Miprind

Patient Information Leaflet

Miprind 5 mg/1.5 mg modified-release hard capsules, 10 mg/1.5 mg modified-release hard capsules

ramipril/indapamide
Please read all of this leaflet carefully before you start 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. Never give it to others. It may be harmful to other people, even if their symptoms are the same as yours.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Miprind is and what it is used for

Miprind modified-release hard capsules can be used for the treatment of high blood pressure (hypertension) in adults.
Miprind contains two different active substances, ramipril and indapamide, in a single capsule. Both active substances contribute to controlling high blood pressure:

• Ramipril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors and works by reducing the production of substances that can cause an increase in blood pressure; it relaxes and widens your blood vessels, making it easier for your heart to pump blood around the body.
• Indapamide is a diuretic. Most diuretics increase the amount of urine produced by the kidneys. However, unlike other diuretics, indapamide causes only a slight increase in the amount of urine produced. In addition, indapamide dilates blood vessels, allowing blood to flow more easily, thereby helping to reduce blood pressure.

Your doctor may prescribe Miprind fixed-dose hard capsules for you only if you are already taking ramipril and indapamide at the same dosage, but as separate products.

2. What you need to know before taking Miprind

Do not take Miprind

• If you are allergic to ramipril or any other ACE inhibitor, to indapamide or any other sulfonamide, or to any of the other ingredients of this medicine (listed in section 6).
• If you have had a severe allergic reaction called "angioedema". These signs include itching, skin rash (urticaria), red spots on the hands, feet and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing.
• If you have taken or are currently taking sacubitril/valsartan, a medicine used to treat a type of long-term (chronic) heart failure in adults, as this increases the risk of angioedema (rapid swelling of mucous membranes, such as in the throat).
• If you are on dialysis or undergoing another type of blood filtration. Depending on the equipment used, Miprind may not be suitable for you.
• If you have severe kidney disease or kidney problems due to insufficient blood supply to the kidney (renal artery stenosis).
• If you have severe liver disease or suffer from a condition called hepatic encephalopathy (a degenerative brain disorder).
• If you have low levels of potassium in your blood.
• If you are more than three months pregnant (use of Miprind is also advised to be avoided during the first months of pregnancy – see the section “Pregnancy and breastfeeding” below).
• If your blood pressure is excessively low or unstable. Your doctor will need to assess this.
• If you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

Do not take Miprind if any of the above conditions apply to you. If you are unsure, ask your doctor before taking Miprind.

Warnings and precautions

Talk to your doctor or pharmacist before taking Miprind:

• If you have liver problems (e.g., cirrhosis or ascites).
• If you have diabetes.
• If you suffer from gout.
• If you have heart problems or heart rhythm disorders.
• If you have kidney problems (including kidney transplant) or are on dialysis.
• If you experience blurred vision or eye pain. These could 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 several weeks after taking Miprind. This may lead to permanent vision loss if not treated. If you have had an allergy to penicillin or sulfonamides, your risk of developing this symptom may be higher.
• If you have lost significant amounts of salts or body fluids (due to illness such as vomiting, diarrhoea, excessive sweating, or following a low-salt diet, or due to long-term use of oral diuretics or after dialysis).
• If you are about to undergo treatment to reduce allergy to bee or wasp stings (desensitisation).
• If you are about to undergo anaesthesia, which may be administered during surgery or dental procedures. You may need to stop taking Miprind the day before; consult your doctor.
• Your doctor may request specific blood tests if you have abnormally high or low levels of potassium and sodium, or high calcium levels in the blood (detected by blood tests).
• If you are taking medicines or have conditions that may reduce sodium levels in your blood. Your doctor may prescribe regular blood tests, especially to monitor sodium levels, particularly if you are elderly.
• If you are taking any of the following medicines, which may increase the risk of angioedema, a severe allergic reaction:
  o Neprilysin inhibitors (NEP) (such as racecadotril, a medicine used to treat diarrhoea);
  o Medicines used to prevent organ rejection after transplantation and for cancer (e.g., temsirolimus, sirolimus, everolimus and other drugs belonging to the mTOR inhibitor class);
• Vildagliptin, a medicine used to treat diabetes. If you are taking sacubitril/valsartan, see section 2 “Do not take Miprind”.
• If you have a vascular collagen disorder such as scleroderma or systemic lupus erythematosus.
• If you are taking any of the following medicines used to treat high blood pressure:
  o An angiotensin II receptor antagonist (AIIRA) (also known as sartans, e.g., valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes;
  o Aliskiren.
• Your doctor may monitor your kidney function, blood pressure, and levels of electrolytes (e.g., potassium, sodium, calcium) in your blood at regular intervals. Also read the information in section “Do not take Miprind”.
• If you suffer from muscle disorders such as muscle pain, tenderness, weakness or cramps.
• If you need to undergo a test to assess parathyroid gland function.
• You must inform your doctor if you think you are pregnant (or might become pregnant). Miprind is not recommended during the first trimester of pregnancy and must not be taken after the first three months of pregnancy, as it may cause serious harm to the baby if taken during this stage of pregnancy (read the information in section “Pregn游戏副本

3. How to take Miprind

Always take this medicine exactly as instructed by your doctor. If you are unsure, you should ask your
doctor or pharmacist for advice.
Treatment for high blood pressure is usually lifelong.
The recommended dose is:

• One capsule (of the prescribed strength) taken at the same time each day, preferably in the morning.
• Do not take more than one capsule per day.
• Take this medicine by mouth. Swallow the capsules whole with a sufficient amount of liquid, without chewing them. Tilt your head slightly forward when swallowing the capsule.
• Miprind may be taken with or without food.

Use in children and adolescents
Miprind is not recommended for use in children and adolescents under 18 years of age.
If you take more Miprind than you should
If you take more capsules than prescribed, inform your doctor immediately or go to the nearest hospital emergency department.
Do not drive to the hospital; have someone take you or call an ambulance. Bring the medicine pack with you.
This is important because the doctor needs to know what you have taken.
The most likely symptom associated with overdose is low blood pressure. Symptoms of excessively low blood pressure include nausea, vomiting, cramps, dizziness, drowsiness, confusion, and changes in the amount of urine produced by the kidneys.
If you forget to take Miprind
If you forget to take a dose, take the next dose at your usual time.
Do not take a double dose to make up for the missed dose.
If you stop taking Miprind
Do not stop treatment with Miprind suddenly or change the dose without first consulting your doctor.
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 Miprind and contact your doctor immediately if you experience any of the following serious side effects – you may need urgent medical treatment:

• Swelling of the face, lips, mouth, tongue or throat, swelling of the mucous membranes in the throat or airways, causing shortness of breath or difficulty swallowing to the point that swallowing or breathing becomes difficult. This could be a sign of a severe allergic reaction (angioedema) to Miprind. If this occurs, contact your doctor immediately (Uncommon) (may affect up to 1 in 100 people).
• Severe skin reactions including rash, mouth ulcers, worsening of pre-existing skin conditions, redness, blistering and peeling of the skin, mucosal inflammation (such as Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme) or other allergic reactions (e.g. urticaria). If this occurs, contact your doctor immediately (Very rare) (may affect up to 1 in 10,000 people).

Contact your doctor immediately if you experience:

• Rapid heartbeat, irregular or forceful heartbeat (which may be life-threatening), chest pain, tightness in the chest, or more serious problems including heart attack and stroke (frequency 'not known').
• Shortness of breath or cough. These may be signs of lung problems.
• Easy bruising, prolonged bleeding more than usual, any signs of bleeding (e.g. bleeding gums), purple spots on the skin, skin spots or increased susceptibility to infections, sore throat and fever, feeling tired, weak, dizzy or pale. These may be signs of circulatory or bone marrow problems.
• Severe stomach pain that may extend to the back. This could be a sign of pancreatitis (inflammation of the pancreas). (Very rare: may affect up to 1 in 10,000).
• Fever, chills, fatigue, loss of appetite, stomach pain, nausea, yellowing of the skin or eyes (jaundice). These may be signs of liver problems such as hepatitis (liver inflammation) or liver damage (hepatic encephalopathy may occur with frequency not known).
• Concentrated urine (dark-colored), feeling unwell or malaise, muscle cramps, confusion and seizures which may be due to inappropriate ADH (antidiuretic hormone) secretion. If you experience these symptoms, contact your doctor promptly (frequency not known).
• Muscle weakness, cramps, tenderness or pain, particularly if accompanied by malaise or high fever, which could be caused by abnormal breakdown of muscle fibers, known as rhabdomyolysis (may occur with frequency not known).

Other side effects include:
Common (affects less than 1 in 10 patients on treatment)

• Allergic/hypersensitivity reactions, predominantly dermatological, in individuals predisposed to allergic reactions and asthma.
• Blood tests show higher than normal potassium levels.
• Dizziness, headache, which are more likely to occur when treatment with Miprind has just started or the dose has recently been increased.
• Fainting, hypotension (unusually low blood pressure, especially when standing up or rising quickly, i.e. orthostatic hypotension).
• Dry, irritating cough, inflammation of the sinuses (sinusitis) or bronchitis (inflammation of the airways), shortness of breath (dyspnea).
• Stomach or intestinal pain or discomfort (inflammation), indigestion (bloating, heartburn), feeling or being sick (nausea or vomiting), diarrhea.
• Skin rash, especially maculopapular, with or without swelling.
• Chest pain.
• Muscle cramps or pain.
• Feeling tired.

Uncommon (affects less than 1 in 100 patients on treatment)

• Increase in the number of white blood cells (eosinophilia) detected during blood tests.
• Loss or decrease in appetite (anorexia).
• Low sodium levels in the blood which may lead to dehydration and low blood pressure (hyponatremia).
• Depressed mood, anxiety, increased nervousness or irritability.
• Sleep disturbances.
• Balance problems (dizziness).
• Small red spots on the skin (purpura), itching and unusual skin sensations such as numbness, tingling, burning, prickling or rubbing sensations (paresthesia).
• Loss or change in taste (ageusia, dysgeusia).
• Eye problems, including blurred vision, visual disturbances.
• Pressure or pain in the chest, usually on the left side of the body, which may be symptoms of a heart attack (e.g. angina pectoris or myocardial infarction), rapid, irregular or forceful heartbeat, palpitations (awareness of heartbeat), and swollen arms and legs, which may be a sign that the body is retaining more fluid than usual (peripheral edema).
• Breathing difficulties or worsening of asthma (including aggravated asthma), nasal congestion.
• Severe allergic reaction (angioedema) with swelling of the face, lips, tongue, swelling of the mucous membranes in the throat or airways, causing shortness of breath or difficulty swallowing.
• Intestinal swelling called "intestinal angioedema" presenting with symptoms such as upper abdominal pain, including stomach inflammation (gastritis), constipation, dry mouth.
• Changes in liver function shown by blood tests (liver enzyme abnormalities, increased bilirubin levels).
• Severe stomach pain that may extend to the back associated with increased pancreatic enzymes. This could be a sign of inflammation of the pancreas (pancreatitis).
• Kidney disease (including renal failure), increased urine output during the day compared to normal, worsening of pre-existing proteinuria, increased levels of urea and creatinine in the blood.
• Excessive sweating.
• Joint pain.
• Sexual dysfunction in men (impotence) or reduced sexual desire in men or women.
• Fever.

Rare (affects less than 1 in 1,000 patients on treatment)

• Decrease in the number of red blood cells (anemia), white blood cells (neutropenia or agranulocytosis [which may cause unexplained fever, sore throat or other flu-like symptoms]) and blood platelets (which may cause easy bruising and nosebleeds) or hemoglobin concentration, shown by blood tests.
• Reduced levels of chloride and magnesium in the blood.
• Feeling of tremor or confusion (confusional state).
• Balance disorders.
• Red, swollen or watery, itchy eyes (conjunctivitis).
• Hearing disorders and ringing in the ears (tinnitus).
• Reduced blood flow through vessels due to vascular stenosis (hypoperfusion), inflammation of blood vessels (vasculitis).
• Red and swollen tongue (glossitis).
• Yellowing of the skin or eyes (cholestatic jaundice) or damage to liver cells.
• Severe peeling or exfoliation of the skin, itching, rash with lumps.
• Urticaria.
• Nail problems (such as loss or separation of the nail from its bed, onycholysis).
• Skin spots and cold extremities.
• Feeling of fatigue or weakness.

Very rare (affects less than 1 in 10,000 patients on treatment)

• High levels of calcium in the blood.
• Increased sensitivity to sunlight (photosensitivity reaction).
• Severe skin reactions, including skin rashes, mouth ulcers, worsening of pre-existing skin diseases, redness of the skin, blisters or peeling of the skin, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme) or other allergic reactions (e.g. urticaria).

Not known (frequency cannot be estimated from the available data):

• Blood tests showing too few blood cells (indicating bone marrow dysfunction).
• Anaphylactic or anaphylactoid reactions, increased levels of antinuclear antibodies.
• Difficulty concentrating, attention disorders.
• Cerebral ischemia, including ischemic stroke and transient ischemic attack.
• Impairment of psychomotor performance, burning sensation, parosmia (altered perception of smells).
• Short-sightedness (myopia).
• 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).
• Changes in the electrocardiogram (ECG) pattern (prolonged QT interval), a specific type of arrhythmia called torsades de pointes (potentially fatal).
• Fingers of the hands and feet changing color when cold, and tingling or hurting when warmed (Raynaud's phenomenon).
• Mouth ulcers (aphthous stomatitis).
• Worsening psoriasis, psoriasiform dermatitis, pemphigoid or lichenoid exanthem or enanthem, pemphigus.
• Hair loss (alopecia).
• If you suffer from systemic lupus erythematosus (a type of collagen disease), your condition may worsen.
• Breast enlargement in men.
• Increased blood glucose levels.
• Increased uric acid in the blood which may cause or worsen gout (joint pain, especially in the feet).
• Muscle weakness, cramps, tenderness or pain, particularly if accompanied by malaise or high fever, which could be caused by abnormal breakdown of muscle fibers, known as rhabdomyolysis.

The adverse effects reported for Miprind have been consistent with the safety profile of the individual active substances of Miprind (ramipril and indapamide) when administered at the same dosage levels.
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 Miprind

Do not store at temperatures above 25 °C.
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after Exp.
The expiry date refers to the last day of the month.
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 Miprind contains
The active substances are: ramipril and indapamide.
Miprind modified-release hard capsules 5 mg/1.5 mg
Each capsule contains 5 mg of ramipril and 1.5 mg of indapamide.
Miprind modified-release hard capsules 10 mg/1.5 mg
Each capsule contains 10 mg of ramipril and 1.5 mg of indapamide.

The other components are:
Capsule contents: monohydrate lactose, microcrystalline cellulose, crospovidone, hypromellose,
magnesium stearate, sodium stearilfumarate, hydrophobic colloidal anhydrous silica, anhydrous colloidal silica, iron oxide yellow (E172).
Capsule shell: gelatin, iron oxide yellow (E172), iron oxide red (E172), titanium dioxide (E171).

Description of the appearance of Miprind and package contents
Miprind modified-release hard capsules 5 mg/1.5 mg
Hard gelatin capsule, unmarked, with automatic closure, size 0, with a light yellow body and a red cap, containing two tablets. The capsule is approximately 21.7 mm long. One tablet, containing ramipril, is round, biconvex, light yellow in colour, unmarked on either side; small white and brownish-yellow specks may be present on the surface of this tablet. The other tablet, containing indapamide, is round, biconvex, white to off-white in colour, with a stylised 'I' on one side and no marking on the other side.

Miprind prolonged-release hard capsules 10 mg/1.5 mg
Hard gelatin capsule, unmarked, with automatic closure, size 0, with a light yellow body and a reddish-brown cap, containing two tablets. The capsule is approximately 21.7 mm long. One tablet, containing ramipril, is round, biconvex, light yellow in colour, unmarked on either side; small white and brownish-yellow specks may be present on the surface of this tablet. The other tablet, containing indapamide, is round, biconvex, white to off-white in colour, with a stylised 'I' on one side and no marking on the other side.

Nature and contents of the packaging:
10, 28, 30, 56, 60, 90, 100 or 112 modified-release hard capsules in OPA/AL/PVC//AL blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Bruno Farmaceutici S.p.A.
Via delle Ande, 15
00144 Rome
Italy

Manufacturer:
Egis Pharmaceuticals PLC, Site 3
9900 Körmend, Mátyás király u. 65, Hungary
Egis Pharmaceuticals PLC, Site 2
1165 Budapest, Bökényföldi út 118-120, Hungary

This medicinal product is authorised in the European Economic Area countries under the following names:
Hungary: Ramipril/Indapamide Egis Pharmaceuticals PLC 5 mg/1.5 mg, 10 mg/1.5 mg modified-release hard capsule