Krupil: detailed information

Package leaflet: Information for the user

KRUPIL 2.5 mg tablets, 5 mg tablets, 10 mg tablets

ramipril
Equivalent medicine
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 other people, even if their symptoms are the same as yours, because it could be harmful.
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:

What KRUPIL is and what it is used for
What you need to know before taking KRUPIL
How to take KRUPIL
Possible side effects
How to store KRUPIL
Contents of the pack and other information

1. What KRUPIL is and what it is used for

KRUPIL contains a medicine called ramipril, which belongs to a group of medicines known as ACE inhibitors (Angiotensin Converting Enzyme inhibitors).
KRUPIL works by:

Reducing the body's production of substances that may cause an increase in blood pressure
Relaxing and widening your blood vessels
Helping your heart to pump blood more easily around the body.

KRUPIL can be used:

To treat high blood pressure (hypertension)
To reduce the risk of heart attack or stroke
To reduce the risk or delay the worsening of kidney problems (with or without diabetes)
To treat your heart when it is unable to pump an adequate amount of blood to the rest of the body (heart failure)
As a treatment following a heart attack (myocardial infarction), when associated with heart failure.

2. What you should know before taking KRUPIL

Do not take KRUPIL:

If you are allergic to ramipril, to other ACE inhibitors, or to any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction may include skin rash, difficulty swallowing or breathing, swelling of the lips, face, throat, or tongue.
If you have ever had a severe allergic reaction called “angioedema”. 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 or 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.
If you are undergoing dialysis or any other type of blood filtration. Depending on the equipment used, KRUPIL may not be suitable for you.
If you 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 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 KRUPIL if any of the above conditions apply to you. If you are unsure,
ask your doctor before taking KRUPIL.
Warnings and precautions
Talk to your doctor or pharmacist before taking KRUPIL:

If you have heart, liver, or kidney problems.
If you have lost significant amounts of body salts or fluids (due to illness such as vomiting, diarrhoea, excessive sweating, a low-salt diet, 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 given during surgery or dental procedures. You may need to stop taking KRUPIL the day before; consult your doctor.
If you have high levels of potassium in your blood (shown by a blood test).
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 medicines that may increase the risk of angioedema, a serious allergic reaction, such as mTOR inhibitors (e.g. temsirolimus, everolimus, sirolimus), vildagliptin, neprilysin inhibitors (NEP) (such as racecadotril), or sacubitril/valsartan. For sacubitril/valsartan, see section 2 “Do not take KRUPIL”.
If you have a vascular collagen disease such as scleroderma or systemic lupus erythematosus.
You must inform your doctor if you think you are pregnant (or might become pregnant). KRUPIL is not recommended during the first 3 months of pregnancy and may cause serious harm to the

baby after the first 3 months of pregnancy (see section below “Pregnancy and
breastfeeding”).

If you are taking any of the following medicines used to treat 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 check your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood at regular intervals. See also the section "Do not take KRUPIL".

Children and adolescents
The use of KRUPIL is not recommended in children and adolescents under 18 years of age
because the safety and efficacy of KRUPIL in children have not yet been established.
If any of the above conditions apply (or you are uncertain), ask your doctor before taking
KRUPIL.
Other medicines and KRUPIL
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines, including those without a prescription (including herbal medicines). This is because
KRUPIL may affect the way some other medicines work. Also, some medicines may affect the
way KRUPIL works.
Tell your doctor if you are taking any of the following medicines. These may interfere with
KRUPIL and alter its effect:

Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indometacin, 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.

Tell your doctor if you are taking any of the following medicines. Taking these with KRUPIL
may increase the likelihood of side effects:

Sacubitril/valsartan – used to treat a type of long-term (chronic) heart failure in adults (see section 2 “Do not take KRUPIL”).
Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indometacin, aspirin).
Medicines for cancer treatment (chemotherapy).
Medicines to prevent organ rejection after transplantation, such as ciclosporin.
Diuretics 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 (used to make blood less thick).
Steroid medicines used to treat inflammation, such as prednisolone.
Allopurinol (used to lower uric acid levels in the blood).
Procainamide (for heart rhythm problems).
Temsirolimus (for cancer).
Sirolimus, everolimus (to prevent transplant rejection).
Vildagliptin (for treatment of type 2 diabetes).
Racecadotril (used to treat diarrhoea).
Your doctor may consider it necessary to adjust the dose and/or take other precautions if you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also section "Do not take KRUPIL" and "Warnings and precautions").

Tell your doctor if you are taking any of the following medicines. The action of these
medicines may be affected by KRUPIL:

Medicines for diabetes such as oral hypoglycaemics and insulin. KRUPIL may lower blood sugar levels. Monitor your blood sugar levels carefully when taking KRUPIL.
Lithium (for psychiatric conditions). KRUPIL may increase lithium levels in the blood. Your doctor must monitor your blood lithium levels carefully. If any of the above conditions apply (or you are uncertain), ask your doctor before taking KRUPIL.

KRUPIL with food and alcohol

Drinking alcohol with KRUPIL may cause dizziness or lightheadedness. If you want to know how much alcohol you can drink while taking KRUPIL, discuss this with your doctor, as blood pressure-lowering medicines and alcohol may have additive effects.
KRUPIL may be taken with or without food.

Pregnancy and breastfeeding
Pregnancy
You must inform your doctor if you think you are pregnant (or might become pregnant).
You must not take KRUPIL during the first 12 weeks of pregnancy and must not take it
at all after week 13, as its use during pregnancy may harm the unborn baby. If you become
pregnant while taking KRUPIL, inform your doctor immediately. Before planning a pregnancy,
you should switch to another medicine more suitable for use in pregnancy.
Breastfeeding
You must not take KRUPIL if you are breastfeeding. Ask your doctor or pharmacist before
taking any medicine.
Driving and using machines
You may feel dizzy while taking KRUPIL. This is more likely when you first start taking KRUPIL or when your dose has just been increased. If this occurs, do not drive or operate tools or machinery.
KRUPIL contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is essentially ‘sodium-free’.

3. How to take KRUPIL

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

Take the medicine by mouth, at the same time each day.
Swallow the tablets whole with liquid.
Do not break or chew the tablets.

Treatment of high blood pressure

The usual starting dose is 1.25 mg or 2.5 mg once daily.
Your doctor will adjust your dose until your blood pressure is under control.
The maximum daily dose is 10 mg.
If you are already taking diuretics, your doctor may stop or reduce them before starting your treatment with KRUPIL.

To reduce the risk of heart attack or stroke

The initial dose is 2.5 mg once daily.
Your doctor may decide to increase your dose.
The usual dose is 10 mg once daily.

Treatment to reduce or prevent worsening of kidney problems

You may be started on a dose of 1.25 mg or 2.5 mg once daily.
Your doctor will adjust your dose accordingly.
The usual dose is 5 mg or 10 mg once daily.

Treatment of heart failure

The usual starting dose is 1.25 mg once daily.
Your doctor will adjust your dose.
The maximum dose is 10 mg daily. It is preferable to divide the dose into two daily administrations.

Treatment after a heart attack

The usual starting dose ranges from 1.25 mg once daily to 2.5 mg twice daily.
Your doctor will adjust your dose.
The usual dose is 10 mg daily. It is preferable to divide the dose into two daily administrations.

Elderly patients
Your doctor will reduce the initial dose and adjust treatment more slowly.

If you take more KRUPIL than you should
Inform your doctor or go immediately to the nearest hospital emergency department. Do not drive to the hospital; have someone accompany you or call an ambulance. Bring the medicine pack with you, as the doctor needs to know what you have taken.

If you forget to take KRUPIL

If you forget a dose, take your usual dose at the next scheduled time.
Do not take a double dose to make up for the missed tablet.

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

4. Possible side effects

Like all medicines, KRUPIL may cause side effects, although not everybody gets them.
Stop taking KRUPIL and contact your doctor immediately if you notice any of the following serious side effects – you may need urgent medical treatment:

Swelling of the face, lips or throat causing difficulty swallowing or breathing, as well as itching or skin rash. This could be a sign of a severe allergic reaction to KRUPIL
Severe skin reactions including rash, mouth ulcers, worsening of pre-existing skin conditions, redness, blistering and peeling of the skin (such as Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme).

Contact your doctor immediately if you experience:

Rapid heartbeat, irregular or forceful heartbeat (palpitations), chest pain, tightness in the chest, or more serious problems including heart attack and stroke
Shortness of breath and cough. These may be signs of lung problems
Easy bruising, prolonged bleeding longer than normal, any sign of bleeding (e.g. bleeding gums), purple spots on the skin or increased susceptibility to infections, sore throat and fever, feeling tired, weak, dizzy or pale appearance. These may be signs of blood or bone marrow problems
Severe stomach pain that may extend to the back. This could be a sign of pancreatitis (inflammation of the pancreas)
Fever, chills, fatigue, loss of appetite, stomach pain, feeling unwell, yellowing of the skin or eyes (jaundice). These may be signs of liver problems such as hepatitis (liver inflammation) or liver damage.

Other side effects include:
Tell your doctor if any of the conditions listed below become severe or persist for longer than a few days:
Common (may affect up to 1 in 10 people)

Headache or feeling tired
Dizziness. This is more likely when treatment with KRUPIL has just started or the dose has recently been increased
Weakness, hypotension (unusually low blood pressure), especially when standing up or getting up quickly
Dry, irritating cough, sinus inflammation (sinusitis) or bronchitis, shortness of breath
Stomach or intestinal pain, diarrhoea, indigestion, nausea or feeling unwell
Rash with or without swelling
Chest pain
Muscle cramps or muscle pain
Blood tests show higher than normal potassium levels

Uncommon (may affect up to 1 in 100 people)

Balance problems (dizziness)
Itching and unusual skin sensations such as numbness, tingling, burning, prickling or crawling sensations (paraesthesia)
Loss or change in taste
Sleep problems
Depressed mood, anxiety, increased nervousness or irritability
Stuffy nose, breathing difficulties or worsening of asthma
Intestinal swelling called "intestinal angioedema" presenting with symptoms such as abdominal pain, vomiting and diarrhoea
Heartburn, constipation or dry mouth
Increased amount of urine during the day
Increased sweating
Loss or decrease in appetite (anorexia)
Rapid or irregular heartbeat
Swollen arms and legs. This may be a sign that your body is retaining more fluid than usual
Hot flushes
Blurred vision
Joint pain
Fever
Impotence in men, reduced sex drive in men and women
Increased number of white blood cells (eosinophilia) detected in blood tests
Changes in liver, pancreas or kidney function shown by blood tests

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

Feeling faint or confused
Swollen and red tongue
Severe peeling or shedding of the skin, itching, rash with pustules
Nail problems (such as loss or separation of the nail from its bed)
Skin rash or bruising
Skin spots and cold extremities
Red, swollen, watery or itchy eyes
Hearing disturbances and ringing in the ears
Feeling weak
Decreased number of red blood cells, white blood cells and platelets, or decreased haemoglobin concentration, shown by blood tests

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

Increased sensitivity to sunlight

Other side effects reported:
Tell your doctor if any of the conditions listed below become severe or persist for longer than a few days.

Difficulty concentrating
Swelling of the mouth
Blood tests showing abnormally low blood cell counts
Blood tests showing low sodium levels in the blood
Concentrated (dark-coloured) urine, feeling unwell, muscle cramps, confusion and seizures which may be due to inappropriate antidiuretic hormone (ADH) secretion. If you experience these symptoms, contact your doctor promptly
Fingers of hands and feet changing colour when cold and tingling or painful upon warming (Raynaud's phenomenon)
Breast enlargement in men
Slowed or altered reactions
Burning sensation
Changes in smell perception
Hair loss

Reporting of side effects
If you get any side effects, including ones 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 . Reporting side effects can help provide more information on the safety of this medicine.

5. How to store KRUPIL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label 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 KRUPIL contains
The active substance is ramipril.
2.5 mg: each tablet contains ramipril 2.5 mg
5 mg: each tablet contains ramipril 5 mg
10 mg: each tablet contains ramipril 10 mg

The other components are:
2.5 mg tablets and 5 mg tablets
Hypromellose, pregelatinized maize starch, microcrystalline cellulose, sodium stearyl fumarate,
yellow iron oxide E172.
10 mg tablets
Hypromellose, pregelatinized maize starch, microcrystalline cellulose, sodium stearyl fumarate.

Description of the appearance of KRUPIL and package contents
2.5 mg tablets
The tablet can be divided into equal parts. KRUPIL 2.5 mg tablets are available in packs of 28 tablets in PVC/aluminum blisters.

5 mg tablets
The tablet can be divided into equal parts. KRUPIL 5 mg tablets are available in packs of 14 and 28 tablets in PVC/aluminum blisters.

10 mg tablets
The tablet can be divided into equal parts. KRUPIL 10 mg tablets are available in packs of 28 tablets in PVC/aluminum blisters.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
So.Se.PHARM S.r.l.
Via dei Castelli Romani, 22
00071 Pomezia (Rome)

Manufacturer
Special Product’s Line S.p.a.
Via Fratta Rotonda Vado Largo 1
03012 Anagni (FR) – Italy