Ramipril and hydrochlorothiazide ratiopharm: detailed information

Patient Information Leaflet

Ramipril Hydrochlorothiazide ratiopharm 2.5 mg/12.5 mg tablets, 5 mg/25 mg tablets

ramipril/hydrochlorothiazide
Generic medicine
Please read all of this leaflet carefully before you start 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 others, even if they have the same symptoms as you, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Ramipril Hydrochlorothiazide ratiopharm 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), and works by:

Reducing the body's production of substances that may cause an increase in blood pressure
Relaxing and widening blood vessels
Helping the heart to pump blood around the body more easily.

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 Hydrochlorothiazide ratiopharm is used to treat high blood pressure. The two active substances work together to lower your blood pressure. They are used in combination when treatment with either component alone is not effective.

2. What you should know before taking Ramipril Hydrochlorothiazide ratiopharm

Do not take Ramipril Hydrochlorothiazide ratiopharm:

If you are allergic to ramipril, hydrochlorothiazide, or any of the excipients of this medicine (listed in section 6).
If you are allergic to medicines similar to Ramipril Hydrochlorothiazide ratiopharm (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 had a severe allergic reaction called "angioedema". Symptoms 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 and swallowing.
If you are on dialysis or undergoing any other type of blood filtration. Depending on the equipment used, Ramipril Hydrochlorothiazide ratiopharm 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).
If you have severe kidney problems and are not on dialysis.
During the last 6 months of pregnancy (see the 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.
If you have taken or are taking sacubitril/valsartan, a medicine used to treat a type of long-term (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 Hydrochlorothiazide ratiopharm if any of the above conditions apply to you. If
you are unsure, ask your doctor before taking Ramipril Hydrochlorothiazide ratiopharm.
Warnings and precautions
Talk to your doctor or pharmacist before taking Ramipril Hydrochlorothiazide ratiopharm:
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 Ramipril
Hydrochlorothiazide ratiopharm, consult a doctor immediately.

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, diarrhoea, excessive sweating, following a low-salt diet, prolonged use of oral diuretics, or if you have undergone dialysis).
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 – for example valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes;
aliskiren. Your doctor may wish to 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 Hydrochlorothiazide ratiopharm".
If you are about to undergo treatment to reduce allergy to bee or wasp stings (desensitisation).
If you are about to undergo anaesthesia. This may be administered for surgery or dental procedures. You may need to stop taking Ramipril Hydrochlorothiazide ratiopharm the day before; consult your doctor.
If you have high levels of potassium in your blood (detected by a blood test).
If you are taking medicines or have conditions that may reduce sodium levels in your blood. Your doctor may prescribe regular blood tests, particularly to monitor sodium levels, especially if you are elderly.
If you are of Black origin, as this medicine may be less effective in lowering blood pressure and may cause more side effects.
If you have very high blood pressure.
Ramipril Hydrochlorothiazide ratiopharm can cause angioedema. Symptoms include swelling of the hands, face, mouth, tongue and/or throat, with difficulty swallowing or breathing.
If you develop a persistent dry cough, contact your doctor or pharmacist.
Ramipril Hydrochlorothiazide ratiopharm can cause hypersensitivity reactions.
If you are taking any of the following medicines, the risk of angioedema may be increased:
racecadotril, a medicine used to treat diarrhoea.
medicines used to prevent rejection of transplanted organs and to treat cancer (such as 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 experience decreased vision or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye and may occur from a few hours to weeks after taking Ramipril Hydrochlorothiazide ratiopharm. This condition may lead to permanent vision loss if untreated. If you have previously had allergic reactions to penicillin or sulfonamides, you may be at higher risk of developing this condition. You must stop taking Ramipril Hydrochlorothiazide ratiopharm and contact your doctor immediately.
If you have previously had skin cancer or develop unexpected skin lesions during treatment. Treatment with hydrochlorothiazide, particularly long-term use with high doses, may increase the risk of certain types of non-melanoma skin and lip cancer. Protect your skin from sun and UV exposure while taking Ramipril Hydrochlorothiazide ratiopharm.
You must inform your doctor if you think you are pregnant (or might become pregnant). Ramipril Hydrochlorothiazide ratiopharm is not recommended during the first 3 months of pregnancy and may cause serious harm to the baby if used after the first 3 months of pregnancy (see section below “Pregnancy and Breastfeeding”).

Children and Adolescents
The use of Ramipril Hydrochlorothiazide ratiopharm is not recommended in children and adolescents under
18 years of age, as this medicine has not been studied in this age group.
If any of the above conditions apply (or if you are unsure), consult your doctor before taking
Ramipril Hydrochlorothiazide ratiopharm.
Other medicines and Ramipril Hydrochlorothiazide ratiopharm
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is because Ramipril Hydrochlorothiazide ratiopharm may affect the action of certain other medicines. In addition, some medicines may affect the action of Ramipril Hydrochlorothiazide ratiopharm.
Inform your doctor if you are taking any of the following medicines. These medicines may interfere
with Ramipril Hydrochlorothiazide ratiopharm and alter its effect:

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 Hydrochlorothiazide ratiopharm may increase the likelihood of side effects:

Sacubitril/valsartan – used to treat a type of long-term (chronic) heart failure in adults (see also information in section “Do not take Ramipril Hydrochlorothiazide ratiopharm”).
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), ACTH (used to check if your adrenal glands are functioning properly).
Medicines for cancer (chemotherapy).
Medicines for heart problems, including heart rhythm disorders.
Medicines to lower blood pressure.
Diuretics such as furosemide.
Potassium supplements (including salt substitutes), potassium-sparing diuretics such as spironolactone, triamterene, amiloride, and other medicines that may increase potassium levels in the blood (such as trimethoprim and cotrimoxazole for bacterial infections; ciclosporin, an immunosuppressant used to prevent transplant rejection; and heparin, a medicine used to thin the blood and prevent clots).
Steroid medicines used to treat 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).
Temsirolimus (for cancer).
Medicines usually used to prevent rejection of transplanted organs (sirolimus, everolimus, and other mTOR inhibitors). See section “Warnings and precautions”.
Vildagliptin (to lower blood sugar).
Racecadotril (used for diarrhoea).

Your doctor may consider adjusting your dose and/or taking other precautions:

If you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also section "Do not take Ramipril Hydrochlorothiazide ratiopharm" 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 Hydrochlorothiazide ratiopharm:

Medicines for diabetes, such as oral hypoglycaemics and insulin. Ramipril Hydrochlorothiazide ratiopharm may lower blood sugar levels. Monitor your blood sugar levels carefully when taking Ramipril Hydrochlorothiazide ratiopharm.
Lithium (for psychiatric conditions). Ramipril Hydrochlorothiazide ratiopharm may increase lithium levels in the blood. Your doctor must closely monitor your blood lithium levels.
Muscle relaxants.
Quinine (for the treatment of malaria).
Medicines containing iodine; these 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 above conditions apply (or if you are unsure), consult your doctor before taking
Ramipril Hydrochlorothiazide ratiopharm.
Tests
Check with your doctor or pharmacist before taking this medicine:

If you are undergoing a test for parathyroid function. Ramipril Hydrochlorothiazide ratiopharm may alter test results.
If you are an athlete undergoing anti-doping testing. Ramipril Hydrochlorothiazide ratiopharm may produce a positive result.

For athletes: using the medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.
Ramipril Hydrochlorothiazide ratiopharm with food and alcohol

Drinking alcohol together with Ramipril Hydrochlorothiazide ratiopharm tablets may cause dizziness or lightheadedness. If you want to know how much alcohol you can consume while taking Ramipril Hydrochlorothiazide ratiopharm, discuss it with your doctor, as blood pressure-lowering medicines and alcohol may have additive effects.
Ramipril Hydrochlorothiazide ratiopharm can be taken with or without food.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult
your doctor or pharmacist before taking this medicine.
Pregnancy
You must inform your doctor if you think you are pregnant (or might become pregnant).
You should not take Ramipril Hydrochlorothiazide ratiopharm during the first 12 weeks of
pregnancy, and must not take it after week 13, as its use during pregnancy may harm the unborn child. If you become pregnant while taking Ramipril Hydrochlorothiazide ratiopharm, contact your doctor immediately. Switching to an appropriate alternative treatment should be done before planning a pregnancy.
Breastfeeding
You must not take Ramipril Hydrochlorothiazide ratiopharm if you are breastfeeding.
Driving and using machines
You may experience dizziness while taking Ramipril Hydrochlorothiazide ratiopharm. This is
more likely when you first start treatment or after a dose increase. If this occurs, do not drive or operate tools or machinery.
Ramipril Hydrochlorothiazide ratiopharm contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking
this medicine.
Ramipril Hydrochlorothiazide ratiopharm 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 Hydrochlorothiazide ratiopharm

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Recommended dose
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.
Taking this medicine

Take the medicine orally at the same time every day, usually in the morning.
Swallow the tablets whole with liquid.
The tablet may be divided into equal doses. To split the tablet, place it on a flat, hard surface (for example, a table) and, placing your thumbs or index fingers on either side of the break line, press down on the surface to split the tablet in half.

If you take more Ramipril Hydrochlorothiazide ratiopharm than you should
Inform your doctor or go immediately 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 because the doctor needs to know what you have taken.
If you forget to take Ramipril Hydrochlorothiazide ratiopharm

If you miss a dose, take your next dose at the usual time.
Do not take a double dose to make up for a forgotten tablet.

If you have any further questions about the use of 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 Hydrochlorothiazide ratiopharm 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 Ramipril Hydrochlorothiazide ratiopharm.
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).
Sudden onset of blurred distance vision (acute myopia), decreased vision or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma) (frequency: not known).
Acute respiratory distress (signs include severe shortness of breath, fever, weakness and confusion) (frequency: very rare).

Contact your doctor immediately if you experience:

Rapid heartbeat, irregular or pounding 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 sign 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 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:
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, feeling weak or tired
Dizziness. This is more likely when treatment with Ramipril Hydrochlorothiazide ratiopharm 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 and 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, burning, prickling or crawling sensations (paresthesia)
Involuntary trembling (tremor)
Psoriasis (a recurring skin disorder causing scaling and dry rash)
Loss or change in taste
Sleep problems
Depressed mood, lack of interest in daily life (apathy), anxiety, increased nervousness or irritability
Stuffy nose, inflammation of the nasal sinuses (sinusitis), shortness of breath
Inflammation of the gums (gingivitis), mouth swelling
Red, swollen, watery or itchy eyes
Ringing in the ears (tinnitus)
Blurred vision
Hair loss
Chest pain
Muscle pain
Constipation, stomach or intestinal pain
Indigestion or discomfort
Digestive disorders
Increased amount of urine during the day
Kidney problems including kidney failure (symptoms include back pain and reduced volume of filtered urine)
Excessive sweating or thirst
Loss or decrease in appetite (anorexia), reduced sense of hunger
Fast or irregular heartbeat
Swollen arms and legs. This may indicate your body is retaining more fluid than usual
Fever
Impotence in men
Inflammation of the gallbladder (which may cause abdominal pain, nausea, vomiting)
Decreased number of red blood cells, white blood cells, 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 diarrhea or stomach burning
Mouth ulcers
Swollen and red tongue or dry mouth
Blood tests show higher than normal potassium levels
Acute respiratory distress (symptoms include shortness of breath, fever, weakness, and confusion)

Not known: frequency cannot be estimated from the available data

Skin and lip cancer (non-melanoma skin cancer)
Concentrated (dark-colored) urine, feeling unwell, muscle cramps, confusion and seizures which may be due to inappropriate secretion of ADH (antidiuretic hormone). If you experience these symptoms, contact your doctor as soon as possible.
Difficulty concentrating, feeling restless or confused
Fingers of hands and feet changing color when cold, and tingling or pain when warmed. This could be Raynaud's phenomenon
Breast enlargement in men
Blood clots
Hearing disorders
Eyes less moist than normal
Objects appear yellow
Decreased vision or eye pain due to increased 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 the cheek (inflammation of a salivary gland)
Intestinal swelling called “intestinal angioedema” presenting with symptoms such as abdominal pain, vomiting and diarrhea
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
Worsening of psoriasis, if you are affected by it
A condition known as systemic lupus erythematosus (SLE) causing joint pain, skin rash and fever
Spots on the skin and cold extremities
Nail problems (such as 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 the urine. This could be a sign of a kidney problem (interstitial nephritis)
Increased amount of sugar in the urine
Blood tests show increased levels of antibodies
Increased number of certain white blood cells (eosinophilia) found in blood tests
Too low a number of blood cells as shown by blood tests (pancytopenia)
Changes in levels of electrolytes such as sodium, calcium, magnesium and chloride in the blood as shown by blood tests
Slowed or altered reactions
Changes in the perception of smells
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 or pharmacist.
You can also report side effects directly via the national reporting system at 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 Ramipril Hydrochlorothiazide ratiopharm

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton/bottle after "Exp.".
The expiry date refers to the last day of that month.
Do not store above 30°C.
For blisters: Store in the original packaging.
For containers: Keep the container tightly closed.
Do not dispose of any medicine via wastewater. 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 Hydrochlorothiazide ratiopharm contains

The active substances are ramipril and hydrochlorothiazide.
Ramipril Hydrochlorothiazide ratiopharm 2.5 mg/12.5 mg tablets
Each tablet contains 2.5 mg of ramipril and 12.5 mg of hydrochlorothiazide.
Ramipril Hydrochlorothiazide ratiopharm 5 mg/25 mg tablets
Each tablet contains 5 mg of ramipril and 25 mg of hydrochlorothiazide.
The other components are pregelatinized starch, sodium stearyl fumarate, sodium bicarbonate, lactose monohydrate and sodium croscarmellose.

Description of the appearance of Ramipril Hydrochlorothiazide ratiopharm and package contents
Tablets
Ramipril Hydrochlorothiazide ratiopharm 2.5 mg/12.5 mg tablets
White to almost white, round, biconvex tablets with a breakline on one side, a "T"-shaped notch on the other side, and a diameter of approximately 6.0 mm.
Ramipril Hydrochlorothiazide ratiopharm 5 mg/25 mg tablets
White to almost white, flat, round, biconvex tablets with a breakline on one side and a diameter of approximately 8.0 mm.
The tablets are available in blisters (aluminum/aluminum) and/or in PP containers (with child-resistant closure) containing a desiccant and with PE cap.
Pack sizes
10, 14, 20, 28, 30, 42, 50, 98 and 100 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
ratiopharm GmbH
Graf-Arco Strasse, 3 – 89079 Ulm, Germany
Manufacturer:
Merckle GmbH, Ludwig-Merckle-Strasse 3, 89143 Blaubeuren, Germany

This medicinal product is authorized in the European Economic Area countries under the following names:
Italy: Ramipril Hydrochlorothiazide ratiopharm