Triamlo

Package leaflet: Information for the patient

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

ramipril/amlodipine
Please read all of 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 others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What TRIAMLO is and what it is used for

TRIAMLO contains two active substances: 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 antagonists.
Ramipril works as follows:

• Reduces the production of a substance in the body that could increase blood pressure;
• Relaxes and widens blood vessels;
• Makes it easier for the heart to pump blood throughout the body.

Amlodipine works as follows:

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

TRIAMLO is used to treat high blood pressure (hypertension) in patients whose blood pressure is
adequately controlled with amlodipine and ramipril given simultaneously at the same dose as in
TRIAMLO, but as individual medicines.

2. What you need to know before taking TRIAMLO

Do not take TRIAMLO

• If you are allergic to ramipril or amlodipine, or to any other ACE inhibitor or calcium antagonist, or to any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction may include skin rashes, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue.
• If you have previously had a severe allergic reaction called "angioedema". Signs 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 and 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. Speak with your doctor or pharmacist if you are using, have recently taken, or might take sacubitril/valsartan.
• If you are undergoing dialysis or another type of blood filtration. Depending on the type of equipment used, treatment with TRIAMLO may not be suitable for you.
• If you have kidney problems due to reduced blood flow to the kidney (renal artery stenosis).
• During the last 6 months of pregnancy (see section below on "Pregnancy, breastfeeding and fertility").
• If you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
• If your blood pressure is too low or unstable. Your doctor will need to assess this.
• If you have narrowing of the heart's aortic valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body).
• If you suffer from heart failure following a heart attack.

Do not take TRIAMLO if any of the above conditions apply to you. If you are unsure, speak with your doctor before taking TRIAMLO.

Warnings and precautions

Talk to your doctor or pharmacist before taking TRIAMLO.

Speak with your doctor if any of the following conditions apply to you:

• If you have heart, liver or kidney problems.
• If you have 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 undergoing treatment to reduce allergy to bee or wasp stings (desensitisation).
• If you are receiving an anaesthetic. This may be administered for surgery or a dental procedure. In such cases, you may need to stop treatment with TRIAMLO the day before; speak with your doctor to inform them.
• If you have high levels of potassium in your blood (detected by blood tests).
• If you are taking medicines or have conditions that may reduce sodium levels in your blood. Your doctor may ask you to have regular blood tests, especially to monitor sodium levels, particularly if you are elderly.
• If you are taking medicines that may increase the risk of angioedema, a serious allergic reaction, such as mTOR inhibitors (e.g. temsirolimus, everolimus, sirolimus), vildagliptin, or neprilysin inhibitors (NEP) (such as racecadotril).
• If you have a collagen-vascular disease such as scleroderma or systemic lupus erythematosus.
• You must inform your doctor if you think you are pregnant (or could become pregnant). TRIAMLO 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 below "Pregnancy and breastfeeding").
• If you are taking any of the following medicines used to treat high blood pressure:
  • An angiotensin II receptor antagonist (ARA-II) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
  • Aliskiren. Your doctor may check your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood at regular intervals. See also the section "Do not take TRIAMLO".
• If you have a sudden, severe increase in blood pressure (hypertensive crisis).
• If you are elderly and a dose increase is needed.
• If you develop a persistent dry cough.
• If your blood pressure is not sufficiently reduced. Medicines of this type appear to be less effective in people of Black origin.

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 may be a sign of a serious allergic reaction. These effects may occur at any time during treatment. People of Black origin may have a higher risk of developing this condition. If you develop such symptoms, inform your doctor immediately.

Children and adolescents

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

Other medicines and TRIAMLO

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 effectiveness of TRIAMLO:

• 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.
• Hypericum perforatum (St. John's wort, used to treat depression).

Talk to your doctor if you are taking any of the following medicines. They may increase the risk of side effects when taken with TRIAMLO. Your doctor may need to adjust your dose and/or take other precautions:

• Sacubitril/valsartan – used to treat a type of long-term (chronic) heart failure in adults (see also information in section 2 "Do not take TRIAMLO").
• Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or indometacine, and acetylsalicylic acid).
• Medicines for cancer (chemotherapy).
• Medicines to prevent organ rejection after transplantation, such as ciclosporin.
• Diuretics (water tablets) such as furosemide.
• An angiotensin II receptor antagonist (ARA-II) or aliskiren (see also information in section "Do not take TRIAMLO" and "Warnings and precautions").
• Medicines that may increase potassium levels in the blood, such as spironolactone, triamterene, amiloride, potassium salts and heparin (to reduce blood clotting).
• Steroid medicines for inflammation, such as prednisolone.
• Allopurinol (used to lower uric acid in the blood).
• Procainamide (for heart rhythm problems).
• Temsirolimus (for cancer).
• Sirolimus, everolimus (to prevent transplant rejection).
• Vildagliptin (used to treat type 2 diabetes).
• Racecadotril (used to treat diarrhoea).
• Ketoconazole, itraconazole (medicines used to treat fungal infections).
• Ritonavir, indinavir, nelfinavir (protease inhibitors used to treat HIV patients).
• Rifampicin, erythromycin, clarithromycin (antibiotics used to treat bacterial infections).
• Trimethoprim and cotrimoxazole (for infections caused by bacteria).
• Verapamil, diltiazem (medicines used to treat heart conditions or high blood pressure).
• Dantrolene (for infusion in severe body temperature abnormalities).
• Tacrolimus (a medicine used to prevent transplant rejection by reducing immune system activity).
• Simvastatin (a medicine that lowers cholesterol in the blood).

Talk to your doctor if you are taking any of the following medicines. Their effect may be influenced by TRIAMLO:

• Medicines for diabetes, such as oral glucose-lowering agents and insulin. TRIAMLO may reduce blood sugar levels. Monitor your blood glucose carefully while taking TRIAMLO.
• Lithium (for mental health conditions). TRIAMLO may increase lithium levels in the blood. Your doctor must monitor your blood lithium levels carefully.
• Simvastatin (a medicine that lowers cholesterol in the blood). TRIAMLO may increase simvastatin levels in the blood.

If any of the above conditions apply to you (or you are unsure), speak with your doctor before taking TRIAMLO.

TRIAMLO with food, drinks and alcohol

TRIAMLO can be taken with or without food.

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

Grapefruit or grapefruit juice must not be consumed by people taking TRIAMLO. 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 (blood pressure reduction) of TRIAMLO.

Pregnancy, breastfeeding and fertility

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy

You must not take TRIAMLO during the first 12 weeks of pregnancy and must not take it at all from week 13 onwards, as its use during pregnancy can harm the unborn baby. If you become pregnant while taking TRIAMLO, inform your doctor immediately. A switch to an appropriate alternative treatment should be made before planning a pregnancy.

Breastfeeding

Amlodipine has been shown to pass into breast milk in small amounts. You must not take TRIAMLO if you are breastfeeding.

Talk to your doctor or pharmacist before taking any medicine.

Fertility

There are insufficient data on the potential effect on fertility.

Driving and using machines

TRIAMLO may affect your ability to drive or use machinery. If TRIAMLO makes you feel unwell, causes dizziness or fatigue, or gives you headaches, do not drive or operate machinery and contact your doctor immediately. This may occur especially at the beginning of treatment or when switching to TRIAMLO from other medicines.

TRIAMLO contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. it is practically "sodium-free".

3. How to take TRIAMLO

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 TRIAMLO is too strong or too weak, talk to your doctor or pharmacist.
Take this medicine at the same time each day, with or without food.
Swallow the capsule whole with liquid.
Do not take TRIAMLO with grapefruit juice.
TRIAMLO should be administered once daily.
Your doctor may adjust the dose depending on how the medicine affects you.
The maximum daily dose is one capsule of 10 mg/10 mg.

Elderly patients
Your doctor may reduce the initial dose and adjust treatment more gradually.

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

Patients with impaired liver function
Your doctor may prescribe you a different dose.

If you take more TRIAMLO than you should
Taking too many capsules may cause a drop in blood pressure that could become dangerous.
You may experience dizziness, lightheadedness, or feel weak. If blood pressure drops severely, shock may occur.
You may feel cold and sweaty skin and may lose consciousness.
Talk to your doctor or go immediately to the nearest hospital emergency department.
Do not drive yourself to the hospital; ask someone to take you or call an ambulance.
Take the medicine package with you so that the doctor knows what you have taken.

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

If you stop taking TRIAMLO
Your doctor will advise you how long to take the medicine. Your condition may return if you stop taking the medicine earlier than recommended.
If you have any questions about using 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 TRIAMLO and contact your doctor immediately if you notice any of the following serious side effects – you may require urgent medical treatment:

• Swelling of the face, lips or throat causing difficulty in swallowing or breathing, as well as itching and skin rash. This may be a sign of a serious allergic reaction to TRIAMLO.
• Severe skin reactions including skin rashes, mouth ulcers, worsening of a pre-existing skin disease, redness, blisters or peeling of the skin (such as in Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme), or other allergic reactions. The frequency of the above-listed side effects is classified as not known (cannot be estimated from the available data).

Speak to your doctor immediately if you experience:

• Rapid heartbeat, irregular or stronger heartbeat (palpitations), chest pain, tightness in the chest or more serious problems such as heart attack and stroke.
• Shortness of breath or cough. These may be signs of lung problems.
• Increased tendency to bruise, bleeding for longer than normal, any sign of bleeding (e.g. bleeding gums), purple spots, skin patches or increased susceptibility to infections, sore throat and fever, feeling tired, fainting, dizziness or appearing pale. These may be signs of blood or bone marrow problems.
• Severe stomach pain that may radiate to the back. This could be a sign of pancreatitis (inflammation of the pancreas).
• Fever, chills, tiredness, loss of appetite, stomach ache, feeling unwell, yellowing of the skin or eyes (jaundice). These may be signs of liver problems, including hepatitis (liver inflammation) or liver damage.

Other side effects include:
Inform your doctor if any of the following side effects become severe or last for more than a few days.
Very common (may affect more than 1 in 10 people)

• Swelling of the ankles (oedema).

Common (may affect up to 1 in 10 people)

• Drowsiness (especially at the beginning of treatment).
• Palpitations (awareness of your heartbeat), hot flushes.
• Headache or feeling tired, weak.
• Dizziness. This is more likely when you first start taking TRIAMLO or when you start taking a higher dose.
• Fainting, hypotension (abnormally low blood pressure), especially when standing up or sitting down quickly.
• Dry, irritating cough, inflammation of the sinuses (sinusitis) or bronchitis, shortness of breath.
• Abdominal, stomach or intestinal pain, altered bowel habits (including diarrhoea or constipation), indigestion, feeling or being unwell.
• Skin rash with or without raised areas.
• Chest pain.
• Visual disturbances, double vision.
• 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, feeling unwell.
• Blurred vision.
• Sneezing/runny nose due to inflammation of the nasal mucosa (rhinitis).
• Heartburn, dry mouth.
• Hair loss, increased sweating, itchy skin, red spots on the skin, skin discolouration.
• Difficulty passing urine, increased need to urinate, especially at night, increased frequency of urination.
• Inability to achieve an erection, sexual dysfunction in men, decreased sexual desire in men or women.
• Breast discomfort or breast enlargement in men.
• Joint or muscle pain, back pain.
• Increase or decrease in body weight.
• Balance problems (dizziness).
• Itching and unusual skin sensations such as numbness, tingling, pricking, burning or the sensation that something is crawling on the skin (paraesthesia), loss of pain sensation.
• Loss or change in taste.
• Sleep problems.
• Feeling depressed, anxious, more nervous than usual or restless.
• Stuffy nose, difficulty breathing or worsening of asthma symptoms.
• Swelling in the intestine called "intestinal angioedema" which presents with symptoms such as abdominal pain and vomiting.
• Loss or decrease in appetite (anorexia).
• Irregular or increased heartbeat.
• Swelling of the arms and legs. This may be a sign that the body is retaining more fluid than normal.
• Fever.
• Blood tests showing an increase in 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 of trembling or confusion.
• Red and swollen tongue.
• Severe peeling or cracking of the skin, itching, raised skin rash.
• Nail problems (e.g. nail loss or nail separation from the nail bed).
• Skin rash or bruising.
• Hives (urticaria).
• Spots on the skin and cold extremities.
• Red, swollen, itchy or watery eyes.
• Hearing problems and ringing in the ears.
• Blood tests showing a decrease in the number of red blood cells, white blood cells or platelets, or in haemoglobin levels.

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

• Increased sensitivity to sunlight.
• High levels of sugar (glucose) in the blood (hyperglycaemia).
• Swelling of the gums.
• Abdominal swelling (gastritis).
• Impaired liver function, liver inflammation (hepatitis), yellowing of the skin (jaundice), increased liver enzymes which may affect certain medical tests.
• Increased muscle tension.
• Inflammation of blood vessels, often with a rash.
• Light sensitivity.
• Disorders associated with stiffness, tremor and/or movement disturbances.
• Nerve disorders that may cause weakness, tingling or numbness (peripheral neuropathy).

Not known (frequency cannot be estimated from the available data)

• Concentrated urine (dark-coloured), feeling unwell, muscle cramps, confusion and seizures which may be due to inadequate secretion of ADH (antidiuretic hormone). If you experience these symptoms, contact your doctor immediately.
• Tremor, rigid posture, mask-like facial expression, slow movements, unbalanced and shuffling gait.

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

• Difficulty concentrating.
• Swollen mouth.
• Blood tests showing abnormally low levels of circulating blood cells.
• Blood tests showing reduced levels of sodium in the blood compared to normal values.
• Fingers of the hands and feet changing colour when cold, followed by tingling or painful sensations when warming up (Raynaud's phenomenon).
• Slowed or impaired reactions.
• Changes in the sense of smell.
• Psoriasis.

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 TRIAMLO

Keep this medicine out of the sight and reach of children.
Store below 30°C and keep the medicine in the original packaging to protect it from light.
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. Package contents and other information

What TRIAMLO contains

• The active substances are:

TRIAMLO 2.5 mg/5 mg:
Each capsule contains 2.5 mg ramipril and amlodipine besylate equivalent to 5 mg amlodipine.
TRIAMLO 5 mg/5 mg:
Each capsule contains 5 mg ramipril and amlodipine besylate equivalent to 5 mg amlodipine.
TRIAMLO 10 mg/5 mg:
Each capsule contains 10 mg ramipril and amlodipine besylate equivalent to 5 mg amlodipine.
TRIAMLO 5 mg/10 mg:
Each capsule contains 5 mg ramipril and amlodipine besylate equivalent to 10 mg amlodipine.
TRIAMLO 10 mg/10 mg:
Each capsule contains 10 mg ramipril and amlodipine besylate equivalent to 10 mg amlodipine.

• Other components are: microcrystalline cellulose, anhydrous dicalcium hydrogen 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 TRIAMLO and the contents of the pack
TRIAMLO 2.5 mg/5 mg:
Hard gelatin capsules, cap: opaque, light pink color; body: opaque, white color.
Capsule contents: white or almost white powder.
TRIAMLO 5 mg/5 mg:
Hard gelatin capsules, cap: opaque, pink color; body: opaque, white color.
Capsule contents: white or almost white powder.
TRIAMLO 10 mg/5 mg:
Hard gelatin capsules, cap: opaque, dark pink color; body: opaque, white color.
Capsule contents: white or almost white powder.
TRIAMLO 5 mg/10 mg:
Hard gelatin capsules, cap: opaque, red-brown color; body: opaque, white color.
Capsule contents: white or almost white powder.
TRIAMLO 10 mg/10 mg:
Hard gelatin capsules, cap: opaque, brown color; body: opaque, white color.
Capsule contents: white or almost white powder.
TRIAMLO 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 Authorization Holder and Manufacturer
Marketing Authorization Holder
Sanofi S.p.A.
Viale L. Bodio, 37/B
20158 Milan, Italy

Manufacturers
Adamed Pharma S.A.
Szkolna 33 str., 95-054 Ksawerów
Poland
Adamed Pharma S.A.
Marszalka Jósefa Pilsudskiego 5 str, 95-200 Pabianice
Poland

This medicinal product is authorized in the European Economic Area Member States under the following names:
Slovak Republic: Ramipril/Amlodipin Sanofi
Czech Republic: Tritace Combi
Poland: Amrap
Bulgaria: Tritace combo
Italy, Greece, Cyprus: Triamlo