Tripliam

Patient Information Leaflet

Tripliam 5 mg/1.25 mg/5 mg film-coated tablets, 5 mg/1.25 mg/10 mg film-coated tablets, 10 mg/2.5 mg/5 mg film-coated tablets, 10 mg/2.5 mg/10 mg film-coated tablets

perindopril arginine/indapamide/amlodipine
Please read all of this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Tripliam is and what it is used for

Tripliam is a combination of three active substances: perindopril, indapamide and amlodipine. It is an antihypertensive medicine used to treat high blood pressure (hypertension).
Patients who are already taking the fixed combination of perindopril/indapamide and amlodipine as separate tablets may instead take one tablet of Tripliam containing the three active substances at the same dosage.
Each active substance helps to reduce blood pressure and, together, they act to control it:

• Perindopril belongs to a class of medicines called Angiotensin-Converting Enzyme (ACE) inhibitors. These medicines work by dilating blood vessels, making it easier for the heart to pump blood through them.
• Indapamide is a diuretic (belonging to a class 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 the amount of urine produced.
• Amlodipine is a calcium channel blocker (belonging to the class of medicines called dihydropyridines). It works by relaxing blood vessels, making it easier for blood to flow through them.

2. What you need to know before taking Tripliam

Do not take Tripliam

• if you are allergic to perindopril or any other ACE inhibitor, to indapamide or any other sulfonamide, to amlodipine or other dihydropyridines, or to any of the other ingredients of this medicine (listed in section 6),
• if you have experienced symptoms such as shortness of breath, swelling of the face or tongue, severe itching, or severe skin rashes related to a previous treatment with ACE inhibitors, or if you or a family member has experienced such symptoms under any circumstances (a condition called angioedema),
• if you have severe liver disease or suffer from a condition called hepatic encephalopathy (a brain disorder caused by liver disease),
• if you suspect you have untreated decompensated heart failure (severe fluid retention, difficulty breathing),
• if you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body),
• if you have heart failure following a heart attack,
• if you suffer from severely low blood pressure (hypotension),
• if you have low potassium levels in your blood,
• if you have severe kidney disease with reduced blood flow to the kidneys (renal artery stenosis),
• if you are undergoing dialysis or any type of blood filtration. Depending on the equipment used, treatment with Tripliam may not be suitable for you,
• if you have moderate kidney problems (for Tripliam doses containing 10 mg/2.5 mg/5 mg and 10 mg/2.5 mg/10 mg),
• if you are more than three months pregnant (Tripliam should also be avoided in early pregnancy) (see "Pregnancy and Breast-feeding"),
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren,
• if you are taking sacubitril/valsartan, a medicine used to treat heart failure (see "Warnings and precautions" and "Other medicines and Tripliam").

Warnings and precautions
Talk to your doctor or pharmacist before taking Tripliam:

• if you have hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidneys),
• if you suffer from other heart or kidney problems,
• if you have a severe increase in blood pressure (hypertensive crisis),
• if you have liver problems,
• if you have a collagen disease (skin disorder) such as systemic lupus erythematosus or scleroderma,
• if you suffer from atherosclerosis (hardening of the arteries),
• if you need to undergo a test to monitor parathyroid gland function,
• if you suffer from gout,
• if you have diabetes,
• if you are on a low-salt diet or use potassium-containing salt substitutes (maintaining balanced blood potassium levels is essential),
• if you are taking lithium or potassium-sparing diuretics (spironolactone, triamterene), as their use with Tripliam must be avoided (see "Other medicines and Tripliam"),
• if you are elderly and your dosage needs to be increased,
• if you have experienced photosensitivity reactions,
• if you are of Black ethnicity, you may have a higher risk of angioedema (swelling of the face, lips, mouth, tongue, or throat that may cause difficulty swallowing or breathing) and a reduced blood pressure-lowering effect,
• if you are a dialysis patient undergoing haemodialysis with high-flux membranes,
• if you have kidney problems or are undergoing dialysis,
• if you experience vision loss or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure, which may occur within hours or weeks after taking Tripliam. This may lead to permanent vision loss if not treated. If you previously had an allergy to penicillin or sulfonamides, you may be at higher risk,
• if you suffer from muscle disorders including muscle pain, tenderness, weakness, or cramps,
• if you have abnormally high levels of a hormone called aldosterone in your blood (primary aldosteronism),
• if you have excess acid in your blood, which may cause rapid breathing,
• if you have cerebral circulatory insufficiency (low blood pressure in the brain),
• if you develop swelling of the face, lips, mouth, tongue, or throat that may cause difficulty swallowing or breathing (angioedema), which can occur at any time during treatment—stop treatment immediately and contact your doctor,
• if you are 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 so-called mTOR inhibitors (used to prevent transplant rejection),
• sacubitril (available as a fixed-dose combination with valsartan), used for long-term treatment of heart failure.
• if you are taking any of the following medicines for high blood pressure:
• an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans—e.g. valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes,
• aliskiren. Your doctor may monitor your kidney function, blood pressure, and electrolyte levels (e.g. potassium) at regular intervals. See also the section "Do not take Tripliam".

Your doctor may order blood tests to check for low levels of sodium or potassium, or high levels of calcium.
You must inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). Tripliam is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the unborn baby if taken during this period (see "Pregnancy and Breast-feeding").
If you are taking Tripliam, inform your doctor or medical staff:

• if you are scheduled for anaesthesia and/or surgery,
• if you have recently had diarrhoea or vomiting, or if you are dehydrated,
• if you are due to undergo dialysis or LDL apheresis (blood purification to remove cholesterol using a machine),
• if you are undergoing desensitisation treatment to reduce allergic reactions to bee or wasp stings,
• if you are scheduled for a medical examination requiring injection of an iodinated contrast agent (a substance that makes organs such as kidneys or stomach visible on X-rays).
  For athletes: using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Children and adolescents
Tripliam must not be administered to children or adolescents.
Other medicines and Tripliam
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not take aliskiren (used to treat high blood pressure) if you have diabetes or kidney problems.
You must not take Tripliam with:

• lithium (used to treat certain mental health disorders such as mania, manic depression, and recurrent depression),
• potassium-sparing diuretics (such as triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes, or other medicines that may increase potassium levels in the blood (such as heparin and co-trimoxazole, also known as trimethoprim/sulfamethoxazole),
• dantrolene (infusion), also used to treat malignant hyperthermia during anaesthesia (symptoms include very high fever and muscle rigidity),
• estramustine (used in cancer therapy),
• medicines primarily used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the so-called mTOR inhibitors). See section "Warnings and precautions",
• sacubitril/valsartan (used for long-term treatment of heart failure). See section "Do not take Tripliam" and "Warnings and precautions",
• other medicines used to treat high blood pressure: angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers.

Treatment with Tripliam may be affected by other medicines. Your doctor may consider it necessary to adjust your dose and/or take other precautions. Make sure to inform your doctor if you are taking any of the following medicines, as special attention may be required:

• other medicines for treating hypertension, including an angiotensin II receptor antagonist (AIIRA), aliskiren (see also "Do not take Tripliam" and "Warnings and precautions") or diuretics (medicines that increase urine production by the kidneys),
• potassium-sparing diuretics used in heart failure treatment: eplerenone and spironolactone at doses between 12.5 mg and 50 mg daily,
• anaesthetics,
• iodinated 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, difemamilide, procainamide, quinidine, hydroquinidine, disopyramide, amiodarone, sotalol),
• verapamil, diltiazem (heart medicines),
• digoxin and other cardioactive glycosides (for treating heart problems),
• antibiotics used to treat bacterial infections (e.g. rifampicin, erythromycin, clarithromycin, sparfloxacin, moxifloxacin),
• antifungal medicines (e.g. itraconazole, ketoconazole, intravenous amphotericin B),
• allopurinol (for treating gout),
• antihistamines used to treat allergic reactions such as hay fever (e.g. mizolastine, terfenadine, or astemizole),
• corticosteroids used to treat various conditions including severe asthma and rheumatoid arthritis, and non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or high-dose salicylates (e.g. acetylsalicylic acid (aspirin)),
• immunosuppressants (medicines used to control the body's immune response) for treating autoimmune diseases or after organ transplantation (e.g. cyclosporine, tacrolimus),
• tetracosactide (for treating Crohn's disease),
• gold salts, especially for intravenous administration (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 for treating diabetes such as insulin or metformin,
• calcium, including calcium supplements,
• stimulant laxatives (e.g. senna),
• cancer treatments,
• vincamine (used to treat symptomatic cognitive disorders in the elderly, including memory loss),
• medicines used to treat mental health disorders such as depression, anxiety, schizophrenia (e.g. tricyclic antidepressants, antipsychotics, imipramine-like 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),
• Hypericum perforatum (St. John's wort),
• trimethoprim (for treating infections),
• medicines used to treat low blood pressure, shock, or asthma (e.g. ephedrine, noradrenaline, or adrenaline),
• nitroglycerin and other nitrates, or other vasodilators that may further reduce blood pressure.

Tripliam with food and drink
People taking Tripliam must not drink grapefruit juice or eat grapefruit, as grapefruit and its juice may increase blood levels of the active substance amlodipine, potentially leading to an unpredictable increase in the blood pressure-lowering effect of Tripliam.
Pregnancy and breast-feeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breast-feeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
Inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Tripliam before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine.
Tripliam is not recommended during early pregnancy, and must not be taken after the third month of pregnancy, as it may cause serious harm to the unborn baby if taken beyond the first trimester.
Breast-feeding
Inform your doctor if you are breast-feeding or planning to start breast-feeding.
Tripliam is not recommended for women who are breast-feeding. Your doctor may choose an alternative treatment if you wish to breast-feed, especially if your baby is newborn or was born prematurely.
Driving and using machines
Tripliam may affect your ability to drive or operate machinery. If the tablets cause you discomfort, dizziness, fatigue, or headache, avoid driving or operating machinery and contact your doctor immediately.
Tripliam contains sodium
Tripliam contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially "sodium-free".

3. How to take Tripliam

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

The tablet should be swallowed with a glass of water, preferably in the morning and before a meal.

Your doctor will determine the correct dose for you. The usual dose is one tablet daily.

If you take more Tripliam than you should
If you take too many tablets, your blood pressure could drop, possibly excessively, which may be dangerous and sometimes associated with nausea, vomiting, cramps, dizziness, drowsiness, mental confusion, oliguria (reduced urine output compared to normal), anuria (absence of urine production or output). You may feel dizzy, weak, or faint. The drop in blood pressure could be so severe as to cause shock. Your skin may become cold and clammy, and you may lose consciousness. If you have taken an excessive number of Tripliam tablets, contact your doctor immediately.

If you forget to take Tripliam
It is important to take the medicine every day, as regular treatment is more effective. However, if you forget to take a dose of Tripliam, take the next dose as usual. Do not take a double dose to make up for the missed dose.

If you stop taking Tripliam
Since treatment with Tripliam for hypertension is usually lifelong, you must speak with your doctor before stopping this medicine.

If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following serious side effects, stop taking the medicine immediately and contact your
doctor straight away:

• sudden onset of breathlessness, chest pain, shortness of breath or difficulty breathing (uncommon) (less than 1 in 100)
• swelling of the eyelids, face or lips (uncommon) (less than 1 in 100)
• swelling of the mouth, tongue and throat which may cause severe breathing difficulties (uncommon) (less than 1 in 100)
• severe skin reactions including intense rash, hives, redness of the skin all over the body, severe itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis) or other allergic reactions (very rare) (less than 1 in 10,000)
• severe dizziness or fainting (common) (less than 1 in 10)
• myocardial infarction (very rare) (less than 1 in 10,000), irregular heartbeat which could be life-threatening (not known)
• inflammation of the pancreas which may cause severe abdominal and back pain associated with a strong feeling of being unwell (very rare) (less than 1 in 10,000)
• muscle weakness, cramps, soreness or pain, particularly if at the same time you feel unwell or have a high fever, which may be due to abnormal muscle breakdown (not known)

In order of decreasing frequency, side effects may include:

• Very common (may affect more than 1 in 10 people): oedema (fluid retention).

• Common (may affect up to 1 in 10 people): headache, dizziness, palpitations (awareness of your heartbeat), hot flushes, vertigo, tingling sensations, visual disturbances, double vision, tinnitus (ringing in the ears), lightheadedness due to low blood pressure, cough, shortness of breath, gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, indigestion or difficulty digesting, diarrhoea, constipation, changes in bowel habits), allergic reactions (such as skin rashes, itching), muscle spasms, feeling of fatigue, weakness, drowsiness, swelling of the ankles.

• Uncommon (may affect up to 1 in 100 people): mood changes, anxiety, depression, sleep disorders, tremors, urticaria, fainting, loss of pain sensation, irregular and/or rapid heartbeat, rhinitis (stuffy or runny nose), hair loss, purpura (red spots on the skin), skin discoloration, skin itching, sweating, chest pain, joint or muscle pain, back pain, pain,
  feeling unwell, kidney disorders, problems passing urine, increased need to urinate at night, increased frequency of urination,
  impotence, fever or high temperature, discomfort or enlargement of the breasts in men, weight gain or loss, increased white blood cell count, elevated plasma potassium levels, hypoglycaemia (very low blood sugar levels), low blood sodium levels, vasculitis (inflammation of blood vessels), photosensitivity reaction (skin changes) after exposure to sunlight or artificial UVA, clusters of blisters on the skin, swelling of hands or feet, increased plasma creatinine and increased plasma urea, falls, dry mouth.

• Rare (may affect up to 1 in 1,000 people): confusion, changes in laboratory parameters: increased liver enzyme levels, high serum bilirubin levels, and worsening of psoriasis.

• Very rare (may affect up to 1 in 10,000 people): decrease in white blood cell count, decrease in platelet count (which may lead to unusual bruising or tendency to bleed), anaemia (reduction in red blood cells), angina pectoris (chest, jaw and back pain caused by physical exertion due to problems with blood flow to the heart), eosinophilic pneumonia (a rare type of pneumonia), gum swelling, severe skin reactions including intense rash, redness of the skin all over the body, severe itching, blisters, peeling or swelling of the skin, erythema multiforme (a skin rash that often starts with itchy red spots on the face, arms and legs), bleeding, soft or enlarged gums, abnormal liver function, inflammation of the liver (hepatitis), severe kidney problems, yellowing of the skin (jaundice), abdominal swelling (gastritis), nerve disorders which may cause weakness, tingling or numbness, increased muscle tension, hyperglycaemia (very high blood sugar levels), high blood calcium levels, stroke possibly secondary to excessive drop in blood pressure.

• Not known (frequency cannot be estimated from the available data): hepatic encephalopathy (brain disorder caused by liver disease), abnormal ECG (electrocardiogram), low blood potassium levels, if you have systemic lupus erythematosus (a collagen disease), this may worsen. Myopia, blurred vision, reduced vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma). Tremors, postural rigidity, mask-like facial expression, slow movements, unbalanced and shuffling gait. Abnormal colour, numbness and pain in fingers or toes (Raynaud's phenomenon). Changes in laboratory parameters (blood tests) may occur. Your doctor may prescribe laboratory tests to monitor your condition.

With the use of ACE inhibitors, very concentrated (dark-coloured) urine, feeling unwell or malaise, muscle cramps, confusion and seizures may occur, probably due to inappropriate secretion of ADH (antidiuretic hormone). If you experience these symptoms, contact your doctor immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tripliam

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and container. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
For the pack containing 28 and 30 film-coated tablets, the stability after first opening is 30 days.
For the pack containing 100 film-coated tablets, the stability after first opening is 100 days.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Tripliam Contains

• The active substances are perindopril arginine, indapamide and amlodipine. One film-coated tablet of Tripliam 5/1.25/5 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 Tripliam 5/1.25/10 mg contains 3.395 mg of perindopril equivalent to 5 mg of perindopril arginine, 1.25 mg of indapamide and 13.870 mg of amlodipine besylate equivalent to 10 mg of amlodipine. One film-coated tablet of Tripliam 10/2.5/5 mg contains 6.790 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 Tripliam 10/2.5/10 mg 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.

The other components are:

• Core: Calcium carbonate starch complex: calcium carbonate 90%, pregelatinized maize starch 10%, microcrystalline cellulose (E460), sodium croscarmellose (E468), magnesium stearate (E572), anhydrous colloidal silica, pregelatinized starch.
• Film coating: glycerol (E422), hypromellose 6 mPa.s (E464), macrogol 6000, magnesium stearate (E572), titanium dioxide (E171).

Description of the Appearance of Tripliam and Contents of the Package
Tripliam 5/1.25/5 mg: film-coated tablet, white, oblong, 9.75 mm in length and 5.16 mm in

width, engraved on one side and on the other.

Tripliam 5/1.25/10 mg: film-coated tablet, white, oblong, 10.7 mm in length and 5.66 mm in
width, engraved on one side and on the other.

Tripliam 10/2.5/5 mg: film-coated tablet, white, oblong, 11.5 mm in length and 6.09 mm in

width, engraved on one side and on the other.

Tripliam 10/2.5/10 mg: film-coated tablet, white, oblong, 12.2 mm in length and 6.46 mm in

width, engraved on one side and on the other.

Tablets are available in packs of 10, 28, 30, 60 (2 containers of 30 tablets), 84 (3 containers of 28 tablets), 90 (3 containers of 30 tablets), 100, and 500 tablets (5 containers of 100 tablets).
A desiccant is present in the cap of the tablet containers.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes Cedex
France

Marketing Authorization Holder for Italy
Servier Italia S.p.A.
Via Luca Passi, 85
00166 Roma
Italy

Manufacturers:
Servier (Ireland) Industries Ltd
Gorey Road
Arklow - Co. Wicklow – Ireland
and
Les Laboratoires Servier Industrie
905 route de Saran
45520 Gidy – France
and
Anpharm Przedsiebiorstwo Farmaceutyczne S.A.
03-236 Warszawa
ul. Annopol 6b – Poland
and
EGIS Pharmaceuticals PLC
H-9900 Körmend, Mátyás király u.65
Hungary

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Belgium TRIPLIXAM, film-coated tablet
Bulgaria TRIPLIXAM, film-coated tablets
Cyprus TRIPLIXAM, film-coated tablets
Czech Republic TRIPLIXAM
Croatia TRIPLIXAM, film-coated tablets
Estonia TRIPLIXAM
Finland TRIPLIXAM, film-coated tablet
France TRIPLIXAM, comprimé pelliculé
Greece TRIPLIXAM, film-coated tablets
Ireland COVERDINE film-coated tablets
Italy TRIPLIAM, film-coated tablets
Latvia TRIPLIXAM, 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, film-coated tablets
Slovenia TRIPLIXAM, film-coated tablets