Duotens

Patient Information Leaflet

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
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 other people, even if they have the same symptoms as yours, as it may be harmful to them.
• 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:

1. What Duotens is and what it is 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
6. Contents of the pack and other information

1. What Duotens is and what it is used for

Duotens contains two active substances called ramipril and amlodipine. Ramipril belongs to a group
of medicines known as ACE inhibitors (Angiotensin-Converting Enzyme inhibitors). Amlodipine
belongs to a group of medicines known as calcium antagonists.
Ramipril works as follows:

• Reduces the body's production of substances that can raise blood pressure.
• Relaxes and widens blood vessels.
• Makes it easier for the heart to pump blood through the body.

Amlodipine works as follows:

• Relaxes and widens blood vessels, allowing blood to flow through them more easily.

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

2. What you should know before taking Duotens

Do not take Duotens:

• If you are allergic to ramipril, amlodipine (active substances), or to any other ACE inhibitor or calcium antagonist medicine, or to any other component of this medicine (listed in section 6). Symptoms may include itching, skin redness, or difficulty breathing.
• If you have had a severe allergic reaction called "angioedema". Symptoms include itching, skin rash (urticaria), red patches on 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, as this increases the risk of angioedema (rapid swelling under the skin, for example in the throat).
• If you are undergoing dialysis or any other type of blood filtration. Depending on the type of equipment used, treatment with Duotens may not be suitable for you.
• If you have kidney problems causing reduced blood flow to the kidneys (renal artery stenosis).
• During the last 6 months of pregnancy (see section "Pregnancy, breastfeeding and fertility").
• If you have diabetes mellitus or kidney damage and are taking aliskiren for high blood pressure.
• If your blood pressure is too low or unstable. Your doctor will need to assess your condition.
• If you have narrowing of the heart's aortic valve (aortic stenosis) or cardiogenic shock (a condition in which the heart cannot pump enough blood to meet the body's needs).
• If you have heart failure following a heart attack.

Do not take Duotens if any of the above conditions apply to you. If you have any doubts, speak with your doctor before taking Duotens.

Warnings and precautions

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

• If you have heart, liver, or kidney problems.
• If you recently had a heart attack.
• If your body has lost significant amounts of salts or fluids (due to vomiting, diarrhoea, excessive sweating, a low-salt diet, long-term use of diuretics (water tablets), or if you are undergoing dialysis).
• If you are scheduled to undergo treatment to reduce allergy to bee or wasp stings (desensitisation).
• If you are due to receive anaesthesia. This may be administered for surgery or dental procedures. 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 (as indicated in blood test results).
• If you have a collagen-vascular disease such as scleroderma or systemic lupus erythematosus.
• If you are taking medicines or have conditions that may lower sodium levels in your blood. Your doctor may prescribe regular blood tests, particularly to monitor blood sodium levels, especially if you are elderly.
• If you are taking any of the following medicines for high blood pressure:
  • an angiotensin II receptor antagonist (ARBs) (also known as sartans – for example valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes;
  • aliskiren. Your doctor may monitor your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood at regular intervals. See also information in section “Do not take Duotens”.
• You must inform your doctor if you think you are pregnant (or could become pregnant). Duotens is not recommended during the first 3 months of pregnancy and can cause serious harm to the unborn baby after 3 months of pregnancy (see section “Pregnancy, breastfeeding and fertility” below).
• If you experience a sudden, severe increase in blood pressure (hypertensive crisis).
• If you are elderly and your dose needs to be increased.
• If you have a persistent dry cough.
• If your blood pressure has not been adequately lowered. Medicines of this type appear to be less effective in people of black origin.
• 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, and possibly hands and feet, difficulty swallowing or breathing, hives, or hoarseness ("angioedema"), this could be a sign of a severe allergic reaction. These effects can occur at any time during treatment. People of black origin may have a higher risk of developing this condition. If these symptoms occur, inform your doctor immediately.

Children and adolescents

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

Other medicines and Duotens

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Inform 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 monitor your blood pressure.
• Rifampicin (an antibiotic used to treat tuberculosis).
• Hypericum perforatum (St. John’s wort – a remedy for depression).

Inform your doctor if you are taking any of the following medicines. They may increase the risk of 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).
• Medicines for cancer (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 acceptance of a 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 (medicines to eliminate fluids) such as furosemide.
• Medicines that may increase potassium levels in the blood such as spironolactone, triamterene, amiloride, potassium supplements (including salt substitutes), trimethoprim alone or in combination with sulfamethoxazole for treating bacterial infections; and heparin, a medicine used to thin the blood and prevent clotting.
• Steroid medicines for inflammation such as prednisolone.
• Allopurinol (used to lower uric acid in the blood).
• Procainamide (for heart rhythm problems).
• Ketoconazole, itraconazole (used to treat fungal infections).
• Ritonavir, indinavir, nelfinavir (protease inhibitors used to treat HIV patients).
• Verapamil, diltiazem (medicines for treating certain heart conditions and high blood pressure).
• Dantrolene (given by infusion for severe abnormalities in body temperature).
• Vildagliptin (for treatment of type 2 diabetes). See section “Warnings and precautions”.
• Racecadotril (used for diarrhoea). See section “Warnings and precautions”.

Your doctor may consider it necessary to adjust your dose and/or take other precautions if you are taking an angiotensin II receptor antagonist (ARB) or aliskiren (see also information in sections “Do not take Duotens” and “Warnings and precautions”).

Inform your doctor if you are taking any of these medicines, as the action of the following medicines may be altered by Duotens:

• Medicines for diabetes such as oral blood glucose-lowering medicines and insulin. Duotens may lower blood sugar levels. Monitor your blood sugar (glucose) levels carefully while taking Duotens.
• Lithium (for mental health conditions). Duotens may increase lithium levels in the blood. Your doctor must closely monitor your blood lithium levels.
• Simvastatin (a medicine to lower cholesterol). Duotens may increase simvastatin levels in the blood.

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

Duotens with food, drinks and alcohol

Duotens can be taken with or without food.

Drinking alcohol during treatment with Duotens may cause dizziness or a feeling of mental confusion. If you want to know how much alcohol you can drink while on Duotens, discuss this with your doctor, as the effects of blood pressure-lowering medicines and alcohol may be additive.

Grapefruit juice or grapefruit must not be consumed by people taking Duotens. This is because grapefruit or grapefruit juice may increase blood levels of the active substance amlodipine, which could lead to an unpredictable increase in the hypotensive effect (lowering of blood pressure) of Duotens.

Pregnancy, breastfeeding and fertility

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

Pregnancy

You must not take Duotens during the first 12 weeks of pregnancy and must not take it at all from week 13 onwards, as its use during pregnancy may harm the unborn baby.

If you become pregnant while taking Duotens, inform your doctor immediately.

Switching to a suitable alternative treatment should be considered before planning a pregnancy.

Breastfeeding

If you are breastfeeding, you must not take Duotens.

Consult your doctor or pharmacist before taking any medicine.

Fertility

There are insufficient data on the potential effects on fertility.

Driving and using machines

Duotens may affect your ability to drive or use machinery. If Duotens makes you feel unwell, causes dizziness, tiredness, or headache, do not drive or operate machinery and contact your doctor immediately. This may especially occur at the beginning of treatment or when switching to Duotens from 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 exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
If you feel that the effect of Duotens is too strong or too weak, talk to your doctor or
pharmacist.
Take this medicine by mouth at the same time each day, with or without food.
Swallow the capsule whole with liquid.
Do not take Duotens with grapefruit juice.
Duotens should be administered once daily.
Depending on the effect, your doctor may adjust your dose.
The maximum dose is 1 capsule once daily of the 10 mg/10 mg strength.
Elderly
Your doctor will reduce the initial dose and adjust treatment more slowly.
Use in children and adolescents
Duotens is not recommended for use in children and adolescents under 18 years of age, as there
are no available data in this population.
If you take more Duotens than you should
Taking too many capsules may cause a drop in blood pressure that could become
dangerous. You may experience dizziness, lightheadedness, fainting, or weakness.
If the drop in blood pressure is severe enough, shock may occur. The skin may become
cold and sweaty, and you may lose consciousness. Seek immediate medical attention
or go to the nearest hospital emergency department. Do not drive yourself to the hospital;
have someone drive you or call an ambulance. Bring the medicine pack with you 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 ingestion.
If you forget to take Duotens
If you forget to take a capsule, skip that dose completely. Take the next dose at the
correct time. Do not take a double dose to make up for the missed dose.
If you stop taking Duotens
Your doctor will advise you on how long you should take this medicine. Your condition may
return if you stop taking the medicine before advised.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this drug can cause side effects, although not everyone experiences them.
Stop treatment with Duotens and contact your doctor immediately if you notice any of the following serious side effects, as you may require urgent medical attention:

• Swelling of the face, lips, or throat causing difficulty swallowing or breathing, as well as itching and skin rash. These could be signs of a severe allergic reaction to Duotens.
• Severe skin reactions, including rashes, mouth ulcers, 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:

• Rapid heartbeat, irregular or forceful heartbeat (palpitations), chest pain, chest tightness, or more serious problems including heart attack or stroke. The frequency of these side effects is common (chest pain, chest tightness, palpitations) or uncommon (rapid heartbeat, heart attack or stroke).
• Wheezing, shortness of breath, or sudden breathing difficulties. These are common side effects and may indicate lung problems.
• Increased tendency to bruise, prolonged bleeding, any sign of bleeding (e.g. bleeding gums), skin spots, including purple spots, or increased susceptibility to infections, sore throat and fever, fatigue, fainting, dizziness, and pale appearance. These may be signs of blood or bone marrow disorders (frequency not known).
• Severe stomach pain that may radiate to the back. This could indicate 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 may be signs of liver problems, including inflammation of the liver (hepatitis) or liver damage (frequency is very rare).

Other side effects include:
Inform your doctor if any of the following side effects worsen or last 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, dizziness (especially at the beginning of treatment)
• Palpitations (awareness of heartbeat), hot flushes
• Swelling of the ankles
• Visual disturbances, double vision
• Headache or feeling of fatigue, weakness
• Fainting, hypotension (abnormally low blood pressure), especially when standing up or bending down quickly
• Dry cough, sinus inflammation (sinusitis), or bronchitis
• Abdominal, stomach, or intestinal pain, diarrhea, constipation, indigestion, nausea or vomiting
• Skin rash with or without raised areas
• Chest pain
• Muscle cramps or muscle pain
• Blood tests showing higher than normal potassium levels in the blood

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

• Mood changes, insomnia
• Tremor, pain, feeling unwell
• Ringing in the ears (tinnitus)
• Sneezing/runny nose due to inflammation of the nasal lining (rhinitis)
• Heartburn, dry mouth
• Hair loss, increased sweating, red spots on the skin, skin discoloration
• Urinary problems, increased need to urinate, especially at night, increased frequency of urination
• Inability to achieve an erection, sexual dysfunction in men, reduced sexual desire in men or women
• Breast discomfort or enlargement in men
• Joint pain, back pain
• Weight gain or weight loss
• Balance problems (dizziness)
• Itching and unusual skin sensations such as numbness, tingling, pricking, burning, or the sensation of something crawling on the skin (paresthesia), loss of pain sensation
• Hives (urticaria)
• Loss or alteration of taste
• Feeling depressed, anxious, more nervous than usual, or restless
• Nasal congestion, difficulty breathing, or worsening of asthma symptoms
• Intestinal swelling called "intestinal angioedema," presenting with symptoms such as abdominal pain, vomiting, and diarrhea
• Loss or decrease of appetite (anorexia)
• Blurred vision
• Fever
• Blood tests showing increased levels 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 people):

• Feeling shaky or confused
• Red and swollen tongue
• Severe peeling or cracking of the skin, itching, raised skin rash
• Nail problems (e.g. nail detachment or separation from the nail bed)
• Skin rash or bruising
• Inflammation of blood vessels, often with a skin rash
• Skin spots and cold extremities
• Red, itchy, swollen, or watery eyes
• Hearing problems
• Blood tests showing a decrease in red blood cells, white blood cells, or platelets (which may lead to unusual bruising or tendency to bleed), or in hemoglobin levels

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

• Increased sensitivity to sunlight
• High blood sugar (hyperglycemia)
• Swollen gums
• Abdominal swelling (gastritis)
• Impaired liver function, liver inflammation (hepatitis), yellowing of the skin (jaundice)
• Increased muscle tension
• Disorders related to stiffness, tremor, and/or movement disorders

Not known:

• Concentrated (dark-colored) urine, feeling unwell or malaise, muscle cramps, confusion, and seizures, which may be due to inappropriate secretion of ADH (anti-diuretic hormone [antidiuretic hormone]). If you experience these symptoms, contact your doctor promptly.
• Tremor, rigid posture, mask-like facial expression, slow movements, and unbalanced, shuffling gait

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

• Difficulty concentrating
• Mouth swelling
• Blood tests showing reduced sodium levels in the blood compared to normal values
• Fingers of hands and feet changing color when cold, followed by tingling or pain when warming up (Raynaud's phenomenon)
• Slowed or impaired reactions
• Burning sensation
• Changes in the perception of smells

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 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 below 30°C.
Keep in the original packaging 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 stated on the carton and blister after EXP.
The expiry date refers to the last day of that month.
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. Contents of the pack and other information

What Duotens contains

• The active substances are:
  2.5 mg/5 mg hard capsules: each capsule contains 2.5 mg ramipril and amlodipine besilate equivalent to 5 mg amlodipine.

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

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

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

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

• The other components are: microcrystalline cellulose, anhydrous dicalcium phosphate, pregelatinized maize starch, sodium glycolate starch (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; body: opaque, white.
Capsule contents: white or almost white powder.

Duotens 5 mg/5 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, pink; body: opaque, white.
Capsule contents: white or almost white powder.

Duotens 5 mg/10 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, red-brown; body: opaque, white.
Capsule contents: white or almost white powder.

Duotens 10 mg/5 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, dark pink; body: opaque, white.
Capsule contents: white or almost white powder.

Duotens 10 mg/10 mg hard capsules
Hard gelatin capsules, approximately 19 mm in length; cap: opaque, brown; body: opaque, white.
Capsule contents: white or almost white powder.

Duotens is available in packs containing 28, 30, 32, 56, 60, 90, 91, 96, 98 or 100 capsules 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 Milano, Italy.

Manufacturing 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