Perindopril

Package leaflet: Information for the patient

Perindopril, 2 mg, tablets
Perindopril, 4 mg, tablets
tert-Butylamini perindoprilum
Please read carefully all the information in this leaflet before taking the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse effects, including any adverse effects not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Perindopril is and what it is used for

The active substance in Perindopril tablets belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors.
Perindopril tablets are used:

• for the treatment of high blood pressure (hypertension),
• for the treatment of symptomatic heart failure (a condition in which the heart is unable to pump enough blood to meet the body's needs),
• to reduce the risk of cardiovascular events such as heart attack in patients with stable coronary artery disease (a condition in which blood flow to the heart is reduced or blocked), and in patients who have had a heart attack and/or undergone a procedure to improve blood supply to the heart, by dilating the blood vessels supplying the heart.

2. Important information before taking Perindopril

When not to take Perindopril

• if you are allergic to perindopril, any other ACE inhibitor, or any of the other ingredients of this medicine (listed in section 6);
• if you have previously experienced hypersensitivity reactions with sudden swelling of the lips, face, neck, and possibly hands and feet, or with breathing difficulties or hoarseness (angioedema) after taking an ACE inhibitor;
• if you have a history of angioedema (vascular swelling), or if a family member has had angioedema;
• after the 3rd month of pregnancy (it is also advisable to avoid using Perindopril during early pregnancy – see section "Pregnancy");
• if you have diabetes or kidney problems and are being treated with a blood pressure-lowering medicine containing aliskiren;
• if you are undergoing dialysis or another form of blood filtration. Depending on the device used, perindopril may not be suitable for you;
• if you have kidney disorders that reduce blood supply to the kidneys (renal artery stenosis);
• if you are taking or currently using sacubitril with valsartan, a medicine used to treat certain types of chronic (long-term) heart failure in adults, because this increases the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat).

Warnings and precautions

Before starting Perindopril, discuss it with your doctor or pharmacist.
Perindopril may not be suitable for you, or you may require regular health monitoring. Therefore, before starting treatment, inform your doctor if you have any of the following conditions:

• reduced or blocked blood flow through the heart (stable coronary artery disease);
• thickening of the heart muscle or heart valve problems;
• narrowing of the artery supplying blood to the kidneys (renal artery stenosis);
• abnormally high blood levels of a hormone called aldosterone (primary hyperaldosteronism);
• diabetes;
• kidney, liver, or heart disease;
• undergoing dialysis or recent kidney transplantation;
• following a low-salt diet, or experiencing severe vomiting or diarrhoea, or taking diuretics (water tablets);
• taking lithium, medicines used to treat mania or depression;
• taking potassium supplements or potassium-containing salt substitutes, or other medicines that may increase potassium levels in plasma, e.g. heparin;
• undergoing cholesterol removal from the body using a special device (LDL apheresis);
• undergoing or planning allergen immunotherapy (desensitisation) for bee or wasp venom;
• having a collagen disease such as systemic lupus erythematosus or scleroderma;
• receiving immunosuppressive medicines;
• uncontrolled blood pressure due to your race (particularly in patients of Black African origin);
• undergoing surgery or general anaesthesia;
• having cerebrovascular disease;
• if you are taking any of the following medicines, which may increase the risk of angioedema (rapid swelling of the skin in areas such as the throat):
  • racecadotril, a medicine used to treat diarrhoea,
  • medicines used to prevent organ transplant rejection or to treat cancer (e.g. sirolimus, everolimus, temsirolimus),
  • vildagliptin, a medicine used to treat diabetes.
• if you are taking any of the following medicines for high blood pressure:
  • an angiotensin II receptor antagonist (ARB) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes,
  • aliskiren.

Angioedema

Angioedema (a severe allergic reaction; symptoms include swelling of the face, lips, tongue or throat, difficulty swallowing or breathing) has been reported in patients treated with ACE inhibitors, including Perindopril. This reaction may occur at any time during treatment. If you experience such symptoms, stop taking Perindopril immediately and contact your doctor without delay. See also section 4.
You must inform your doctor if you think you are (or might be) pregnant. Perindopril is not recommended during early pregnancy and must not be taken after the 3rd month of pregnancy, as it may cause serious harm to the unborn child if used during this period (see section on pregnancy).

Children and adolescents

The use of perindopril in children and adolescents under 18 years of age is not recommended.

Perindopril with other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Do not take over-the-counter medicines without consulting your doctor. This includes in particular:

• cold remedies containing pseudoephedrine or phenylephrine as the active ingredient;
• painkillers, including acetylsalicylic acid (the substance found in many medicines used to relieve pain and reduce fever, as well as to prevent blood clots);
• potassium supplements;
• potassium-containing salt substitutes.

Inform your doctor if you are taking any of the following medicines to ensure that it is safe to take Perindopril at the same time:

• other medicines used to treat high blood pressure and/or heart failure, including diuretics (water tablets);
• potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (e.g. trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole, used for bacterial infections; cyclosporine or tacrolimus, immunosuppressive medicines used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots);
• potassium-sparing medicines used in heart failure: eplerenone and spironolactone at doses of 12.5 mg to 50 mg per day;
• medicines used to treat irregular heart rhythm (procainamide);
• medicines used to treat diabetes (insulin or oral antidiabetic medicines such as vildagliptin);
• baclofen (used to treat muscle stiffness in conditions such as multiple sclerosis);
• medicines used to treat gout (allopurinol);
• non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac, including acetylsalicylic acid used for pain relief;
• vasodilating medicines, including nitrates;
• estramustine (used in the treatment of cancer);
• medicines that stimulate certain parts of the nervous system (sympathomimetics), such as ephedrine, noradrenaline, or adrenaline;
• medicines used to treat mania or depression (lithium);
• medicines used for psychiatric disorders such as depression, anxiety, schizophrenia, or other psychoses (tricyclic antidepressants and antipsychotics);
• gold salts administered by injection for the treatment of arthritis (sodium aurothiomalate);
• medicines most commonly used to treat diarrhoea (racecadotril) or medicines frequently used to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, or other medicines belonging to the so-called mTOR inhibitors). See section "Warnings and precautions".

Your doctor may need to adjust your dose and/or take other precautions:

• if you are taking an angiotensin II receptor antagonist (ARB) or aliskiren (see also information under the headings "When not to take Perindopril" and "Warnings and precautions").

Taking Perindopril with food, drink and alcohol

It is recommended to take Perindopril before meals to reduce the influence of food on the medicine's action.

Pregnancy and breastfeeding

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

Pregnancy
Inform your doctor if you suspect (or are planning) pregnancy. Your doctor will usually advise stopping Perindopril before planned pregnancy or immediately after confirming pregnancy, and will recommend an alternative medicine. Perindopril is not recommended during early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child if used during this period.

Breastfeeding
Inform your doctor if you are breastfeeding or plan to breastfeed. Perindopril is not recommended during breastfeeding, especially when breastfeeding a newborn or premature infant. Your doctor may recommend an alternative medicine.

Driving and operating machinery

Perindopril usually does not affect alertness, but some patients may experience dizziness or weakness related to low blood pressure. Therefore, your ability to drive or operate machinery may be impaired.

Perindopril contains lactose and sodium

If you have been previously diagnosed with intolerance to certain sugars, you should consult your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Perindopril

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you are unsure,
you should consult your doctor or pharmacist.
The usual dose for the treatment of high blood pressure is 4 mg of perindopril (1 tablet of 4 mg Perindopril)
once daily. If necessary, the dose may be increased to 8 mg of perindopril (2 tablets of 4 mg Perindopril)
once daily.
The usual dose for the treatment of symptomatic heart failure is 2 mg of perindopril (1 tablet of 2 mg Perindopril)
once daily; if necessary, this dose may be increased to 4 mg of perindopril (1 tablet of 4 mg Perindopril)
once daily.
The usual dose for the treatment of stable coronary artery disease is 4 mg of perindopril (1 tablet of 4 mg Perindopril)
once daily; if necessary, this dose may be increased to 8 mg of perindopril (2 tablets of 4 mg Perindopril)
once daily.
The tablets should be taken with a glass of water, preferably at the same time each day, in the morning, before a meal.
Depending on treatment outcomes, your doctor will adjust the dosage individually for each patient.
Dosage may be lower than usual, depending on the doctor's decision: in elderly patients, in patients with
renal impairment, in patients with high blood pressure caused by narrowing of the artery supplying blood to the kidneys
(renovascular hypertension), in patients concurrently treated with diuretics (water tablets), in patients with
hypertension in whom diuretic therapy cannot be discontinued, in patients with severe heart failure, and in patients
treated with vasodilating medicines.
The duration of treatment will be determined by the doctor based on the patient's health condition.
Use in children and adolescents
The efficacy and safety of this medicine in children have not been established. Therefore, its use is not recommended
in this age group.
If you feel that the effect of the medicine is too strong or too weak, you should consult your doctor or pharmacist.
Taking more Perindopril than recommended
If you have taken too many tablets, seek medical advice immediately from your doctor or pharmacist.
The most likely symptom of overdose is a sudden drop in blood pressure (hypotension). Other possible symptoms may include:
rapid or slow heartbeat, unpleasant sensation of irregular and (or) stronger than usual heartbeat, increased rate and depth of breathing,
dizziness, anxiety, and (or) cough.
In case of a significant drop in blood pressure, lie down and elevate your legs so they are higher than your body, placing only a flat cushion under your head.
Missing a dose of Perindopril
It is important to take the medicine every day. However, if you forget to take one dose, simply continue taking the medicine as usual with the next dose.
Do not take a double dose to make up for a missed dose. If you have missed more than one dose, take the next dose as soon as possible, then continue taking the medicine according to the instructions.
Stopping treatment with Perindopril
Once treatment is discontinued, blood pressure may rise again, increasing the risk of complications related to hypertension, particularly affecting the heart, brain, and kidneys.
The condition of patients with heart failure may deteriorate to such an extent that hospitalization becomes necessary. Therefore, if you are considering stopping treatment with Perindopril, you should first discuss this with your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
You must stop taking this medicine and contact your doctor immediately if any of the following adverse effects occur, as they may be serious:

• swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema; see section 2 "Warnings and precautions") (uncommon – may occur in up to 1 in 100 patients);
• severe dizziness or fainting caused by low blood pressure (hypotension) (common – may occur in up to 1 in 10 patients);
• very rapid or irregular heartbeat, chest pain (angina) or heart attack (very rare – may occur in up to 1 in 10,000 patients);
• sudden weakness in the arms or legs, or difficulty speaking, which may be signs of stroke (very rare – may occur in up to 1 in 10,000 patients);
• sudden onset of wheezing, chest pain, shortness of breath or difficulty breathing (bronchospasm; uncommon – may occur in up to 1 in 100 patients);
• pancreatitis, which may cause severe upper abdominal pain radiating to the back and general malaise (very rare – may occur in up to 1 in 10,000 patients);
• yellowing of the skin or eyes (jaundice), which may be a sign of liver inflammation (very rare – may occur in up to 1 in 10,000 patients);
• rash, often starting with red, itchy spots on the face, arms or legs (erythema multiforme; very rare – may occur in up to 1 in 10,000 patients).

You should inform your doctor if you experience any of the following adverse effects:
Common adverse effects (may occur in less than 1 in 10 patients):

• headache, dizziness, sensation of spinning (vestibular vertigo), tingling or numbness in hands or feet (paresthesia),
• visual disturbances,
• ringing, buzzing, crackling or pulsating sounds in the ears (tinnitus),
• low blood pressure (hypotension) and symptoms related to hypotension,
• cough, shortness of breath,
• nausea, vomiting, abdominal pain, taste disturbances, indigestion, diarrhoea and constipation,
• rash, itching,
• muscle cramps,
• fatigue.

Uncommon adverse effects (may occur in less than 1 in 100 patients):

• hypoglycemia (very low blood sugar levels),
• high potassium levels in blood, transient after discontinuation of treatment,
• low sodium levels,
• mood disturbances, sleep disturbances,
• depression,
• drowsiness, fainting,
• palpitations, tachycardia,
• vasculitis (inflammation of blood vessels),
• wheezing (bronchospasm),
• dryness of the oral mucosa,
• hypersensitivity reaction with sudden swelling of the face, neck, lips, mucous membranes, tongue or throat (with hoarseness or shortness of breath), possibly also swelling of hands and feet (angioedema), urticaria,
• excessive sweating,
• photosensitivity reaction (increased skin sensitivity to sunlight), pemphigoid (an autoimmune skin disease, symptoms include large tense blisters),
• joint pain, muscle pain,
• kidney function disorders,
• inability to achieve or maintain an erection (impotence),
• chest pain, malaise, peripheral edema, fever,
• increased blood urea levels, increased blood creatinine levels,
• falls.

Rare adverse effects (may occur in less than 1 in 1,000 patients):

• exacerbation of psoriasis,
• abnormal laboratory test results: increased liver enzyme activity, elevated serum bilirubin levels,
• worsening of psoriasis,
• dark urine, nausea or vomiting, muscle cramps, confusion and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion),
• reduced urine output or absence of urine,
• sudden redness of the face and neck,
• acute renal failure.

Very rare adverse effects (may occur in less than 1 in 10,000 patients):

• decreased hemoglobin and hematocrit levels, thrombocytopenia, leukopenia/neutropenia, agranulocytosis or pancytopenia, hemolytic anemia in patients with congenital glucose-6-phosphate dehydrogenase deficiency,
• confusion,
• cardiac arrhythmias, chest pain (angina), myocardial infarction, and stroke probably secondary to excessive lowering of blood pressure in high-risk patients,
• lung inflammation with accumulation of a certain type of white blood cells (eosinophils) in lung tissue (eosinophilic pneumonia), inflammation of the nasal mucosa (rhinitis),
• pancreatitis,
• hepatitis,
• allergic rash presenting as pink-red flat spots (erythema multiforme).

Frequency unknown (frequency cannot be estimated from available data):

• bluish discoloration, numbness and pain in fingers or toes (Raynaud's phenomenon).

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store the medicine Perindopril

Keep the medicine out of the sight and reach of children.
Store in the original packaging.
Store at a temperature not exceeding 30°C.
Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the packaging and other information

What Perindopril contains

• The active substance is perindopril tert-butylamine. Perindopril, 2 mg and 4 mg tablets: Each tablet contains 2 mg or 4 mg of perindopril tert-butylamine.
• Other ingredients: monohydrate lactose, microcrystalline cellulose, sodium bicarbonate, colloidal anhydrous silica, magnesium stearate. See section 2 "Perindopril contains lactose".

What Perindopril looks like and contents of the pack
The 2 mg tablets are white, round, biconvex.
The 4 mg tablets are white, oblong, biconvex with bevelled edges and a central break-line on one side.
Pack sizes available:
30, 60 or 90 tablets in blister packs, packed in a cardboard box.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA-POLSKA Sp. z o.o., Równoległa 5, 02-235 Warsaw, Poland
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5
02-235 Warsaw
Tel. + 48 22 57 37 500