Ramipril and hydrochlorothiazide Krka

Patient Information Leaflet

Ramipril and Hydrochlorothiazide Krka 2.5 mg/12.5 mg tablets, 5 mg/25 mg tablets

ramipril/hydrochlorothiazide
Equivalent medicine
Please read this leaflet carefully before taking this medicine, as 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 they have the same symptoms as yours, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist (see section 4).

Contents of this leaflet

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

1. What Ramipril and Hydrochlorothiazide Krka is and what it is used for

Ramipril and Hydrochlorothiazide Krka 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 can cause an increase in blood pressure.
• Relaxing and widening blood vessels.
• Helping the heart to pump blood more easily around the body.

Hydrochlorothiazide belongs to a group of medicines called "thiazide diuretics" or water tablets. It works by increasing the amount of water (urine) produced. This lowers blood pressure.

Ramipril and Hydrochlorothiazide Krka is used for the treatment of high blood pressure. The two active substances 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 Ramipril and Hydrochlorothiazide Krka

Do not take Ramipril and Hydrochlorothiazide Krka

• If you are allergic to ramipril, hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6).
• If you are allergic (hypersensitive) to medicines similar to Ramipril and Hydrochlorothiazide Krka (other ACE inhibitors or medicines derived from sulfonamides). 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”. These 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 are on dialysis or undergoing any other type of blood filtration. Depending on the equipment used, Ramipril and Hydrochlorothiazide Krka may not be suitable for you.
• If you have severe liver problems.
• If you have abnormal levels of electrolytes (calcium, potassium, sodium) in your blood.
• If you have kidney problems in which blood flow to the kidneys is reduced (renal artery stenosis).
• During the last 6 months of pregnancy (see the section below “Pregnancy and breastfeeding”).
• If you are breastfeeding (see the 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 you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin, such as in the throat).

Do not take Ramipril and Hydrochlorothiazide Krka if any of these apply to you. If you are unsure, consult your doctor before taking Ramipril and Hydrochlorothiazide Krka.
Warnings and precautions
Talk to your doctor or pharmacist before taking Ramipril and Hydrochlorothiazide Krka:

• If you have heart, liver, or kidney problems.
• If you have lost a significant amount of salts or fluids (due to illness, vomiting, diarrhoea, excessive sweating, following a low-salt diet, taking diuretics (water tablets) for a long time, or having undergone dialysis).
• If you are about to undergo treatment to reduce your allergy to bees or wasps (desensitization).
• If you are about to undergo anaesthesia. This may be administered for surgery or dental procedures. You may need to stop taking Ramipril and Hydrochlorothiazide Krka 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 are in conditions where sodium levels in your blood may decrease. Your doctor may perform regular blood tests, especially to monitor sodium levels, particularly if you are elderly.
• If you are taking any of the following medicines, the risk of angioedema may increase:
• racecadotril (used to treat diarrhoea),
• medicines used to prevent rejection of transplanted organs and for cancer (e.g. temsirolimus, sirolimus, everolimus),
• vildagliptin, a medicine used to treat diabetes.
• If you have a vascular collagen disorder such as scleroderma or systemic lupus erythematosus.
• If you have previously had skin cancer or are developing 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 and lip cancer. Protect your skin from sun exposure and UV rays while taking Ramipril and Hydrochlorothiazide Krka.
• If you are taking any of the following medicines used to treat high blood pressure:
• an angiotensin II receptor antagonist (ARBs) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
• aliskiren. Your doctor may regularly check your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood. See also information in section “Do not take Ramipril and Hydrochlorothiazide Krka”.
• 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 from a few hours to a week after taking Ramipril and Hydrochlorothiazide Krka. This may lead to

permanent vision loss if not treated. If you previously had an allergy to
penicillin or sulfonamides, you have a higher risk of developing this condition.
Inform your doctor if you think you are pregnant (or could become pregnant). Ramipril and Hydrochlorothiazide Krka
is not recommended during the first trimester of pregnancy and may cause serious harm to the baby
after the first three months of pregnancy (see section below “Pregnancy and breastfeeding”).
Children and adolescents
The use of Ramipril and Hydrochlorothiazide Krka is not recommended in children and adolescents under
18 years of age. This is because the safety and efficacy of the medicine have not been established in
this age group.
If any of the above conditions apply to you (or if you have any doubts), consult your doctor before taking
Ramipril and Hydrochlorothiazide Krka.
Other medicines and Ramipril and Hydrochlorothiazide Krka
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 Ramipril and Hydrochlorothiazide Krka may affect how other medicines work.
In addition, some medicines may affect the action of Ramipril and Hydrochlorothiazide Krka.
Inform your doctor if you are taking any of the following medicines. These may interfere with the effectiveness of Ramipril and Hydrochlorothiazide Krka:

• Medicines used 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 should monitor your blood pressure.

Inform your doctor if you are taking any of the following medicines. Taking these with
Ramipril and Hydrochlorothiazide Krka may increase the likelihood of side effects:

• Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indomethacin, aspirin).
• Medicines that may lower potassium levels in the blood. These include laxatives, diuretics (water tablets), amphotericin B (used for fungal infections), and ACTH (used to check adrenal gland function).
• Temsirolimus for cancer.
• Medicines for heart problems, including irregular heartbeat.
• Diuretics (water tablets) such as furosemide.
• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (e.g. trimethoprim and co-trimoxazole (for bacterial infections); cyclosporine, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood and prevent clots).
• Steroid medicines for treating 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).
• Medicines often used to prevent organ transplant rejection (sirolimus, everolimus, and other mTOR inhibitors) or vildagliptin (for diabetes). See section “Warnings and precautions”.

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 Ramipril and Hydrochlorothiazide Krka” 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 Ramipril and Hydrochlorothiazide Krka:

• Medicines for diabetes such as oral hypoglycaemics and insulin. Ramipril and Hydrochlorothiazide Krka may lower blood sugar levels. Monitor your blood sugar levels carefully when taking Ramipril and Hydrochlorothiazide Krka.
• Lithium (for psychiatric conditions). Ramipril and Hydrochlorothiazide Krka may increase lithium levels in the blood. Your doctor must closely monitor your blood lithium levels.
• Medicines used to relax muscles.
• Quinine (for malaria).
• Medicines containing iodine, which may be used if you need a scan or X-ray in hospital.
• Penicillins (for infections).
• Oral anticoagulants (blood thinners) such as warfarin.

If any of the above conditions apply to you (or if you have any doubts), consult your doctor before taking
Ramipril and Hydrochlorothiazide Krka.
Tests
Check with your doctor or pharmacist before taking the medicine:

• If you need to undergo a test for parathyroid function. Ramipril and Hydrochlorothiazide Krka may affect test results.
• If you are an athlete required to undergo anti-doping testing. Ramipril and Hydrochlorothiazide Krka may give a positive result.

Ramipril and Hydrochlorothiazide Krka with food, drinks, and alcohol

• Drinking alcohol while taking Ramipril and Hydrochlorothiazide Krka may cause dizziness or lightheadedness. If you are concerned about how much alcohol you can drink while taking Ramipril and Hydrochlorothiazide Krka, discuss it with your doctor, as blood pressure-lowering medicines and alcohol may have additive effects.
• Ramipril and Hydrochlorothiazide Krka can be taken with or without food.

Pregnancy, breastfeeding, and fertility
You must inform your doctor if you think you are pregnant (or could become pregnant).
Pregnancy
You must not take Ramipril and Hydrochlorothiazide Krka during the first 12 weeks of pregnancy and must not take it at all after week 13, as it may harm the unborn baby.
If you become pregnant while taking Ramipril and Hydrochlorothiazide Krka, inform your doctor immediately. Before planning a pregnancy, you should switch to an alternative suitable medicine.
Breastfeeding
You must not take Ramipril and Hydrochlorothiazide Krka while breastfeeding.
Consult your doctor or pharmacist before taking any medicine.
Driving and using machines
Do not drive or operate machinery until you know how Ramipril and Hydrochlorothiazide Krka affects you. You may feel drowsy or dizzy while taking Ramipril and Hydrochlorothiazide Krka. This is more likely when you first start taking the medicine or have just increased your dose. If this occurs, do not drive or operate machinery.
Ramipril and Hydrochlorothiazide Krka contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Ramipril and Hydrochlorothiazide Krka

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
When taking this medicine:

• Take this 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.

How much to take
Treatment of high blood pressure
Your doctor will adjust your dose until your blood pressure is under
control.
Elderly patients
Your doctor will reduce the initial dose and adjust treatment more slowly.
If you take more Ramipril and Hydrochlorothiazide Krka than you should
Inform your doctor 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 package
with you. This way, the doctor will know what you have taken.
If you forget to take Ramipril and Hydrochlorothiazide Krka
If you miss a dose, take your usual dose at the next scheduled time.
Do not take a double dose to make up for the missed dose.
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 Ramipril and Hydrochlorothiazide Krka 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 or throat causing difficulty swallowing or breathing, together with itching and skin rash. This may be a sign of a severe allergic reaction to Ramipril and Hydrochlorothiazide Krka.
• 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 pounding heartbeat (palpitations), chest pain, feeling of tightness in the chest or more serious problems including heart attack and stroke.
• Shortness of breath or cough for two or three days and feeling tired. These may be signs of lung problems, including inflammation.
• Bruising more easily, bleeding that lasts longer than normal, any sign of bleeding (e.g. bleeding gums), purple spots, spots on the skin or increased tendency to get infections, sore throat and fever, feeling tired, weak, dizzy or pale. These may be signs of blood or bone marrow problems.
• Severe stomach pain that may spread to the back. This may be a sign of pancreatitis (inflammation of the pancreas).
• 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 (liver inflammation) or liver damage.

Other side effects include:
Inform 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 weak or tired.
• Dizziness. This is more likely when you have just started taking Ramipril and Hydrochlorothiazide Krka or have recently increased your dose.
• Low blood pressure (hypotension), especially when standing up or getting up quickly.
• Dry, persistent cough or bronchitis.
• Blood tests showing higher blood sugar levels than normal. If you have diabetes, this may worsen your diabetes.
• Blood tests showing higher levels of uric acid in the blood or increased blood fats compared to normal.
• Joint pain, redness and swelling.
• Blood tests showing higher levels of potassium in the blood than normal.

Uncommon (may affect up to 1 in 100 people)

• Skin rashes with or without red areas.
• Flushing, fainting.
• Balance problems (dizziness).
• Itching and unusual skin sensations such as numbness, tingling, itching, burning or crawling sensations on the skin (paresthesia).
• Loss or change in taste.
• Sleep problems.
• Depressed mood, anxiety, increased nervousness or restlessness.
• Stuffy nose, inflammation of the sinuses (sinusitis), breathing difficulties.
• Inflammation of the gums (gingivitis), swelling of the mouth.
• Redness, itching, swelling or watering of the eyes.
• Ringing in the ears.
• Blurred vision.
• Hair loss.
• Abdominal pain.
• Muscle pain.
• Constipation, stomach or intestinal pain.
• Indigestion or feeling unwell.
• Increased amount of urine during the day.
• Increased sweating or feeling thirsty.
• Loss of appetite (anorexia) or feeling of not wanting to eat.
• Increased or irregular heartbeat.
• Swollen arms and legs. This may be a sign that your body is retaining more fluid than usual.
• Fever.
• Impotence in men, reduced sex drive in men and women.
• Decreased number of blood cells, white blood cells or platelets or hemoglobin found during blood tests.
• Changes in liver, pancreas or kidney function shown by blood tests.
• Lower than normal potassium levels in the blood shown by blood tests.

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

• Feeling confused.
• Spots on the skin and cold extremities.

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

• Feeling unwell, with diarrhea and stomach pain.
• Red and swollen tongue or dry mouth.

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

• Skin and lip cancer (non-melanoma skin cancer)
• Concentrated urine (dark-colored), feeling unwell, muscle cramps, confusion and seizures which may be due to inadequate secretion of ADH (antidiuretic hormone). If you experience these symptoms, contact your doctor as soon as possible.
  Other side effects observed: Inform your doctor if any of the conditions listed below become severe or persist for longer than a few days.
• Difficulty concentrating.
• Fingers of hands and feet changing color when cold, and tingling or pain when warmed (Raynaud's phenomenon).
• Enlargement of breasts in men.
• Blood clots.
• Hearing disorders.
• Reduced tear production.
• Yellow vision of objects.
• Decreased vision or eye pain due to increased eye pressure (possible symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or angle-closure glaucoma).
• Dehydration.
• Swelling, pain and redness of the cheeks (inflammation of the salivary glands).
• A swelling in your intestine called "intestinal angioedema" which presents with symptoms such as abdominal pain, vomiting and diarrhea.
• Increased sensitivity to sunlight.
• Severe peeling or shedding of the skin, itching, rash with pustules or other skin reactions such as rashes on the face or forehead.
• Skin rash or bruising.
• Nail problems (e.g. loosening or separation of a nail from its bed).
• Stiffness of the musculoskeletal system or inability to move the jaw (tetany).
• Weakness or cramps in the muscles.
• Blood in the urine. This could be a sign of a kidney problem (interstitial nephritis).
• More sugar than usual in your urine.
• Blood tests showing an increase in certain white blood cells (eosinophilia).
• Blood tests showing a decrease in red blood cells in the blood (pancytopenia).
• Blood tests showing changes in the levels of salts such as sodium, calcium, magnesium and chloride in the blood.
• Slowed or impaired reactions.
• Changes in the perception of smells.
• Breathing difficulties or worsening of asthma.

Reporting of side effects
If you experience any side effects, 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 the website: 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 Ramipril and Hydrochlorothiazide Krka

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after EXP. The expiry date refers to the last day of that month.
Do not store above 30°C.
Keep in the original packaging to protect the medicine from moisture.
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 Ramipril and Hydrochlorothiazide Krka contains

• The active substances are ramipril and hydrochlorothiazide. Each tablet contains 2.5 mg of ramipril and 12.5 mg of hydrochlorothiazide. Each tablet contains 5 mg of ramipril and 25 mg of hydrochlorothiazide.
• The other components are hypromellose, microcrystalline cellulose, pregelatinized maize starch, and sodium stearyl fumarate. See section 2 “Ramipril and Hydrochlorothiazide Krka contains sodium”.

Description of the appearance of Ramipril and Hydrochlorothiazide Krka and the package contents
Tablets 2.5 mg/12.5 mg: white to almost white, round, bevelled-edge tablets, engraved with the letter C on one side. Tablet diameter: 5.5 mm.
Tablets 5 mg/25 mg: white to almost white, round tablets, scored on one side and engraved with the letter S on the other side. Tablet diameter: 7.5 mm. The tablet can be divided into equal parts.
Ramipril and Hydrochlorothiazide Krka is available in packs of 14, 28, 30, 56, 98 or 100 tablets in blister packs.
Not all pack sizes may be marketed.

Marketing Authorization Holder
KRKA, d. d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Local representative in Italy:
KRKA Farmaceutici Milano S.r.l. – Italy

Responsible manufacturers for batch release
KRKA, d. d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

This medicinal product is authorised in the European Economic Area countries under the following names: