DUOTENS 2.5 mg/5 mg Hard capsules

Зміст інструкції

1. Duotens 2.5 mg/5 mg hard capsules, 5 mg/5 mg hard capsules, 5 mg/10 mg hard capsules, 10 mg/5 mg hard capsules, 10 mg/10 mg hard capsules
   1. What is Duotens and what is it used for
   2. What you need to know before taking Duotens
   3. How to take Duotens
   4. Possible side effects
   5. How to store Duotens

Duotens 2.5 mg/5 mg hard capsules, 5 mg/5 mg hard capsules, 5 mg/10 mg hard capsules, 10 mg/5 mg hard capsules, 10 mg/10 mg hard capsules

Ramipril/Amlodipine
Read 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Duotens and what is it used for

Duotens contains two active ingredients called ramipril and amlodipine. Ramipril belongs to a group
of medicines called ACE inhibitors (Angiotensin Converting Enzyme Inhibitors). Amlodipine
belongs to a group of medicines called calcium channel blockers.
Ramipril works in the following way:

• It decreases the production by the body of substances that can increase blood pressure.
• It relaxes and dilates blood vessels.
• It makes it easier for the heart to pump blood around the body. Amlodipine works in the following way:
• It relaxes and dilates blood vessels, so that blood can flow through them more easily.

Duotens is used to treat high blood pressure (hypertension) in those patients whose high blood pressure is
adequately controlled with ramipril and amlodipine administered simultaneously in the form of
separate tablets, at the same dosage levels present in Duotens.

2. What you need to know before taking Duotens

Do not take Duotens:

• If you are allergic to ramipril, amlodipine (active ingredients), or to any other ACE-inhibitor or calcium-antagonist or to any other component of this medicine (listed in section 6). The symptoms can be itching, redness of the skin or difficulty breathing.

• If you have had a severe allergic reaction called “angioedema”. The symptoms include itching, skin rash (urticaria), red marks on hands, feet and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing.
• 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 in areas such as the throat).
• If you are undergoing dialysis or any other type of blood filtration. Depending on the type of machine used, treatment with Duotens may not be suitable for you.
• If you have kidney problems where the blood supply to the kidneys is reduced (renal artery stenosis).
• In the last 6 months of pregnancy (see section “Pregnancy and breastfeeding and fertility”).
• If you have diabetes mellitus or kidney damage and are taking aliskiren to treat high blood pressure.
• If your blood pressure is too low or unstable. Your doctor will need to make an assessment.
• If you have a narrowing of the aortic valve of the heart (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply enough blood to the body).
• If you suffer from heart failure following a heart attack.

Do not take Duotens if any of the above applies to you. If you have doubts, talk to your doctor before taking Duotens.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Duotens. Tell your doctor if you have or have had any of the following conditions:

• If you have problems with your heart, liver or kidneys.
• If you have recently had a heart attack.
• If your body has lost a lot of salts or fluids (due to vomiting, diarrhoea, sweating more than normal, following a low-salt diet, if you have been taking diuretics (water tablets) for a long time or if you are undergoing dialysis).
• If you are going to undergo treatment to reduce an allergy to bee or wasp stings (desensitisation).
• If you are going to receive an anaesthetic. This may be given for an operation or for a dental procedure. In such cases, you may need to stop taking Duotens the day before; consult your doctor for advice.
• If you have high levels of potassium in your blood (indicated in blood test results).
• If you have a connective tissue disease such as scleroderma or systemic lupus erythematosus.
• If you are taking medicines or are in conditions that may cause sodium levels in the blood to decrease. Your doctor may prescribe blood tests at regular intervals, especially to check sodium levels in the blood, particularly if you are elderly.
• If you are taking any of the following medicines to treat high blood pressure:
• an angiotensin II receptor blocker (ARBs) (also known as sartans - for example valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes;
• 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 in the section “Do not take Duotens”.
• You must tell your doctor if you think you may be pregnant (or might become pregnant). Duotens is not recommended in the first 3 months of pregnancy and can cause serious harm to the baby after 3 months of pregnancy (see section “Pregnancy, breastfeeding and fertility”).
• If you experience a severe increase in blood pressure (hypertensive crisis).
• If you are elderly and your dose needs to be increased.
• If you have a dry cough that persists for a long time.
• If your blood pressure has not been lowered sufficiently. Drugs of this type appear to be less effective in people of black skin.
• 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.
• Sacubitril/valsartan (see section 2 “Do not take Duotens”)

If you experience sudden swelling of the lips and face, tongue and throat, neck, possibly also hands and feet, difficulty swallowing or breathing, urticaria or hoarseness ('angioedema'). This could be a sign of a severe allergic reaction. These effects can occur at any time during treatment. People with black skin may have a higher risk of developing this condition. If you develop these symptoms, tell your doctor immediately.

Children and adolescents
The use of Duotens is not recommended in children and adolescents under 18 years of age due to the lack of data in this patient population.

Other medicines and Duotens
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Tell your doctor if you are taking any of the following medicines. They may reduce the effect of Duotens:

• Medicines used to relieve pain and inflammation (e.g. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen, indometacin, acetylsalicylic acid).
• Medicines used to treat blood pressure, shock, heart failure, asthma or allergies, such as ephedrine, noradrenaline or adrenaline. Your doctor will need to check your blood pressure.
• Rifampicin (antibiotic used to treat tuberculosis).
• Hypericum perforatum (St John's Wort - remedy for depression). Tell your doctor if you are taking any of the following medicines. They may increase the possibility of having side effects when taken with Duotens:
• Sacubitril/valsartan - used to treat a type of long-term (chronic) heart failure in adults (see section 2 “Do not take Duotens”).
• Erythromycin, clarithromycin (antibiotics).
• Cancer medicines (chemotherapy).
• Medicines belonging to the class of mTOR inhibitors, for example temsirolimus, everolimus, sirolimus, tacrolimus (used to treat certain types of cancer or to prevent rejection of transplanted organs). See section “Warnings and precautions”.
• Tacrolimus (used to control the immune response, to allow the body to accept the transplanted organ). See section “Warnings and precautions”.
• Cyclosporine, an immunosuppressant medicine used to prevent rejection of transplanted organs.
• Medicines used to relieve pain and inflammation (e.g. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen, indometacin, acetylsalicylic acid).
• Diuretics (water tablets) such as furosemide.
• Medicines that can increase the amount of potassium in the blood such as spironolactone, triamterene, amiloride, potassium supplements (including salt substitutes), trimethoprim alone or

in combination with sulfamethoxazole to treat bacterial infections; and heparin, a medicine used to thin the blood and prevent the formation of clots)

• Steroid medicines for inflammation such as prednisolone.
• Allopurinol (used to lower uric acid levels in the blood).
• Procainamide (for heart rhythm problems).
• Ketoconazole, itraconazole (used to treat fungal infections).
• Ritonavir, indinavir, nelfinavir (called protease inhibitors used to treat patients with HIV).
• Verapamil, diltiazem (medicines for the treatment of certain heart diseases and for high blood pressure).
• Dantrolene (in infusion, for severe abnormalities of body temperature).
• Vildagliptin (for the treatment of type 2 diabetes). See section “Warnings and precautions”.
• Racecadotril (used against diarrhoea). See section “Warnings and precautions”.

Your doctor may need to change the dosage and/or take other precautions:
if you are taking an angiotensin II receptor blocker (ARB) or aliskiren (see also the information in the sections “Do not take Duotens” and “Warnings and precautions”).
Tell your doctor if you are taking any of these medicines, the action of the following medicines may be modified by Duotens:

• Medicines for diabetes such as oral medicines that lower blood sugar and insulin. Duotens can lower blood sugar levels. Check your blood sugar (glucose) levels carefully while taking Duotens.
• Lithium (for mental health problems). Duotens can increase the amount of lithium in the blood. Your doctor needs to check the amount of lithium in your blood carefully.
• Simvastatin (medicine to reduce cholesterol). Duotens can increase the levels of simvastatin in the blood. If any of the above applies to you (or if you are unsure), consult your doctor before taking Duotens.

Duotens with food, drink and alcohol
Duotens can be taken with or without food.
Drinking alcohol during treatment with Duotens can cause dizziness or a feeling of mental confusion. If you want to know how much alcohol you can drink during therapy with Duotens, talk to your doctor, as the effects of medicines used to lower blood pressure and the effects of alcohol can add up.
Grapefruit juice or grapefruit should not be consumed by people who are taking Duotens. This is because grapefruit or grapefruit juice can lead to an increase in the levels of the active ingredient amlodipine in the blood, which can cause an unpredictable increase in the hypotensive effect (lowering of blood pressure) of Duotens.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
You should not take Duotens in the first 12 weeks of pregnancy and should definitely not take it from the 13th week because its use during pregnancy can be harmful to the baby.
If you become pregnant during treatment with Duotens, tell your doctor immediately.
Switching to an appropriate alternative treatment should be initiated before planning a pregnancy.

Breastfeeding
You should not take Duotens if you are breastfeeding.
Consult your doctor or pharmacist before taking any medicine.

Fertility
There is insufficient data regarding potential effects on fertility.

Driving and using machines
Duotens can change your ability to drive vehicles or use machines. If Duotens makes you feel unwell, dizzy or tired or if it gives you a headache, do not drive or use machines and contact your doctor immediately. This can happen especially at the beginning of treatment, or when switching to Duotens from therapies carried out with other medicines.

Duotens contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially “sodium-free”.

3. How to take Duotens

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.
If you feel that the effect of Duotens is too strong or too weak, consult your doctor or
pharmacist.
Take this medicine by mouth at the same time of each day, before or after a meal.
Swallow the capsule whole with some liquid.
Do not take Duotens with grapefruit juice.
Duotens must be administered once a day.
Depending on the effect, your doctor may modify the dose.
The maximum dose is 1 capsule, once a day, of the concentration of 10 mg/10 mg.

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

Use in children and adolescents
Duotens is not recommended for use in children and adolescents under 18 years of age, as
data are not available in this population.

If you take more Duotens than you should
Taking too many capsules can cause a lowering of blood pressure to the point of being
even dangerous. You may feel dizzy, stunned, faint or weak.
If the drop in blood pressure is significant enough, shock may occur. The skin may
become cold and sweaty and the subject may lose consciousness. Consult a doctor immediately or
go to the nearest hospital emergency room. Do not drive to the hospital, have someone accompany you or
call an ambulance. Bring the package of the medicine with you. This
so that the doctor knows what you have taken.
Excess fluid may accumulate in the lungs (pulmonary edema) causing shortness of breath
which may develop up to 24-48 hours after taking it.

If you forget to take Duotens
If you forget to take a capsule, completely skip that dose. Take the
next dose at the right time. Do not take a double dose to make up for the missed dose.

If you stop taking Duotens
Your doctor will advise you how long you should take the medicine. Your condition may
reappear if you stop taking the medicine before as recommended.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Duotens and contact your doctor immediately if you notice any of the following serious side effects, as you may need urgent medical treatment:

• Swelling of the face, lips or throat that makes it difficult to swallow or breathe, as well as itching and rash. This could be a sign of a severe allergic reaction to Duotens.
• Severe skin reactions, including rash, ulcers in the mouth, worsening of a pre-existing skin condition, redness, blisters or peeling of the skin (such as in Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme).

Contact your doctor immediately if you experience:

• Fast heartbeat, irregular or stronger heartbeat (palpitations), chest pain, tightness in the chest, or more serious problems including heart attack or stroke. The frequency of these side effects is common (chest pain, feeling of tightness in the chest, palpitations) or uncommon (fast heartbeat, heart attack or stroke).
• Wheezing, shortness of breath or sudden difficulty breathing. These are common side effects. These could be signs of lung problems.
• Increased ease of bruising, bleeding for longer than normal, any sign of bleeding (e.g. bleeding gums), spots on the skin, even purple in color, or increased susceptibility to infections, sore throat and fever, feeling tired, fainting, dizziness and pale skin. These can be signs of problems with the blood or bone marrow (frequency is unknown).
• Severe stomach pain that can radiate to the back. This could be a sign of pancreatitis (inflammation of the pancreas). This is an uncommon side effect.
• Fever, chills, fatigue, loss of appetite, stomach pain, feeling unwell, yellowing of the skin or eyes (jaundice). These can be signs of problems with the liver, such as liver inflammation (hepatitis) or liver damage (frequency is very rare). Other side effects include:

Tell your doctor if any of the following effects worsen or lasts more than a few days.
Very common (may affect more than 1 in 10 people):

• Edema (fluid retention)

Common (may affect up to 1 in 10 people):

• Drowsiness, feeling dizzy (especially at the beginning of treatment)
• Palpitations (feeling your heartbeat), hot flushes
• Swelling of the ankles
• Vision disturbances, double vision
• Headache or feeling tired, weakness
• Fainting, hypotension (abnormally low blood pressure), especially when getting up or lying down quickly
• Dry cough, inflammation of the sinuses (sinusitis) or bronchitis
• Abdominal pain, stomach pain or intestinal pain, diarrhea, constipation, indigestion, feeling or being sick (vomiting)
• Rash with or without raised areas
• Chest pain
• Muscle cramps or pain
• Blood tests showing more potassium than normal in the blood

Uncommon (may affect up to 1 in 100 people):

• Mood changes, insomnia
• Tremor, pain, feeling unwell
• Tinnitus (ringing in the ears)
• Sneezing/runny nose due to inflammation of the lining of the nose (rhinitis)
• Heartburn, dry mouth
• Hair loss, increased sweating, red spots on the skin, skin discoloration
• Urinary disturbances, increased need to urinate, especially at night, increased number of times you urinate
• Inability to have an erection, sexual dysfunction in men, reduced sexual desire in men or women
• Discomfort or enlargement of the breasts in men
• Joint pain, back pain
• Weight gain or loss
• Balance problems (dizziness)
• Itching and unusual skin sensations such as numbness, tingling, prickling, burning or feeling something crawling on the skin (paresthesia), loss of pain sensation
• Urticaria (hives)
• Loss or alteration of taste
• Feeling depressed, anxious, more nervous than usual or restless
• Blocked nose, difficulty breathing or worsening of asthma
• A swelling in the intestine called “intestinal angioedema” which presents with symptoms such as abdominal pain, vomiting and diarrhea
• Loss or decrease of appetite (anorexia)
• Blurred vision
• Fever
• Blood tests showing an increase in the number of certain white blood cells (eosinophilia)
• Blood tests showing changes in liver, pancreas or kidney function

Rare (may affect up to 1 in 1,000)

• Feeling of trembling or confusion
• Red and swollen tongue
• Severe scaling or cracking of the skin, itching, raised rash
• Problems with nails (e.g. detachment or separation of the nail from its bed)
• Rash or bruising
• Inflammation of blood vessels, often with a rash
• Spots on the skin and cold extremities
• Red, itchy, swollen or moist eyes
• Hearing disturbances
• Blood tests showing a decrease in the number of red blood cells, white blood cells or platelets (which can cause unusual bruising or a tendency to bleed), or the amount of hemoglobin.

Very rare (may affect up to 1 in 10,000)

• Increased sensitivity to sunlight than usual
• Excess sugar (glucose) in the blood (hyperglycemia)
• Swelling of the gums
• Swelling of the stomach (gastritis)
• Impaired liver function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice)
• Increased muscle tension
• Disorders related to stiffness, tremor, and/or movement disorders

Not known

• concentrated urine (dark in color), feeling unwell or sick, muscle cramps, confusion and convulsions which may be due to inappropriate secretion of ADH (anti-diuretic hormone[antidiuretic hormone]). If you experience these symptoms, contact your doctor promptly
• tremor, stiff posture, mask-like face, slow movements and an unbalanced, shuffling walk

Other side effects reported:
Tell your doctor if any of the following side effects worsen or lasts more than a few
days.

• Difficulty concentrating
• Swelling of the mouth
• Blood tests showing a reduction in the levels of sodium in the blood compared to normal values
• Fingers of the hands and feet that change color when you are cold and then tingling or a sensation of pain when they warm up (Raynaud's phenomenon)
• Slowed or impaired reactions
• Burning sensation
• Change in the perception of smells

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. You can also report side effects directly through 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 Duotens

Store at a temperature below 30°C.
Keep in the original package to protect the medicine from light.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is reported on the box and blister after
EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine in the wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6Package contents and other information
What Duotens contains

• The active ingredients are: 2.5 mg/5 mg hard capsules:

each capsule contains 2.5 mg of ramipril and amlodipine besilate equivalent to 5 mg of
amlodipine.
5 mg/5 mg hard capsules:
each capsule contains 5 mg of ramipril and amlodipine besilate equivalent to 5 mg of amlodipine.
5 mg/10 mg hard capsules:
each capsule contains 5 mg of ramipril and amlodipine besilate equivalent to 10 mg of amlodipine.
10 mg/5 mg hard capsules:
each capsule contains 10 mg of ramipril and amlodipine besilate equivalent to 5 mg of amlodipine.
10 mg/10 mg hard capsules:
each capsule contains 10 mg of ramipril and amlodipine besilate equivalent to 10 mg of
amlodipine.

• The other ingredients are: microcrystalline cellulose, anhydrous dibasic calcium phosphate, pregelatinized corn starch, sodium starch glycolate (Type A), sodium stearyl fumarate, red iron oxide (E 172), titanium dioxide (E 171), gelatin, yellow iron oxide (E 172) (10 mg/10 mg), black iron oxide (E 172) (10 mg/10 mg).

Description of the appearance of Duotens and contents of the pack
Duotens 2.5 mg/5 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, light pink in color; body: opaque,
white in color. Capsule content: white to off-white powder.
Duotens 5 mg/5 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, pink in color; body: opaque, in
white color.
Capsule content: white to off-white powder.
Duotens 5 mg/10 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, reddish-brown in color, body:
opaque, white in color. Capsule content: white to off-white powder.
Duotens 10 mg/5 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, dark pink in color; body: opaque,
white in color. Capsule content: white to off-white powder
Duotens 10 mg/10 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, brown in color; body: opaque, in
white color.
Capsule content: white to off-white powder
Duotens is available in packs containing 28, 30, 32, 56, 60, 90, 91, 96, 98 or 100 capsules
contained in blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
SPA - Società Prodotti Antibiotici S.p.A. - Via Biella, 8 - 20143 Milan.

Production and batch release
Adamed Pharma S.A.
ul. Szkolna 33
95-054 Ksawerów
Poland

Batch release
Adamed Pharma S.A.
ul. Marszałka Jósefa Piłsudskiego 5
95-200 Pabianice
Poland