Entelromesis 75 mg Film-Coated Tablets

ENTELROMESIS contains the active substances clopidogrel and acetylsalicylic acid (aspirin), which belongs to a group of medicines called antiplatelet medicines. Platelets are very small structures in the blood which clump together during blood clotting. By preventing this clumping in some types of blood vessels, antiplatelet medicines reduce the chances of blood clots forming (a process called atherothrombosis). ENTELROMESIS is used to treat adult patients who have suffered with angina (a severe type of chest pain), or who have had a heart attack by preventing blood clots forming and reducing the risk of further atherothrombotic events (such as stroke, heart attack, or death).

Do not take ENTELROMESIS:

• if you are hypersensitive (allergic) to clopidogrel, acetylsalicylic acid (aspirin) or to any of the ingredients of ENTELROMESIS (see section 6)
• if you are allergic to other medicines called non-steroidal anti-inflammatory drugs (NSAIDs) usually used to treat painful and/or inflammatory conditions of muscles and joints
• if you have been diagnosed with mastocytosis (a condition where certain immune cells, called mast cells, build up under the skin and/or in the bones) as taking ENTELROMESIS may cause a severe hypersensitivity (allergic) reaction
• if you have a history of gastrointestinal bleeding, gastrointestinal ulcer or gastrointestinal perforation related to previous use of an NSAID
• if you have a medical condition that is currently causing bleeding such as a stomach ulcer, haemophilia or bleeding within the brain or bowel or a history of such a condition
• if you are under the age of 18 years
• if you have a medical condition that includes the combination of asthma, nasal discharge (runny nose) and polyps (a type of growth in the nose)
• if you have heart problems which can cause shortness of breath or ankle swelling (heart failure)
• if you suffer from severe liver disease
• if you suffer from severe kidney disease
• if you suffer from a dysfunction of, or reduction in, blood platelets which increases risk of bleeding and bruising (thrombocytopenia)
• if you are pregnant or breastfeeding your baby.

Warnings and precautions

Take special care with ENTELROMESIS: Inform your doctor or health care provider before taking ENTELROMESIS if any of the following apply to you, if:

• you develop a medical condition (also known as Thrombotic Thrombocytopenic Purpura or TTP) that includes fever and bruising under the skin that may appear as red pinpoint dots, with or without unexplained extreme tiredness, confusion, yellowing of the skin or eyes (jaundice) (see section 4)
• you start retaining fluid (symptoms include swelling of feet, ankles and hands, stiff joints, rapid weight gain over a few days or weeks, unexplained weight fluctuations, when pressed, the skin may hold the indent for a few seconds)
• you have had a clot in an artery of your brain (ischaemic stroke) which occurred in the last seven days
• you have a history of asthma or allergic reactions including allergy to any medicine used to treat your disease
• if you have a history of heart problems which can cause shortness of breath or ankle swelling (heart failure) or high blood pressure
• you at risk of bleeding, including:
• a medical condition that puts you at risk of internal bleeding (such as a stomach ulcer)
• a blood disorder that makes you prone to internal bleeding (bleeding inside any tissues, organs or joints of your body)
• a recent serious injury
• a recent surgery (including dental)
• a planned surgery (including dental) in the next seven days
• a planned spinal, epidural anaesthetic or lumbar puncture in the next seven days
• you have gout
• you drink alcohol, because of the increased risk of bleeding or gastrointestinal injury
• you have a condition known as glucose-6-phosphate dehydrogenase (G6PD) deficiency because of the risk of a particular form of anaemia (low number of red blood cells)
• you have a history of inflammation of the colon which causes abdominal pain or diarrhoea or any other gastrointestinal conditions
• you are taking any other type of medication (see Other medicines with ENTELROMESIS)
• you are a CYP2C19 poor metaboliser (you have very little or no function of the CYP2C19 enzyme, used to break down medicines, in your body)
• you are taking water tablets (used to treat high blood pressure and swelling associated with heart failure, renal failure, or liver disease)
• you are hypersensitive (allergic) to other antiplatelet medicines used to prevent clots (such as ticlopidine or prasugrel)
• you have kidney or liver disease.

Before surgery is planned (including dental), inform your doctor and anaesthetist that you are taking ENTELROMESIS. Inform your doctor immediately should you develop any stomach or abdominal pain or bleeding in the stomach or bowels (red stools or black stools) whilst taking ENTELROMESIS. If you cut or injure yourself, it may take longer than usual for bleeding to stop. This is linked to the way your medicine works as it prevents the ability of blood clots to form. For minor cuts and injuries e.g., cutting yourself or shaving, this is usually of no concern. However, if you are concerned by your bleeding, you should contact your doctor straightaway (see section 4). Your doctor may order blood tests before or during treatment.

Children and adolescents

ENTELROMESIS is not intended for use in children or adolescents less than 18 years of age. There is a possible association between acetylsalicylic acid (ASA) and Reye’s Syndrome when products containing ASA are given to children or adolescents with a viral infection. Reye’s Syndrome is a very rare disease which can be fatal.

Other medicines and ENTELROMESIS

Always tell your healthcare provider if you are taking any other medicine. (This includes complementary or traditional medicines.) Some other medicines may influence the use of ENTELROMESIS or vice versa. Inform your doctor if you take any of the following:

• medicine that may increase your risk of bleeding such as:
• oral anticoagulants, thrombolytics, medicines used to reduce blood clotting
• aspirin or another non-steroidal anti-inflammatory medicine usually used to treat painful and/or inflammatory conditions of muscle or joints
• heparin or any other injectable medicine used to reduce blood clotting
• ticlopidine or prasugrel or other antiplatelet medicines used to reduce blood clotting
• a selective serotonin re-uptake inhibitor (SSRI) (e.g. fluoxetine or fluvoxamine), medicines usually used to treat depression
• rifampicin (used to treat severe infections)
• omeprazole, esomeprazole or cimetidine, medicines to treat upset stomach or to prevent gastric reflux (heartburn)
• methotrexate, a medicine used to treat severe joint disease (rheumatoid arthritis) or skin disease (psoriasis)
• probenecid, benzbromarone, or sulfinpyrazone, medicines used to treat gout
• fluconazole, voriconazole, ciprofloxacin or chloramphenicol, medicines to treat bacterial and fungal infections
• moclobemide, a medicine to treat depression
• nicorandil, a medicine to treat cardiac chest pain
• repaglinide, a medicine to treat diabetes
• paclitaxel, a medicine to treat cancer
• metamizole, a medicine to treat pain, muscle spasms and fever
• corticosteroids, used to treat inflammation (such a cortisone, prednisolone, hydrocortisone)
• acetazolamide, a medicine to treat glaucoma
• the varicella vaccine, a medicine to prevent chickenpox or shingles, within 6 weeks of taking ENTELROMESIS, or if you have an active chickenpox or shingles infection
• levothyroxine, a medicine to treat low thyroid activity
• valproic acid, valproate and carbamazepine, medicines to treat some forms of epilepsy
• tenofovir, an antiretroviral medicine used in the treatment of HIV
• rosuvastatin (used to lower your cholesterol level)
• opioids: while you are treated with clopidogrel, you should inform your doctor before being prescribed any opioids (used to treat severe pain, e.g. morphine).

Alcohol: The consumption of alcohol may affect how well ENTELROMESIS works; it may increase blood loss and stomach irritation. Please ask your doctor for more information. Alcohol should be used with caution if you are taking ENTELROMESIS. You should stop other clopidogrel treatments and talk to your doctor before taking any other using other aspirin containing medicines while you are taking ENTELROMESIS.

ENTELROMESIS with food and drink: ENTELROMESIS can be taken with or without food. Alcohol should be used with caution if you are taking ENTELROMESIS (see Other medicine with ENTELROMESIS).

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding your baby, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist or other healthcare provider for advice before using ENTELROMESIS. You should not take ENTELROMESIS if you are pregnant or breastfeeding your baby (see section 2).

Do not share medicines prescribed for you with any other person. Always use ENTELROMESIS exactly as your doctor has told you. You should check with your doctor or pharmacist if you are unsure.

Adults: The usual dose is one tablet of ENTELROMESIS per day to be taken orally with a glass of water, with or without food. You should take your medicines at the same time each day. You should take ENTELROMESIS for as long as your doctor continues to prescribe it.

Children: ENTELROMESIS is not prescribed for children. Your doctor will tell you how long your treatment with ENTELROMESIS will last. Do not stop treatment early.

If you have the impression that the effect of ENTELROMESIS is too strong or too weak, tell your doctor or pharmacist.

If you take/use more ENTELROMESIS than you should: In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison control centre.

If you forget/use to take ENTELROMESIS: If you forget to take ENTELROMESIS, but remember within 12 hours of your usual time, take your tablet straightaway and then take your next tablet at the usual time. If you forget for more than 12 hours, simply take the next single dose at the usual time. Do not take a double dose to make up for forgotten individual doses.

If you stop taking/using ENTELROMESIS: Do not stop the treatment unless your doctor tells you so. Contact your doctor before stopping or restarting your treatment.

ENTELROMESIS can have side effects. Not all side effects reported for ENTELROMESIS are included in this leaflet. Should your general health worsen, or if you experience any untoward effects while using ENTELROMESIS, please consult your healthcare provider for advice. The most frequent side effect which has been seen with ENTELROMESIS is bleeding. Bleeding may occur as bleeding in the stomach or bowels, bruising, haematoma (unusual bleeding or bruising under the skin), nosebleed, blood in the urine. In a small number of cases, bleeding in the eye, inside the head, the lung or the joints has also been reported.

If you experience prolonged bleeding when taking ENTELROMESIS: If you cut or injure yourself, it may take slightly longer than usual for bleeding to stop. This is linked to the way ENTELROMESIS works as it prevents the ability of blood clots to form. For minor cuts and injuries e.g., cutting yourself or shaving, this is usually of no concern. However, if you are concerned by your bleeding, you should contact your doctor straight away (see section 2).

If any of the following happens, stop using ENTELROMESIS and tell your doctor immediately or go to the casualty department at your nearest hospital:

• swelling of the hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing
• rash or itching
• fainting
• if you develop a medical condition known as Thrombotic Thrombocytopenic Purpura (also known as TTP) – the symptoms may include fever, bruising under the skin that may appear as red pinpoint dots, with or without unexplained extreme tiredness, confusion, yellowing of the skin or eyes (jaundice) - see section 2
• chest pain that may radiate to the neck or left arm, pallor, sweatiness, nausea, breathlessness, low blood pressure. These symptoms may be signs of heart problems due to an allergy to clopidogrel or aspirin (Kounis syndrome)
• sudden severe headache, seizures with no previous history of seizures, weakness in your arm or leg, nausea or vomiting (severe and continuing), sudden tiredness, difficulty speaking or understanding speech, loss of balance, hand tremors or loss of consciousness. These symptoms may be signs of life-threatening bleeding within your skull
• tightness in the chest, wheezing, coughing or difficulty breathing, fatigue
• blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You may also have flu-like symptoms at the same time, such as fever, chills or aching muscles, rash, facial swelling, enlarged lymph nodes and kidney or liver injury. These may be signs of serious skin disorders such as Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN) and Drug reaction with eosinophilia and systemic symptoms (DRESS).

These are all very serious side effects. If you have them, you may have had a serious allergic reaction to ENTELROMESIS. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• fever, signs of infection or extreme tiredness. These may be due to rare decrease of some blood cells (agranulocytosis, granulocytopenia)
• signs of liver problems such as yellowing of the skin and/or the eyes (jaundice, liver failure, hepatitis, liver injury)
• hallucinations (seeing and hearing things that are not there), confusion
• shortness of breath, fatigue, swollen legs and rapid heartbeat (symptoms of cardiac failure)
• reduction in the number of your red blood cells (anaemia) – symptoms may include that you feel weak and tired, and looking pale and that you are more susceptible to infections and uncontrolled bleeding (aplastic anaemia)
• bleeding (including nose bleeds) or bruising more easily than normal. Signs of bleeding may include unusually heavy bleeding from cuts and wounds, coughing up blood, blood in the urine, vomiting of blood or vomit that looks like coffee grounds, bloody or black bowel motions, unusually heavy or unexpected menstrual bleeding, bleeding in the eyes
• reduction in your red and white blood cells and blood platelets (aplastic anaemia) – symptoms may include that you feel weak and tired, and that you are more susceptible to infections and uncontrolled bleeding
• a serious skin reaction called acute generalized exanthematous pustulosis (AGEP) - symptoms may include a red, scaly widespread rash with bumps under the skin (including your skin folds, trunk, and upper extremities) and blisters filled with white/yellow fluid accompanied by fever
• inflammation of the pancreas with symptoms such as severe upper abdominal pain, the abdominal pain may radiate to your back, nausea, vomiting, diarrhoea, tenderness when touching your abdomen, fever
• lung problems called non-cardiogenic pulmonary oedema causing a fluid build-up in the lung - symptoms may include dry cough, fever, difficulty breathing when lying down, chest pain, shortness of breath
• a condition where a certain type of white blood cell called eosinophils accumulates in your lungs (eosinophilic pneumonia) - symptoms may include fever, chest pain worsened by deep breathing, shortness of breath, cough and generally feeling unwell
• low blood sugar (hypoglycaemia) - symptoms may include feeling shaky, anxious or nervous, light-headed, dizzy, chills, sweating or clammy skin, fast heartbeat
• insulin autoimmune syndrome a condition which can cause persistent low blood sugar levels
• increase in blood pressure (hypertension)
• decrease in blood pressure (hypotension)
• severe abdominal pain, with or without back pain, worsening of inflammation of the colon (colitis) which causes abdominal pain and diarrhoea
• ulcer perforation (where an ulcer burns through the stomach or duodenal wall, causing severe, sharp abdominal pain)
• inflammation of your blood vessels with symptoms such as fever, headache, tiredness, weight loss, general aches and pains, night sweats, rash or nerve problems such as numbness or weakness
• presence of blood in urine, kidney failure or inflammation of the kidneys – symptoms may include swelling of legs, ankles, feet or face due to fluid retention, reduction in your urine output, shortness of breath, fatigue, confusion
• fever.

These are all serious side effects. You may need urgent medical attention. Tell your doctor if you notice any of the following:

• Frequent side effects:
• abdominal pain, indigestion, diarrhoea
• bleeding in the digestive tract (mouth to anus)
• bruising
• bleeding at puncture site
• vomiting, nausea, constipation, excessive gas in stomach or intestines, gastritis (an inflammation of the stomach lining)
• Less frequent side effects:
• eye bleeding, broken blood vessels in the eye, bleeding in the retina
• vertigo (loss of balance, spinning sensation)
• rash, itching, rash of purple spots on the skin caused by internal bleeding from small blood vessels.

The following side effects have been reported but the frequency for them to occur is not known:

• taste disturbances, loss of taste
• hives, eczema, purplish, itchy, flat-topped bumps or lacy, white patches, sometimes with painful sores in the mouth
• arthritis, joint pain, muscle pain
• abnormal urine test results
• enlarged breasts in men
• gout
• hearing loss, ringing in the ears
• oedema - swelling caused by fluid trapped in your body's tissues (mainly in the feet, legs and ankles).

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects: If you get side effects, talk to your doctor or pharmacist or nurse. You can also report side effects to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. An email can be sent directly to the company, [email protected] to ensure safety of the product. By reporting side effects, you can help provide more information on the safety of ENTELROMESIS.

Store all medicines out of reach of children. Store at or below 25 °C. Keep blisters in carton until required for use. Do not use after the expiry date stated on the carton. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).