Package Insert: Information for the User

Trinomia 100 mg/20 mg/2.5 mg Hard Capsules

Acid Acetilsalicylic/Atorvastatin/Ramipril

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed to you alone, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Trinomia capsules contain three substances: acetylsalicylic acid, atorvastatin, and ramipril.

• Acetylsalicylic acid belongs to a group of substances called antiplatelet agents, which help prevent blood cells from adhering to each other and forming a clot.
• Atorvastatin belongs to a group of substances called statins, which are medications that regulate lipids (fats) and are used to reduce the amount of cholesterol and triglycerides in the blood, when this cannot be achieved through a low-fat diet and the necessary lifestyle changes of the patient. If you have an increased risk of suffering from heart diseases, atorvastatin may also be used to reduce this risk, even when your cholesterol levels are normal. During treatment, you must follow a standard low-cholesterol diet.
• Ramipril belongs to a group of substances called ACE inhibitors that act by reducing the production of substances in the body that could increase blood pressure; it makes blood vessels relax and increase in diameter, making it easier for the heart to pump blood throughout the body.

Trinomia is used as a substitute treatment in adequately controlled adult patients with the three substances (acetylsalicylic acid, atorvastatin, and ramipril) taken at the same time at equivalent doses, to reduce the risk of suffering a cardiovascular accident, when the patient has already suffered a previous cardiovascular event.

Do not take Trinomia:

• if you areallergic to acetylsalicylic acid, other salicylates, or tartrazine (a coloring agent). Signs of an allergic reaction include, among others, rash, difficulty swallowing or breathing, swelling of the lips, face, throat, or tongue.
• if you are allergic to ramipril or another ACE inhibitor.
• if you are allergic to atorvastatin, other similar compounds used to lower blood lipids, or any of the other components of the medication (listed in Section 6).
• if you are allergic to soy or peanuts.
• if you have previously experienced asthma attacks or other hypersensitivity reactions to certain medications for pain, fever, or inflammation (salicylates or other nonsteroidal anti-inflammatory drugs).
• if you have recurrent active peptic ulcers or a history of and/or gastrointestinal bleeding, or other types of bleeding such as cerebral hemorrhage.
• if you have a high risk of bleeding (hemophilia).
• if you have uncontrolled heart disease (severe heart failure).
• if you are taking 15 mg or more of methotrexate per week.
• if you have diabetes or kidney disease and are being treated with a blood pressure medication containing aliskiren.
• if you have nasal polyps (inflamed nodules inside the nose)associated with asthma.
• if you have a severe liver or kidney disease.
• if abnormal liver function test results have been obtained in blood tests.
• if you are a fertile woman and do not use a reliable contraceptive method.
• if you are pregnant or trying to become pregnant.
• if you are breastfeeding.
• if you are taking:
• • protease inhibitors for HIV, such as tipranavir or ritonavir (medications used to treat HIV).
  • ciclosporina (a medication often used in patients undergoing organ transplantation).
• if you have ever experienced a severe allergic reaction called "angioedema". Its symptoms are: itching, urticaria, red marks on the hands, feet, and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing.
• if you are undergoing dialysis or any other type of blood filtration procedure. Depending on the device used, Trinomia may not be suitable for you.
• if you have kidney problems that involve reduced blood flow to the kidneys (renal artery stenosis).
• if you have abnormally low or unstable blood pressure. Your doctor will perform the necessary evaluation.
• if the patient is under 18 years of age. In children under 16 years with fever, flu, or chickenpox, there is a risk of Reye's syndrome.
• if you are using the combination of glecaprevir/pibrentasvir for the treatment of hepatitis C.
• if you have taken or are currently taking sacubitril/valsartan, a medication used to treat a type of chronic heart failure in adults, as the risk of angioedema (rapid swelling under the skin in an area such as the throat) is high.
• if you are taking any of the following medications, the risk of angioedema may increase:

• racecadotril, a medication used to treat diarrhea.
• medications used to prevent organ transplant rejection and for cancer (e.g., temsirolimus, sirolimus, everolimus).
• vildagliptin, a medication used to treat diabetes.

Especially, consult your doctor or pharmacist if you are taking, have taken recently, or may need to take any of the following medications:

potassium supplements (including salt substitutes) and diuretics that save potassium, and other medications that may increase the amount of potassium in the blood (e.g., trimethoprim and cotrimoxazole for bacterial infections; ciclosporina, an immunosuppressive medication used to prevent organ transplant rejection; and heparin, a medication used to dilute the blood to prevent clots).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Trinomia:

• if you are allergic to other pain medications or anti-inflammatory medications, other fever or rheumatism medications other than acetylsalicylic acid or other substances that cause allergies.
• if you suffer from any other type of allergy (e.g., skin reactions, itching, urticaria).
• if you have asthma bronchitis, hay fever, nasal mucosa inflammation, or chronic lung diseases.
• before a surgical operation or small interventions, such as tooth extractions, as there may be a greater tendency to bleeding. You may need to stop taking Trinomia for a short period.
• if you have had ulcers or intestinal or stomach bleeding in the past.
• if you are receiving simultaneous treatment with medications to prevent blood clot formation, pain medications, fever, or inflammation medications (other than nonsteroidal anti-inflammatory drugs such as ibuprofen), corticosteroids (to treat allergies or inflammation) or antidepressants such as selective serotonin reuptake inhibitors (SSRIs)
• if you are taking or have taken in the last 7 days a medication containing fusidic acid, (used to treat bacterial infections) by mouth or injection. The combination of fusidic acid and Trinomia may cause severe muscle problems (rhabdomyolysis).
• if you are taking any of the following medications used to treat high blood pressure (hypertension):
• • an angiotensin II receptor antagonist (ARA) (also known as "sartanes" - e.g., valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.
  • Aliskiren
• Your doctor may need to monitor your renal function, blood pressure, and electrolyte levels in the blood (e.g., potassium) at regular intervals. See also the information under the heading “Do not take Trinomia”
• if you have or have had heart, liver, or kidney problems, Trinomia may not be suitable for you.
• if you have a deficiency of the glucose-6-phosphate dehydrogenase enzyme.
• if you are at risk of developing gout, as acetylsalicylic acid may reduce the excretion of uric acid. In certain circumstances, this could cause a gout attack.
• Your doctor will perform a blood test before you start taking Trinomia and, subsequently, at regular intervals during treatment. This will allow them to check the proper functioning of your liver.
• if you drink large amounts of alcohol.
• if you have severe respiratory failure.
• if you have lost a large amount of salt or fluid from your body (through vomiting, diarrhea, excessive sweating, low-sodium diet, long-term diuretic use, or dialysis treatment).
• if you are undergoing desensitization treatment for bee or wasp stings.
• if you have high levels of potassium in your blood (detected in blood tests).
• if you have a vascular collagen disease, such as scleroderma or systemic lupus erythematosus.
• if you have or have had myasthenia (a disease that causes generalized muscle weakness that, in some cases, affects the muscles used for breathing) or ocular myasthenia (a disease that causes weakness of the eye muscles), as statins may sometimes worsen the disease or cause myasthenia (see Section 4).

Immediately contact your doctor if you experience muscle pain, tenderness, or weakness of unknown origin. This is because, in rare cases, muscle disorders can be severe, such as renal damage; in very rare cases, patient death has occurred.

Also inform your doctor or pharmacist if you experience persistent muscle weakness. Additional tests and medications may be necessary to diagnose and treat this problem.

The risk of muscle destruction is higher in certain patients. Consult your doctor if you fall into any of the following categories:

• if you have had a previous stroke with cerebral bleeding, or have small fluid embolisms in the brain due to previous strokes.
• if you have kidney problems.
• if you have thyroid problems.
• if you have experienced muscle problems during treatment with other medications to lower lipids (e.g., other statins or fibrates).
• if you or a close relative suffer from inherited muscle disorders.
• if you regularly consume large amounts of alcohol.
• if you are over 70 years old.

If so, your doctor will ask you to undergo a blood test before and, possibly, during treatment to assess the risk of you experiencing adverse muscle effects.

It is known that the risk of adverse muscle effects, e.g., rhabdomyolysis, increases when certain medications are taken simultaneously (see Section 2. Taking Trinomia with other medications).

While taking this medication, your doctor will perform strict monitoring if you are diabetic or at risk of developing diabetes. You are at risk of developing diabetes if you have high blood sugar and lipid levels, obesity, and high blood pressure.

Generally, it is recommended to correct dehydration, hypovolemia, or electrolyte deficiency before starting treatment (in patients with heart failure, however, this correction should be carefully weighed against the risk of volume overload).

Taking Trinomia with other medications

Consult your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. This is because Trinomia may affect the way other medications work. Additionally, some medications may affect the way Trinomia works.

Trinomia contains acetylsalicylic acid, a substance that may affect the way other medications work. Additionally, some medications may affect the way acetylsalicylic acid works. Consult your doctor if you are taking any of the following medications, which may increase the risk of adverse effects:

• anticoagulants (e.g., warfarin and heparin) and medications to dissolve blood clots, as they may increase the risk of bleeding. Be very attentive to signs of internal and external bleeding (e.g., hematomas) before starting treatment with these medications.
• other inhibitors of platelet aggregation (medications that inhibit platelet coagulation) such as ticlopidine and clopidogrel, as they may increase the risk of bleeding.
• medications containing cortisone or cortisone-like substances, such as prednisolone (except for products applied to the skin or cortisone treatment for Addison's disease), as they increase the risk of adverse effects in the digestive tract.
• other pain or anti-inflammatory medications (nonsteroidal anti-inflammatory drugs such as ibuprofen or indomethacin) and for rheumatism, as they generally increase the risk of bleeding and gastrointestinal ulcers.
• medications to lower blood sugar levels (antidiabetics) as they may cause low blood sugar levels.
• digoxin (a medication to strengthen the heart).
• metotrexate (cancer treatment and certain rheumatic diseases).
• valproic acid for epilepsy treatment.
• selective serotonin reuptake inhibitors (SSRIs) for depression treatment, as they may increase the risk of gastrointestinal bleeding.
• ciclosporina (a medication often used in patients undergoing organ transplantation).
• vancomycin (an antibiotic) as it may cause hearing problems.

Consult your doctor if you are taking any of the following medications, which may make acetylsalicylic acid less effective:

• diuretics (e.g., furosemide, aldosterone antagonists such as spironolactone and canrenone, and diuretics such as furosemide).
• medications that enhance uric acid excretion (e.g., probenecid and benzbromarone)
• ibuprofen: it may reduce the anti-aggregatory effect of acetylsalicylic acid.
• if administered together, metamizole (a substance to reduce pain and fever) may reduce the effect of acetylsalicylic acid on platelet aggregation (blood cells coagulate and form a blood clot). Therefore, this combination should be used with caution in patients taking low doses of acetylsalicylic acid as a cardioprotector.

Consult your doctor if you are taking any of the following medications. They may be affected by acetylsalicylic acid:

• interferon-alpha: acetylsalicylic acid may reduce the effect of interferon-alpha.
• medications for manic-depressive syndromes (lithium).
• anti-acids (for indigestion).
• barbiturates (for convulsive disorders).
• zidovudine (for HIV treatment).
• phenytoin (for epilepsy treatment).
• Acetylsalicylic acid may alter the results of blood and urine tests.

Trinomia contains atorvastatin, a substance that may affect the way other medications work. Additionally, some medications may affect the way Trinomia works. Furthermore, it may increase the risk of adverse effects or their intensity, including the severe muscle disorder described in the previous section “Warnings and precautions”). Consult your doctor if you are taking any of the following medications:

• ciclosporina (a medication often used in patients undergoing organ transplantation).
• certain antibiotics or antifungals, such as erythromycin, clarithromycin, telithromycin, ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole, rifampicin
• if you need to take fusidic acid orally to treat a bacterial infection, you will need to stop using this medication. Your doctor will indicate when you can restart Trinomia. The use of Trinomia with fusidic acid may cause muscle weakness, sensitivity, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see Section 4.
• medications for HIV treatment, such as ritonavir, lopinavir, atazanavir, indinavir, darunavir, saquinavir, efavirenz,the combination of tipranavir/ritonavir, etc.
• other medications to regulate lipid levels, such as gemfibrozil, other fibrates, or colestipol.
• some medications used to treat hepatitis C, e.g., telaprevir, boceprevir, and the combination of elbasvir/grazoprevir.
• some calcium channel blockers used to treat angina or hypertension, such as amlodipine, diltiazem; medications to regulate heart rhythm, such as digoxin, verapamil, or amiodarone.
• other medications known to interact with atorvastatin are ezetimibe (which reduces cholesterol), warfarin (to prevent blood clots), oral contraceptives, stiripentol (an anticonvulsant for epilepsy treatment), phenazone (a pain medication), cimetidine (an H2 receptor antagonist), colchicine (used to treat gout) and anti-acids (products for indigestion containing aluminum or magnesium).
• over-the-counter medications: St. John's Wort or hypericum

Trinomia contains ramipril, a substance that may affect the way other medications work. Additionally, some medications may affect the way ramipril works. Consult your doctor if you are taking any of the following medications, which may increase the risk of adverse effects:

• medications for cancer (chemotherapy).
• medications to prevent organ transplant rejection, such as ciclosporina.
• diuretics such as furosemide.
• medications that may increase potassium levels in the blood, such as spironolactone, triamterene, amiloride, potassium salts, and heparin (to prevent clots).
• steroidal anti-inflammatory medications, such as prednisolone.
• allopurinol (to reduce uric acid levels in the blood).
• procainamide (for heart rhythm problems).

Consult your doctor if you are taking any of the following medications, which may make ramipril less effective:

• medications to treat hypotension, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, or adrenaline. Your doctor will need to check your blood pressure.

Consult your doctor if you are taking any of the following medications. They may be affected by ramipril:

• medications for diabetes, such as oral medications to lower blood sugar and insulin. Ramipril may lower your blood sugar levels. Closely monitor your blood sugar levels when taking Trinomia.
• lithium (for mental health problems). Ramipril may increase lithium levels in the blood. Your doctor will need to closely monitor your lithium levels in the blood.

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

if you are taking an angiotensin II receptor antagonist (ARA) or aliskiren (see also the information under the headings “Do not take Trinomia” and “Warnings and precautions”).

if you fall into any of the above categories (or are unsure), consult your doctor before taking Trinomia.

Taking Trinomia with food, drinks, and alcohol

Alcohol increases the risk of bleeding and stomach or intestinal ulcers. Additionally, alcohol may have additive effects with medications used to lower blood pressure. Therefore, it is not recommended to drink alcohol while taking Trinomia.

Orange juice contains one or more compounds that alter the way the body uses medications, including Trinomia. It is recommended to avoid consuming orange juice.

Trinomia should be taken preferably after a meal (see Section 3).

Pregnancy, breastfeeding, and fertility

Do not take Trinomia if you are pregnant, think you may be pregnant, or plan to become pregnant.

If you become pregnant while taking Trinomia, stop taking it immediately and contact your doctor.

Before a planned pregnancy, you should switch to an alternative suitable treatment.

Do not take Trinomia if you are breastfeeding.

Women of childbearing age should use a reliable contraceptive method during treatment.

Consult your doctor or pharmacist before starting to take any medication.

Driving and operating machinery

You may feel dizzy while taking Trinomia. This is more likely to occur when switching from other medications to Trinomia or taking a higher dose. If so, do not drive or operate tools or machinery.

Trinomia contains lactose, sodium, and soy lecithin

Trinomia contains a sugar called lactose. If you have intolerance to certain sugars, consult your doctor before taking this medication.

This medication contains less than 1 mmol of sodium (23 mg) per hard capsule; it is essentially “sodium-free”.

Trinomia contains soy oil. It should not be used in case of allergy to peanuts or soy.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Trinomia Dosage

• Take this medication orally, after a meal.
• Swallow the capsules whole with liquid.
• Do not open, crush, or chew the capsules.

How Much to Take

The usual dose is one capsule once a day.

Your doctor will determine the appropriate dose for you, based on your health status, current treatment, and personal risks.

If You Take More Trinomia Than You Should

Dizziness and ringing in the ears, especially in older patients, may be symptoms of severe poisoning.

Call your doctor or go immediately to the nearest hospital emergency services. Do not drive to the hospital; ask someone to take you or call an ambulance. Bring the medication packaging with you. This way, the doctor who treats you will know what you have taken.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If You Forget to Take Trinomia

• If you have forgotten a dose, take your regular dose with the next dose.
• Do not take a double dose to make up for the missed doses.

Stopping Treatment with Trinomia

Do not stop treatment with Trinomia until you have spoken with your doctor.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The evaluation of side effects is based on the following frequency table:

Stop taking Trinomia and seek immediate medical attention if you notice any of the following serious side effects or symptoms (may require urgent medical treatment),inform your doctor immediately, or go to the nearest hospital emergency department.:

• In very rare cases, black stools or vomiting blood (signs of severe stomach bleeding) have been reported.
• In rare cases, skin, respiratory tract, digestive tract, and cardiovascular system allergic reactions have been reported, especially in patients with asthma. The following symptoms may occur: low blood pressure, difficulty breathing, rhinitis, nasal congestion, anaphylactic shock, facial swelling, tongue swelling, and laryngeal edema (Quincke's edema).
• In rare or very rare cases, severe bleeding, such as cerebral hemorrhage, which can be life-threatening, especially in patients with uncontrolled high blood pressure and/or concomitant treatment with anticoagulants (medicines that inhibit blood coagulation).
• Muscle pain, sensitivity, weakness, muscle rupture, muscle cramps, or urine color change to reddish-brown. If muscle weakness, muscle sensitivity, pain, or urine color change to reddish-brown occur simultaneously with a feeling of discomfort or high temperature that may be caused by abnormal muscle destruction, which can be potentially fatal and trigger kidney problems. In very rare cases, patient death has been reported.
• Rare cases of hypersensitivity reactions, such as: facial swelling, tongue swelling, and throat swelling, with subsequent difficulty breathing or swallowing, as well as itching and skin rashes.
• Severe skin disease with intense peeling and inflammation, blisters on the skin, mouth, eyes, and genitals, and fever. Skin rash with pink or reddish spots, especially on the palms of the hands or soles of the feet, which can transform into blisters.
• In rare cases, liver inflammation with yellow skin and eye discoloration, itching, dark urine, or pale stools and liver insufficiency (very rare).
• In rare cases, pancreatitis (pancreas inflammation), often with severe abdominal pain.
• Lupus-like syndrome (including rash, joint disorders, and blood cell effects).

Seek immediate medical attention if you experience:

• Accelerated heart rate, irregular heartbeats, or chest pain, or more serious problems, such as myocardial infarction or stroke.
• Shortness of breath or cough. These may be symptoms of respiratory problems.
• Easy bruising, prolonged bleeding, any sign of bleeding (e.g., from the gums), purple spots on the skin, or increased susceptibility to infections, sore throat, fever, fatigue, weakness, dizziness, or paleness. These may be symptoms of blood or bone marrow problems.
• Severe abdominal pain that may radiate to the back. This may be a symptom of pancreatitis (pancreas inflammation).
• Fever, chills, fatigue, loss of appetite, abdominal pain, nausea, yellow skin or eye discoloration (jaundice). These may be symptoms of liver problems, such as hepatitis (inflammation) or liver damage.

Side effects of acetylsalicylic acid, atorvastatin, or ramipril alone:

Consult your doctor if any of the following symptoms worsen or last more than a few days:

Acetylsalicylic acid

Very common (may affect up to 1 in 10 people):

• Gastrointestinal discomfort, such as stomach pain, nausea, vomiting, abdominal pain, and diarrhea.
• Mild gastrointestinal bleeding.

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

• Bleeding and ulcers in the gastrointestinal tract.
• Tract gastrointestinal bleeding.
• Tract gastrointestinal ulcers.
• Tract gastrointestinal inflammation.
• Tract gastrointestinal reactions.

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

• Bleeding from the nose, gums, skin, urinary tract, or reproductive organs, with prolonged bleeding time. This effect may last from 4 to 8 days after treatment.

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

• Increased liver enzyme levels.
• Renal function disorders.
• Low blood sugar (hypoglycemia).
• In low doses, acetylsalicylic acid reduces uric acid excretion. In patients at risk, this could trigger a gout attack in certain circumstances.
• Skin rash with fever, affecting mucous membranes (erythema multiforme).

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

Headache, dizziness, confusion, hearing disorders, or ringing in the ears (tinnitus), especially in elderly patients, which may be symptoms of an overdose (see "If you take more Trinomia than you should").

Atorvastatin

The possible side effects of some statins (medicines of the same type):

-Sexual difficulties

-Depression

-Respiratory problems, such as persistent cough and/or difficulty breathing or fever

• Diabetes. It is more likely to occur if you have high blood sugar and cholesterol levels, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine.

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

• Nasal congestion, sore throat, and nosebleeds.
• Allergic reactions.
• Increased blood sugar levels (if you have diabetes, carefully monitor your blood sugar levels), increased creatine kinase levels in the blood.
• Headache.
• Nausea, constipation, flatulence, indigestion, diarrhea.
• Muscle and joint pain, back pain.
• Abnormal liver function test results.

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

• Loss of appetite, weight gain, decreased blood sugar levels (if you have diabetes, carefully monitor your blood sugar levels).
• Nightmares, insomnia.
• Dizziness, numbness or tingling in the fingers of the hands and feet, decreased pain or tactile sensation, changes in taste, memory loss.
• Blurred vision.
• Tinnitus in the ears and/or in the head.
• Changes in the sense of taste, loss of taste.
• Vomiting, belching, upper and lower abdominal pain, pancreatitis (pancreas inflammation).
• Hepatitis (liver inflammation).
• Skin rash and itching, urticaria, hair loss.
• Neck pain, muscle fatigue.

• Fatigue, feeling unwell, weakness, chest pain, swelling, especially in the ankles (edema), increased body temperature.
• Presence of leukocytes in the urine.

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

• Vision disorders.
• Numbness or tingling in the fingers of the hands and feet.
• Unexpected bleeding or bruising.
• Bile duct obstruction (yellow skin and eye discoloration).
• Tendon damage.

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

• Increased sensitivity to sunlight.

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

• Attention disorders.
• Mouth swelling.
• Low white blood cell count.
• Low sodium levels in the blood.
• Raynaud's phenomenon, caused by cold, with subsequent tingling or painful sensation when warmed (change in color in the fingers of the hands and feet).
• Male breast enlargement.
• Slow or altered reactions.
• Burning sensation.
• Changes in the sense of smell.
• Hair loss.

Side effects of Trinomia (acetylsalicylic acid, atorvastatin, or ramipril)

Very common (may affect more than 1 in 10 people):

• Gastrointestinal discomfort, such as stomach pain, nausea, vomiting, abdominal pain, and diarrhea.
• Mild gastrointestinal bleeding.

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

• Nasal congestion, sore throat, and nosebleeds.
• Dry cough, nasal congestion, sinusitis, or bronchitis, feeling of suffocation.
• Chest pain.
• Constipation, flatulence, indigestion.
• Abdominal pain or intestinal pain, nausea.
• Headache and fatigue.
• Dizziness. This is more likely to occur when starting treatment with Trinomia or when starting a high dose.
• Loss of consciousness, low blood pressure, especially when standing up or sitting quickly.
• Allergic reactions.
• Skin rash with or without swelling.
• Muscle cramps or muscle pain.
• Joint pain and back pain.
• Abnormal liver function test results.
• Increased blood sugar levels (if you have diabetes, carefully monitor your blood sugar levels), increased creatine kinase levels in the blood.
• High potassium levels in the blood.

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

• Bleeding and ulcers in the gastrointestinal tract, but very rarely perforate the lining.
• Gastrointestinal inflammation.
• Loss of appetite, weight gain, decreased blood sugar levels (if you have diabetes, carefully monitor your blood sugar levels).
• Belching, upper and lower abdominal pain, pancreatitis (pancreas inflammation).
• Angioedema intestinal (a type of intestinal inflammation) that manifests with symptoms such as abdominal pain, vomiting, and diarrhea.
• Tract gastrointestinal bleeding.
• Reactions to the skin.
• Skin rash and itching, urticaria, hair loss.
• Nightmares, insomnia.
• Problems with sleep.
• Dizziness, numbness or tingling in the fingers of the hands and feet, decreased pain or tactile sensation, changes in taste, memory loss.
• Problems with balance (dizziness).
• Blurred vision.
• Tinnitus in the ears and/or in the head.
• Changes in the sense of taste, loss of taste.
• Painful or abnormal sensations in the skin, such as numbness, tingling, pinching, burning, or numbness (paresthesia).
• Feeling of depression, anxiety, nervousness, or restlessness.
• Hepatitis (liver inflammation).
• Muscle pain in the neck, muscle fatigue.
• Feeling unwell, feeling of discomfort, weakness, chest pain, swelling, especially in the ankles (edema), increased body temperature.
• Nasal congestion, difficulty breathing, or worsening of asthma.
• Dry mouth.
• Increased urine production.
• Swelling of the arms and legs. This may be a sign that the body is retaining more fluid than normal.
• Rubefaction.
• Fever.
• Irregular heart rhythm or accelerated heart rate.
• Impotence in men, reduced sexual desire in both men and women.
• Presence of leukocytes in the urine.
• Increased eosinophil count in the blood.
• Changes in liver, pancreas, or kidney function, detected in blood tests.

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

• Bleeding from the nose, gums, skin, urinary tract, or reproductive organs, with prolonged bleeding time. This effect may last from 4 to 8 days after treatment.

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

• Numbness or tingling in the fingers of the hands and feet.
• Unexpected bleeding or bruising.
• Bile duct obstruction (yellow skin and eye discoloration).
• Tendon damage.
• Feeling of instability or confusion.
• Swollen tongue.
• Intense skin peeling, itching, skin rash.
• Problems with nails (e.g., falling or separation between the nail and its bed).
• Skin rash or hematomas.
• Spots on the skin and cold extremities.
• Excessive tearing, redness, itching, or swelling of the eyes.
• Auditory disorders and tinnitus.
• Feeling of weakness.
• Decreased red blood cell, white blood cell, or platelet count, or decreased hemoglobin levels.

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

• Increased liver enzyme levels.
• Severe liver problems.
• In low doses, acetylsalicylic acid reduces uric acid excretion. In patients at risk, this could trigger a gout attack in certain circumstances.
• Allergic reaction, with symptoms such as sudden wheezing and chest pain, swelling of the eyelids, face, lips, mouth, tongue, or throat, difficulty breathing, and collapse.
• Increased sensitivity to sunlight.
• Loss of hearing.
• Male breast enlargement.

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

• Attention disorders.
• Mouth swelling.
• Low white blood cell count.
• Low sodium levels in the blood.

The possible side effects of some statins:

-Sexual difficulties

-Depression

-Respiratory problems, such as persistent cough and/or difficulty breathing or fever

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is not listed in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use, Website: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

No special storage conditions are required.

Do not use Trinomia after the expiration date that appears on the box and on the blister pack. The expiration date is the last day of the month indicated.

Do not dispose of medications through the drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Trinomia100 mg/20 mg/2.5 mg hard capsules

• The active ingredients are acetylsalicylic acid, atorvastatin, and ramipril. Each capsule contains 100 mg of acetylsalicylic acid, 20 mg of atorvastatin (as atorvastatin calcium trihydrate), and 2.5 mg of ramipril.

• The other components (excipients) are:

Core: microcrystalline cellulose (E460); talc (E553); sodium carboxymethylcellulose (type A) (potato starch); lactose monohydrate; pregelatinized starch (cornstarch); calcium carbonate (E170); hydroxypropylcellulose (E463); polisorbate 80 (E433); crospovidone (type A); anhydrous colloidal silica; magnesium stearate; hypromellose (E464); fumaric acid and sodium esterate.

Coating:poly(vinyl alcohol); titanium dioxide (E171); talc (E553); soy lecithin (E322); xanthan gum (E415); hypromellose (E464); triethyl citrate (E1505); povidone; yellow iron oxide (E172); black iron oxide (E172).

Capsule coating: gelatin (E441); titanium dioxide (E171); black iron oxide (E172); shellac; black iron oxide (E172).

Appearance of Trinomia and packaging contents

Trinomia 100 mg/20 mg/2.5 mg hard capsules consist of hard gelatin capsules of size 0 (approximate length 21.7 mm) with opaque grayish-colored caps and bodies, bearing the imprint "AAR 100/20/2.5" and containing: 2 coated tabletswithfilm, white or off-white in color, with 50 mg of acetylsalicylic acid, with the letters "AS" engraved; 2 coated tabletswithfilm, brownish-green in color, with 10 mg of atorvastatin, with the letters "AT" engraved; 1 coated tabletwithfilm, pale yellow in color, with 2.5 mg of ramipril, with the letters "R2" engraved.

Trinomia 100 mg/20 mg/2.5 mg hard capsules are marketed in blister packaging, in boxes with 7, 14, 28, 56, 84, or 98 capsules.

Only some packaging sizes may be marketed.

Marketing authorization holder and manufacturer

For more information about this medication, please contact the marketing authorization holder.

This medication has been authorized in the EEA member states listed below, with the following names:

Bélgica:Trinomia 100mg/20mg/2.5mg gélule

Bulgaria:Trinomia 100mg/20mg/2.5mg ?????? ???????

Germany:Iltria100mg/20mg/2.5mg hartkapseln

Finland:Trinomia 100mg/20mg/2.5mg kapseli, kova

France:Iltria 100mg/20mg/2.5mg gélules

Greece:Trinomia 100mg/20mg/2.5mg καψ?κια σκληρ?

Ireland:Trinomia 100mg/20mg/2.5mg hard capsules

Italy:Trinomia 100mg/20mg/2.5mg capsule rigide

Austria:Trinomia 100mg/20mg/2.5mg hartkapseln

Poland:Trinomia 100mg/20mg/2.5mg kapsulki twarde

Portugal:Trinomia 100mg/20mg/2.5mg cápsulas

Romania:Trinomia 100mg/20mg/2,5mg capsule

Spain:Trinomia 100mg/20mg/2.5mg cápsulas duras

Sweden:Trinomia 100mg/20mg/2.5mg kapslar, hårda

Czech Republic:Trinomia 100mg/20mg/2.5mg tvrdé tobolky

Last review date of this leaflet:March 2023

For detailed and updated information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/