Triplixam

Package leaflet: Information for the patient

Warning! Keep the leaflet, information on the immediate packaging in a foreign language!
Triplixam (Tripliam)
10 mg + 2.5 mg + 10 mg, film-coated tablets
Perindoprilum argininum + Indapamidum + Amlodipinum
Triplixam and Tripliam are different trade names for the same medicinal product.
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 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 others, 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:

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 medicinal product containing three active substances: perindopril,
indapamide, and amlodipine. It is an antihypertensive medicine used in the treatment of high
arterial pressure (hypertension).
Patients already taking perindopril and indapamide in one medicine and amlodipine in another
may instead take a single tablet of Triplixam, which contains these three active substances in
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 during treatment with an ACE inhibitor such as wheezing, facial or tongue swelling, intense itching or severe rashes, 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 the patient has untreated, uncontrolled heart failure (severe 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 other blood filtration methods. Depending on the equipment used, Triplixam may not be suitable;
• 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 to treat heart failure, as this increases the risk of angioedema (rapid swelling of tissues under the skin 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 significantly elevated 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 uses potassium-containing salt substitutes (maintaining appropriate blood potassium levels is important);
• if the patient is taking lithium or potassium-sparing diuretics (spironolactone, triamterene), as these should be avoided 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;
• 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 with 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.

• 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 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 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 to treat chronic heart failure;
• linagliptin, saxagliptin, sitagliptin, vildagliptin and other medicines belonging to the group of drugs called 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 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 sodium or potassium levels have decreased or calcium levels have increased.
Inform the doctor if you are pregnant, planning pregnancy, or suspect pregnancy. 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 planned;
• desensitisation treatment is planned to reduce allergic reactions after bee or wasp stings;
• an imaging test requiring iodine-containing contrast agents (substances allowing visualisation 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 or recently taken, as well as any medicines you plan 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 mental disorders such as mania, bipolar disorder and recurrent depression);
• potassium-sparing diuretics (triamterene, amiloride), potassium supplements or 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 co-trimoxazole, 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 a dose adjustment and/or additional precautions. Inform your doctor if you are 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 (AIIRA), 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);
• 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 in conditions 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 mental 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 this may increase the concentration of the active substance – amlodipine – which could lead to an unpredictable intensification of Triplixam's blood pressure-lowering effect.
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 planned pregnancy or immediately after pregnancy is confirmed, and will advise using an alternative medicine instead of Triplixam. 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. Triplixam is not recommended during breastfeeding, especially when nursing 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 take Triplixam

This medicine should always be taken exactly as directed by your doctor or pharmacist. If in doubt,
you should consult your doctor or pharmacist.
The tablet should be swallowed with a glass of water, preferably in the morning, before a meal. Your doctor 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, which may sometimes be accompanied by nausea, vomiting, cramps, dizziness, drowsiness, disorientation, oliguria (passing less urine than usual), or anuria (absence of urine production or excretion). The patient may experience a "blank" feeling in the head, 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 oedema) may occur even 24–48 hours after taking the medicine.
If too many Triplixam tablets have been taken, seek immediate medical advice from your doctor or go 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, take the next dose at the usual time. Do not take a double dose to make up for the missed dose.
Stopping Triplixam treatment
Treatment of high blood pressure is usually long-term, therefore you should consult your doctor before stopping this medicine.
If you have any further questions about the use of this medicine, consult your doctor 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 immediately and medical advice must be sought urgently:

• 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 breathing difficulties (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, peeling and swelling of the skin, 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);
• heart attack (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 general malaise (very rare – may affect 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 not known).

Adverse effects, grouped by decreasing frequency of occurrence:

• very common (affects at least 1 in 10 patients): fluid retention (oedema).
• 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 disturbances, double vision, tinnitus (sensation of ringing or other noise in the ears), sensation of "emptiness" in the head due to low blood pressure, cough, dyspnoea, gastrointestinal disorders (nausea, vomiting, abdominal pain, taste disturbances, indigestion or digestive disturbances, diarrhoea, constipation, changes in bowel rhythm), allergic reactions (such as rashes, itching), muscle cramps, fatigue, weakness, somnolence, swelling of the ankle area.
• uncommon (affects less than 1 in 100 patients): mood swings, anxiety, depression, sleep disorders, tremor, urticaria, fainting, loss of pain sensation, irregular and/or rapid heartbeat, nasal mucosal inflammation (nasal swelling or discharge), hair loss, purpura (small red spots on the skin), skin discoloration, itching, sweating, chest pain, muscle or joint pain, back pain, pain, malaise, kidney disorders, urinary disorders, nocturia, increased frequency of urination, impotence (inability to achieve or maintain an erection), fever or elevated body temperature, discomfort or enlargement of the 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, skin blistering, 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 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 heart blood supply), 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 function impairment, yellowing of the skin (jaundice), abdominal distension (gastritis),

nerve disorders, which may cause weakness, tingling or numbness, increased muscle tone, hyperglycaemia (very high blood sugar levels), high blood calcium levels, stroke, possibly secondary to a significant 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 choroidal layer of the eye (choroidal effusion) or acute angle-closure glaucoma). Tremor, rigidity, facial masking, bradykinesia and shuffling gait. Bluish discoloration, numbness and pain in fingers or toes (Raynaud's phenomenon).

Changes in laboratory test results (blood tests) may occur. 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 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 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 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 with 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 medicine are: perindopril with arginine, indapamide and amlodipine. One coated tablet contains 6.790 mg of perindopril (equivalent to 10 mg of perindopril arginine), 2.5 mg of indapamide and 13.870 mg of amlodipine besylate (equivalent to 10 mg of amlodipine).
• Other components of the tablet:
• tablet core: calcium carbonate with starch composed of: calcium carbonate (90%); pregelatinized starch, maize (10%); microcrystalline cellulose; sodium croscarmellose; magnesium stearate; colloidal anhydrous silica; pregelatinized starch.
• tablet coating: glycerol; hypromellose 6 mPas; polyethylene glycol 6000; magnesium stearate; titanium dioxide (E 171).

What Triplixam looks like and contents of the packaging
Triplixam is a white, elongated coated tablet measuring 12.2 mm in length and 6.46 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 tablet containers with 30 tablets each) or 90 (3 tablet containers with 30 tablets each) tablets.
Inside the closure cap of the tablet container there is a moisture-absorbing agent.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Italy, country of export:
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes cedex
France
Manufacturer:
Les Laboratoires Servier Industrie
905 route de Saran
45520 Gidy
France

Anpharm Pharmaceutical Enterprise S.A.
Annopol 6B
03-236 Warsaw, Poland
EGIS Pharmaceuticals Private Limited Company
Mátyás király u. 65
H-9900 Körmend
Hungary
Parallel importer:
Medezin Sp. z o.o.
Zbąszyńska 3
91-342 Łódź
Repackaged in:
Medezin Sp. z o.o.
Zbąszyńska 3
91-342 Łódź
This medicinal product is authorized for marketing in the European Economic Area member states under the following names:
Belgium TRIPLIXAM, film-coated tablet
Bulgaria TRIPLIXAM, coated tablets
Croatia TRIPLIXAM, film-coated tablets
Cyprus TRIPLIXAM, film-coated tablets
Czech Republic TRIPLIXAM
Estonia TRIPLIXAM
Finland TRIPLIXAM, film-coated tablet
France TRIPLIXAM, film-coated tablet
Greece TRIPLIXAM, film-coated tablets
Ireland COVERDINE film-coated tablets
Italy TRIPLIAM, film-coated tablets
Latvia TRIPLIXAM, film-coated tablets
Lithuania TRIPLIXAM, film-coated tablets
Luxembourg TRIPLIXAM, comprimé pelliculé
Malta TRIPLIXAM film-coated tablets
Netherlands TRIPLIXAM, filmomhulde tabletten
Poland TRIPLIXAM
Portugal TRIPLIXAM
Romania TRIPLIXAM film-coated tablets
Slovakia TRIPLIXAM, filmom obalené tablety
Slovenia TRIPLIXAM filmsko obložene tablete
Marketing authorization number in Italy, country of export: 042407217
Parallel import authorization number: 73/26