Imbaxir

Package leaflet: Information for the patient

Imbaxir 5 mg/1.5 mg modified-release tablets, 10 mg/1.5 mg modified-release tablets

Ramipril/Indapamide
Please 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 only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Imbaxir is and what it is used for

Imbaxir contains two active substances: ramipril and indapamide. It is an antihypertensive medicine used in the treatment of high blood pressure (hypertension). Ramipril belongs to a group of medicines called ACE inhibitors (angiotensin-converting enzyme inhibitors). These work by dilating blood vessels, making it easier for the heart to pump blood around the body. 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 of the active substances helps reduce blood pressure, and together they act to control blood pressure.
Imbaxir is used to treat hypertension (high blood pressure) in adult patients whose blood pressure is adequately controlled with concomitant use of indapamide and ramipril administered at the same dose as in Imbaxir, but as separate medicines.

2. What you need to know before taking Imbaxir

Do not take Imbaxir

• if you are allergic to ramipril, indapamide (active substances), to any other ACE inhibitor, or to any other sulfonamide, or to any of the other ingredients of this medicine (listed in section 6). Allergic reactions may include itching, skin redness, or difficulty breathing
• if you have ever had a severe allergic reaction called "angioedema". Signs include itching, hives, red spots on the hands, feet, and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing or swallowing
• if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults: the risk of angioedema (rapid swelling beneath the skin, such as in the throat area) is increased
• if you are undergoing dialysis or any other type of blood filtration. Depending on the equipment used, Imbaxir may not be suitable for you
• if you have severe kidney disease or have kidney problems due to reduced blood flow to the kidneys (renal artery stenosis)
• during the last 6 months of pregnancy (see section below "Pregnancy and breastfeeding")
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren
• if your blood pressure is abnormally low or unstable. Your doctor must assess this
• if you have liver disease or suffer from a condition called hepatic encephalopathy (a degenerative brain disorder)
• if you have low levels of potassium in your blood.

Do not take Imbaxir if any of these conditions apply to you. If you are unsure, consult your doctor before taking Imbaxir.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before taking Imbaxir. Consult your doctor if any of the following conditions apply to you:

• if you have heart, heart rhythm, liver, or kidney problems
• if you have lost significant amounts of body salts or fluids (due to illness (vomiting), diarrhoea, excessive sweating, low-salt diet, long-term use of diuretics (water tablets), or previous dialysis)
• if you are about to undergo treatment to reduce allergy to bee or wasp stings (desensitisation)
• if you are about to receive an anaesthetic. This may be administered for surgery or any dental procedure. You may need to stop taking Imbaxir one day before the procedure. Ask your doctor for advice
• if you have high levels of potassium in your blood (shown by blood tests)
• if you suffer from a collagen vascular disease such as scleroderma or systemic lupus erythematosus
• if you are taking medicines or have conditions that may reduce sodium levels in your blood. Your doctor may request regular blood tests, particularly to monitor sodium levels, especially if you are elderly
• if you are taking any of the following medicines for high blood pressure:
  • an angiotensin II receptor antagonist (ARB) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes
  • aliskiren
• you must inform your doctor if you think you are pregnant (or could become pregnant). Ramipril is not recommended during the first 3 months of pregnancy and may cause severe harm to the unborn baby after the third month of pregnancy (see section below "Pregnancy, breastfeeding and fertility")
• if you have diabetes
• if you have gout
• if you experience 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 may occur from a few hours to a week after taking Imbaxir. If untreated, this condition may lead to permanent vision loss. If you have previously had an allergy to penicillin or sulfonamide, you may be at higher risk of developing these symptoms.
• if you have muscle disorders, including pain, tenderness, weakness, or cramps
• if you are due to undergo a test to assess the function of your parathyroid glands
• if you are taking any of the following medicines, as the risk of angioedema may be higher:
  • neprilysin inhibitors (such as racecadotril), a medicine used to treat diarrhoea
  • medicines used to prevent rejection of an organ transplant or to treat cancer, such as mTOR inhibitors (e.g. temsirolimus, sirolimus, everolimus)
  • vildagliptin, a medicine used to treat diabetes
  • sacubitril/valsartan (see section 2 "Do not take Imbaxir").

Inform your doctor if you have experienced photosensitivity reactions.

Your doctor may regularly monitor your kidney function, blood pressure, and levels of electrolytes (e.g. sodium, potassium, or calcium) in your blood. See also the information in section "Do not take Imbaxir".

Children and adolescents

The use of Imbaxir is not recommended in children and adolescents under 18 years of age, as there is insufficient information available in this population.

Other medicines and Imbaxir

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

Do not take Imbaxir with lithium (used to treat depression) due to the risk of increased lithium levels in the blood.

Inform your doctor if you are taking any of the following medicines, as they may reduce the effect of Imbaxir:

• medicines to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or indomethacin, and aspirin)
• medicines used to treat low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, or adrenaline. Your doctor will need to monitor your blood pressure.

Inform your doctor if you are taking any of the following medicines. They may increase the likelihood of developing side effects when taken with Imbaxir:

• sacubitril/valsartan – used to treat chronic heart failure in adults (see section 2 "Do not take Imbaxir")
• sirolimus, everolimus (to prevent rejection of an organ transplant)
• cyclosporine, an immunosuppressive medicine used to prevent rejection of an organ transplant
• medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or indomethacin, and acetylsalicylic acid)
• anticancer medicines (chemotherapeutics) such as temsirolimus
• diuretics (water tablets), such as furosemide
• medicines that may increase potassium levels in the blood, such as spironolactone, triamterene, amiloride, potassium salts, trimethoprim alone or in combination with sulfamethoxazole (for infections), and heparin, a medicine used to thin the blood to prevent clotting
• allopurinol (used to reduce uric acid levels in the blood)
• procainamide (for heart rhythm disorders)
• vildagliptin (to treat type 2 diabetes)
• racecadotril (used to treat diarrhoea)
• medicines used to treat heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis, bretylium)
• medicines used to treat mental disorders such as depression, anxiety, and schizophrenia (e.g. tricyclic antidepressants, antipsychotics, neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol))
• bepridil (used to treat angina pectoris, a condition causing chest pain)
• cisapride, difemanil (used to treat gastrointestinal problems)
• antibiotics to treat bacterial infections (e.g. sparfloxacin, moxifloxacin, injectable erythromycin)
• injectable vincamine (used to treat symptomatic cognitive disorders in the elderly, including memory loss)
• halofantrine (an antiparasitic drug used to treat certain types of malaria)
• pentamidine (used to treat certain types of pneumonia)
• antihistamines to treat allergic reactions, such as hay fever (e.g. mizolastine, astemizole, terfenadine)
• injectable amphotericin B (an antifungal medicine)
• oral corticosteroids used to treat various conditions, including inflammation, severe asthma, and rheumatoid arthritis
• stimulant laxatives
• baclofen (to treat muscle stiffness occurring in diseases such as multiple sclerosis)
• digitalis preparations (to strengthen the heart and reduce heart rate)
• metformin (to treat diabetes)
• iodinated contrast media (used in X-ray examinations)
• calcium tablets or other calcium supplements
• tacrolimus (to prevent rejection of an organ transplant)
• tetracosactide (to treat Crohn's disease)
• methadone (used to treat addiction).

Your doctor may need to adjust your dose and/or take other precautions:

If you are taking an angiotensin II receptor antagonist (ARB) or aliskiren (see also information in sections "Do not take Imbaxir" and "Warnings and precautions").

Inform your doctor if you are taking any of the following medicines. Imbaxir may alter their effect:

• medicines for diabetes, such as oral hypoglycaemics and insulin. Imbaxir may reduce blood sugar levels. Monitor your blood sugar levels carefully while taking Imbaxir.

If any of the above conditions apply to you (or you are unsure), contact your doctor before taking Imbaxir.

For athletes: using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Imbaxir with food, drinks, and alcohol

Imbaxir can be taken with or without food.

Drinking alcohol with Imbaxir may cause dizziness or lightheadedness. If you have any doubts about how much alcohol you can consume while taking Imbaxir, consult your doctor, as blood pressure-lowering medicines and alcohol may have additive effects.

Pregnancy, breastfeeding and fertility

If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy

Your doctor will usually advise you to stop taking Imbaxir before becoming pregnant or as soon as pregnancy is confirmed, and will recommend an alternative medicine instead of Imbaxir.

Imbaxir is not recommended during early pregnancy and must not be taken after the first 3 months of pregnancy, as it may cause severe harm to the unborn baby if used beyond the third month of pregnancy.

Breastfeeding

Imbaxir is not recommended for breastfeeding mothers, and your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is a newborn or was born prematurely.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Imbaxir may affect your ability to drive or operate machinery. Do not drive or operate machinery if Imbaxir makes you feel unwell, dizzy, tired, or causes headache.

Imbaxir contains lactose

If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

Imbaxir contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially "sodium-free".

3. How to take Imbaxir

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Contact your doctor or pharmacist if you think that the effect of Imbaxir is too strong or too weak.
The recommended dose is one tablet daily. Take the tablet preferably in the morning and before a meal.
Swallow the tablet whole with a glass of water; do not chew it.
Your doctor may adjust the dose depending on how the medicine affects you.

Use in children and adolescents
Imbaxir is not recommended for use in children and adolescents under 18 years of age, as there is no available information in this population.

If you take more Imbaxir than you should
If you take too many tablets, contact your doctor or the nearest hospital immediately.
The most likely effect in case of overdose is low blood pressure. In the case of marked low blood pressure (associated with nausea, vomiting, cramps, dizziness, drowsiness, confusion, changes in the amount of urine produced by the kidneys), it may be helpful to lie down with your legs raised.

If you forget to take Imbaxir
If you forget to take a tablet, completely skip that dose. Take the next tablet at your usual time. Do not take a double dose to make up for the forgotten dose.

If you stop taking Imbaxir
Since the treatment of hypertension usually lasts a lifetime, you must consult 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, this medicine can cause side effects, although not everybody gets them.

Stop taking Imbaxir and contact your doctor immediately if you notice any of the following serious side effects – you may require urgent medical treatment:

• swelling of the face, lips or throat causing difficulty in swallowing or breathing, together with itching and skin rashes. This could be a sign of a severe allergic reaction to Imbaxir (frequency not known).
• angioedema: angioedema is characterised by swelling of the skin of the extremities or face, swelling of the lips or tongue, swelling of the mucous membranes of the throat or airways causing shortness of breath or difficulty in swallowing. If this occurs, contact your doctor immediately (not common) (may affect up to 1 in 100 people).
• severe skin reactions, including severe rash, redness of the skin all over the body, intense itching, skin rash with blisters, peeling and swelling of the skin, inflammation of the mucous membranes (Stevens-Johnson syndrome) or other allergic reactions (very rare) (may affect up to 1 in 10,000 people)
• irregular heartbeat that could be life-threatening (frequency not known)
• inflammation of the pancreas which may cause severe abdominal and back pain, together with a feeling of severe illness (very rare) (may affect up to 1 in 10,000 people)
• brain disease caused by liver disease (hepatic encephalopathy) (frequency not known)
• inflammation of the liver (hepatitis) (frequency not known)
• muscle weakness, cramps, soreness or muscle pain, particularly if, at the same time, you feel unwell or have a high temperature, which may be due to abnormal muscle breakdown (frequency not known).

Contact your doctor immediately if you experience:

• rapid, irregular or fast heartbeat (palpitations), chest pain, chest tightness or more serious problems, including heart attack and stroke. The frequencies of these side effects are common (chest pain, chest tightness, palpitations) or not common (rapid heartbeat, heart attack or stroke).
• shortness of breath or cough. These may be signs of lung problems. These are common side effects.
• easier bruising, bleeding that lasts longer than normal, any sign of bleeding (e.g. bleeding gums), development of purple spots or spots on the skin, or increased susceptibility to infections, sore throat and fever, feeling tired, weak, dizzy or pale complexion. These may be signs of blood or bone marrow problems (frequency not known).
• severe stomach pain spreading to the back. This could be a sign of pancreatitis (inflammation of the pancreas). These are uncommon side effects.
• fever, chills, tiredness, loss of appetite, stomach pain, feeling unwell, yellowing of the skin or eyes (jaundice). These may be signs of liver problems such as hepatitis (inflammation of the liver) or liver damage (frequency very rare).

Other side effects include:
Inform your doctor if any of the following side effects worsen or persist for more than a few days.
Common (may affect up to 1 in 10 people):

• dizziness (especially at the beginning of treatment)
• headache or feeling tired
• fainting, hypotension (abnormally low blood pressure), especially when standing up or getting up quickly
• dry, irritable cough, inflammation of the sinuses (sinusitis) or bronchitis, shortness of breath
• stomach or intestinal pain, diarrhoea, indigestion, feeling unwell or nausea (vomiting)
• skin rash with or without swellings
• allergic reactions, mainly dermatological, in individuals predisposed to allergic and asthmatic reactions
• chest pain
• muscle cramps or muscle pain
• blood tests showing higher than usual levels of potassium in the blood
• low levels of potassium in the blood

Uncommon (may affect up to 1 in 100 people):

• sleep problems
• heartburn, constipation or dry mouth
• production of larger than usual amounts of urine during the day
• increased sweating
• sudden redness of the face, neck or upper chest due to increased blood flow
• sexual problems in men (inability to achieve or maintain an erection), reduced sexual desire in women
• balance problems (dizziness)
• itching and unusual sensations on the skin, such as numbness, tingling, pins and needles, burning or stinging on the skin (paraesthesia)
• blurred vision
• loss or change in taste
• feeling depressed, anxious, more nervous than usual or restless
• stuffy nose, difficulty breathing or worsening of asthma
• intestinal swelling, known as “intestinal angioedema” with symptoms such as abdominal pain, vomiting and diarrhoea
• loss or reduction of appetite (anorexia)
• rapid or irregular heartbeat
• swollen arms and legs. This may be a sign that your body is retaining more water than usual.
• joint pain
• fever
• an increase in the number of certain white blood cells in the blood (eosinophilia) detected in blood tests
• altered liver, pancreas or kidney function detected in blood tests
• vomiting
• red spots on the skin (purpura)
• low levels of sodium in the blood which may cause dehydration and low blood pressure.

Rare (may affect up to 1 in 1,000 people):

• feeling unsteady or confused
• red and swollen tongue
• severe peeling or shedding of the skin, itching and nodular skin rash
• nail problems (e.g. loss or detachment of a nail from its bed)
• skin rash or bruising
• patches on the skin and cold extremities
• red, itchy, swollen or watery eyes
• hearing problems and ringing in the ears
• feeling weak
• involuntary, rhythmic, trembling movements of part of the body (tremor)
• inadequate blood flow
• reduction in the number of red blood cells, white blood cells or platelets shown in blood tests (which may cause unusual bruising or increased tendency to bleed) or levels of haemoglobin
• nausea
• low chloride levels in the blood
• low magnesium levels in the blood

Very rare (may affect up to 1 in 10,000 people):

• increased sensitivity to sunlight
• hives (urticaria)
• high levels of calcium in the blood
• irregular heart rhythm, low blood pressure
• kidney disease
• abnormal liver function

Not known:

• fainting
• if you suffer from systemic lupus erythematosus (a type of collagen disease), this may worsen
• myopia
• impaired vision
• 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)
• laboratory test parameter changes may occur and your doctor may request blood tests to monitor your condition. The following laboratory parameter changes may occur:
  o increased levels of uric acid, a substance that may cause or worsen gout (joint pain, especially in the feet),
  o increased blood glucose levels in diabetic patients,
  o high levels of calcium in the blood,
  o increased levels of liver enzymes
• abnormal ECG trace.

Other reported side effects:
Inform your doctor if any of the following side effects worsen or persist for more than a few days.

• difficulty concentrating
• swollen mouth
• lower than usual levels of sodium in the blood shown in blood tests
• concentrated urine (dark-coloured), feeling unwell or nausea, muscle cramps, confusion and seizures possibly due to inappropriate secretion of ADH hormone (antidiuretic hormone). If you have these symptoms, consult your doctor as soon as possible.
• fingers of hands and feet changing colour when cold and then tingling or hurting when warmed (Raynaud's phenomenon)
• breast enlargement in men
• slowed or altered reactions
• burning sensation
• changes in smell
• hair loss.

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 Imbaxir

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 on the blister after Exp. The expiry date refers to the last day of that month.
Do not store above 25 °C.
Do not dispose of any medicine 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 Imbaxir contains

• The active substances are: 5 mg/1.5 mg modified-release tablet: each tablet contains 5 mg of ramipril and 1.5 mg of indapamide.

10 mg/1.5 mg, modified-release tablet:
each tablet contains 10 mg of ramipril and 1.5 mg of indapamide.

• The other components are: monohydrate lactose, povidone K 30, hypromellose, anhydrous colloidal silica, magnesium stearate, sodium croscarmellose, polyvinyl alcohol, sodium stearyl fumarate, polyvinyl alcohol – partially hydrolysed, calcium carbonate, macrogol 4000, talc, yellow iron oxide (E 172) (10 mg/1.5 mg and 5 mg/1.5 mg), red iron oxide (E 172) (10 mg/1.5 mg).

Description of the appearance of Imbaxir and contents of the pack
Imbaxir 5 mg/1.5 mg modified-release tablet:
Film-coated tablet, yellow to pale yellow in colour, round, biconvex, 9 mm in diameter, with "5"
engraved on one side.
Imbaxir 10 mg/1.5 mg modified-release tablet:
Film-coated tablet, orange to pale orange in colour, round, biconvex, 9 mm in diameter, with
"10" engraved on one side.
Imbaxir is available in blister packs containing 30, 60 or 100 modified-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Adamed S.r.l., Via G. Mazzini 20, 20123 Milano, Italy
Manufacturer
Adamed Pharma S.A., ul. Marszałka Józefa Piłsudskiego 5, 95-200 Pabianice, Poland

This medicinal product is authorised in the European Economic Area countries under the following names:
Poland: Ramizek Inda
Germany: Indiace
Italy: Imbaxir
Spain: Imbarix
Portugal: Imbarix