Unipril Diur

Package leaflet: Information for the patient

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

Ramipril/Hydrochlorothiazide
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 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, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What UNIPRILDIUR is and what it is used for

UNIPRILDIUR 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 your blood vessels
• Helping your heart to 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) that is produced. This lowers blood pressure.
UNIPRILDIUR 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 should know before taking UNIPRILDIUR

Do not take UNIPRILDIUR:

• If you are allergic to ramipril, hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6).
• If you are currently being treated with sacubitril/valsartan (for long-term treatment of heart failure).
• If you are allergic to medicines similar to UNIPRILDIUR (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 previously experienced 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 on dialysis or undergoing any other type of blood filtration. Depending on the equipment used, UNIPRILDIUR 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 UNIPRILDIUR if any of the conditions listed above apply to you. If you are unsure, consult your doctor before taking UNIPRILDIUR.

Warnings and precautions

Talk to your doctor or pharmacist before taking UNIPRILDIUR:

• If you have previously had skin cancer or 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 non-melanoma skin cancer and lip cancer. Protect your skin from exposure to sunlight and UV rays while taking UNIPRILDIUR.
• 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 low-salt diet, long-term use of oral diuretics, or after dialysis).
• If you are taking medicines called mTOR inhibitors (e.g., temsirolimus, everolimus, sirolimus), vildagliptin, or neprilysin inhibitors (NEP) (e.g., racecadotril and sacubitril/valsartan), as these may increase the risk of angioedema, a serious allergic reaction.
• If you are about to undergo treatment to reduce allergy to bee or wasp stings (desensitization).
• If you are about to undergo anesthesia, which may be administered for surgery or dental procedures. You may need to stop taking UNIPRILDIUR the day before; consult your doctor.
• If you have high levels of potassium in your blood (as shown by a blood test).
• If you have a collagen vascular disease such as scleroderma or systemic lupus erythematosus.
• If you experience decreased vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased intraocular pressure, which may occur from a few hours to a week after taking UNIPRILDIUR. This may lead to permanent vision loss if not treated. Your risk may be higher if you have previously been allergic to penicillins or sulfonamides.
• If you have previously experienced respiratory 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 UNIPRILDIUR, consult a doctor immediately.
• You must inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). UNIPRILDIUR is not recommended during the first trimester of pregnancy and may cause serious harm to the unborn child after the first three months of pregnancy (see section “Pregnancy and breastfeeding”).
• 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 levels of electrolytes (e.g., potassium) in your blood.
See also the section "Do not take UNIPRILDIUR".

Children
UNIPRILDIUR is not recommended for children and adolescents under 18 years of age, as this medicine has never been studied in this age group.

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

Other medicines and UNIPRILDIUR
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is because UNIPRILDIUR may affect the action of certain other medicines, and some medicines may affect the action of UNIPRILDIUR. Your doctor may need to adjust your dose and/or take additional precautions.

Do not use UNIPRILDIUR with sacubitril/valsartan (for long-term treatment of heart failure).

Inform your doctor if you are taking any of the following medicines. These may interfere with UNIPRILDIUR and alter its effect:

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

Inform your doctor if you are taking any of the following medicines. When taken with UNIPRILDIUR, these may increase the likelihood of side effects:

• Medicines used to relieve pain and inflammation (e.g., NSAIDs such as ibuprofen, indomethacin, 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).
• Temsirolimus (for cancer treatment).
• Medicines for heart problems, including heart rhythm disorders.
• Medicines to prevent organ rejection after transplantation, such as cyclosporine.
• Sirolimus (to prevent transplant rejection).
• Everolimus (to prevent transplant rejection and for cancer treatment).
• 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).
• Colestipol (to reduce blood fat levels).
• Carbamazepine (for treating epilepsy).
• An angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "Do not take UNIPRILDIUR" and "Warnings and precautions").
• Vildagliptin (for treating type 2 diabetes).
• Racecadotril (used to treat diarrhea).
• Sacubitril/valsartan (for long-term treatment of heart failure).

Inform your doctor if you are taking any of the following medicines. Their effectiveness may be affected by UNIPRILDIUR:

• Medicines for diabetes, such as oral hypoglycemics and insulin. UNIPRILDIUR may lower blood sugar levels. Monitor your blood glucose levels carefully while taking UNIPRILDIUR.
• Lithium (for psychiatric conditions). UNIPRILDIUR 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 an X-ray or scan.
• Penicillin (for treating infections).
• Oral anticoagulants (blood thinners) such as warfarin.

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

Monitoring

Inform your doctor or pharmacist before taking this medicine:

• If you are undergoing a test for parathyroid function. UNIPRILDIUR may alter test results.
• If you are an athlete undergoing doping control. UNIPRILDIUR may result in a positive test.

UNIPRILDIUR with food and alcohol

• Drinking alcohol while taking UNIPRILDIUR may cause dizziness or lightheadedness. Discuss with your doctor how much alcohol, if any, you may consume while taking UNIPRILDIUR. Alcohol may enhance the blood pressure-lowering effect of the medicine.
• UNIPRILDIUR may be taken with or without food.

Pregnancy, breastfeeding, and fertility
You must inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant).
You should not take UNIPRILDIUR during the first 12 weeks of pregnancy, and must not take it at all from week 13 onward, as its use during pregnancy may harm the unborn child.
Inform your doctor immediately if you become pregnant while taking UNIPRILDIUR.
Before planning a pregnancy, you should switch to an appropriate alternative treatment.
You should not take UNIPRILDIUR while breastfeeding.
Ask your doctor or pharmacist before taking any medicine.

Driving and using machines
You may experience dizziness while taking UNIPRILDIUR. This is more likely when you first start taking the medicine or after an increase in dose. If this occurs, do not drive or operate tools or machinery.

UNIPRILDIUR contains sodium
UNIPRILDIUR contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to take UNIPRILDIUR

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Taking this medicine

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

How much to take
Treatment of high blood pressure
Your doctor will adjust your dosage 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 UNIPRILDIUR 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 important so the doctor knows what you have taken.
If you forget to take UNIPRILDIUR

• 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, this medicine can cause side effects, although not everybody will get them.
Stop taking UNIPRILDIUR 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. This could be a sign of a severe allergic reaction to UNIPRILDIUR.
• 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 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, any sign of bleeding (e.g. bleeding gums), purple spots on the skin, or increased susceptibility to infections, sore throat and fever, feeling tired, fainting, dizziness or pale appearance. 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:
Tell your doctor if any of the conditions listed below become severe or last longer than a few days:
Common (affects less than 1 in 10 people)

• Headache or feeling weak or tired
• Dizziness. This is more likely when treatment with UNIPRILDIUR has just started or the dose has recently been increased
• Dry, persistent cough or bronchitis
• Blood tests show higher than normal blood 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 (affects less than 1 in 100 people)

• Skin rash with or without swelling
• Flushing, fainting, 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 or burning (paresthesia)
• Loss or change in taste
• Sleep problems
• Depressed mood, anxiety, increased nervousness or tremor
• Stuffy nose, inflammation of the sinuses (sinusitis), shortness of breath
• Inflammation of the gums (gingivitis), mouth swelling
• Red, swollen, watery or 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
• Rapid or irregular heartbeat
• Swollen arms and legs. This may indicate 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 in haemoglobin 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 (affects less than 1 in 10,000 people)

• Malaise causing diarrhoea or heartburn
• Swollen and red tongue or dry mouth
• Blood tests show higher than normal potassium levels
• Acute breathing difficulty (symptoms include severe shortness of breath, fever, weakness and confusion)

Not known (frequency cannot be estimated from available data)

• Skin and lip cancer (non-melanoma skin cancer)
• Sudden-onset blurred 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)

Other reported side effects:
Tell your doctor if any of the following conditions become severe or last longer than a few days:

• Difficulty concentrating, restlessness or confusion
• 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 disorders
• Eyes drier than normal
• Objects appearing yellow, transient visual disturbances, severe eye pain accompanied by redness and sudden blurred vision. Patients experiencing red, painful eyes should contact a doctor immediately; if untreated, this condition may lead to permanent vision loss
• Dehydration
• Swelling, pain and paleness 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, bumpy rash or other skin reactions such as facial or forehead redness
• Skin rash or bruising
• Skin spots 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 (tetanus)
• Muscle weakness or cramps
• Reduced sexual desire in men and women
• Presence of blood in urine. This could be a sign of a kidney problem (interstitial nephritis)
• Higher than normal sugar levels in urine
• Increased number of certain 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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 UNIPRILDIUR

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (Exp) stated on the blister and the outer carton.
The expiry date refers to the last day of that month.
Store this medicine in the original packaging to protect the contents from light.
Do not dispose of medicines 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 UNIPRILDIUR contains

• The active substances are ramipril and hydrochlorothiazide.
• The other components are: hypromellose, microcrystalline cellulose, pregelatinized corn starch, sodium stearyl fumarate.

Description of the appearance of UNIPRILDIUR and package contents
Tablets 2.5 mg + 12.5 mg: white, oblong tablets, 8x4.4 mm, with a score line on both sides, imprinted "HNV/HNV" on one side.
Tablets 5 mg + 25 mg: white, oblong tablets, 10x5.6 mm, with a score line on both sides, imprinted "HNW/Marketing Authorisation Holder logo" on one side and "Marketing Authorisation Holder logo/HNW" on the other.
UNIPRILDIUR is available in packages containing blisters of 14, 20, 28, 50 and 100 tablets.
Packages containing 28-tablet blisters may also be available with days of the week marked.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Global Pharmacies Partners S.r.l.
Via Cesare Battisti 1, 20122 Milano, Italy

Manufacturer
Sanofi-aventis S.p.A.
S.S. n. 17, km. 22 – 67019 Scoppito (AQ), Italy

This medicinal product is authorised in the European Economic Area Member States under the following names:
Italy:
Uniprildiur 2.5 mg/12.5 mg tablets, Uniprildiur 5 mg/25 mg tablets

This patient information leaflet does not contain all the information about this medicine. If you have any further questions or are unsure about any aspect, please consult your doctor or pharmacist.

Other sources of information
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco).