Kruplus: detailed information

Package leaflet: Information for the user

KRUPLUS 2.5 mg + 12.5 mg tablets, 5 mg + 25 mg tablets

ramipril + hydrochlorothiazide
Equivalent medicinal product
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. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What KRUPLUS is and what it is used for

KRUPLUS is a combination of two medicines called ramipril and hydrochlorothiazide.
Ramipril belongs to a group of medicines known as “ACE inhibitors” (Angiotensin-Converting Enzyme inhibitors).
It 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 throughout the body.

Hydrochlorothiazide belongs to a group of medicines called “thiazide diuretics” or oral diuretics. It works by increasing the amount of water (urine) produced. This lowers blood pressure.
KRUPLUS is used to treat high blood pressure (hypertension). The two active ingredients work together to lower blood pressure. They are used in combination when treatment with either component alone is not effective.

2. What you need to know before taking KRUPLUS

Do not take KRUPLUS:

If you are allergic to ramipril, hydrochlorothiazide, or any of the excipients of this medicine (listed in section 6)
If you are allergic to medicines similar to KRUPLUS (other ACE inhibitors or sulfonamide-derived medicines)

Signs of an allergic reaction may include skin rashes, difficulty swallowing or breathing, swelling of the lips, face, throat, or tongue.

If you have ever had a severe allergic reaction called “angioedema”. Symptoms 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 are undergoing dialysis or any other type of blood filtration. Depending on the equipment used, KRUPLUS may not be suitable for you
If you have severe liver problems
If you have abnormal levels of salts (calcium, potassium, sodium) in your blood
If you have kidney problems due to insufficient blood supply to the kidney (renal artery stenosis)
During the last 6 months of pregnancy (see section below “Pregnancy and breastfeeding”)
If you are breastfeeding (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.

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

Warnings and precautions

Talk to your doctor or pharmacist before taking KRUPLUS:

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, following a low-salt diet, prolonged 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 that may be administered during surgery or dental procedures. You may need to stop taking KRUPLUS 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 cause low 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 called mTOR inhibitors (e.g. temsirolimus, everolimus, sirolimus) or vildagliptin, as they may increase the risk of angioedema, a serious allergic reaction
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 could become pregnant). KRUPLUS is not recommended during the first trimester of pregnancy and can cause serious harm to the unborn child after the first three months of pregnancy (see section “Pregnancy and breastfeeding”)
If you have previously had skin cancer or develop unexpected skin lesions during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from sun exposure and UV radiation while taking KRUPLUS
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 eye pressure, which may occur from a few hours to weeks after taking KRUPLUS. This may lead to permanent vision loss if not treated. If you previously had an allergy to penicillin or sulfonamides, you may have a higher risk of developing this condition
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 regularly monitor your kidney function, blood pressure, and electrolyte levels (e.g. potassium) in your blood
If you have previously experienced breathing or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe breathing difficulties after taking IDROTENS, consult a doctor immediately. See also the section "Do not take KRUPLUS"

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

Children and adolescents

KRUPLUS is not recommended for children and adolescents under 18 years of age, as this medicine has not been studied in this age group.

If any of the above conditions apply to you or you are unsure, consult your doctor before taking KRUPLUS.

Other medicines and KRUPLUS

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is because KRUPLUS may affect the action of certain other medicines, and some medicines may affect the action of KRUPLUS.

Inform your doctor if you are taking any of the following medicines. These may interfere with KRUPLUS and reduce its effectiveness:

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.

Inform your doctor if you are taking any of the following medicines. Taking these with KRUPLUS may increase the risk of side effects:

Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indometacin, aspirin)
Medicines that may lower potassium levels in the blood. These include laxatives, diuretics, amphotericin B (used for fungal infections), and adrenocorticotropic hormone (used to check adrenal gland function)
Cancer medicines (chemotherapy)
Medicines for heart problems, including heart rhythm disorders
Medicines to prevent organ rejection after transplantation, such as cyclosporine
Diuretics such as furosemide
Medicines that may increase potassium levels in the blood, such as spironolactone, triamterene, amiloride, potassium salts, and heparin (used to thin the blood)
Steroid medicines for inflammation, such as prednisolone
Calcium supplements
Allopurinol (used to lower uric acid levels in the blood)
Procainamide (for heart rhythm problems)
Cholestyramine (to reduce blood fat levels)
Carbamazepine (for epilepsy)
Heparin (to thin the blood)
Temsirolimus (for cancer)
Sirolimus, everolimus (to prevent transplant rejection)
Vildagliptin (for type 2 diabetes)

Your doctor may consider it necessary to adjust your dose and/or take other precautions if you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also section "Do not take KRUPLUS" and “Warnings and precautions”).

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

Medicines for diabetes, such as oral hypoglycaemics and insulin. KRUPLUS may lower blood sugar levels. Monitor your blood sugar levels carefully when taking KRUPLUS.
Lithium (for psychiatric conditions). KRUPLUS may increase lithium levels in the blood. Your doctor must closely monitor your blood lithium levels.
Muscle relaxants
Quinine (for the treatment of malaria)
Medicines containing iodine, which may be used in hospital before X-ray or scanning procedures
Penicillin (for treating infections)
Oral medicines that thin the blood (oral anticoagulants) such as warfarin.

If any of the above conditions apply (or if you are unsure), consult your doctor before taking KRUPLUS.

Monitoring

Inform your doctor or pharmacist before taking this medicine:

If you are undergoing tests for parathyroid function. KRUPLUS may alter the test results.

KRUPLUS with food and alcohol

Drinking alcoholic beverages together with KRUPLUS may cause dizziness or drowsiness. Discuss with your doctor how much alcohol you may drink while taking KRUPLUS. Alcohol may enhance the effects of blood pressure medicines.
KRUPLUS can be taken with or without food.

Pregnancy and breastfeeding

Pregnancy

Inform your doctor if you think you are pregnant (or could become pregnant).
You must not take KRUPLUS during the first 12 weeks of pregnancy and must not take it at all after the 13th week, as it may harm the unborn child.
If you become pregnant while taking KRUPLUS, inform your doctor immediately. Before planning a pregnancy, you should switch to another, more suitable medicine.

Breastfeeding

You must not take KRUPLUS if you are breastfeeding.
Ask your doctor or pharmacist before taking any medicine.

Driving and using machines

You may experience dizziness while taking KRUPLUS. This is more likely when you first start taking KRUPLUS or when your dose has just been increased. If this occurs, do not drive or operate tools or machinery.

3. How to take KRUPLUS

Take this medicine exactly as your doctor has instructed. If you have any doubts,
consult your doctor or pharmacist.
How much you should take
Treatment of high blood pressure
Your doctor will adjust your dose until your blood pressure is under control.
Elderly population
Your doctor will reduce the initial dose and adjust treatment more slowly.
Taking this medicine

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

If you take more KRUPLUS than you should
Inform your doctor or go to the nearest hospital emergency department. Do not drive to the
hospital; have someone drive you or call an ambulance. Take the medicine pack with you.
This is because the doctor needs to know what you have taken.
If you forget to take KRUPLUS

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 forgotten tablet.

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

4. Possible side effects

Like all medicines, KRUPLUS can cause side effects, although not everyone experiences them.

Stop taking KRUPLUS 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. These may be signs of a severe allergic reaction to KRUPLUS.
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 or irregular or forceful heartbeat (palpitations), chest pain, tightness in the chest, or more serious problems including heart attack and stroke.
Shortness of breath or cough, fever lasting 2 to 3 days, and reduced appetite. These may be signs of lung problems, including inflammation.
Easy bruising, prolonged bleeding more than usual, any signs 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 skin. 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:
Inform your doctor if any of the following conditions become severe or persist for longer than a few days.

Common (may affect up to 1 in 10 people)

Headache or feeling weak or tired
Dizziness. This is more likely when starting treatment with KRUPLUS or when the dose has just been increased
Dry, irritating cough or bronchitis
Blood tests show higher than normal sugar levels. If you have diabetes, this may worsen
Blood tests show higher than normal levels of uric acid or fats
Painful, red, and swollen joints

Uncommon (may affect up to 1 in 100 people)

Skin rash with or without swellings
Flushing, weakness, hypotension (unusually low blood pressure), especially when standing up or rising quickly
Balance problems (dizziness)
Itching and unusual skin sensations such as numbness, tingling, prickling, burning, or crawling sensations (paresthesia)
Loss or change in taste
Sleep disturbances
Depressed mood, anxiety, increased nervousness or irritability
Nasal congestion, inflammation of the sinuses (sinusitis), shortness of breath
Inflammation of the gums (gingivitis), swelling in the mouth
Red, swollen, watery, or itchy eyes
Ringing in the ears (tinnitus)
Blurred vision
Hair loss
Chest pain
Muscle pain
Constipation, stomach or intestinal pain
Indigestion or feeling unwell
Increased amount of urine during the day
Increased sweating or thirst
Loss or decrease in appetite (anorexia), reduced feeling of hunger
Rapid or irregular heartbeat
Swollen arms and legs. This may be a sign that your body is retaining more fluid than usual
Fever
Erectile dysfunction in men
Decreased number of red blood cells, white blood cells, and platelets, or hemoglobin concentration, as shown by blood tests
Changes in liver, pancreas, or kidney function as shown by blood tests
Blood tests show lower than normal potassium levels.

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

Feeling unwell, causing diarrhea or heartburn
Swollen and red tongue or dry mouth
Blood tests show higher than normal potassium levels
Acute respiratory distress (symptoms include severe shortness of breath, fever, weakness, and confusion)

Frequency not known:

Skin and lip cancer (non-melanoma skin cancer)

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

Difficulty concentrating, feeling restless or confused
Fingers of hands and feet changing color when cold, and tingling or pain when warmed (Raynaud's phenomenon)
Breast enlargement in men
Blood clots
Hearing disturbances
Eyes less moist than usual
Objects appearing yellow
Dehydration
Swelling, pain, and redness of the cheeks (inflammation of a salivary gland)
Intestinal swelling called "intestinal angioedema," presenting with symptoms such as abdominal pain, vomiting, and diarrhea
Increased sensitivity to sunlight
Severe peeling or shedding of the skin, itching, rash, or other skin reactions such as facial or forehead redness
Skin rash or bruising
Skin spots and cold extremities
Nail problems (such as loss or separation of the nail from its bed)
Musculoskeletal stiffness or inability to move the jaw (tetany)
Muscle weakness or cramps
Reduced sexual desire in men and women
Presence of blood in the urine. This could be a sign of a kidney problem (interstitial nephritis)
Higher than normal amount of sugar in the urine
Increased number of white blood cells in the blood (eosinophilia) detected during blood tests
Abnormally low number of blood cells shown by blood tests (pancytopenia)
Changes in blood levels of electrolytes such as sodium, calcium, magnesium, and chloride, as shown by blood tests
Slowed or altered reactions
Changes in sense of smell
Breathing difficulties or worsening of asthma
Severe eye pain, blurred vision, seeing halos around lights, headache, excessive tearing, nausea, and vomiting, which may indicate a condition called glaucoma.
Sudden onset of reduced distance vision (acute 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).

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.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store KRUPLUS

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date 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. Contents of the pack and other information

What KRUPLUS contains
KRUPLUS 2.5 mg + 12.5 mg tablets
One divisible tablet contains:
Active substances: ramipril 2.5 mg + hydrochlorothiazide 12.5 mg;
Other components: hypromellose, pregelatinized starch, microcrystalline cellulose and sodium stearyl fumarate.
KRUPLUS 5 mg + 25 mg tablets
One divisible tablet contains:
Active substances: ramipril 5 mg + hydrochlorothiazide 25 mg;
Other components: hypromellose, pregelatinized starch, microcrystalline cellulose and sodium stearyl fumarate.

Description of the appearance of KRUPLUS and pack contents
Tablets.
KRUPLUS 2.5 mg + 12.5 mg tablets: box of 14 divisible tablets in blister packs.
KRUPLUS 2.5 mg + 12.5 mg tablets: box of 28 divisible tablets in blister packs.
KRUPLUS 5 mg + 25 mg tablets: box of 14 divisible tablets in blister packs.
KRUPLUS 5 mg + 25 mg tablets: box of 28 divisible tablets in blister packs.

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

Manufacturer
SPECIAL PRODUCT’S LINE S.p.A.
Via Fratta Rotonda Vado Largo, 1
03012 Anagni (FR) - Italy

November 2021