Patient Information Leaflet

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language
Co-Amlessa, 8 mg + 5 mg + 2.5 mg, tablets
tert-Butylamini perindoprilum + Amlodipinum + Indapamidum
Please read all of this leaflet carefully before taking this medicine, as it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual only. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

What Co-Amlessa is and what it is used for
Important information before taking Co-Amlessa
How to take Co-Amlessa
Possible side effects
How to store Co-Amlessa
Contents of the pack and other information

1. What Co-Amlessa is and what it is used for

Co-Amlessa is used to treat high blood pressure (hypertension). All three active substances help control high blood pressure. Patients already taking perindopril/indapamide and amlodipine as separate tablets may instead take a single tablet of Co-Amlessa containing all three components.
Co-Amlessa is a combination of three active substances: perindopril, indapamide, and amlodipine. Perindopril belongs to a group of medicines known as angiotensin-converting enzyme (ACE) inhibitors. Amlodipine is a calcium antagonist (belonging to a group of medicines called dihydropyridines). Indapamide is a diuretic.
In patients with high blood pressure, perindopril and amlodipine help relax blood vessels, allowing blood to flow more easily. Indapamide increases the amount of urine produced by the kidneys. Each of the active substances lowers blood pressure, and together they effectively control it.

2. Important information before using Co-Amlessa

When not to use Co-Amlessa

if the patient is allergic to perindopril or any other ACE inhibitor, indapamide or any other sulfonamide, amlodipine besylate or any other dihydropyridine, or to any of the other ingredients of this medicine (listed in section 6);
if the patient has experienced symptoms such as wheezing, facial or tongue swelling, intense itching or severe skin rashes during previous treatment with an ACE inhibitor, or if such symptoms occurred in the patient or a family member under any circumstances (a condition known as angioedema);
if the patient has liver disease or a condition called hepatic encephalopathy (a disease causing brain damage);
if the patient has severe kidney function impairment (creatinine clearance below 30 ml/min);
if the patient has severe kidney disease causing reduced blood supply to the kidneys (renal artery stenosis). Co-Amlessa 8 mg + 5 mg + 2.5 mg is contraindicated in severe or moderate kidney disease;
if the patient is undergoing dialysis or blood filtration by another method. Depending on the device used, Co-Amlessa may not be suitable;
if the patient has abnormally low or high blood potassium levels;
if untreated, unbalanced heart failure is suspected (symptoms include fluid retention and breathing difficulties);
if the patient has cardiogenic shock (a condition in which the heart cannot deliver enough blood to meet the body's needs), aortic stenosis (narrowing of the main blood vessel leaving the heart), or unstable angina (chest pain that may occur at rest);
if the patient has very low blood pressure (severe hypotension);
if the patient has heart failure (the heart is unable to pump blood strongly enough, leading to breathlessness and peripheral oedema, e.g. in legs, ankles or feet) following acute myocardial infarction;
if the patient is more than 3 months pregnant (use of Co-Amlessa is also not recommended in early pregnancy – see "Pregnancy and breastfeeding");
if the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medicine containing aliskiren;
if the patient is taking or has recently taken a medicine containing sacubitril and valsartan (used to treat certain types of chronic heart failure in adults), because this increases the risk of angioedema (rapid swelling of tissues beneath the skin, such as in the throat).

Warnings and precautions
Before starting Co-Amlessa, discuss this with your doctor or pharmacist.

If the patient recently suffered a myocardial infarction;
If the patient has aortic stenosis (narrowing of the main blood vessel leaving the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the artery supplying blood to the kidney);
If the patient has heart failure or any other heart disease;
If the patient has kidney disease or is undergoing dialysis;
If the patient has experienced a significant increase in blood pressure (hypertensive crisis);
If the patient has muscle disorders, including muscle pain, tenderness, weakness or cramps;
If the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
If the patient has liver disorders;
If the patient has a collagen disease such as systemic lupus erythematosus or scleroderma;
If the patient has atherosclerosis (hardening of the arteries);
If the patient has hyperparathyroidism;
If the patient has gout;
If the patient has diabetes;
If the patient is on a low-salt diet or uses potassium-containing salt substitutes;
If the patient is taking lithium or potassium-sparing diuretics (spironolactone, triamterene) or potassium supplements, as their use with Co-Amlessa is not recommended (see "Co-Amlessa with other medicines");
If the patient is elderly and requires a dose increase;
If the patient has previously experienced photosensitivity reactions;
If the patient develops a severe allergic reaction with swelling of the face, lips, mouth, tongue or throat, causing difficulty in swallowing or breathing (angioedema). Swelling may occur at any time during treatment. If such symptoms occur, stop treatment immediately and consult a doctor;
If the patient is 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 the patient has kidney problems related to diabetes,
aliskiren. The treating doctor may monitor kidney function, blood pressure and blood electrolyte levels (e.g. potassium) at regular intervals. See also information under "When not to use Co-Amlessa".
If the patient is of Black race – in such cases, there may be a higher risk of angioedema, and the medicine may be less effective in lowering blood pressure compared to patients of other races;
If the patient is undergoing dialysis with high-flux membranes;
If the patient is taking any of the following medicines, which increase the risk of angioedema (rapid swelling of the skin in areas such as the throat):
racecadotril (used to treat diarrhoea),
sirolimus, everolimus, temsirolimus and other medicines belonging to mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment),
linagliptin, saxagliptin, sitagliptin, vildagliptin used in diabetes treatment,
sacubitril (available in a combination medicine containing sacubitril and valsartan), used in the treatment of chronic heart failure.

Angioedema
Angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat and difficulty in swallowing or breathing) has been reported in patients treated with ACE inhibitors, including Co-Amlessa. This reaction may occur at any time during treatment. If such symptoms occur, discontinue Co-Amlessa immediately and contact a doctor without delay. See also section 4.
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning pregnancy. Use of Co-Amlessa is not recommended during early pregnancy and must not be used after 3 months of pregnancy, as it may seriously harm the unborn child if taken during this period (see section "Pregnancy and breastfeeding").
While taking Co-Amlessa, inform your doctor or healthcare provider:

if you develop a dry cough;
if you are to undergo general anaesthesia and/or surgery;
if you have recently had diarrhoea or vomiting, or if you are dehydrated;
if you are to undergo dialysis or LDL apheresis (removal of cholesterol from the blood using a special device);
if you are to undergo desensitisation to reduce allergic reactions following bee or wasp stings;
if you are to undergo imaging tests requiring iodine-containing contrast agents (substances that make organs such as kidneys or stomach visible in X-ray examinations);
if you experience blurred vision or eye pain. These may be symptoms of fluid accumulation in the uvea (excessive fluid build-up between the choroid and sclera) or increased intraocular pressure – they may occur from several hours to weeks after taking Co-Amlessa. Untreated, they may lead to permanent vision loss. Patients with a history of penicillin or sulfonamide allergy may be at higher risk of developing this condition. Discontinue
use of Co-Amlessa and consult a doctor.

Athletes should be informed that Co-Amlessa contains an active substance (indapamide) that
may lead to a positive result in anti-doping tests.
Children and adolescents
Co-Amlessa is not recommended for use in children and adolescents.
Co-Amlessa with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Avoid using Co-Amlessa with:

lithium (used to treat depression);
aliskiren (a medicine used to treat high blood pressure) in patients who do not have diabetes or kidney dysfunction;
potassium-sparing diuretics (e.g. triamterene, amiloride), potassium salts, and other medicines that may increase potassium levels in the body (e.g. trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole, used for bacterial infections; cyclosporine, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots);
sacubitril/valsartan (used to treat chronic heart failure). See sections "When not to use Co-Amlessa" and "Warnings and precautions";
estramustine (used to treat cancer);
other medicines used to treat high blood pressure: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists.

Other medicines may affect the action of Co-Amlessa.
Inform your doctor if you are taking any of the following medicines, as special care may be needed:

other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (ARBs) or aliskiren (see also sections "When not to use Co-Amlessa" and "Warnings and precautions"), or diuretics (medicines that increase urine output by the kidneys);
potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses of 12.5 mg to 50 mg per day;
anaesthetics;
iodine-containing contrast agents;
moxifloxacin, sparfloxacin, rifampicin, erythromycin, clarithromycin (antibiotics used to treat infections);
methadone (used to treat addiction);
procainamide (used to treat heart rhythm disorders);
allopurinol (used to treat gout);
antihistamines used to treat allergic reactions such as hay fever (e.g. mizolastine, terfenadine or astemizole);
corticosteroids (used to treat various conditions, including asthma and rheumatoid arthritis);
immunosuppressive medicines used to treat autoimmune disorders or to prevent organ rejection after transplantation (e.g. cyclosporine);
ritonavir, indinavir, nelfinavir (protease inhibitors used to treat HIV infection);
medicines used to treat cancer;
ketoconazole, itraconazole (antifungal medicines);
halofantrine (used to treat certain forms of malaria);
pentamidine (used to treat pneumonia);
gold in injectable medicines (used to treat rheumatoid arthritis);
vincamine (used to treat symptomatic cognitive disorders in the elderly, including memory problems);
bepridil, verapamil, diltiazem (heart medicines);
medicines used to treat heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis, bretylium);
cisapride, difenamid (used to treat gastrointestinal disorders);
digoxin or other cardiac glycosides (used to treat heart disease);
baclofen (used to treat muscle stiffness, e.g. in multiple sclerosis);
medicines used to treat diabetes, e.g. insulin, metformin or gliptins;
calcium, including calcium supplements;
stimulant laxatives (e.g. senna);
non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or high doses of salicylates (e.g. acetylsalicylic acid);
amphotericin B in injectable medicines (used to treat severe fungal infections);
medicines used to treat psychiatric disorders, e.g. depression, anxiety, schizophrenia (e.g. tricyclic antidepressants, neuroleptics such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol);
tetracosactide (used to treat Crohn's disease);
trimethoprim (used to treat infections);
vasodilators, including nitrates;
medicines used to treat low blood pressure, shock or asthma (e.g. ephedrine, noradrenaline or adrenaline);
Hypericum perforatum (St. John's wort);
dantrolene (used intravenously for serious body temperature disorders);
tacrolimus (used to modify the patient's immune system);
simvastatin (a medicine that lowers cholesterol);
cyclosporine (an immunosuppressant);
medicines most commonly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus or other mTOR inhibitors). See section "Warnings and precautions".

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

if you are taking an angiotensin II receptor antagonist (ARB) or aliskiren (see also information under "When not to use Co-Amlessa" and "Warnings and precautions").

Taking Co-Amlessa with food and drink
Co-Amlessa should be taken before a meal.
Patients taking Co-Amlessa should not consume grapefruit juice or grapefruits, as they may increase blood levels of the active substance amlodipine, potentially leading to an unexpected intensification of Co-Amlessa's blood pressure-lowering effect.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a child, consult your doctor or pharmacist before using this medicine.
Pregnancy
Inform your doctor if you are pregnant, suspect pregnancy, or are planning pregnancy. Your doctor will usually advise stopping Co-Amlessa before a planned pregnancy or immediately after pregnancy is confirmed, and will recommend an alternative medicine. Co-Amlessa is not recommended during the first trimester of pregnancy and must not be used after 3 months of pregnancy, as it may seriously harm the unborn child if taken during this period.
Breastfeeding
It has been shown that small amounts of amlodipine pass into human milk.
Inform your doctor if you are breastfeeding or intend to breastfeed. Co-Amlessa is not recommended for breastfeeding women. Your doctor may recommend an alternative medicine if you wish to continue breastfeeding, especially if the infant is a newborn or premature. Consult your doctor immediately.
Driving and using machines
Co-Amlessa does not affect concentration, but dizziness or weakness due to low blood pressure may occur, which could impair the ability to drive or operate machinery. Do not drive or operate machinery until you know how Co-Amlessa affects you individually.
Co-Amlessa contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".

3. How to use Co-Amlessa

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you have any doubts,
you should consult your doctor or pharmacist.
Co-Amlessa is available in the following strengths: 2 mg + 5 mg + 0.625 mg; 4 mg + 5 mg +
1.25 mg; 4 mg + 10 mg + 1.25 mg; 8 mg + 5 mg + 2.5 mg; 8 mg + 10 mg + 2.5 mg.
The recommended dose is one tablet daily. It is recommended to take the medicine in the morning before a meal.
The tablet should be swallowed with a glass of water.
Your doctor will decide which strength is appropriate for you. Co-Amlessa is intended for patients
already being treated with perindopril/indapamide and amlodipine as separate tablets.
Taking more Co-Amlessa than recommended
If you take more medicine than recommended, contact your doctor immediately or go to the nearest hospital emergency department.
The most likely adverse effect following overdose is hypotension. If there is a significant drop in blood pressure (symptoms such as dizziness or fainting), you should lie down with your legs raised.
Breathlessness caused by fluid accumulation in the lungs (pulmonary oedema) may occur up to 24–48 hours after taking the medicine.
Missing a dose of Co-Amlessa
It is important to take the medicine every day, as this ensures effective therapy. If you miss a dose of Co-Amlessa, take the next dose at your usual time.
Do not take a double dose to make up for the missed tablet.
Stopping Co-Amlessa treatment
Since antihypertensive therapy is usually long-term, you should talk to your doctor before stopping the medicine.
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.
If the patient experiences any of the following serious adverse effects, treatment with this medicine should be stopped and medical advice should be sought immediately:

Severe dizziness or fainting due to low blood pressure (common – may occur in up to 1 in 10 patients),
Bronchospasm (feeling of tightness in the chest, wheezing and shortness of breath) (uncommon – may occur in up to 1 in 100 patients),
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 skin reactions, including erythema multiforme (skin rash often starting with red, itchy spots on the face, arms or legs) or severe skin rash, urticaria, redness of the entire body, intense itching, blistering, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome), or other allergic reactions (very rare – may occur in up to 1 in 10,000 patients),
Cardiovascular disorders (heart rhythm disturbances, angina pectoris (chest pain radiating to the jaw and back, caused by physical exertion), myocardial infarction) (very rare – may occur in up to 1 in 10,000 patients),
Weakness of arms or legs, or speech disturbances, which may be signs of stroke (very rare – may occur in up to 1 in 10,000 patients),
Pancreatitis, which may cause severe upper abdominal pain radiating to the back, accompanied by a very poor general condition (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),
Life-threatening heart rhythm disturbances (frequency unknown),
Brain disease caused by liver disease (hepatic encephalopathy) (frequency unknown),
Muscle weakness, cramps, tenderness or pain, especially if the patient simultaneously feels unwell or has a high temperature, which may be due to abnormal muscle breakdown (rhabdomyolysis) (frequency unknown).

Adverse effects listed by decreasing frequency of occurrence may include:

Very common (may occur in more than 1 in 10 patients): swelling (fluid retention).
Common (may occur in up to 1 in 10 patients): skin reactions in patients prone to allergic and asthmatic reactions, low blood potassium levels, headache, dizziness, balance disorders, tingling and numbness, drowsiness, visual disturbances, feeling of "emptiness" in the head due to low blood pressure, tinnitus (perception of noise in the ears), low blood pressure, palpitations (very fast heartbeat), sudden redness of the skin, especially the face (feeling of warmth or heat in the face), shortness of breath, cough, gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, changes in bowel rhythm, indigestion or digestive disorders, diarrhoea, constipation), dryness of the oral mucosa, allergic reactions (such as skin rashes, itching), muscle cramps, ankle swelling, weakness, feeling of fatigue.
Uncommon (may occur in up to 1 in 100 patients): rhinitis (nasal congestion or runny nose), increased eosinophil count (a type of white blood cell), hypoglycaemia (very low blood sugar), changes in laboratory test results: high blood potassium levels, transient after discontinuation of treatment, low blood sodium levels, which may cause dehydration and low blood pressure, mood changes, sleep disturbances, insomnia, tremor, loss of pain sensation, tachycardia (fast heartbeat), heart rhythm disturbances, vasculitis (inflammation of blood vessels), bronchospasm (tightness in the chest, wheezing and shortness of breath), angioedema (symptoms such as wheezing, swelling of the face or tongue), urticaria, formation of blisters on the skin, purpura (red spots on the skin), skin discoloration, sweating, alopecia, red or discoloured skin patches, photosensitivity reactions (increased skin sensitivity to sunlight), back, muscle or joint pain, kidney disorders, increased frequency of urination (especially at night), impotence (inability to achieve or maintain an erection), breast enlargement in men, chest pain, pain, general malaise, fever, increased blood urea levels, increased blood creatinine levels, weight gain or weight loss, falls, fainting.

In patients with systemic lupus erythematosus (a type of collagenosis), symptoms may worsen.

Rare (may occur in up to 1 in 1,000 patients): disorientation, exacerbation of psoriasis, acute kidney failure, reduced or absent urine output, changes in laboratory test results: increased calcium levels, increased liver enzyme activity, high serum bilirubin levels, dark urine, nausea or vomiting, muscle cramps, disorientation and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion), low blood chloride levels, low blood magnesium levels.
Very rare (may occur in up to 1 in 10,000 patients): changes in blood parameters such as decreased white blood cell and red blood cell count, decreased haemoglobin and haematocrit values, decreased platelet count, high blood glucose levels (hyperglycaemia), cardiovascular disorders (e.g. dyspnoea, myocardial infarction, stroke), eosinophilic pneumonia (a rare type of lung inflammation), gum swelling, pancreatitis, abdominal distension (gastritis), peripheral neuropathy (a disease causing loss of sensation, pain, inability to control muscles), severe skin symptoms (e.g. erythema multiforme). Abnormal liver function, hepatitis, yellowing of the skin (jaundice), increased liver enzyme activity detected in blood tests.
Unknown (frequency cannot be estimated from available data): Abnormal heart function detected on ECG, changes in laboratory test results: high uric acid levels, myopia, blurred vision, visual impairment or eye pain due to increased pressure (possible signs of fluid accumulation in the avascular membrane surrounding the eye – excessive accumulation of fluid between the choroid and sclera – or acute angle-closure glaucoma), life-threatening heart rhythm disturbances (torsade de pointes). In patients with liver impairment (liver disorders), there is a risk of developing hepatic encephalopathy (a disease causing brain damage). Tremor, postural rigidity, facial masking, slowed movements and shuffling gait. 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, 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.
Reporting adverse effects helps to gather more information on the safety of using the medicine.

5. How to store Co-Amlessa

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.
Store below 30°C.
Keep in the original packaging to protect from light and moisture.
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 pack and other information

What Co-Amlessa contains

The active substances in Co-Amlessa are perindopril tert-butylamine, amlodipine (as amlodipine besylate) and indapamide. Each tablet contains 8 mg of perindopril tert-butylamine, 5 mg of amlodipine (as amlodipine besylate) and 2.5 mg of indapamide.
Other ingredients are: microcrystalline cellulose (E 460), pregelatinized maize starch (type 1500), sodium carboxymethyl starch (type A), calcium chloride dihydrate, sodium hydrogen carbonate, colloidal hydrated silica, magnesium stearate (E 470b). See section 2 "Co-Amlessa contains sodium".

What Co-Amlessa looks like and contents of the pack
White to almost white, round, biconvex tablets with bevelled edges, 9 mm in diameter.
Pack sizes: 30 and 60 tablets in blisters OPA/Al/PVC/Al, in a cardboard box.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Latvia, country of export:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
Manufacturer:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
KRKA Polska Sp. z o.o., ul. Równoległa 5, 02-235 Warsaw, Poland
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany
Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing authorisation number in Latvia, country of export: 14-0028
Parallel import authorisation number: 302/24