Triplixam

Leaflet attached to the packaging: patient information

Triplixam, 5 mg + 1.25 mg + 5 mg, film-coated tablets

Triplixam, 5 mg + 1.25 mg + 10 mg, film-coated tablets

Triplixam, 10 mg + 2.5 mg + 5 mg, film-coated tablets

Triplixam, 10 mg + 2.5 mg + 10 mg, film-coated tablets

Perindopril arginine + Indapamide + Amlodipine

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Triplixam and what is it 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 packaging and other information

1. What is Triplixam and what is it used for

Triplixam is a combination preparation 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 can take one Triplixam tablet instead, which contains these three active substances in the same doses. Each of the active substances lowers blood pressure, and together they help control blood pressure in the patient:

• perindopril belongs to a group of medicines called angiotensin-converting enzyme inhibitors (ACE inhibitors). It works by dilating blood vessels, making it easier for the heart to pump blood through them.
• indapamide is a diuretic (a medicine that increases the amount of urine produced by the kidneys). Diuretics increase the amount of urine produced by the kidneys. However, indapamide differs from other diuretics because it only causes 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 taking Triplixam

When not to take Triplixam:

• if the patient is allergic to perindopril or other ACE inhibitors, indapamide or other sulfonamides, amlodipine or other dihydropyridines, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has experienced symptoms such as wheezing, swelling of the face or tongue, intense itching, or severe rash during previous treatment with an ACE inhibitor;

or if such symptoms have occurred in the patient or someone in their family in any other circumstances (a condition called angioedema);

• if the patient has severe liver disease or a condition called hepatic encephalopathy (a brain disorder caused by liver disease);
• if the patient is suspected of having untreated, uncontrolled heart failure (severe water retention, breathing difficulties);
• if the patient has a narrowing of the aortic valve in the heart (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply enough blood to the body);
• if the patient has heart failure after 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 that reduces blood flow to the kidneys (renal artery stenosis);
• if the patient is undergoing dialysis or blood filtration by other means. Depending on the device used, Triplixam may not be suitable for the patient;
• if the patient has moderate kidney disease (applies to Triplixam 10 mg + 2.5 mg + 5 mg and 10 mg + 2.5 mg + 10 mg);
• after the third month of pregnancy (it is also recommended to avoid taking Triplixam during early pregnancy);
• if the patient has diabetes or kidney problems 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 chronic heart failure, as the risk of angioedema (rapid swelling of tissues under the skin in the throat area) increases (see "Warnings and precautions" and "Triplixam and other medicines").

Warnings and precautions

If any of the following conditions apply to the patient, they should consult a doctor or pharmacist before taking Triplixam:

• if the patient has hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the blood vessel supplying the kidney);
• if the patient has heart failure or any other heart disease;
• if the patient has a significant increase in blood pressure (hypertensive crisis);
• if the patient has liver disease;
• if the patient has collagenosis (a 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 salt substitutes containing potassium (it is essential to have the correct potassium level in the blood);
• if the patient is taking lithium or potassium-sparing diuretics (spironolactone, triamterene), as they should be avoided when taking Triplixam (see "Triplixam and other medicines");
• if the patient is elderly and the dose needs to be increased;
• if the patient has had allergic reactions to light;
• in black patients, angioedema (swelling of the face, lips, mouth, tongue, or throat, which can 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 vision loss or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye, which can occur within hours or weeks of taking Triplixam. Untreated symptoms can lead to permanent vision loss. If the patient has previously been allergic to penicillin or sulfonamides, there is a higher risk of these disorders.

The doctor may recommend blood tests to check if the patient's potassium or sodium levels have decreased or if their calcium levels have increased.

• if the patient is about to undergo anesthesia and/or surgery;
• if the patient has recently had diarrhea or vomiting, or is dehydrated;
• if the patient is to undergo LDL apheresis (mechanical removal of cholesterol from the blood);
• if the patient is to undergo desensitization treatment to reduce allergic reactions to bee or wasp stings;
• if the patient is to undergo a test that requires the use of a contrast agent containing iodine (a substance that allows organs such as the kidney or stomach to be seen on an X-ray).

Athletes should be aware that Triplixam contains the active substance indapamide, which may cause a positive doping test result.

Children and adolescents

Triplixam should not be given to children and adolescents.

Triplixam and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.

• lithium (used to treat certain mental illnesses, such as mania, manic-depressive illness, and recurrent depression);
• potassium-sparing medicines (triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, or other medicines that may increase potassium levels in the body (such as heparin, a medicine used to thin the blood and prevent blood clots; trimethoprim and cotrimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole, used to treat bacterial infections);
• dantrolene (used to treat malignant hyperthermia that occurs during anesthesia);
• estramustine (used to treat cancer);
• medicines used to treat diarrhea (racecadotril) or medicines used to prevent transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the group of so-called mTOR inhibitors). See "Warnings and precautions".
• a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to take Triplixam" and "Warnings and precautions".
• other medicines used to treat high blood pressure: angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists.

Taking other medicines may affect treatment with Triplixam. The doctor may recommend changing the dose and/or taking other precautions. The patient should tell their doctor if they are taking any of the following medicines, as they may require special precautions:

• other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (AIIRAs), aliskiren (see also sections "When not to take Triplixam" and "Warnings and precautions"), or diuretics (medicines that increase the amount of urine produced 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;
• anesthetics;
• 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, cyzapride, difemanil, procainamide, quinidine, hydroquinidine, disopyramide, amiodarone, sotalol);
• verapamil, diltiazem (used to treat heart diseases);
• digoxin or other cardiac glycosides (used to treat heart diseases);
• antibiotics used to treat bacterial infections (e.g., rifampicin, erythromycin injection, clarithromycin, sparfloxacin, moxifloxacin);
• antifungal medicines (e.g., itraconazole, ketoconazole, amphotericin B injection);
• 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, as well as non-steroidal anti-inflammatory medicines (e.g., ibuprofen) or high doses of salicylates (e.g., acetylsalicylic acid, a substance found in many medicines, used as a pain reliever and to reduce fever, as well as to prevent blood clots);
• immunosuppressive medicines (given to control the immune system's response) used to treat autoimmune diseases or after organ transplantation (e.g., cyclosporine, tacrolimus);
• tetracosactide (used to treat Crohn's disease);
• gold salts, especially those given intravenously (used to treat symptoms of rheumatoid arthritis);
• halofantrine (used to treat certain types of malaria);
• baclofen (used to treat muscle stiffness in diseases such as multiple sclerosis);
• medicines used to treat diabetes, such as insulin or metformin;
• calcium, including calcium supplements;
• laxatives with a stimulating effect (e.g., senna);
• medicines used to treat cancer;
• vincamine (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, antipsychotic medicines, antidepressant medicines of the imipramine type, 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 vasodilators, as they may further lower blood pressure.

Triplixam with food and drink

While taking Triplixam, the patient should not consume grapefruits or grapefruit juice, as this may increase the levels of the active substance amlodipine, leading to unpredictable intensification of the blood pressure-lowering effect of Triplixam.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor or pharmacist before taking this medicine.

Pregnancy

The patient should tell their doctor about pregnancy, suspected pregnancy, or plans to become pregnant. The doctor will usually recommend stopping Triplixam before planned pregnancy or as soon as possible after confirming pregnancy and will recommend an alternative medicine instead of Triplixam. Triplixam should not be taken during early pregnancy and should not be taken after the third month of pregnancy, as it may seriously harm the baby.

Breastfeeding

The patient should tell their doctor if they are breastfeeding or plan to breastfeed. Triplixam should not be taken during breastfeeding, especially when breastfeeding a newborn or premature baby. The doctor may recommend an alternative medicine.

Driving and using machines

Triplixam may affect the patient's ability to drive or operate machines. If taking the medicine causes nausea, dizziness, fatigue, or headache, the patient should not drive or operate machines and should contact their doctor immediately.

Triplixam contains sodium

Triplixam contains less than 1 mmol of sodium (23 mg) per tablet, which means that the medicine is considered "sodium-free".

3. How to take Triplixam

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. If the patient has any doubts, they should consult their doctor or pharmacist.

The tablet should be swallowed with a glass of water, preferably in the morning, before breakfast. The doctor will determine the correct dose for the patient. The recommended dose is usually one tablet per day.

Taking a higher dose of Triplixam than recommended

Taking too many tablets may cause a significant drop in blood pressure, which can be dangerous, and may be accompanied by symptoms such as nausea, vomiting, cramps, dizziness, drowsiness, disorientation, and decreased urine production or anuria (lack of urine production or excretion). The patient may feel "empty" in the head or may experience fainting or weakness. If the drop in blood pressure is significant, shock may occur, characterized by cold and sweaty skin, and the patient may lose consciousness.

Even 24-48 hours after taking the medicine, shortness of breath due to excess fluid accumulation in the lungs (pulmonary edema) may occur.

If the patient has taken too many Triplixam tablets, they should contact their doctor or go to the emergency department of the nearest hospital immediately.

Missing a dose of Triplixam

It is essential to take the medicine every day, as regular treatment ensures more effective action. However, if a dose of Triplixam is missed, the next dose should be taken at the usual time. The patient should not take a double dose to make up for the missed dose.

Stopping Triplixam treatment

Treatment for high blood pressure is usually long-term, so the patient should consult their doctor before stopping Triplixam.

If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Triplixam can cause side effects, although not everyone gets them.

If the patient experiences any of the following severe side effects, they should stop taking the medicine and contact their doctor immediately:

• 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 membrane of the mouth, tongue, or throat, causing significant difficulty breathing (uncommon - may occur in less than 1 in 100 patients);
• severe skin reactions, including severe rash, hives, redness of the skin all over the body, severe itching, blistering, peeling, and swelling of the skin, 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);
• heart attack (very rare - may occur in less than 1 in 10,000 patients), life-threatening arrhythmias (frequency not known);
• pancreatitis, which can cause severe abdominal pain and very poor health (very rare - may occur in less than 1 in 10,000 patients);
• muscle weakness, cramps, tenderness, or pain, especially if the patient feels unwell or has a high temperature, which may be caused by abnormal muscle breakdown (frequency not known).

Side effects, grouped by decreasing frequency:

• very common (occurring in at least 1 in 10 patients): edema (fluid retention).
• common (occurring in less than 1 in 10 patients): low potassium levels in the blood, headache, dizziness of central origin, palpitations (feeling of heartbeat), sudden reddening of the face and neck, dizziness of labyrinthine origin, feeling of tingling or numbness, visual disturbances, double vision, tinnitus (feeling of hearing sounds), feeling of "emptiness" in the head due to low blood pressure, cough, shortness of breath, gastrointestinal disorders (nausea, vomiting, abdominal pain, taste disturbances, indigestion or digestive disorders, diarrhea, constipation, changes in bowel movements), allergic reactions (such as rash, itching), muscle cramps, feeling of tiredness, weakness, drowsiness, swelling of the ankles.
• uncommon (occurring in less than 1 in 100 patients): mood changes, anxiety, depression, sleep disturbances, tremors, hives, fainting, loss of sensation, irregular or rapid heartbeat, nasal congestion (swelling or discharge from the nose), hair loss, purpura (red spots on the skin), skin discoloration, itching, sweating, chest pain, muscle or joint pain, back pain, pain, poor health, kidney disorders, urinary disorders, need to urinate at night, 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 loss, increased white blood cell count, high potassium levels in the blood, hypoglycemia (very low blood sugar), low sodium levels in the blood, which can cause dehydration and low blood pressure, vasculitis (inflammation of blood vessels), photosensitivity reaction (skin changes after sun exposure), blistering skin, swelling of the hands or feet, increased creatinine and urea levels in the blood, falls, dryness of the mucous membrane of the mouth.
• rare (occurring in less than 1 in 1,000 patients):
• disorientation, abnormal laboratory test results: low chloride levels in the blood, low magnesium levels in the blood, increased liver enzyme activity, high bilirubin levels in the blood; worsening of systemic lupus erythematosus. Decreased urine production or anuria. Dark urine, nausea, or vomiting, muscle cramps, disorientation, and seizures. These may be symptoms of a condition called SIADH (inappropriate antidiuretic hormone secretion).
• very rare (occurring in less than 1 in 10,000 patients): decreased white blood cell count, decreased platelet count (which can cause easy bruising and nosebleeds), anemia (decreased red blood cell count), angina pectoris (chest pain, jaw pain, and back pain caused by heart disease), eosinophilic pneumonia (a rare type of pneumonia), gum hypertrophy, severe skin reactions, including severe rash, redness of the skin all over the body, severe itching, blistering, peeling, and swelling of the skin, or other allergic reactions, erythema multiforme (rash, often starting with the appearance of red, itching spots on the face, arms, or legs), bleeding, sensitive, or swollen gums, liver dysfunction, hepatitis, severe kidney dysfunction, jaundice (yellowing of the skin), abdominal distension (gastritis), nerve disorders that can cause weakness, tingling, or numbness, increased muscle tone, hyperglycemia (very high blood sugar), high calcium levels in the blood, stroke, possibly due to significant lowering of blood pressure, hepatic encephalopathy (a brain disease caused by liver disease); abnormal ECG (electrocardiogram) results; in the case of systemic lupus erythematosus, worsening of symptoms may occur. Myopia, blurred vision, or eye pain due to high pressure (possible symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma). Tremors, stiffness, mask-like face, slow movements, and shuffling gait. Cyanosis, numbness, and pain in the fingers of the hands or feet (Raynaud's phenomenon).
• frequency not known (cannot be estimated from available data): hepatic encephalopathy (a brain disease caused by liver disease), abnormal ECG results; in the case of systemic lupus erythematosus, worsening of symptoms may occur. Myopia, blurred vision, or eye pain due to high pressure (possible symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma). Tremors, stiffness, mask-like face, slow movements, and shuffling gait. Cyanosis, numbness, and pain in the fingers of the hands or feet (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 the patient experiences any of these symptoms, they should contact their doctor as soon as possible.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of 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. Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Triplixam

The medicine should be stored out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging after the words "EXP" (abbreviation used to describe the expiry date). The expiry date refers to the last day of the specified month. The "Lot" number on the packaging is the batch number of the medicine.

There are no special storage instructions for the medicinal product.

The shelf life after opening the container with 30 film-coated tablets is 30 days.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Triplixam contains

• The active substances of Triplixam are perindopril arginine, indapamide, and amlodipine. One film-coated tablet of Triplixam 5 mg + 1.25 mg + 5 mg contains 3.395 mg of perindopril (equivalent to 5 mg of perindopril arginine), 1.25 mg of indapamide, and 6.935 mg of amlodipine besylate (equivalent to 5 mg of amlodipine). One film-coated tablet of Triplixam 5 mg + 1.25 mg + 10 mg contains 3.395 mg of perindopril (equivalent to 5 mg of perindopril arginine), 1.25 mg of indapamide, and 13.87 mg of amlodipine besylate (equivalent to 10 mg of amlodipine).

One film-coated tablet of Triplixam 10 mg + 2.5 mg + 5 mg contains 6.79 mg of perindopril (equivalent to 10 mg of perindopril arginine), 2.5 mg of indapamide, and 6.935 mg of amlodipine besylate (equivalent to 5 mg of amlodipine). One film-coated tablet of Triplixam 10 mg + 2.5 mg + 10 mg contains 6.79 mg of perindopril (equivalent to 10 mg of perindopril arginine), 2.5 mg of indapamide, and 13.87 mg of amlodipine besylate (equivalent to 10 mg of amlodipine).

• Other ingredients of the tablet are:
• tablet core: calcium carbonate with cornstarch composition: calcium carbonate (90%), cornstarch (10%), microcrystalline cellulose, sodium croscarmellose, magnesium stearate, silicon dioxide, cornstarch.
• 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, film-coated tablet, 9.75 mm long and 5.16 mm wide, with a logo embossed on one side.

Triplixam 5 mg + 1.25 mg + 10 mg: white, elongated, film-coated tablet, 10.7 mm long and 5.66 mm wide, with a logo embossed on one side and a logo embossed on the other side.

Triplixam 10 mg + 2.5 mg + 5 mg: white, elongated, film-coated tablet, 11.5 mm long and 6.09 mm wide, with a logo embossed on one side and a logo embossed on the other side.

Triplixam 10 mg + 2.5 mg + 10 mg: white, elongated, film-coated tablet, 12.2 mm long and 6.46 mm wide, with a logo embossed on one side and a logo embossed on the other side.

Tablets are available in cardboard boxes containing 30, 60 (2 containers of 30 tablets each), or 90 (3 containers of 30 tablets each) film-coated tablets. The cap of the container with tablets contains a desiccant. Not all pack sizes may be marketed.

Marketing authorization holder

Servier

Manufacturer

Servier Industries

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Belgium: TRIPLIXAM, film-coated tablets

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

Date of last revision of the leaflet: 07/2022