Perindopril and amlodipine Zentiva

Package leaflet: Information for the patient

Perindopril and Amlodipine Zentiva 4 mg/5 mg tablets, 4 mg/10 mg tablets, 8 mg/5 mg tablets, 8 mg/10 mg tablets

Read this entire 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 their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Perindopril and Amlodipine Zentiva contains two active substances called perindopril and amlodipine.
Perindopril and Amlodipine Zentiva is prescribed for the treatment of high blood pressure
(hypertension) and for the treatment of stable coronary artery disease (a condition in which blood
flow to the heart is reduced or blocked).
Patients who are already taking perindopril and amlodipine as separate tablets may instead take a single tablet of Perindopril and Amlodipine Zentiva containing both active substances.
Perindopril belongs to a group of medicines called ACE (angiotensin-converting enzyme) inhibitors. Amlodipine belongs to a group of medicines called calcium channel blockers. Together, they work by dilating and relaxing blood vessels, thereby lowering blood pressure. Blood can then flow through the body more easily, and the heart does not have to work as hard.

2. What you need to know before taking Perindopril and Amlodipine Zentiva

Do not take Perindopril and Amlodipine Zentiva

• if you are allergic to perindopril or any other ACE inhibitor, or to amlodipine or any other calcium antagonist, or to any of the other ingredients of this medicine (listed in section 6).
• if you have had symptoms such as wheezing, swelling of the face, tongue or throat, severe itching or serious skin rashes related to previous treatment with ACE inhibitors, or if you or a family member has experienced such symptoms under any circumstances (a condition called angioedema).
• if you are more than three months pregnant. (It is best to avoid Perindopril and Amlodipine Zentiva in early pregnancy – see section “Pregnancy”.)
• if you are breastfeeding (see section “Pregnancy and breastfeeding”).
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
• if you are undergoing dialysis or any type of blood filtration. Depending on the equipment used, treatment with Perindopril and Amlodipine Zentiva may not be suitable for you.
• if you have kidney problems causing reduced blood flow to the kidneys (renal artery stenosis).
• if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin, for example in the throat).
• if you suffer from severely low blood pressure (hypotension).
• if you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body).
• if you have heart failure following a heart attack.

Warnings and precautions
Talk to your doctor or pharmacist before taking Perindopril and Amlodipine Zentiva.
You must inform your doctor if you have or have had any of the following conditions:

• aortic stenosis (narrowing of the main blood vessel leaving the heart) or hypertrophic cardiomyopathy (a disease of the heart muscle).
• recent heart attack.
• heart failure.
• severe high blood pressure (hypertensive crisis).
• any other heart problems.
• liver disease.
• kidney problems or if you are undergoing dialysis.
• abnormally high blood levels of a hormone called aldosterone (primary hyperaldosteronism).
• collagen vascular disease (connective tissue disease) such as systemic lupus erythematosus or scleroderma.
• diabetes.
• if you are on a low-salt diet or use salt substitutes containing potassium.
• if you are elderly and your dose needs to be increased.
• if you are taking any of the following medicines, which increase the risk of angioedema (rapid swelling under the skin, for example in the throat):
  • Racecadotril, a medicine used to treat diarrhoea.
  • Medicines used to prevent rejection of transplanted organs and to treat cancer (such as temsirolimus, sirolimus, everolimus) and other medicines belonging to the class of mTOR inhibitors.
  • Vildagliptin, a medicine used to treat diabetes.
• if you are of Black origin, as you may have a higher risk of angioedema and this medicine may be less effective in lowering blood pressure compared to non-Black patients.
• if you are taking any of the following medicines used to treat high blood pressure:
  • an angiotensin II receptor antagonist (AIIRA) (also known as sartans – for example valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes;
  • aliskiren. Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals.

See also the information under “Do not take Perindopril and Amlodipine Zentiva”.
While taking Perindopril and Amlodipine Zentiva, you should also inform your doctor or
medical staff:

• if you are due to undergo anaesthesia and/or major surgery.
• if you are scheduled for LDL apheresis (a procedure involving removal of cholesterol from the blood using a machine).
• if you are planning to undergo desensitisation treatment to reduce the effects of allergy to bee or wasp stings.
• if you have recently had diarrhoea or vomiting, or are dehydrated.

Angioedema
In patients treated with ACE inhibitors, including perindopril, angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat, causing difficulty in swallowing or breathing) has been reported. This may occur at any time during treatment. If you develop such symptoms, you must stop taking Perindopril and Amlodipine Zentiva and consult a doctor immediately. See also section 4.
You should inform your doctor if you are pregnant (or planning a pregnancy).
Perindopril and Amlodipine Zentiva is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn baby if taken during this period (see section “Pregnancy”).

Children and adolescents
There is no experience with the use of Perindopril and Amlodipine Zentiva in children (under 18 years of age). Therefore, Perindopril and Amlodipine Zentiva must not be administered to children or adolescents.

Other medicines and Perindopril and Amlodipine Zentiva
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Your doctor may need to adjust the dose and/or take other precautions.
Perindopril and Amlodipine Zentiva may affect or be affected by other medicines, such as:

• Other medicines for high blood pressure, including diuretics (medicines that increase the amount of urine produced by the kidneys).
• An angiotensin II receptor blocker (ARB) or aliskiren (see also information under “Do not take Perindopril and Amlodipine Zentiva” and “Warnings and precautions”).
• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (such as trimethoprim and cotrimoxazole used to treat bacterial infections; ciclosporin, an immunosuppressive medicine used to prevent rejection of transplanted organs; and heparin, a medicine used to thin the blood and prevent clotting).
• Potassium-sparing medicines used in the treatment of heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg daily.
• Sacubitril/valsartan – used to treat chronic heart failure in adults (see also information under “Do not take Perindopril and Amlodipine Zentiva”).
• Lithium (a medicine for mental health conditions).
• Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen for pain relief or high doses of acetylsalicylic acid.
• Medicines for the treatment of diabetes (such as insulin, vildagliptin or metformin).
• Baclofen (used to treat muscle stiffness in conditions such as multiple sclerosis).
• Medicines for the treatment of mental disorders such as depression, anxiety, schizophrenia, etc. (e.g. tricyclic antidepressants, antipsychotics).
• Immunosuppressants (medicines that suppress the body’s defence system), used to treat autoimmune diseases or to help your body accept a transplanted organ (e.g. tacrolimus).
• Estramustine (used in the treatment of cancer).
• Allopurinol (for the treatment of gout).
• Procainamide (for the treatment of irregular heartbeat).
• Vasodilators including nitrates (substances that dilate blood vessels).
• Medicines used to treat low blood pressure, shock or asthma (e.g. ephedrine, noradrenaline or adrenaline).
• Gold salts, especially when administered intravenously (used to treat symptoms of rheumatoid arthritis).
• Ketoconazole, itraconazole (antifungal medicines).
• Ritonavir, indinavir, nelfinavir (so-called protease inhibitors used in the treatment of HIV).
• Rifampicin, erythromycin, clarithromycin (antibiotics – for bacterial infections).
• Hypericum perforatum (St. John’s wort).
• Verapamil, diltiazem (heart medicines).
• Dantrolene (infusion for the treatment of severe temperature regulation disorders).
• Simvastatin (a medicine that lowers cholesterol).
• Medicines mainly used to treat diarrhoea (racecadotril) and other medicines belonging to the class of neprilysin inhibitors (NEP) or medicines used to prevent rejection after organ transplantation (sirolimus, everolimus, temsirolimus and other medicines belonging to the class of mTOR inhibitors). See section “Warnings and precautions”.

Perindopril and Amlodipine Zentiva with food, drinks and alcohol
Grapefruit and grapefruit juice must not be consumed by people taking Perindopril and Amlodipine Zentiva. This is because grapefruit and grapefruit juice may increase blood levels of the active substance amlodipine, which could lead to an unpredictable increase in the blood pressure-lowering effect of Perindopril and Amlodipine Zentiva.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Inform your doctor if you think you may be pregnant (or are planning a pregnancy). Your doctor will usually advise you to stop taking Perindopril and Amlodipine Zentiva before starting pregnancy or as soon as you know you are pregnant, and will recommend an alternative medicine.
Perindopril and Amlodipine Zentiva is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn baby if taken after the third month of pregnancy.

Breastfeeding
It has been shown that amlodipine passes into breast milk in small amounts. If you are breastfeeding or about to start breastfeeding, you must inform your doctor before taking Perindopril and Amlodipine Zentiva.
Perindopril and Amlodipine Zentiva is not recommended for breastfeeding mothers, and your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is newborn or was born prematurely.

Driving and using machines
Perindopril and Amlodipine Zentiva may affect your ability to drive or use machinery. If the tablets make you feel unwell, dizzy or tired, or cause headaches, do not drive or operate machinery and contact your doctor immediately.

Perindopril and Amlodipine Zentiva contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially “sodium-free”.

3. How to take Perindopril and Amlodipine Zentiva

Take this medicine exactly as your doctor or pharmacist has told you.
If you are unsure, consult your doctor or pharmacist.
Your doctor will decide the appropriate dose for you. Perindopril and Amlodipine Zentiva is usually
prescribed for patients who are already taking perindopril and amlodipine as separate tablets.
The recommended dose of Perindopril and Amlodipine Zentiva 4 mg / 5 mg is 1 or 2 tablets daily.
The recommended dose of Perindopril and Amlodipine Zentiva 4 mg / 10 mg, 8 mg / 5 mg and 8 mg / 10 mg is 1 tablet daily.
Swallow the tablets with a glass of water, preferably at the same time each day, in the morning and before a meal.

If you take more Perindopril and Amlodipine Zentiva than you should
Taking too many tablets may cause a dangerous drop in blood pressure. You may feel dizzy, lightheaded, faint, or weak. If the drop in blood pressure is severe enough, shock may occur.
Your skin may become cold and clammy, and you may lose consciousness. If you take too many tablets of Perindopril and Amlodipine Zentiva, seek medical help immediately.

If you forget to take Perindopril and Amlodipine Zentiva
If you forget to take a tablet, 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 Perindopril and Amlodipine Zentiva
Your doctor will advise you on how long to take the medicine. Your condition may return if you stop taking the medicine too soon. Therefore, do not stop taking Perindopril and Amlodipine Zentiva without first talking to your doctor.

If you have any doubts about how to use 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.
Contact your doctor immediately if you experience any of the following side effects after taking this medicine:

• Swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (uncommon – may affect up to 1 in 100 people).
• Severe dizziness or fainting due to low blood pressure (common – may affect up to 1 in 10 people).
• Heart attack, unusually fast or irregular heartbeat, chest pain (angina) (very rare – may affect up to 1 in 10,000 people).
• Weakness in the arms or legs, or difficulty speaking, which may be signs of a possible stroke (very rare – may affect up to 1 in 10,000 people).
• Sudden wheezing, chest pain, shortness of breath or difficulty breathing (bronchospasm) (uncommon – may affect up to 1 in 100 people).
• Severe skin reactions, including intense rash, hives, redness of the skin all over the body, severe itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions (very rare – may affect up to 1 in 10,000 people).
• Inflammation of the pancreas, which may cause severe abdominal and back pain accompanied by a strong feeling of illness (very rare – may affect up to 1 in 10,000 people).
• Yellowing of the skin or eyes (jaundice), which may be a sign of hepatitis (very rare – may affect up to 1 in 10,000 people).
• Skin rash, often starting with red, itchy spots on the face, arms or legs (erythema multiforme) (very rare – may affect up to 1 in 10,000 people).

Since Perindopril and Amlodipine Zentiva is a combination of two active substances, the side effects reported are related to the use of both perindopril and amlodipine.

Side effects related to the use of perindopril
Common (may affect up to 1 in 10 people):

• Headache, dizziness, vertigo.
• Tingling sensation (paraesthesia).
• Vision disturbances.
• Ringing in the ears (tinnitus).
• Lightheadedness due to low blood pressure.
• Cough.
• Shortness of breath.
• Feeling unwell (nausea), vomiting.
• Abdominal pain.
• Taste disturbances.
• Dyspepsia or indigestion.
• Diarrhoea, constipation.
• Rash, itching.
• Muscle cramps.
• Feeling of weakness.

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

• Mood changes.
• Sleep disturbances.
• Depression.
• Dry mouth.
• Kidney problems.
• Impotence.
• Sweating.
• Increased eosinophils (a type of white blood cells).
• Drowsiness.
• Fainting.
• Palpitations.
• Tachycardia.
• Vasculitis (inflammation of blood vessels).
• Photosensitivity reactions (increased skin sensitivity to sunlight).
• Joint pain.
• Muscle pain.
• Chest pain.
• Malaise.
• Peripheral oedema.
• Fever.
• Fall.
• Laboratory test changes: high potassium levels in the blood (reversible upon discontinuation of the medicine), low sodium levels, hypoglycaemia (very low blood sugar levels) in diabetic patients, increased plasma urea and increased plasma creatinine.

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

• Dark-coloured urine, feeling unwell (nausea) or unwell state (vomiting), muscle cramps, confusion and seizures. These symptoms may be related to a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion).
• Flushing.
• Worsening of psoriasis.
• Reduced or absent urine output.
• Acute renal failure.
• Changes in laboratory parameters: increased liver enzymes, elevated serum bilirubin levels.

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

• Confusion.
• Eosinophilic pneumonia (a rare type of pneumonia).
• Stuffy or runny nose (rhinitis).
• Changes in blood values, such as reduced numbers of white and red blood cells, reduced haemoglobin, reduced platelet count.

Not known (frequency cannot be estimated from the available data):
Abnormal colour, numbness and pain in fingers and toes (Raynaud's phenomenon).

Side effects related to the use of amlodipine
Very common (may affect more than 1 in 10 people):

• Swelling (oedema).

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

• Headache, dizziness, drowsiness (especially at the beginning of treatment).
• Awareness of heartbeat (palpitations), hot flushes.
• Abdominal pain, feeling unwell (nausea).
• Altered bowel habits, diarrhoea, constipation, indigestion.
• Fatigue, weakness.
• Swelling of the ankles, muscle cramps.
• Visual disturbances, double vision.

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

• Mood changes, anxiety, depression, insomnia.
• Tremor, taste disturbances, fainting.
• Numbness or tingling sensation in limbs, loss of pain sensation.
• Ringing in the ears (tinnitus).
• Low blood pressure.
• Stuffy or runny nose (rhinitis).
• Cough.
• Dry mouth, vomiting (feeling sick).
• Hair loss, increased sweating, itching, red spots on the skin, skin discoloration.
• Urinary problems, increased need to urinate at night, increased frequency of urination.
• Inability to achieve an erection; discomfort or breast enlargement in men.
• Pain, feeling unwell.
• Joint or muscle pain, back pain.
• Weight gain or weight loss.

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

• Confusion.

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

• Decreased number of white blood cells, decreased platelet count in the blood, which may lead to unusual bruising or easy bleeding (damage to red blood cells).
• High blood sugar (hyperglycaemia).
• A nerve disorder that may cause muscle weakness, tingling or numbness.
• Swelling of the gums.
• Abdominal swelling (gastritis).
• Abnormal liver function, increased liver enzymes, which may lead to abnormal test results.
• Increased muscle tension.
• Inflammation of blood vessels, often with skin rash.
• Light sensitivity.

Not known (frequency cannot be estimated from the available data):
Tremor, rigid posture, facial masking, slow and clumsy movements, unbalanced gait.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform 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 Perindopril 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/blister after EXP.
The expiry date refers to the last day of that month.
Do not store above 30°C. Keep in the original packaging to
protect the medicine from light and moisture.
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 Perindopril and Amlodipine Zentiva contains
The active substances are perindopril erbumine and amlodipine besilate.
Perindopril and Amlodipine Zentiva 4 mg/5 mg: Each tablet contains 4 mg of perindopril erbumine,
equivalent to 3.338 mg perindopril, and 5 mg of amlodipine (as besilate).
Perindopril and Amlodipine Zentiva 4 mg/10 mg: Each tablet contains 4 mg of perindopril erbumine,
equivalent to 3.338 mg perindopril, and 10 mg of amlodipine (as besilate).
Perindopril and Amlodipine Zentiva 8 mg/5 mg: Each tablet contains 8 mg of perindopril erbumine,
equivalent to 6.676 mg perindopril, and 5 mg of amlodipine (as besilate).
Perindopril and Amlodipine Zentiva 8 mg/10 mg: Each tablet contains 8 mg of perindopril erbumine,
equivalent to 6.676 mg perindopril, and 10 mg of amlodipine (as besilate).
The other ingredients are microcrystalline cellulose, calcium hydrogen phosphate dihydrate, sodium
croscarmellose, anhydrous colloidal silica and magnesium stearate.

Description of the appearance of Perindopril and Amlodipine Zentiva and package contents
Perindopril and Amlodipine Zentiva 4 mg/5 mg: Tablets are white to almost white, round, with "4/5" engraved on one side.
Perindopril and Amlodipine Zentiva 4 mg/10 mg: Tablets are white to almost white, round, with "4/10" engraved on one side.
Perindopril and Amlodipine Zentiva 8 mg/5 mg: Tablets are white to almost white, round, with "8/5" engraved on one side.
Perindopril and Amlodipine Zentiva 8 mg/10 mg: Tablets are white to almost white, round, with "8/10" engraved on one side.

Pack sizes:
Perindopril and Amlodipine Zentiva 4 mg/5 mg: 10, 15, 30, 90 tablets.
Perindopril and Amlodipine Zentiva 4 mg/10 mg, 8 mg/5 mg, 8 mg/10 mg: 30, 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Zentiva Italia S.r.l.
Viale L. Bodio, 37/B
20158 Milano
Italy

Manufacturer
ZENTIVA, k.s.
U Kabelovny 130,
Dolní Měcholupy
102 37 Praha 10
Czech Republic

UAB “Oriola Vilnius”
Laisvės pr. 75
06144 Vilnius
Lithuania

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

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