RAMIPRIL/HYDROCHLOROTHIAZIDE KRKA 5 mg/25 mg TABLETS

Introduction

Package Leaflet: Information for the User

Ramipril/Hydrochlorothiazide Krka 5 mg/25 mg Tablets EFG

ramipril/hydrochlorothiazide

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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

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

Ramipril/Hydrochlorothiazide Krka is a combination of two medicines called ramipril and hydrochlorothiazide.

Ramipril belongs to a group of medicines called ACE inhibitors (angiotensin-converting enzyme inhibitors). It works in the following ways:

• Reducing the production by the body of substances that can increase blood pressure.
• Relaxing and dilating blood vessels.
• Making it easier for the heart to pump blood through the body.

Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics (diuretics are also known as "water tablets"). It works by increasing the amount of water (urine) that is removed from the body. This reduces blood pressure. Ramipril/Hydrochlorothiazide Krka is used to treat high blood pressure. The two active ingredients it contains work together to reduce blood pressure. They are used together when treatment with only one of them does not provide adequate control of your blood pressure.

2. What you need to know before you take Ramipril/Hydrochlorothiazide Krka

Do not take Ramipril/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/Hydrochlorothiazide Krka (other ACE inhibitors or other sulfonamide derivatives).
• Symptoms of an allergic reaction can include rash, problems with swallowing or breathing, swelling of the lips, face, throat or tongue.
• If you have ever had a severe allergic reaction called "angioedema". Symptoms can be itching, hives (urticaria), red spots on hands, feet, and throat, swelling of the throat and tongue, swelling of eyelids and lips, difficulty breathing and swallowing.
• If you are having dialysis or any other type of blood filtration. Depending on the machine used, Ramipril/Hydrochlorothiazide Krka 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 where the blood flow to your kidneys is reduced (renal artery stenosis).
• During the last 6 months of pregnancy (see also the section on "Pregnancy and Breast-feeding").
• If you are breast-feeding (see also the section on "Pregnancy and Breast-feeding").
• 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 a type of long-term (chronic) heart failure in adults, as the risk of angioedema (rapid swelling under the skin in an area such as the throat) is increased.

Do not take Ramipril/Hydrochlorothiazide Krka if any of the above applies to you.

If you are not sure, talk to your doctor before taking Ramipril/Hydrochlorothiazide Krka.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Ramipril/Hydrochlorothiazide Krka:

• If you have heart, liver or kidney problems.
• If you have lost a lot of body salts or fluids (for example, due to vomiting, diarrhea, excessive sweating, a low-salt diet, long-term diuretic use, or dialysis).
• If you are going to have treatment to reduce your allergy to bee or wasp stings (desensitization).
• If you are going to receive an anesthetic, for example, for an operation or dental procedure. You may need to stop taking Ramipril/Hydrochlorothiazide Krka one day beforehand; consult your doctor.
• If you have high levels of potassium in your blood (shown in blood test results).
• If you are taking medicines or have conditions that may decrease sodium levels in your blood. Your doctor may perform regular blood tests, especially to monitor sodium levels in your blood, particularly if you are elderly.
• If you are taking any of the following medicines, the risk of angioedema may increase:

• Racecadotril, a medicine used to treat diarrhea.
• Medicines used to prevent organ transplant rejection and for cancer (e.g., temsirolimus, sirolimus, everolimus).
• Vildagliptin, a medicine used to treat diabetes.

• If you have a collagen vascular disease, such as scleroderma or systemic lupus erythematosus.
• If you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Ramipril/Hydrochlorothiazide Krka.
• If you have had respiratory or lung problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience shortness of breath or severe difficulty breathing after taking Ramipril/Hydrochlorothiazide Krka, seek medical attention immediately.
• If you are taking any of the following medicines used to treat high blood pressure:

• Angiotensin receptor blockers (ARBs) (also known as sartans, e.g., valsartan, telmisartan, irbesartan), particularly if you have diabetes-related kidney problems.
• Aliskiren.

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g., potassium) in your blood at regular intervals.

See also the information under the heading "Do not take Ramipril/Hydrochlorothiazide Krka" and "Warnings and precautions".

• If you experience a decrease in 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 and can occur within hours to weeks after taking Ramipril/Hydrochlorothiazide Krka. This can lead to loss of vision if not treated. If you have previously been allergic to penicillin or sulfonamide, you may have a higher risk of developing it.

Tell your doctor if you are pregnant (or think you might be). Ramipril/Hydrochlorothiazide Krka is not recommended during the first 3 months of pregnancy and may cause serious harm to your baby after the third month of pregnancy (see section on "Pregnancy and Breast-feeding" below).

Children and adolescents

Ramipril/Hydrochlorothiazide Krka is not recommended for use in children and adolescents under 18 years of age because it has not been used in these age groups.

If any of the above applies to you (or you are not sure), talk to your doctor before taking Ramipril/Hydrochlorothiazide Krka.

Other medicines and Ramipril/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/Hydrochlorothiazide Krka can affect the way other medicines work. Some medicines also can affect the way Ramipril/Hydrochlorothiazide Krka works.

Tell your doctor if you have taken or are taking any of the following medicines, which may make Ramipril/Hydrochlorothiazide Krka work less effectively:

• Pain and inflammation relievers (e.g., non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or indomethacin, and aspirin).
• Medicines for low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, or adrenaline. Your doctor will need to check your blood pressure.

Tell your doctor if you are taking any of the following medicines, which may increase the risk of side effects if taken with Ramipril/Hydrochlorothiazide Krka:

• Pain and inflammation relievers (e.g., non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or indomethacin, and aspirin).
• Medicines that can reduce potassium levels in the blood, such as laxatives, diuretics, amphotericin B (for fungal infections), and ACTH (to check if your adrenal glands are working properly).
• Temsirolimus (for cancer).
• Heart medicines, including those for heart rhythm problems.
• Diuretics such as furosemide.
• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that can increase potassium levels in the blood (e.g., trimethoprim and co-trimoxazole for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection; heparin, a medicine used to thin the blood and prevent clots).
• Steroid medicines for inflammation, such as prednisolone.
• Calcium supplements.
• Allopurinol (to reduce uric acid levels in the blood).
• Procainamide (for heart rhythm problems).
• Colestyramine (to reduce blood fat levels).
• Carbamazepine (for epilepsy).
• Medicines that are commonly used to prevent organ transplant rejection (e.g., sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of mTOR inhibitors) or vildagliptin (for diabetes). See the section "Warnings and precautions".

Your doctor may need to change the dose and/or take other precautions:

• If you are taking angiotensin receptor blockers (ARBs) or aliskiren (see also the information under the heading "Do not take Ramipril/Hydrochlorothiazide Krka" and "Warnings and precautions").

Tell your doctor if you are taking any of the following medicines, as they may be affected by Ramipril/Hydrochlorothiazide Krka:

• Diabetes medicines, such as oral glucose-lowering medicines and insulin. Ramipril/Hydrochlorothiazide Krka may reduce blood sugar levels. Monitor your blood sugar levels carefully while taking Ramipril/Hydrochlorothiazide Krka.
• Lithium (for mental health problems). Ramipril/Hydrochlorothiazide Krka may increase lithium levels in the blood. Your doctor will closely monitor your lithium levels in the blood.
• Muscle relaxants.
• Quinine (for malaria).
• Medicines containing iodine (such as those used in hospitals for scanning or certain X-rays).
• Penicillin (for infections).
• Oral blood thinners (anticoagulants) such as warfarin.

If any of the above applies to you (or you are not sure), consult your doctor before taking Ramipril/Hydrochlorothiazide Krka.

Tests

Check with your doctor or pharmacist before taking your medicine:

• If you are going to have a parathyroid function test, Ramipril/Hydrochlorothiazide Krka may affect the results.
• If you are participating in athletic competitions subject to doping control, be aware that Ramipril/Hydrochlorothiazide Krka may give a positive result.

Using Ramipril/Hydrochlorothiazide Krka with food, drinks, and alcohol

• Drinking alcohol with Ramipril/Hydrochlorothiazide Krka may make you feel dizzy or lightheaded. If you are concerned about how much you can drink while taking Ramipril/Hydrochlorothiazide Krka, talk to your doctor, as blood pressure medicines and alcohol can have additive effects.
• Ramipril/Hydrochlorothiazide Krka can be taken with or without food.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine.

Pregnancy

You should not take Ramipril/Hydrochlorothiazide Krka during the first 12 weeks of pregnancy, and you should not take it at all after the 13th week, as its use during pregnancy may be harmful to the baby.

If you become pregnant while taking Ramipril/Hydrochlorothiazide Krka, inform your doctor immediately. Alternative treatment should be initiated if you plan to become pregnant.

Breast-feeding

You should not use Ramipril/Hydrochlorothiazide Krka if you are breast-feeding.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

It is recommended that you do not drive or use machines until you know how Ramipril/Hydrochlorothiazide Krka affects you.

You may feel dizzy while taking Ramipril/Hydrochlorothiazide Krka, which is more likely to happen when you start taking Ramipril/Hydrochlorothiazide Krka or start taking a higher dose. If you feel dizzy, do not drive or operate tools or machines.

Ramipril/Hydrochlorothiazide Krka contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially "sodium-free".

3. How to take Ramipril/Hydrochlorothiazide Krka

Follow exactly the instructions of administration of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Taking this medicine

• Take this medicine orally at the same time each day, usually in the morning.
• Swallow the tablets whole with liquid.
• Do not crush or chew the tablets.

How much to take

Treatment of high blood pressure

Your doctor will adjust the amount you need to take to control your blood pressure.

Elderly patients

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

If you take more Ramipril/Hydrochlorothiazide Krka than you should

Consult your doctor immediately or go to the nearest hospital emergency department. Do not drive to the hospital: ask someone to drive you or call an ambulance. Take the medicine pack with you, so your doctor knows what you have taken.

You can also contact the Toxicology Information Service, telephone 91 562 04 20, stating the medicine and the amount taken.

If you forget to take Ramipril/Hydrochlorothiazide Krka

If you forget to take a dose, take your normal dose when it is next due.

Do not take a double dose to make up for forgotten doses.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Stop taking Ramipril/Hydrochlorothiazide Krka and consult your doctor immediately if you notice any of the following serious adverse effects, as you may need urgent medical treatment:

• Swelling of the face, lips, or throat, which can make swallowing or breathing difficult, as well as itching and rash, which can be a sign of a significant allergic reaction to Ramipril/Hydrochlorothiazide Krka.
• Severe skin reactions, such as rash, mouth ulcers, worsening of pre-existing skin disease, redness, blisters, or skin peeling (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or erythema multiforme).
• Acute respiratory distress (symptoms include severe breathing difficulties, fever, weakness, and confusion) (very rare, affecting less than 1 in 10,000 people).

Inform your doctor immediately if you experience:

• Faster heart rate, irregular or strong heartbeats (palpitations), chest pain, chest tightness, or more serious problems such as heart attack and stroke.
• Difficulty breathing, cough, and fever lasting two to three days, and loss of appetite, which could be symptoms of lung problems, including inflammation.
• Easy bruising, bleeding for longer than normal, any sign of bleeding (e.g., from the gums), purple spots on the skin, skin spots, or getting infections more easily than usual, sore throat, and fever, feeling tired, dizzy, or pale skin, which could be signs of blood or bone marrow problems.
• Severe stomach pain, which can radiate to the back, which could be a symptom of pancreatitis (inflammation of the pancreas).
• Fever, chills, fatigue, loss of appetite, stomach pain, nausea (vomiting), yellowing of the skin or eyes (jaundice), which could be symptoms of liver problems, such as hepatitis (inflammation of the liver) or liver damage.

Other adverse effects may be:

Inform your doctor if any of the following adverse effects worsen or last more than a few days.

Frequent(affecting less than 1 in 10 people)

• Headache or feeling of weakness or fatigue.
• Feeling dizzy. This is more likely to occur when starting to take Ramipril/Hydrochlorothiazide Krka or starting a higher dose.
• Hypotension (abnormally low blood pressure), especially when standing up and sitting down quickly.
• Dry, irritating cough or bronchitis.
• Blood tests showing higher than normal sugar levels. If you have diabetes, this may worsen.
• Blood tests showing higher than normal uric acid or fat levels.
• Pain, redness, or swelling of the joints.
• Blood tests showing higher than normal potassium levels.

Uncommon(affecting less than 1 in 100 people)

• Skin rash, with or without raised areas.
• Redness, feeling of fainting.
• Balance problems (vertigo).
• Itching and abnormal sensations in the skin, such as numbness, tingling, pinching, burning, or prickling sensation of the skin (paresthesias).
• Loss or change in taste.
• Sleep problems.
• Depression, anxiety, more nervousness or restlessness than usual.
• Stuffy nose, inflammation of the facial sinuses (sinusitis), difficulty breathing.
• Gingivitis (gum inflammation), mouth inflammation.
• Redness, itching, or swelling of the eyes or tearing.
• Ringing in the ears.
• Blurred vision.
• Hair loss.
• Chest pain.
• Muscle pain.
• Constipation, stomach pain, or abdominal pain.
• Stomach upset after meals or nausea (vomiting).
• Urinating more frequently during the day.
• Sweating more than usual or feeling thirsty.
• Loss or decrease in appetite (anorexia), having less hunger.
• Faster or irregular heartbeats.
• Swelling of arms and legs, which can be a sign that your body is retaining more fluid than usual.
• Fever.
• Impotence in men, reduced sexual desire in men or women.
• Blood tests showing a decrease in the number of red blood cells, white blood cells, or platelets, or the amount of hemoglobin.
• Blood tests showing changes in how your liver, pancreas, or kidney is functioning.
• Blood tests showing lower than normal potassium levels.

Rare(affecting less than 1 in 1,000 people)

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

Very Rare(affecting less than 1 in 10,000 people)

• Feeling sick, having diarrhea, or stomach burning.
• Inflamed tongue and redness or dry mouth.

Frequency Not Known(cannot be estimated from the available data)

• Skin and lip cancer (non-melanoma skin cancer).
• Concentrated urine (dark color), feeling or being sick, having muscle cramps, confusion, and seizures that may be due to inadequate ADH (antidiuretic hormone) secretion. If you have these symptoms, consult your doctor as soon as possible.

Other Observed Adverse Effects:

Inform your doctor if any of the following adverse effects worsen or last more than a few days.

• Difficulty concentrating.
• Fingers and toes changing color with cold and then tingling or pain when warming up, which could be a Raynaud's phenomenon.
• Male breast growth.
• Blood clot formation.
• Hearing problems.
• Less tear formation than usual.
• Seeing objects in yellow color.
• 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)
• Dehydration.
• Swelling, pain, and redness in one cheek (inflammation of a salivary gland).
• Intestinal inflammation called "intestinal angioedema", with symptoms such as abdominal pain, vomiting, and diarrhea.
• Increased sensitivity to sunlight.
• Severe skin peeling or flaking, rash with itching and lumps, or other skin reactions, such as red rash on the face or forehead.
• Rash or bruising on the skin.
• Nail problems (nail detachment or separation from the nail bed).
• Musculoskeletal stiffness or inability to move the jaw (tetany).
• Weakness or muscle cramps.
• Blood in the urine, which could be a sign of kidney problems (interstitial nephritis).
• Higher than normal sugar levels in the urine.
• Increased number of a certain type of white blood cell (eosinophilia) in a blood test.
• Blood tests showing very few blood cells (pancytopenia).
• Blood tests showing changes in the amount of salts, such as sodium, calcium, magnesium, and chloride, in the blood.
• Slowness or difficulty reacting.
• Change in the smell of things.
• Breathing problems or worsening of asthma.

Reporting of Adverse Effects:

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Ramipril/Hydrochlorothiazide Krka

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Store in the original packaging to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Ramipril/Hydrochlorothiazide Krka

• The active ingredients are ramipril and hydrochlorothiazide.

Each tablet contains 5 mg of ramipril and 25 mg of hydrochlorothiazide.

• The other ingredients (excipients) are hypromellose, microcrystalline cellulose, pregelatinized corn starch, and sodium stearyl fumarate. See section 2 "Ramipril/Hydrochlorothiazide Krka contains sodium".

Appearance of the Product and Package Contents

White or almost white, round tablets with beveled edges, scored on one side, and marked with an "S" on one side. Tablet diameter: 7.5 mm. The tablet can be divided into equal doses.

The tablets are presented in a blister pack of 14, 28, 30, 56, 98, and 100 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

KRKA Farmacéutica, S.L., C/ Anabel Segura 10, Pta. Baja, Oficina 1, 28108 Alcobendas, Madrid, Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of the Last Revision of this Leaflet:April 2022

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/