiety, depression, sleep disturbances, tremor, urticaria, fainting, loss of pain sensation, irregular and/or rapid heart rate, rhinitis (nasal mucosa inflammation – swelling or nasal 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 breasts in men, weight gain or weight loss, 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 low blood pressure), vasculitis, photosensitivity reaction (skin changes) after exposure to sunlight or artificial UVA radiation, clusters of blisters on the skin, swelling of hands or feet, increased creatinine and urea levels in blood, falls, dryness of the oral mucosa.

• rare (occurring in 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 may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion).

• very rare (occurring in 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 due to impaired cardiac blood flow), eosinophilic pneumonia (a rare type of lung inflammation), gum swelling, severe skin reactions including severe rash, redness of the entire skin surface, intense itching, blistering, peeling and swelling of the skin, 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 dysfunction, 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 marked drop in blood pressure.

• frequency not known (cannot be estimated from available data): hepatic encephalopathy (brain disorder caused by liver disease), abnormal 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 choroid layer of the eye (choroidal effusion) or acute angle-closure glaucoma). Tremor, rigidity, mask-like facial expression, bradykinesia and shuffling 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, pharmacist or nurse. Adverse effects 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
Phone: +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 the 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 required. This will help protect the environment.

6. Contents of the packaging and other information

What Triplixam contains

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

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One coated tablet of Triplixam contains 3.395 mg of perindopril (equivalent to 5 mg of perindopril with arginine), 1.25 mg of indapamide and 6.935 mg of amlodipine besylate (equivalent to 5 mg of amlodipine).

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

What Triplixam looks like and contents of the pack
Triplixam 5 mg + 1.25 mg + 5 mg: white, elongated coated tablet, 9.75 mm in length and

5.16 mm in width, with an imprint on one side and an imprint on the other side.
Tablets are available in cardboard boxes containing 30, 60 (2 containers with 30 tablets each) or 90 (3 containers with 30 tablets each) tablets.
The container cap contains a desiccant to absorb moisture.
For further information, contact the responsible party or the parallel importer:
Responsible entity in Latvia, country of export:
Les Laboratoires Servier, 50, rue Carnot, 92284 Suresnes cedex, France
Manufacturer:
Servier (Ireland) Industries Ltd, Gorey Road, Arklow - Co. Wicklow, Ireland
Les Laboratoires Servier Industrie, 905 route de Saran, 45520 Gidy, France
Anpharm Przedsiebiorstwo Farmaceutyczne S.A., ul. Annopol 6b, 03-236 Warsaw, Poland
Parallel importer:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Authorisation number in Latvia, country of export: 14-0057
Parallel import authorisation number: 47/25
This medicinal product is authorised 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
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