Ramipril and hydrochlorothiazide Zentiva: detailed information

Package leaflet: Information for the patient

RAMIPRIL AND HYDROCHLOROTHIAZIDE ZENTIVA 2.5 mg/12.5 mg tablets, 5 mg/25 mg tablets

Please read this leaflet carefully before 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 give it to other people, even if they have the same symptoms as you, because it may be harmful.
If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Ramipril and Hydrochlorothiazide Zentiva 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 pump blood more easily around 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.
Ramipril and Hydrochlorothiazide Zentiva is used to treat high blood pressure (hypertension). 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 Zentiva

Do not take Ramipril and Hydrochlorothiazide Zentiva:

If you are allergic to ramipril, hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6).
If you are allergic to medicines similar to Ramipril and Hydrochlorothiazide Zentiva (other ACE inhibitors or sulfonamide-derived medicines).
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”. 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 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 on dialysis or undergoing another type of blood filtration. Depending on the equipment used, Ramipril and Hydrochlorothiazide Zentiva 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 reduced blood flow 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 Ramipril and Hydrochlorothiazide Zentiva if any of the above conditions apply. If you are unsure, consult your doctor before taking Ramipril and Hydrochlorothiazide Zentiva.

Warnings and precautions
Talk to your doctor or pharmacist before taking Ramipril and Hydrochlorothiazide Zentiva:

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, diarrhea, excessive sweating, a very low-salt diet, long-term use of oral diuretics, or dialysis).
If you are about to undergo treatment to reduce allergy to bee or wasp stings (desensitization).
If you are about to receive an anesthetic that may be used during surgery or dental procedures. You may need to stop taking Ramipril and Hydrochlorothiazide Zentiva 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 order 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 (NEP) inhibitors (such as racecadotril), or sacubitril/valsartan. For sacubitril/valsartan, see also section 2 “Do not take Ramipril and Hydrochlorothiazide Zentiva”.
If you have a vascular collagen disease such as scleroderma or systemic lupus erythematosus.
You must inform your doctor if you think you may be pregnant (or could become pregnant). Ramipril and Hydrochlorothiazide Zentiva is not recommended during the first 3 months of pregnancy and may cause serious harm to the unborn child after 3 months of pregnancy (see section below “Pregnancy and breastfeeding”).
If you experience a decrease in vision 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 Ramipril and Hydrochlorothiazide Zentiva. This condition can lead to permanent vision loss if not treated. If you have previously had an allergy to penicillin or sulfonamides, you may be at higher risk.
- If you are taking any of the following medicines for 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 Ramipril and Hydrochlorothiazide Zentiva".

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 exposure to sunlight and UV rays while taking Ramipril and Hydrochlorothiazide Zentiva.

Children and adolescents
Ramipril and Hydrochlorothiazide Zentiva is not recommended for children and adolescents under 18 years of age, as the medicine has never been studied in this age group.
If any of the above conditions apply or you are unsure, consult your doctor before taking Ramipril and Hydrochlorothiazide Zentiva.

Other medicines and Ramipril and Hydrochlorothiazide Zentiva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is because Ramipril and Hydrochlorothiazide Zentiva may affect how some other medicines work. Likewise, some medicines may affect how Ramipril and Hydrochlorothiazide Zentiva works.
Inform your doctor if you are taking any of the following medicines. These may interfere with Ramipril and Hydrochlorothiazide Zentiva and alter its effect:

Sacubitril/valsartan—used to treat a type of chronic heart failure in adults (see also section "Do not take Ramipril and Hydrochlorothiazide Zentiva").
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 Ramipril and Hydrochlorothiazide Zentiva 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, 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 test adrenal gland function).
Medicines for cancer (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, trimethoprim alone or in combination with sulfamethoxazole (for infections), and heparin (used to thin the blood).
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).
Heparin (to thin the blood).
Temsirolimus (for cancer).
Sirolimus, everolimus (to prevent transplant rejection).
Vildagliptin (for type 2 diabetes).
Racecadotril (used to treat diarrhea).

Your doctor may need 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 Ramipril and Hydrochlorothiazide Zentiva" and "Warnings and precautions"). Inform your doctor if you are taking any of the following medicines. Their effects may be altered by Ramipril and Hydrochlorothiazide Zentiva:

Medicines for diabetes, such as oral hypoglycemics and insulin. Ramipril and Hydrochlorothiazide Zentiva may lower blood sugar levels. Monitor your blood sugar levels carefully when taking Ramipril and Hydrochlorothiazide Zentiva.
Lithium (for psychiatric conditions). Ramipril and Hydrochlorothiazide Zentiva may increase lithium levels in the blood. Your doctor must closely monitor your blood lithium levels.
Muscle relaxants.
Quinine (for treating malaria).
Medicines containing iodine, which may be used in hospital before X-rays or scans.
Penicillin (for treating infections).
Oral anticoagulants (blood thinners) such as warfarin.

If any of the above conditions apply (or you are unsure), consult your doctor before taking Ramipril and Hydrochlorothiazide Zentiva.

Medical tests
Inform your doctor or pharmacist before taking this medicine:

If you are having a test for parathyroid function. Ramipril and Hydrochlorothiazide Zentiva may alter test results.
If you are an athlete undergoing anti-doping testing. Ramipril and Hydrochlorothiazide Zentiva may result in a positive test.

Ramipril and Hydrochlorothiazide Zentiva with food and alcohol

Drinking alcohol while taking Ramipril and Hydrochlorothiazide Zentiva may cause dizziness or lightheadedness. If you want to know how much alcohol you can drink while on this medicine, discuss it with your doctor. Alcohol increases the blood pressure-lowering effect of this medicine.
Ramipril and Hydrochlorothiazide Zentiva can be taken with or without food.

Pregnancy and breastfeeding
Pregnancy
Inform your doctor if you think you may be pregnant (or could become pregnant).
You must not take Ramipril and Hydrochlorothiazide Zentiva during the first 12 weeks of pregnancy and must not take it at all from week 13 onwards, as it may harm the unborn child.
If you become pregnant while taking Ramipril and Hydrochlorothiazide Zentiva, inform your doctor immediately. Before planning a pregnancy, you should switch to a more suitable medicine.

Breastfeeding
You must not take Ramipril and Hydrochlorothiazide Zentiva while breastfeeding.
Consult your doctor or pharmacist before taking any medicine.

Effects on ability to drive and use machines
You may experience dizziness while taking Ramipril and Hydrochlorothiazide Zentiva. This is more likely when you first start treatment or when you start taking a higher dose. If this occurs, do not drive or operate tools or machinery.

3. How to take Ramipril and Hydrochlorothiazide Zentiva

Always take this medicine exactly as directed by your doctor. 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 gradually.

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 crush or chew the tablets.

If you take more Ramipril and Hydrochlorothiazide Zentiva 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. Bring the medicine’s packaging with you, so the doctor knows what you have taken.

If you forget to take Ramipril and Hydrochlorothiazide Zentiva

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 tablet.

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

4. Possible side effects

Like all medicines, Ramipril and Hydrochlorothiazide Zentiva can cause side effects, although
not everyone experiences them.
Stop taking Ramipril and Hydrochlorothiazide Zentiva 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 in swallowing or breathing, as well as itching or skin rash. These may be signs of a severe allergic reaction to Ramipril and Hydrochlorothiazide Zentiva.
Severe skin reactions including rash, mouth ulcers, worsening of pre-existing skin disorders, 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, cough, fever lasting 2 to 3 days and reduced appetite. These may be signs of lung problems, including inflammation.
Easy bruising, prolonged bleeding longer than normal, 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. These may be signs of blood or bone marrow problems.
Severe stomach pain that may extend to the back. This may 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.
Decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion), acute myopia or acute angle-closure glaucoma).

Other side effects include:
Inform your doctor if any of the following conditions become severe or persist for more 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 treatment with Ramipril and Hydrochlorothiazide Zentiva has just started or the dose has recently been increased
Dry, irritating cough or bronchitis
Blood tests show higher than normal sugar levels. If you have diabetes, this may worsen it
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)

Rash with or without swelling
Flushing, weakness, hypotension (unusually low blood pressure), especially when standing up or getting up quickly
Balance problems (dizziness)
Itching and unusual skin sensations such as numbness, tingling, prickling, burning or stinging (paraesthesia)
Loss or change in taste
Sleep problems
Depressed, anxious mood, more nervousness than usual or irritability
Stuffy nose, sinus inflammation (sinusitis), shortness of breath
Inflammation of the gums (gingivitis), mouth swelling
Red, swollen or watery, itchy eyes
Ringing in the ears
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
Fast 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
Decrease in the 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 diarrhoea or stomach burning
Swollen and red tongue or dry mouth
Blood tests show higher than normal potassium levels.

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

Difficulty concentrating, feeling restless or confused
Fingers of hands and feet changing colour when cold, and tingling or painful when warmed (Raynaud's phenomenon)
Breast enlargement in men
Blood clots
Hearing disturbances
Eyes less moist than normal
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 diarrhoea
Increased sensitivity to sunlight
Severe peeling or shedding of the skin, itching, rash or other skin reactions such as redness of the face or forehead
Skin rash or bruising
Spots on the skin and cold extremities
Nail problems (such as nail 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 certain white blood cells in the blood (eosinophilia) found during blood tests
Too low a number of blood cells shown by blood tests (pancytopenia)
Changes in levels of salts such as sodium, calcium, magnesium and chloride in the blood shown by blood tests
Concentrated urine (dark-coloured), feeling unwell or malaise, muscle cramps, confusion and seizures which may be due to inappropriate ADH (antidiuretic hormone) secretion. If you experience these symptoms, contact your doctor promptly
Slowed or altered reactions
Changes in the perception of smells
Breathing difficulties or worsening of asthma
Skin and lip cancer (non-melanoma skin cancer).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please 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
. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ramipril and Hydrochlorothiazide Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cartons and blisters after Exp..
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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 Zentiva 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, pregelatinized corn starch, microcrystalline cellulose, and
sodium stearyl fumarate.

Description of the Appearance of Ramipril and Hydrochlorothiazide Zentiva and Package Contents
The 2.5 mg/12.5 mg tablets are oblong, white to almost white, 8 x 4.4 mm, with a score line, marked on both sides with HNV and the company logo. The tablet can be divided into equal doses.
Ramipril and Hydrochlorothiazide Zentiva 2.5 mg/12.5 mg tablets are available in packs of 10, 14,
18, 20, 28, 30, 45, 50, 56, 60, 98, 99, 100, and 300 tablets in PVC/aluminum blisters.

The 5 mg/25 mg tablets are oblong, white to almost white, 10 x 5.6 mm, with a score line, marked on both sides with HNW and the company logo. The tablet can be divided into equal doses.
Ramipril and Hydrochlorothiazide Zentiva 5 mg/25 mg tablets are available in packs of 10, 14, 18,
20, 28, 30, 45, 50, 56, 98, 99, 100, and 300 tablets in PVC/aluminum blisters.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturers
Marketing Authorization Holder
Zentiva Italia S.r.l.
Viale Bodio, 37/B – Milan

Manufacturers
Sanofi S.p.A.
S.S. n. 17, km. 22 – 67019 Scoppito (AQ)
S.C. ZENTIVA S.A.
B-dul Theodor Pallady nr. 50, Sector 3, Bucharest, 032266 (Romania)

This medicinal product has been authorized in the Member States of the European Economic Area under the following names:
Germany:
Ramilich Comp
Hungary:
Ramipril HCT – ZENTIVA
Italy:
Ramipril and Hydrochlorothiazide Zentiva

This Patient Information Leaflet was last updated on: