Package Leaflet: Information for the User

Ramipril/Hydrochlorothiazide Krka 5 mg/25 mg Tablets EFG

ramipril/hydrochlorothiazide

Read this leaflet carefully before you start to take this medicine because it contains important information for you.

• Keep this leaflet, as 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 others even if they have similar symptoms to you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Ramipril/Hidroclorotiazida Krka is a combination of two medicines called ramipril and hidroclorotiazida.

Ramipril belongs to a group of medicines called ACE inhibitors (angiotensin-converting enzyme inhibitors). It works as follows:

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

Hidroclorotiazida belongs to a group of medicines called "thiazide diuretics" (diuretics are also known as "urine tablets"). It works by increasing the amount of water (urine) that is eliminated. This reduces blood pressure.Ramipril/Hidroclorotiazida 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 blood pressure.

Do not take Ramipril/Hidroclorotiazida KrkaKrka

• If you are allergic to ramipril, hidroclorotiazida or to any of the other components of this medication (listed in section 6).
• If you are allergic (hypersensitive) to similar medications to Ramipril/Hidroclorotiazida Krka (other ACE inhibitors or other sulfonamide derivatives).
• The symptoms of an allergic reaction may include skin rash, difficulty swallowing or breathing, swelling of lips, face, throat or tongue.
• If you have ever had a severe allergic reaction called “angioedema”. The symptoms may be itching, hives (urticaria), red patches on hands, feet and throat, swelling of throat and tongue, swelling of eyelids and lips, difficulty breathing and swallowing.
• If you are undergoing dialysis or any other type of blood filtration. Depending on the machine used, Ramipril/Hidroclorotiazida Krka may not be suitable for you.
• If you have significant liver problems.
• If you have abnormal levels of salt substances (calcium, potassium, sodium) in your blood.
• If you have kidney problems due to which the blood that reaches your kidneys is less than normal (renal artery stenosis).
• During the last 6 months of pregnancy (see, below, the section on “Pregnancy and breastfeeding”).
• If you are breastfeeding (see, below, the section on "Pregnancy and breastfeeding").
• If you have diabetes or damaged renal function and are being treated with a medication to reduce blood pressure that contains aliskiren.
• If you have taken or are currently taking sacubitril/valsartán, a medication used to treat a type of chronic heart failure in adults, as the risk of angioedema (rapid swelling under the skin in an area such as the throat) is high.

Do not take Ramipril/Hidroclorotiazida Krka if any of the above conditions apply to you.

If you are unsure, speak with your doctor before taking Ramipril/Hidroclorotiazida Krka.

Warnings and precautions

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

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

• racecadotril, a medication used to treat diarrhea.
• medications used to prevent organ transplant rejection and for cancer (e.g., temsirolimus, sirolimus, everolimus).
• vildagliptin, a medication used to treat diabetes.

• If you have a vascular collagen disease, such as scleroderma or systemic lupus erythematosus.
• If you have had skin cancer or if a skin lesion appears unexpectedly during treatment. The treatment with hidroclorotiazida, 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 and UV rays while taking Ramipril/Hidroclorotiazida Krka.
• If you have had respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hidroclorotiazida in the past. If you experience severe shortness of breath or difficulty breathing after taking Ramipril/Hidroclorotiazida Krka, seek medical attention immediately.
• If you are taking any of the following medications used to treat high blood pressure:

-angiotensin receptor blockers (ARBs), (also known as sartans, for example valsartán, telmisartán, irbesartán), particularly if you have diabetes-related kidney problems,

-aliskiren.

Your doctor may check your renal function, blood pressure, and electrolyte levels (e.g., potassium) at regular intervals.

See also the information under the title "Do not take Ramipril/Hidroclorotiazida Krka".

• If you experience a decrease in vision or eye pain, it may be a symptom of fluid accumulation in the blood vessel layer of the eye (choroidal effusion) or increased eye pressure, which can occur within a few hours to several weeks after taking Ramipril/Hidroclorotiazida Krka. This can lead to vision loss if not treated. If you have previously had an allergy to penicillin or sulfonamide, you may be at higher risk of developing it.

Inform your doctor if you are pregnant (or if you suspect you may be). Ramipril/Hidroclorotiazida Krka is not recommended for use in the first 3 months of pregnancy and may cause serious harm to your baby after the third month of pregnancy (see section below on “Pregnancy and breastfeeding”).

Children and adolescents

Ramipril/Hidroclorotiazida Krka is not recommended for use in children and adolescents under 18 years of age because it has never been used in these age groups.

If any of the above conditions apply to you (or you are unsure), speak with your doctor before taking Ramipril/Hidroclorotiazida Krka.

Other medications and Ramipril/Hidroclorotiazida Krka

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including over-the-counter medications (including herbal remedies). This is because Ramipril/Hidroclorotiazida Krka may affect the functioning of other medications. Some medications may also affect how Ramipril/Hidroclorotiazida Krka works.

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

• Medications to relieve pain and inflammation (e.g., non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or indomethacin and aspirin).
• Medications to treat low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, or adrenaline. Your doctor will need to take your blood pressure.

Inform your doctor if you are taking any of the following medications, which may increase the risk of adverse effects if taken with Ramipril/Hidroclorotiazida Krka:

• Medications to relieve pain and inflammation (e.g., non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or indomethacin and aspirin).
• Medications that may reduce potassium levels in the blood, such as medications for constipation, diuretics, amphotericin B (for fungal infections) and ACTH (to see if your adrenal glands are functioning properly).
• Temsirolimus (for cancer).
• Medications for heart problems, including arrhythmia problems.
• Diuretics such as furosemide.
• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medications that may increase potassium levels in the blood, (e.g., trimethoprim and co-trimoxazole for bacterial infections; ciclosporin, an immunosuppressant used to prevent organ transplant rejection and heparin, a medication used to thin the blood and prevent clots).
• Medications containing steroids for inflammation, such as prednisolone.
• Calcium supplements.
• Alopurinol (to reduce uric acid levels in the blood).
• Procainamide (to treat arrhythmia problems).
• Colestiramina (to reduce cholesterol levels in the blood).
• Carbamazepine (for epilepsy).
• Medications that are more frequently used to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other medications 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 takingangiotensin receptor blockers (ARBs) or aliskiren (see also the information under the title “Do not take Ramipril/Hidroclorotiazida Krka” and “Warnings and precautions”).

Inform your doctor if you are taking any of the following medications, which may be affected by Ramipril/Hidroclorotiazida Krka:

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

If any of the above conditions apply to you (or you are unsure), consult your doctor before taking Ramipril/Hidroclorotiazida Krka.

Tests

Check with your doctor or pharmacist before taking your medication:

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

Use of Ramipril/Hidroclorotiazida Krka with food, drinks, and alcohol

• Drinking alcohol with Ramipril/Hidroclorotiazida Krka may make you feel dizzy or disoriented. If you are concerned about how much you can drink while taking Ramipril/Hidroclorotiazida Krka, speak with your doctor, as medications used to reduce blood pressure and alcohol may have additive effects.
• Ramipril/Hidroclorotiazida Krka can be taken with or without food.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medication.

Pregnancy

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

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

Breastfeeding

You should not use Ramipril/Hidroclorotiazida Krka if you are breastfeeding.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

It is recommended that you do not drive or operate machinery until you know how Ramipril/Hidroclorotiazida Krka affects you.

You may feel dizzy while taking Ramipril/Hidroclorotiazida Krka, which is more likely to occur when starting Ramipril/Hidroclorotiazida Krka or starting a higher dose. If you feel dizzy, do not drive or operate tools or machinery.

Ramipril/Hidroclorotiazida Krka contains sodium

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

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Medication intake

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

How much medication to take

Hypertension treatment

Your doctor will adjust the amount you should take until your blood pressure is under control.

Older patients

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

If you take more Ramipril/Hidroclorotiazida 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 take you or call an ambulance. Bring the medication packaging with you, so your doctor knows what you have taken.

You can also call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount taken.

If you forgot to take Ramipril/Hidroclorotiazida Krka

If you forgot to take a dose, take your regular dose when it is next due.

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Stop taking Ramipril/Hidroclorotiazida Krka and consult 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, which can make it difficult to swallow or breathe, as well as itching and hives, which can be a sign of a serious allergic reaction to Ramipril/Hidroclorotiazida Krka.
• Important skin reactions, such as rashes, mouth sores, worsening of an existing skin condition, redness, blisters, or skin peeling (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or multiform erythema).
• Acute respiratory distress (symptoms include severe difficulty breathing, fever, weakness, and confusion) (very rare, affecting fewer than 1 in 10,000 people).

Inform your doctor immediately if you experience:

• Fast or irregular heartbeat, 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, prolonged bleeding, any sign of bleeding (e.g., from the gums), purple spots on the skin, skin spots, or catching infections more easily than normal, sore throat, and fever, feeling tired, dizziness, 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 (urge to vomit), yellow skin or eyes (jaundice), which could be symptoms of liver problems, such as hepatitis (inflammation of the liver) or liver damage.

Other side effects may be:

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

Frequent(affecting fewer than 1 in 10 people)

• Headache or feeling weak or tired.
• Feeling dizzy. This is more likely to occur when starting to take Ramipril/Hidroclorotiazida Krka or starting a higher dose.
• 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 could worsen.
• Blood tests showing higher-than-normal levels of uric acid or fats.
• Joint pain, redness, or inflammation.
• Blood tests showing higher-than-normal potassium levels.

Rare(affecting fewer than 1 in 100 people)

• Skin rash, with or without raised areas.
• Redness, feeling faint.
• Balance problems (vertigo).
• Itching and abnormal sensations in the skin, such as numbness, tingling, pinching, burning, or aching (paresthesias).
• Loss or changes in the taste of things.
• Difficulty sleeping.
• Depression, anxiety, more nervousness or restlessness than normal.
• Blocked nose, sinusitis, difficulty breathing.
• Gum inflammation (gingivitis), mouth inflammation.
• Redness, itching, or swelling of the eyes or tearing.
• Ear ringing.
• Blurred vision.
• Hair loss.
• Chest pain.
• Muscle pain.
• Constipation, stomach pain, or abdominal pain.
• Discomfort in the stomach after eating or urge to vomit.
• Urinating more than normal during the day.
• Sweating more than normal or feeling thirsty.
• Loss or decrease in appetite (anorexia), feeling less hungry.
• Fast or irregular heartbeat.
• Swelling of arms and legs, which can be a sign that your body is retaining more fluids than normal.
• Fever.
• Impotence in men, reduced sex drive in men or women.
• Blood tests showing fewer red blood cells, white blood cells, or platelets, or lower hemoglobin levels.
• Blood tests showing changes in how your liver, pancreas, or kidneys are functioning.
• Blood tests showing lower-than-normal potassium levels.

Very rare(affecting fewer than 1 in 10,000 people)

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

Unknown frequency(cannot be estimated from available data)

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

Other side effects observed:

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

• Difficulty concentrating.
• Fingers and toes that change color with cold and, afterwards, with tingling or pain when warming up, which could be a phenomenon of Raynaud.
• Enlargement of breasts in men.
• Formation of blood clots.
• Auditory problems.
• Less tear formation than normal.
• Yellow vision of objects.
• Decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) 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.
• Significant skin peeling or shedding, skin rash with itching and swelling, or other skin reactions, such as red face or forehead rash.
• Rash or petechiae on the skin.
• Nail problems (separation or detachment of a nail from its bed).
• Musculoskeletal stiffness or inability to move the jaw (tetany).
• Muscle weakness or cramps.
• Blood in the urine, which could be a sign of kidney problems (interstitial nephritis).
• Increased sugar in urine.
• Increased number of a certain type of white blood cell (eosinophilia) in a blood test.
• Blood test showing very few blood cells (pancytopenia).
• Blood test showing a change 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.
• Difficulty breathing or worsening of asthma.

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use: https://www.notificaram.es.

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

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

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not store above 86°F (30°C).

Store in the original packaging to protect it from moisture.

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

Composition of Ramipril/Hydrochlorothiazide Krka

• The active principles are ramipril and hydrochlorothiazide.

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

• The other components (excipients) are hypromellose, microcrystalline cellulose, pregelatinized maize starch, and sodium fumarate stearate. See section 2 “Ramipril/Hydrochlorothiazide Krka contains sodium”.

Appearance of the product and contents of the package

White or off-white, round, beveled-edge tablets, scored on one face and marked with an “S” on one face. 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.

Only some package sizes may be commercially available.

Marketing Authorization Holder

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

Responsible for manufacturing

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

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

For more information about this medicine, please contact 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 theEuropean Economic Area withthe following names:

Last review date of this leaflet:April 2022

More detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/