Ramipril and amlodipine Zentiva

Package leaflet: Information for the patient

Ramipril and Amlodipine Zentiva 5 mg/5 mg hard capsules, 5 mg/10 mg hard capsules, 10 mg/5 mg hard capsules, 10 mg/10 mg hard capsules

Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Ramipril and Amlodipine Zentiva is and what it is used for

Ramipril and Amlodipine Zentiva 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 in your body of substances that can cause an increase in blood pressure.
• Relaxes and widens your blood vessels.
• Makes it easier for your heart to pump blood around your body.

Amlodipine works as follows:

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

Ramipril and Amlodipine Zentiva is used to treat hypertension (high blood pressure) in adult patients whose high blood pressure is adequately controlled with ramipril and amlodipine administered simultaneously as separate tablets with the same dosages as those contained in Ramipril and Amlodipine Zentiva.

2. What you should know before taking Ramipril and Amlodipine Zentiva

Do not take Ramipril and Amlodipine Zentiva:

• If you are allergic to ramipril, amlodipine (active substances), or to any other ACE inhibitor or calcium antagonist medicine, or to any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction may include itching, skin redness, rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue.
• 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, such as in the throat) (see section “Other medicines and Ramipril and Amlodipine Zentiva”).
• If you have previously experienced 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 are undergoing dialysis or any other type of blood filtration. Depending on the type of equipment used, treatment with Ramipril and Amlodipine Zentiva 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 impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
• If your blood pressure is too low (hypotension) or unstable. Your doctor will need to assess your condition.
• If you have a narrowing of the heart’s aortic valve (aortic stenosis) or cardiogenic shock (a condition in which the heart cannot supply sufficient blood to the body).
• If you have heart failure following a heart attack.

Do not take Ramipril and Amlodipine Zentiva if any of the above conditions apply to you. If you are in doubt, speak with your doctor before taking Ramipril and Amlodipine Zentiva.

Warnings and precautions

Talk to your doctor or pharmacist before taking Ramipril and Amlodipine Zentiva. Inform your doctor if any of the following apply to you:

• If you have heart, liver or kidney problems.
• 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 an allergy, e.g. to bee or wasp stings (desensitisation).
• If you are due to receive anaesthesia. This may be administered during surgery or a dental procedure. In such cases, you may need to stop taking Ramipril and Amlodipine Zentiva 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 are taking medicines or have conditions that may reduce sodium levels in your blood. Your doctor may perform regular blood tests, particularly to monitor sodium levels, especially if you are elderly.
• If you have a collagen-vascular disease such as scleroderma or systemic lupus erythematosus.
• You must inform your doctor if you think you are (or could become) pregnant. Ramipril and Amlodipine Zentiva is not recommended during the first 3 months of pregnancy and may cause severe harm to the unborn baby after 3 months of pregnancy (see the section below on “Pregnancy and breastfeeding”).
• If you are taking any of the following medicines for high blood pressure:
  • an angiotensin II receptor antagonist (ARBs) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes;
  • aliskiren. Your doctor may regularly monitor your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood. See also information in the section “Do not take Ramipril and Amlodipine Zentiva”.
• 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 develop sudden swelling of the lips and face, tongue and throat, neck, and possibly also hands and feet, difficulty swallowing or breathing, hives or hoarseness (“angioedema”), this could be a sign of a serious allergic reaction. These effects may occur at any time during treatment. People with black skin may have a higher risk of developing this condition. If you experience these symptoms, inform your doctor immediately.

Children and adolescents

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

Other medicines and Ramipril and Amlodipine Zentiva

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

This is because Ramipril and Amlodipine Zentiva may affect how some other medicines work. In addition, some medicines may affect how Ramipril and Amlodipine Zentiva works.

Inform your doctor if you are taking any of the following medicines. They may reduce the effect of Ramipril and Amlodipine Zentiva:

• Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indomethacin and acetylsalicylic acid).
• Medicines used to treat blood pressure, shock, heart failure, asthma or allergies, such as ephedrine, noradrenaline or adrenaline. Your doctor should 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 Ramipril and Amlodipine Zentiva:

• Sacubitril/valsartan – used to treat a type of long-term (chronic) heart failure in adults (see section 2 “Do not take Ramipril and Amlodipine Zentiva”).
• If you are taking any of the following medicines, your 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 (e.g. temsirolimus, sirolimus, everolimus).
  • Vildagliptin, a medicine used in the treatment of diabetes.
• Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indomethacin, acetylsalicylic acid).
• Cancer medicines (chemotherapy).
• Potassium supplements (including salt substitutes), potassium-sparing diuretics (spironolactone, triamterene and amiloride), and other medicines that may increase potassium levels in the blood (such as trimethoprim and cotrimoxazole) used to treat bacterial infections; ciclosporin, an immunosuppressant medicine used to prevent rejection of transplanted organs; and heparin, a medicine used to thin the blood and prevent clotting.
• Diuretics (water-eliminating medicines) such as furosemide.
• 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).
• Erythromycin, clarithromycin (antibiotics).
• Verapamil, diltiazem (heart medicines).
• Dantrolene (given by infusion for severe body temperature abnormalities).

Your doctor may consider it necessary to adjust your dosage 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 Ramipril and Amlodipine Zentiva” and “Warnings and precautions”).

Inform your doctor if you are taking any of these medicines. The effects of the following medicines may be influenced by Ramipril and Amlodipine Zentiva:

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

Ramipril and Amlodipine Zentiva may further lower your blood pressure if you are already taking other medicines for high blood pressure.

If any of the above situations apply to you (or if you are uncertain), consult your doctor before taking Ramipril and Amlodipine Zentiva.

Ramipril and Amlodipine Zentiva with food, drinks and alcohol

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

Grapefruit and grapefruit juice must not be consumed by people taking Ramipril and Amlodipine Zentiva. 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 blood pressure-lowering effect (hypotensive effect) of Ramipril and Amlodipine Zentiva.

Pregnancy, breastfeeding and fertility

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

Pregnancy

You must not take Ramipril and Amlodipine Zentiva during pregnancy.

If you become pregnant while being treated with Ramipril and Amlodipine Zentiva, inform your doctor immediately. A switch to an appropriate alternative treatment should be made before planning a pregnancy.

Breastfeeding

If you are breastfeeding, you must not take Ramipril and Amlodipine Zentiva. Consult your doctor or pharmacist before taking any medicine.

Fertility

There are insufficient data on potential effects on fertility.

Driving and using machines

Ramipril and Amlodipine Zentiva may affect your ability to drive or use machinery. If Ramipril and Amlodipine Zentiva makes you feel unwell, causes dizziness or tiredness, or gives you a headache, do not drive or operate machinery and contact your doctor immediately. This is more likely to occur when you first start taking Ramipril and Amlodipine Zentiva, when switching from another medicine, or when starting a higher dose.

Ramipril and Amlodipine Zentiva contains sodium:

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

3. How to take Ramipril and Amlodipine Zentiva

Take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
If you feel that the effect of Ramipril and Amlodipine Zentiva is too strong or too weak,
contact your doctor or pharmacist.
Take this medicine orally at the same time each day. Ramipril and Amlodipine Zentiva can
be taken with or without food.
Swallow the capsule whole with liquid.
Do not take Ramipril and Amlodipine Zentiva with grapefruit juice.
Ramipril and Amlodipine Zentiva should be administered once daily.
Depending on the effect, your doctor may adjust the dose.
The maximum daily dose is 1 capsule of 10 mg/10 mg.
Elderly
Your doctor will reduce the initial dose and adjust treatment more slowly.
Use in children and adolescents
Ramipril and Amlodipine Zentiva 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 Ramipril and Amlodipine Zentiva 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 a feeling of weakness. If the drop in
blood pressure is severe enough, shock may occur. The skin may become cold and
clammy, and you may lose consciousness.
Excess fluid may accumulate in the lungs (pulmonary edema), causing shortness of breath, which may
develop within 24–48 hours after ingestion.
Contact a doctor immediately or go to the nearest hospital emergency department. Do not drive
to the hospital; have someone drive you or call an ambulance. Take the medicine pack with you.
This will allow the doctor to know what you have taken.
If you forget to take Ramipril and Amlodipine Zentiva
If you forget to take a capsule, simply skip that dose. Take the next dose at the correct time. Do not
take a double dose to make up for a missed dose.
If you stop taking Ramipril and Amlodipine Zentiva
Your doctor will advise you on how long you should continue taking the 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 medicine can cause side effects, although not everybody gets them.
Stop taking Ramipril and Amlodipine Zentiva 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, eyelids, lips, tongue or throat causing difficulty swallowing or breathing, as well as itching and skin rash. These could be signs of a severe allergic reaction to Ramipril and Amlodipine Zentiva.
• Severe skin reactions, including severe rashes, mouth ulcers, hives, redness of the skin all over the body, intense itching, peeling and swelling of the skin, mucosal inflammation, worsening of a pre-existing skin disease, blisters or skin detachment (as in Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme), or other allergic reactions.

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.
• Shortness of breath or coughing. These could be signs of lung problems.
• Increased tendency to bruise, bleeding for longer than normal, any sign of bleeding (e.g. bleeding gums), spots on the skin, including purple spots, increased susceptibility to infections, sore throat and fever, feeling tired, fainting, dizziness and pale appearance. 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, 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.

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

• Fluid retention (oedema).

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

• Drowsiness (especially at the beginning of treatment)
• Palpitations (awareness of your heartbeat), hot flushes
• Swelling of the ankles
• Headache or feeling weak or tired
• Dizziness. This is more likely when you first start taking Ramipril and Amlodipine Zentiva or when you start taking a higher dose
• Fainting, low blood pressure (hypotension), especially when standing up or sitting down quickly
• Dry cough, inflammation of the sinuses (sinusitis) or bronchitis, shortness of breath
• Abdominal, stomach or intestinal pain, changes in bowel habits, diarrhoea, constipation, indigestion, feeling unwell (nausea)
• Vision disturbances, double vision
• 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, anxiety, depression, feeling depressed, insomnia
• Tremor, fainting, 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, itchy skin, red spots on the skin, skin discolouration
• Problems with urination, increased need to urinate at night, increased frequency of urination, need to urinate more often than usual during the day
• 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)
• Numbness or tingling in the limbs, loss of pain sensation
• Loss or change in taste
• Sleep problems
• Feeling more nervous or restless than usual
• Stuffy nose, difficulty breathing or worsening of asthma symptoms
• Swelling in the intestine called "intestinal angioedema" presenting with symptoms such as abdominal pain, vomiting and diarrhoea
• Loss of appetite (anorexia)
• Increased or irregular heartbeat
• Swelling of arms and legs. This could be a sign that your body is retaining more fluid than normal
• Blurred vision
• Cough
• Low blood pressure
• 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 tremor or confusion
• Red and swollen tongue
• Severe peeling or cracking of the skin, itching, raised rash
• Nail problems (e.g. detachment or separation of the nail from its bed)
• Skin rash or bruising
• Spots on the skin and cold extremities
• Red, itchy, swollen or watery eyes
• Hearing disturbances
• Blood tests showing a decrease in red blood cells, white blood cells or platelets, or in haemoglobin levels.

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

• Decrease in platelets in the blood which may cause unusual bruising or easy bleeding
• Increased sensitivity to sunlight
• High blood sugar (glucose) (hyperglycaemia)
• A nerve disorder which may cause muscle weakness, tingling or numbness
• Swollen gums, bleeding gums
• Abdominal swelling (gastritis)
• Impaired liver function, inflammation of the liver (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 related to stiffness, tremor, and/or movement disorders.

Frequency not known (cannot be estimated from the available data):

• Concentrated urine (dark coloured), feeling unwell or malaise, muscle cramps, confusion and seizures which may be due to inappropriate secretion of ADH (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 for more than a few days.

• Difficulty concentrating
• Swollen mouth
• 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
• 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 Ramipril and Amlodipine Zentiva

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.
Store below 30°C.
Keep in the original packaging to protect the medicine from light.
Do not dispose of any medicine 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 Ramipril and Amlodipine Zentiva contains

• The active substances are: 5 mg/5 mg hard capsules: each capsule contains 5 mg of ramipril and amlodipine besylate equivalent to 5 mg of amlodipine. 5 mg/10 mg hard capsules: each capsule contains 5 mg of ramipril and amlodipine besylate equivalent to 10 mg of amlodipine. 10 mg/5 mg hard capsules: each capsule contains 10 mg of ramipril and amlodipine besylate equivalent to 5 mg of amlodipine. 10 mg/10 mg hard capsules: each capsule contains 10 mg of ramipril and amlodipine besylate equivalent to 10 mg of amlodipine.
• Other components: microcrystalline cellulose, anhydrous dibasic calcium phosphate, pregelatinized maize 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 Ramipril and Amlodipine Zentiva and contents of the pack
Ramipril and Amlodipine Zentiva 5 mg/5 mg hard capsules: hard gelatin capsules; approximately 19.1 – 19.7 mm long, cap: opaque, pink in colour; body: opaque, white in colour. Capsule contents: white or almost white powder.
Ramipril and Amlodipine Zentiva 5 mg/10 mg hard capsules: hard gelatin capsules; approximately 19.1 – 19.7 mm long, cap: opaque, red-brown in colour; body: opaque, white in colour. Capsule contents: white or almost white powder.
Ramipril and Amlodipine Zentiva 10 mg/5 mg hard capsules: hard gelatin capsules; approximately 19.1 – 19.7 mm long, cap: opaque, dark pink in colour; body: opaque, white in colour. Capsule contents: white or almost white powder.
Ramipril and Amlodipine Zentiva 10 mg/10 mg hard capsules: hard gelatin capsules; cap: opaque, brown in colour; body: opaque, white in colour. Capsule contents: white or almost white powder.
Ramipril and Amlodipine Zentiva is available in packs containing 28, 30, 32, 50, 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
Zentiva k.s.
U kabelovny 130
102 37 Prague 10
Czech Republic

Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Poland

This medicinal product is authorised in the Member States of the European Economic Area under the following names: