Noliterax

Package leaflet: information for the patient

NOLITERAX 10 mg/2.5 mg film-coated tablets

perindopril arginine/indapamide
Read this leaflet carefully before taking this medicine because 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 personally. Never give it to others. It may be harmful to other people, even if their symptoms are the same as yours.
• If any of the side effects worsens, or if you notice any side effect not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What NOLITERAX is and what it is used for

NOLITERAX is a combination of two active substances, perindopril and indapamide. It is an antihypertensive
and is used in the treatment of high blood pressure (hypertension). NOLITERAX is indicated for
patients who are already taking perindopril 10 mg and indapamide 2.5 mg separately, and who may instead take a single tablet of NOLITERAX containing both active substances.
Perindopril belongs to a class of medicines called ACE inhibitors. These medicines work
by dilating blood vessels, making it easier for the heart to pump blood through them. Indapamide
is a diuretic. 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. Each active substance reduces blood pressure, and together they act to control blood pressure.

2. What you need to know before taking NOLITERAX

Do not take NOLITERAX

• if you are allergic (hypersensitive) to perindopril or any other ACE inhibitor, or to indapamide or any other sulfonamide, or to any of the excipients of this medicine (listed in section 6),
• if you have experienced symptoms such as shortness of breath, facial or tongue swelling, intense itching, or severe skin rashes related to previous treatment with ACE inhibitors, or if you or a family member has ever had such symptoms under any circumstances (a condition called angioedema),
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren,
• if you have severe liver disease or suffer from a condition called hepatic encephalopathy (a degenerative brain disorder),
• if you have a kidney disease causing 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, NOLITERAX therapy may not be suitable for you,
• if you have low plasma potassium levels,
• if you suspect you have untreated decompensated heart failure (severe fluid retention, breathing difficulties),
• if you are more than three months pregnant. (NOLITERAX should also be avoided during early pregnancy – see section “Pregnancy”),
• if you are being treated with sacubitril/valsartan, a medicine used to treat heart failure (see information under “Warnings and precautions” and “Other medicines and NOLITERAX”).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using NOLITERAX:

• if you have aortic stenosis (narrowing of the main artery leaving the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the artery supplying blood to the kidneys),
• if you suffer from heart failure or other heart problems,
• if you have kidney problems or are on dialysis,
• if you experience vision changes 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 of taking NOLITERAX. 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 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 have hyperparathyroidism (overactivity of the parathyroid glands),
• if you suffer from gout,
• if you have diabetes,
• if you are on a low-salt diet or use potassium-containing salt substitutes,
• if you are taking lithium or potassium-sparing medicines (spironolactone, triamterene) or potassium supplements; their use with NOLITERAX should be avoided (see “Taking with other medicines”),
• if you are elderly,
• if you have had photosensitivity reactions,
• if you suffer from severe allergic reactions with swelling of the face, lips, mouth, tongue, or throat that may cause difficulty swallowing or breathing (angioedema). This may occur at any time during treatment. If such symptoms develop, stop treatment and contact a doctor immediately,
• 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 blood electrolyte levels (e.g., potassium) at regular intervals. See also section “Do not take NOLITERAX”.
• if you are of Black origin, as you may have a higher risk of angioedema and this medicine may be less effective in lowering your blood pressure compared to non-Black patients,
• if you are a patient undergoing hemodialysis with high-flux dialysis membranes,
• if you are taking any of the following medicines, which increase the risk of angioedema:
• racecadotril (used to treat diarrhea),
• 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.

Angioedema
Angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat, causing difficulty swallowing or breathing) has been reported in patients treated with ACE inhibitors, including NOLITERAX. This may occur at any time during treatment. If such symptoms develop, stop treatment with NOLITERAX and contact a doctor immediately. See also section 4.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). NOLITERAX is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn baby if taken during this period (see “Pregnancy and breastfeeding”).
If you are taking NOLITERAX, inform your general practitioner or medical staff:

• if you are scheduled for anesthesia and/or surgery,
• if you have recently had diarrhea or vomiting, or if you are dehydrated,
• if you are scheduled for dialysis or LDL apheresis (blood purification to remove cholesterol using a machine),
• if you are undergoing desensitization 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 used to make organs such as kidneys or stomach visible on X-rays),
• if you experience vision disturbances or pain in one or both eyes while taking NOLITERAX. This could be a sign of developing glaucoma, increased pressure in the eye(s). Stop treatment with NOLITERAX and consult a doctor.

Athletes should be aware that NOLITERAX contains an active substance (indapamide) that may lead to a positive result in doping tests.
For individuals engaged in sports: using the medicine without therapeutic need constitutes doping and may result in a positive doping test.

Children and adolescents
NOLITERAX must not be administered to children or adolescents.

Other medicines and NOLITERAX
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Do not take NOLITERAX with:

• lithium (used to treat manic disorder and depression),
• aliskiren (a medicine used to treat hypertension) if you have diabetes or kidney problems,
• potassium-sparing diuretics (triamterene, amiloride), potassium salts, or other medicines that may increase potassium levels in the blood (such as heparin and co-trimoxazole, also known as trimethoprim/sulfamethoxazole),
• estramustine (used in cancer therapy),
• other medicines used to treat high blood pressure: angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers.

Treatment with NOLITERAX may be affected by other medicines. Your doctor may need 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 high blood pressure, including an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections “Do not take NOLITERAX” 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,
• medicines mainly used to treat diarrhea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other mTOR inhibitors). See section “Warnings and precautions”,
• sacubitril/valsartan (used for long-term treatment of heart failure). See section “Do not take NOLITERAX” and “Warnings and precautions”,
• anesthetics,
• iodinated contrast agents,
• antibiotics used to treat bacterial infections (e.g., moxifloxacin, sparfloxacin, injectable erythromycin),
• methadone (used to treat addiction),
• procainamide (for irregular heartbeat),
• allopurinol (for gout treatment),
• antihistamines used for allergic reactions such as hay fever (e.g., mizolastine, terfenadine, astemizole),
• corticosteroids used to treat various conditions including severe asthma and rheumatoid arthritis,
• immunosuppressants used to treat autoimmune diseases or prevent transplant rejection (e.g., cyclosporine, tacrolimus),
• halofantrine (used to treat certain types of malaria),
• pentamidine (used to treat pneumonia),
• injectable gold (used to treat rheumatoid arthritis),
• vincamine (used to treat symptomatic cognitive disorders in the elderly, including memory loss),
• bepridil (used to treat angina pectoris),
• medicines used to treat heart rhythm disorders (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis, bretylium),
• cisapride, difemanil (used to treat gastrointestinal and digestive problems),
• digoxin or other digitalis glycosides (for heart problems),
• baclofen (to treat muscle stiffness in conditions such as multiple sclerosis),
• medicines for diabetes such as insulin, metformin, or gliptins,
• calcium, including calcium supplements,
• stimulant laxatives (e.g., senna),
• non-steroidal anti-inflammatory drugs (e.g., ibuprofen) or high-dose salicylates (e.g., aspirin),
• injectable amphotericin B (for serious fungal infections),
• medicines used to treat mental disorders such as depression, anxiety, schizophrenia (e.g., tricyclic antidepressants, neuroleptics such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol),
• tetracosactide (for Crohn’s disease treatment),
• trimethoprim (for infections),
• vasodilators including nitrates (substances that widen blood vessels),
• medicines used to treat low blood pressure, shock, or asthma (e.g., ephedrine, noradrenaline, or adrenaline).

NOLITERAX with food and drinks
It is preferable to take NOLITERAX before a meal.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking any medicine.

Pregnancy
Your doctor will normally advise you to stop taking NOLITERAX before planning a pregnancy or as soon as you know you are pregnant, and will recommend an alternative medicine.
NOLITERAX 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 third month.

Breastfeeding
NOLITERAX is not recommended for breastfeeding mothers. Your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is newborn or was born prematurely.
Inform your doctor immediately.

Driving and using machines
NOLITERAX does not affect alertness, but in some patients, side effects such as dizziness or fatigue may occur due to blood pressure reduction. If you experience such symptoms, your ability to drive or operate machinery may be impaired.

NOLITERAX contains lactose (a type of sugar).
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

NOLITERAX contains sodium
NOLITERAX contains less than 1 mmol of sodium (23 mg) per tablet and is therefore essentially "sodium-free".

3. How to take NOLITERAX

Always take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose is one tablet daily. Take the tablet preferably in the morning and
before a meal. Swallow the tablet with a glass of water.
If you take more NOLITERAX than you should
If you have taken an excessive amount of tablets, consult your doctor immediately or go
immediately to the nearest emergency room. The most likely effect in case of overdose is a
lowering of blood pressure. If a marked drop in blood pressure occurs (associated with
nausea, vomiting, cramps, dizziness, drowsiness, mental confusion, changes in the amount of urine
produced by the kidneys), it may help to lie down with your legs elevated.
If you forget to take NOLITERAX
It is important to take the medicine every day, as regular treatment is more effective. If
however you forget to take a dose of NOLITERAX, take the next dose at your usual time.
Do not take a double dose to make up for the forgotten previous dose.
If you stop taking NOLITERAX
Since treatment for hypertension is usually lifelong, you must speak with your doctor before
stopping this medicine.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, NOLITERAX can cause side effects, although not everyone gets them.
Stop taking the medicine immediately and contact your doctor straight away if you experience
any of the following, which may be serious:

• Severe dizziness or fainting due to low blood pressure (common) (up to 1 in 10 people),
• Bronchospasm (tightness of the chest, wheezing and breathlessness) (uncommon) (up to 1 in 100 people),
• Swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (see section 2 “Warnings and precautions”) (uncommon) (up to 1 in 100 people),
• Severe skin reactions including intense rash, urticaria, redness of the skin all over the body, severe itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome) or other allergic reactions (very rare) (up to 1 in 10,000 people),
• Cardiovascular disorders (irregular heartbeat, angina pectoris (chest, jaw and back pain caused by physical exertion)) (very rare) (up to 1 in 10,000 people),
• Weakness in arms or legs, or speech problems which could be signs of a possible stroke (very rare) (up to 1 in 10,000 people),
• Inflammation of the pancreas which may cause severe abdominal pain and backache accompanied by feeling unwell (very rare) (up to 1 in 10,000 people),
• Yellowing of the skin or eyes (jaundice) which may be a sign of hepatitis (very rare) (up to 1 in 10,000 people),
• Life-threatening irregular heartbeat (frequency not known),
• Brain disorder caused by liver disease (hepatic encephalopathy) (frequency not known),
• Muscle weakness, cramps, tenderness or pain, particularly if at the same time you feel unwell or have a high fever, which could be due to abnormal muscle breakdown (frequency not known).

In decreasing order of frequency, side effects may include:

• Common (up to 1 in 10 people): Skin reactions in people predisposed to allergies and asthmatic reactions, headache, dizziness, vertigo, tingling, visual disturbances, tinnitus (sensation of noise in the ears), cough, shortness of breath (dyspnoea), gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, dyspepsia or indigestion, diarrhoea, constipation), allergic reactions (such as skin rashes, itching), cramps, feeling of fatigue,
• Uncommon (up to 1 in 100 people): Mood changes, sleep disorders, urticaria, purpura (red spots on the skin), blistering in clusters, kidney disorders, impotence, sweating, eosinophilia (an increased number of eosinophils, a type of white blood cell), changes in laboratory parameters: high blood potassium levels (reversible upon discontinuation), low blood sodium levels, drowsiness, fainting, palpitations (awareness of heartbeat), tachycardia (fast heartbeat), hypoglycaemia (low blood sugar levels) in diabetic patients, vasculitis (inflammation of blood vessels), dry mouth, photosensitivity reactions (increased skin sensitivity to sunlight), arthralgia (joint pain), myalgia (muscle pain), chest pain, malaise, peripheral oedema, fever, increased blood urea, increased blood creatinine, falls,
• Rare (up to 1 in 1,000 people): Worsening of psoriasis, changes in laboratory parameters: increased liver enzyme levels, elevated serum bilirubin levels, fatigue,
• Very rare (up to 1 in 10,000 people):

Confusion, eosinophilic pneumonia (a rare type of pneumonia), rhinitis (blocked or runny nose),
severe kidney problems, changes in blood parameters such as reduced numbers of white and red blood cells, lower haemoglobin, reduced platelet count, elevated blood calcium levels, abnormal liver function.

• Not known (frequency cannot be estimated from the available data):
• Abnormal ECG trace, changes in laboratory parameters: low potassium levels, high uric acid levels and high blood sugar levels, reduced vision (myopia), blurred vision, visual impairment, decreased 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), abnormal colour, numbness and pain in fingers of hands or feet (Raynaud's phenomenon). If you suffer from systemic lupus erythematosus (a connective tissue disease), this may worsen.

Haematological, renal, hepatic or pancreatic disorders and 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, sensation or state of malaise, muscle cramps, confusion and seizures may occur, probably due to inappropriate ADH (antidiuretic hormone) secretion. 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, pharmacist or nurse. 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 NOLITERAX

Keep this medicine out of the reach and sight 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 the month.
Keep the container tightly closed to protect the product from moisture. This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What NOLITERAX contains

• The active substances are perindopril arginine and indapamide. One film-coated tablet contains 10 mg of perindopril arginine (equivalent to 6.79 mg of perindopril) and 2.5 mg of indapamide.
• The excipients in the tablet core are: monohydrate lactose, magnesium stearate (E470B), maltodextrin, anhydrous colloidal silicon dioxide (E551), sodium starch glycolate (type A), and in the
  film coating: glycerol (E422), hypromellose (E464), macrogol 6000, magnesium stearate (E470B), titanium dioxide (E171).

Description of the appearance of NOLITERAX and contents of the pack
NOLITERAX tablets are white, round, film-coated tablets with a diameter of 8 mm and a curvature radius of 11 mm. Each film-coated tablet contains 10 mg of perindopril arginine and 2.5 mg of indapamide.
Tablets are available in containers containing 14, 20, 28, 30, 50, 56, 60, 90, 100 or 500 tablets.
Not all pack sizes may be marketed.

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

Manufacturer
Les Laboratoires Servier Industrie
905 route de Saran
45520 Gidy – France
and
Servier (Ireland) Industries Ltd
Gorey Road
Arklow – Co. Wicklow – Ireland
and
ANPHARM Przedsiębiorstwo Farmaceutyczne S.A.
ul. Annopol 6B
03-236 Warszawa – Poland

Local Representative of the Marketing Authorization Holder
Servier Italia S.p.A.
Via Luca Passi, 85
00166 Roma – Italy

This medicinal product is authorized in the European Economic Area countries under the following names:
Belgium PRETERAX 10mg/2.5mg
Bulgaria NOLIPREL Bi-FORTE
Cyprus Preterax 10 mg/2.5 mg
Czech Republic Prestarium Neo Combi 10mg/2.5mg
Estonia NOLITERAX 10 mg /2.5 mg
Finland COVERSYL COMP NOVUM 10 mg/2.5mg
France BIPRETERAX 10mg/2.5mg comprimé pelliculé
Greece Preterax 10mg/2.5mg
Ireland COVERSYL ARGININE PLUS 10mg/2.5mg
Italy NOLITERAX 10 /2.5
Latvia NOLITERAX 10 mg /2.5 mg apvalkotās tabletes
Lithuania NOLITERAX 10 mg /2.5 mg plėvelė dengtos tabletės
Luxembourg PRETERAX 10 mg/2.5mg
Malta COVERSYL PLUS 10mg/2.5mg
Netherlands COVERSYL PLUS arg 10mg/2.5mg
Poland NOLIPREL Bi-FORTE
Portugal PRETERAX
Romania NOLITERAX 10 mg/2.5 mg
Slovakia NOLIPREL Bi-FORTE A
Slovenia BIONOLIPREL 10mg/2.5mg filmsko obložene tablete