TRINOMIA 100 mg/40 mg/5 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Trinomia 100 mg/40 mg/5 mg hard capsules

acetylsalicylic acid/atorvastatin/ramipril

Read the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only, 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 side effects, consult your doctor or pharmacist, even if they are side effects not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

1. What Trinomia is and what it is used for
2. What you need to know before taking Trinomia
3. How to take Trinomia
4. Possible side effects
5. Storage of Trinomia
6. Package contents and additional information

1. What Trinomia is and what it is used for

The 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 sticking together and forming a clot.
• Atorvastatin belongs to a group of substances called statins, which are medications that regulate lipids (fats) and are used to decrease the amount of cholesterol and triglycerides in the blood, when this cannot be achieved through a low-fat diet and necessary lifestyle changes. If you have an increased risk of suffering from heart disease, atorvastatin can also be used to reduce this risk, even when your cholesterol levels are normal. During treatment, you should follow a standard low-cholesterol diet.
• Ramipril belongs to a group of substances called ACE inhibitors (angiotensin-converting enzyme) that act by decreasing the production of substances in the body that could increase blood pressure; it causes the blood vessels to relax and increase in diameter, making it easier for the heart to pump blood throughout the body.

Trinomia is used as a replacement treatment in adult patients who are adequately controlled 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 event, when the patient has already experienced a previous cardiovascular event.

2. What you need to know before taking Trinomia

Empty section

Do not take Trinomia:

• if you are allergic to acetylsalicylic acid, other salicylates, or tartrazine (a coloring substance). The signs of an allergic reaction are, among others, rash, swallowing or breathing problems, swelling of the lips, face, throat, or tongue.
• if you are allergic to ramipril or another ACE inhibitor medication.
• if you are allergic to atorvastatin, other similar compounds used to reduce blood lipids, or any of the other components of the medication (included in Section 6).
• if you are allergic to soy or peanuts.
• if you have previously suffered from asthma attacks or other hypersensitivity reactions to certain medications for pain, fever, or inflammation (salicylates or other non-steroidal anti-inflammatory medications).
• if you have active recurrent peptic ulcer or a history of and/or gastrointestinal bleeding, or other types of bleeding such as cerebrovascular hemorrhages.
• if you have a high risk of bleeding (hemophilia).
• if you suffer from a heart condition that is not sufficiently controlled (severe heart failure).
• if you take 15 mg or more of methotrexate per week.
• if you have diabetes or kidney failure 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 severe liver or kidney disease.
• if you have unexplained abnormal blood test results for liver function.
• if you are a woman of childbearing age 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:
• • HIV protease inhibitors, such as tipranavir or ritonavir (medications used to treat HIV).
  • Cyclosporine (a medication commonly used in patients undergoing organ transplants).
• if you have ever had a severe allergic reaction called "angioedema". The symptoms are: itching, hives, 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 a reduction in blood flow to the kidneys (renal artery stenosis).
• if you have abnormally low or unstable blood pressure. Your doctor will need to evaluate you accordingly.
• if the patient is under 18 years of age. In children under 16 years of age 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 long-term (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 cancer (e.g., temsirolimus, sirolimus, everolimus).
• Vildagliptin, a medication used to treat diabetes.

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

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

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, or to other medications for fever or rheumatism different from acetylsalicylic acid or to other substances that cause allergies.
• if you suffer from any other type of allergy (e.g., skin reactions, itching, hives).
• if you have bronchial asthma, hay fever, nasal mucosa inflammation, or chronic lung diseases.
• before undergoing surgery or minor 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, fever, or inflammation (different from non-steroidal anti-inflammatory medications like ibuprofen), corticosteroids (to treat allergy or inflammation), or antidepressants like selective serotonin reuptake inhibitors (SSRIs)
• if you are taking or have taken in the last 7 days a medication that contains fusidic acid (used to treat bacterial infections) orally or by injection. The combination of fusidic acid and Trinomia can cause serious 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 "sartans" - e.g., valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
  • Aliskiren
• Your doctor may need to check your kidney function, blood pressure, and blood electrolyte levels (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 enzyme glucose-6-phosphate dehydrogenase.
• if you are at risk of developing gout, as acetylsalicylic acid can reduce the excretion of uric acid. In certain circumstances, this could lead to a gout attack.
• your doctor will perform a blood test before you start taking Trinomia and, possibly, at regular intervals during treatment, to assess the risk of you suffering from muscle-related side effects.
• if you drink large amounts of alcohol.
• if you have severe respiratory failure.
• if you have lost a large amount of salts or fluids from the body (due to vomiting, diarrhea, excessive sweating, low-salt diet, long-term use of diuretics, or dialysis treatment).
• if you are undergoing treatment to reduce allergic reactions to bee or wasp stings (desensitization).
• if you have high levels of potassium in the blood (detected in blood tests).
• if you have a collagen vascular 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 can sometimes worsen the disease or cause myasthenia to appear (see section 4).

Immediately contact your doctor if you experience pain, sensitivity, or muscle weakness of unknown origin. This is because, in rare cases, muscle disorders can be severe, such as muscle destruction that causes kidney damage; in very rare cases, it has led to the patient's death.

Also, inform your doctor or pharmacist if you have constant 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 are in any of the following cases:

• if you have had a previous stroke with bleeding in the brain, or have small fluid-filled sacs in the brain due to previous strokes.
• you have kidney problems.
• you have thyroid problems.
• you have ever had muscle problems during treatment with other lipid-lowering medications (e.g., other statins or fibrates).
• you or a close relative have hereditary muscle disorders.
• you regularly consume large amounts of alcohol.
• you are over 70 years old.

If so, your doctor will ask you to have a blood test before and, possibly, during treatment, to assess the risk of you suffering from muscle-related side effects.

It is known that the risk of muscle-related side effects, e.g., rhabdomyolysis, increases when certain medications are taken at the same time (see Section 2. Taking Trinomia with other medications).

While taking this medication, your doctor will closely monitor you if you are diabetic or at risk of developing diabetes. You are at risk of developing diabetes if you have high levels of sugar and fat in the blood, are overweight, and have high blood pressure.

It is generally recommended to correct dehydration, hypovolemia, or reduction of mineral salts before starting treatment (in patients with heart failure, however, such correction should be carefully evaluated against the risk of volume overload).

Taking Trinomia with other medications

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

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

• Anticoagulants (e.g., coumarin and heparin) and medications to dissolve blood clots, as they can increase the risk of bleeding. Pay close attention to signs of internal and external bleeding (e.g., bruising) before starting treatment with these medications.
• Other platelet aggregation inhibitors (medications that inhibit the cohesion or agglutination of blood platelets) such as ticlopidine and clopidogrel, as they can increase the risk of bleeding.
• Medications containing cortisone or cortisone-like substances, such as prednisolone (except for products applied to the skin or treatment with cortisone for Addison's disease), as they increase the risk of side effects in the digestive tract.
• Other pain or inflammation medications (non-steroidal anti-inflammatory medications like ibuprofen or indomethacin) and for rheumatism, as they generally increase the risk of bleeding and gastrointestinal ulcers.
• Medications to reduce blood sugar levels (antidiabetics), as they can cause low blood sugar levels.
• Digoxin (a medication to strengthen the heart).
• Methotrexate (treatment for cancer and certain rheumatic diseases).
• Valproic acid for the treatment of seizures (epilepsy).
• Selective serotonin reuptake inhibitors (for the treatment of depression), as they can increase the risk of bleeding in the digestive tract.
• Cyclosporine (a medication commonly used in patients undergoing organ transplants).
• Vancomycin (an antibiotic), as it can cause hearing problems.

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

• Medications that increase urine excretion (diuretics; aldosterone antagonists, such as spironolactone and canrenoate; loop diuretics, such as furosemide).
• Medications that enhance uric acid excretion (such as probenecid and benzbromarone)
• Ibuprofen: may reduce the antiplatelet 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 stick together 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).
• Antacids (for the treatment of indigestion).
• Barbiturates (for the treatment of convulsive disorders).
• Zidovudine (for the treatment of HIV).
• Phenytoin (for the treatment of epilepsy).
• Acetylsalicylic acid may alter the results of blood and urine tests.

Trinomia contains atorvastatin, a substance that can affect how other medications work. Additionally, some medications can affect how Trinomia works. Moreover, it could increase the risk of side effects or their intensity, including the serious muscle disorder described in the previous section "Warnings and precautions"). Consult your doctor if you are taking any of the following medications:

• Cyclosporine (a medication commonly used in patients undergoing organ transplants).
• Certain antibiotics or antifungals, such as erythromycin, clarithromycin, telithromycin, ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole, rifampicin
• If you need to take oral fusidic acid to treat a bacterial infection, you will need to stop using this medication. Your doctor will indicate when you can restart treatment with Trinomia. The use of Trinomia with fusidic acid can cause muscle weakness, sensitivity, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.
• Medications for the treatment of HIV, 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.
• Certain medications used to treat hepatitis C, e.g., telaprevir, boceprevir, and the combination of elbasvir/grazoprevir.
• Certain 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 reduce blood clots), oral contraceptives, stiripentol (an anticonvulsant for the treatment of epilepsy), phenazone (a pain reliever), cimetidine (an H2 receptor antagonist), colchicine (used to treat gout), and antacids (products to treat indigestion that contain aluminum or magnesium).
• Over-the-counter medications: Hypericum or St. John's Wort

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

• Medications for cancer (chemotherapy).
• Medications to prevent organ rejection after transplantation, such as cyclosporine.
• Diuretics such as furosemide.
• Medications that can increase potassium levels in the blood, such as spironolactone, triamterene, amiloride, potassium salts, and heparin (to prevent blood clots).
• Steroidal medications for inflammation, 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 for hypotension, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, or adrenaline. Your doctor should 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 should 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 are in any of the above cases (or are unsure), consult your doctor before taking Trinomia.

Taking Trinomia with food, drinks, and alcohol

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

Grapefruit juice contains one or more compounds that alter the way the body uses medications, including Trinomia. Grapefruit juice should be avoided.

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 are planning to become pregnant.

3. How to take Trinomia

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

Taking this medication

• 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 suitable dose for you, based on your state of health, current treatment, and personal risks.

If you take more Trinomia than you should

Dizziness and ringing in the ears, especially in elderly patients, can be symptoms of severe poisoning.

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology 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 normal dose with the next intake.
• Do not take a double dose to make up for forgotten doses.

If you interrupt treatment with Trinomia

Do not interrupt 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.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

The assessment of adverse effects is based on the following frequency table:

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

• In very rare cases, tar-like stools or vomiting blood (signs of severe stomach bleeding) have been reported.
• In rare cases, allergic skin reactions, respiratory tract, gastrointestinal tract, and cardiovascular system reactions have been reported, especially in asthmatic patients. The following symptoms may occur: low blood pressure, difficulty breathing, rhinitis, nasal congestion, allergic shock, swelling of the face, tongue, and larynx (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 clotting), have been reported.
• Pain, sensitivity, weakness, muscle rupture, muscle cramps, or change in urine color to reddish-brown. If weakness, muscle sensitivity, pain, or change in urine color to reddish-brown occurs, along with a feeling of discomfort or high temperature, it may be due to abnormal muscle destruction that can be potentially fatal and cause kidney problems. In very rare cases, patient death has occurred.
• In rare cases, hypersensitivity reactions (allergic reactions), such as swelling of the face, tongue, and throat, with subsequent difficulty breathing or swallowing, as well as itching and skin rashes, have been reported.
• Severe disease with intense peeling and inflammation of the skin, 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 yellowing of the skin and eyes, itching, dark urine, or pale stools, and liver failure (very rare) have been reported.
• In rare cases, pancreatitis, often with severe abdominal pain, has been reported.
• Lupus-like syndrome (including rash, joint disorders, and effects on blood cells).

Contact your doctor immediately if you experience:

• Accelerated heart rate, irregular heartbeats, or violent heartbeats (palpitations), chest pain or pressure, or more serious problems, such as a heart attack or stroke.
• Shortness of breath or cough. These may be symptoms of lung problems.
• Easy bruising, bleeding for longer than usual, any sign of bleeding (e.g., from the gums), purple spots or patches on the skin, or more frequent infections, sore throat, and fever, feeling of tiredness, weakness, dizziness, or paleness. These may be symptoms of blood or bone marrow problems.
• Severe stomach pain that can radiate to the back. This may be a symptom of pancreatitis (inflammation of the pancreas).
• Fever, chills, fatigue, loss of appetite, stomach pain, nausea, yellowing of the skin or eyes (jaundice). These may be symptoms of liver problems, such as hepatitis (inflammation) or liver damage.

Adverse Effects of Aspirin, Atorvastatin, or Ramipril Alone:

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

Aspirin

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

• Gastrointestinal disorders such as heartburn, nausea, vomiting, stomach pain, and diarrhea.
• Mild gastrointestinal bleeding (microbleeding).

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

• Gastrointestinal bleeding and ulcers.
• After long-term administration of Trinomia, iron-deficiency anemia due to occult gastrointestinal bleeding from the gastrointestinal tract may occur.
• Gastrointestinal ulcers may occur, but very rarely perforate the lining.
• Gastrointestinal inflammation.
• Skin reactions.

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

• Nasal bleeding, gum bleeding, skin bleeding, urinary tract bleeding, or reproductive organ bleeding, with prolonged bleeding time. This effect may continue for 4 to 8 days after treatment.

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

• Increased liver function test values.
• Kidney function disorders.
• Reduced blood glucose levels (hypoglycemia).
• At low doses, aspirin reduces uric acid excretion. In patients at risk, this may trigger a gout attack under certain circumstances.
• Skin rashes with fever, affecting the mucous membranes (erythema multiforme).

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

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

Atorvastatin

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. This is more likely to occur if you have high sugar and fat levels in your blood, 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 cavity inflammation, sore throat, nasal bleeding.
• Allergic reactions.
• Increased blood sugar levels (if you have diabetes, carefully monitor your blood sugar levels), increased creatine kinase level in blood.
• Headache.
• Nausea, constipation, flatulence, indigestion, diarrhea.
• Joint pain, muscle pain, and back pain.
• Blood test results indicating abnormal liver function.

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

• Anorexia (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 sensation of pain or touch, changes in taste, memory loss.
• Blurred vision.
• Ringing in the ears and/or head.
• Vomiting, belching, upper and lower abdominal pain, pancreatitis (inflammation of the pancreas that causes stomach pain).
• Hepatitis (inflammation of the liver).
• Skin rash and itching, urticaria, hair loss.
• Neck pain, muscle fatigue.

• Fatigue, feeling of discomfort, weakness, chest pain, swelling, especially of the ankles (edema), increased body temperature.
• Presence of white blood cells in the urine.

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

• Visual disturbances.
• Numbness or tingling in the fingers of the hands and feet.
• Unexpected bleeding or bruising.
• Cholestasis (yellowing of the skin and eyes).
• Tendon lesions.

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

• Allergic reaction, with symptoms such as sudden wheezing and chest pain or tightness, swelling of the eyelids, face, lips, mouth, tongue, or throat, difficulty breathing, and collapse.
• Hearing loss.
• Gynecomastia (breast enlargement in men and women).
• Severe liver problems.

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

• Constant muscle weakness.
• Severe myasthenia (a disease that causes generalized muscle weakness that, in some cases, affects the muscles used for breathing).
• Ocular myasthenia (a disease that causes weakness of the eye muscles).

Consult your doctor if you experience weakness in your arms or legs that worsens after periods of activity, double vision, or drooping eyelids, difficulty swallowing, or difficulty breathing.

Ramipril

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

• Headache and feeling of tiredness.
• Feeling of dizziness. This is more likely to occur when starting treatment with Trinomia or when starting to take a high dose.
• Fainting, hypotension (abnormally low blood pressure), especially when standing up or sitting down quickly.
• Dry cough, nasal sinus inflammation (sinusitis) or bronchitis, feeling of shortness of breath.
• Stomach or intestinal pain, diarrhea, indigestion, nausea.
• Skin rash with or without hives.
• Chest pain.
• Muscle cramps or pain.
• High potassium levels in the blood.

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

• Balance problems (vertigo).
• Itching and abnormal skin sensations, such as numbness, tingling, pinching, burning, or numbness (paresthesia).
• Loss or changes in taste.
• Sleep problems.
• Feeling of depression, anxiety, nervousness, or restlessness.
• Nasal congestion, difficulty breathing, or worsening of asthma.
• Intestinal angioedema (a type of intestinal inflammation) that manifests with symptoms such as abdominal pain, vomiting, and diarrhea.
• Heartburn, constipation, or dry mouth.
• Increased urination frequency.

• Increased sweating.
• Loss or decreased appetite (anorexia).
• Accelerated heart rate or irregular heartbeats.
• Swelling of arms and legs. This may be a symptom of the body retaining more fluids than usual.
• Flushing.
• Blurred vision.
• Joint pain.
• Fever.
• Impotence in men, reduced sexual desire in both men and women.
• Increased number of a certain type of white blood cell in the blood (eosinophilia).
• Changes in liver, pancreas, or kidney function, detected in blood tests.

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

• Feeling of instability or confusion.
• Red and swollen tongue.
• Intense skin peeling, itching, skin rash.
• Nail problems (e.g., nail loss or separation from the nail bed).
• Skin spots and cold extremities.
• Tearing, redness, itching, or swelling of the eyes.
• Hearing disorders and ringing in the ears.
• Feeling of weakness.
• Decreased number of red blood cells, white blood cells, or platelets, or decreased hemoglobin levels.

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.
• Very low blood cell count.
• Low sodium levels in the blood.
• Color change in the fingers and toes caused by cold, followed by tingling or painful sensation when warming up (Raynaud's phenomenon).
• Breast enlargement in men.
• Slowed or altered reactions.
• Burning sensation.
• Changes in sense of smell.
• Hair loss.

Adverse Effects of Trinomia (Aspirin, Atorvastatin, or Ramipril)

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

• Gastrointestinal disorders such as heartburn, nausea, vomiting, stomach pain, and diarrhea.
• Mild gastrointestinal bleeding (microbleeding).

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

• Nasal cavity inflammation, sore throat, nasal bleeding.
• Dry cough, nasal sinus inflammation (sinusitis) or bronchitis, feeling of shortness of breath.
• Chest pain.
• Constipation, flatulence, indigestion.
• Stomach or intestinal pain, nausea.
• Headache and feeling of tiredness.
• Feeling of dizziness. This is more likely to occur when starting treatment with Trinomia or when starting to take a high dose.
• Fainting, hypotension (abnormally low blood pressure), especially when standing up or sitting down quickly.
• Allergic reactions.
• Skin rash with or without hives.
• Muscle cramps or pain.
• Joint pain and back pain.
• Blood test results indicating abnormal liver function.
• Increased blood sugar levels (if you have diabetes, carefully monitor your blood sugar levels), increased creatine kinase level in blood.
• High potassium levels in the blood.

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

• Gastrointestinal bleeding and ulcers, but very rarely perforate the lining.
• Gastrointestinal inflammation.
• Anorexia (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 (inflammation of the pancreas that causes stomach pain).
• Intestinal angioedema (a type of intestinal inflammation) that manifests with symptoms such as abdominal pain, vomiting, and diarrhea.
• After long-term administration of Trinomia, iron-deficiency anemia due to occult gastrointestinal bleeding from the gastrointestinal tract may occur.
• Skin reactions.
• Skin rash and itching, urticaria, hair loss.
• Nightmares, insomnia.
• Sleep problems.
• Dizziness, numbness or tingling in the fingers of the hands and feet, decreased sensation of pain or touch, changes in taste, memory loss.
• Balance problems (vertigo).
• Blurred vision.
• Ringing in the ears and/or head.
• Loss or changes in taste.
• Itching and abnormal skin sensations, such as numbness, tingling, pinching, burning, or numbness (paresthesia).
• Feeling of depression, anxiety, nervousness, or restlessness.
• Hepatitis (inflammation of the liver).
• Neck pain, muscle fatigue.
• Fatigue, feeling of discomfort, weakness, chest pain, swelling, especially of the ankles (edema), increased body temperature.
• Nasal congestion, difficulty breathing, or worsening of asthma.
• Dry mouth.
• Increased sweating.
• Increased urination frequency.
• Swelling of arms and legs. This may be a symptom of the body retaining more fluids than usual.
• Flushing.
• Fever.
• Accelerated heart rate or irregular heartbeats.
• Impotence in men, reduced sexual desire in both men and women.
• Presence of white blood cells in the urine.
• Increased number of a certain type of white blood cell in the blood (eosinophilia).
• Changes in liver, pancreas, or kidney function, detected in blood tests.

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

• Nasal bleeding, gum bleeding, skin bleeding, urinary tract bleeding, or reproductive organ bleeding, with prolonged bleeding time. This effect may continue for 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.
• Cholestasis (yellowing of the skin and eyes).
• Tendon lesions.
• Feeling of instability or confusion.
• Red and swollen tongue.
• Intense skin peeling, itching, skin rash.
• Nail problems (e.g., nail loss or separation from the nail bed).
• Skin spots and cold extremities.
• Tearing, redness, itching, or swelling of the eyes.
• Hearing disorders.
• Decreased number of red blood cells, white blood cells, or platelets, or decreased hemoglobin levels.

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

• Increased liver function test values.
• Severe liver problems.

5. Storage of Trinomia

Keep this medicine out of sight and reach of children.

Store below 25°C.

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

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point in your pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Trinomia100 mg/40 mg/5 mg hard capsules

• The active ingredients are acetylsalicylic acid, atorvastatin, and ramipril. Each capsule contains 100 mg of acetylsalicylic acid, 40 mg of atorvastatin (as atorvastatin calcium trihydrate), and 5 mg of ramipril.

• The other components (excipients) are:

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

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

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

Appearance of Trinomia and package contents

Trinomia 100 mg/40 mg/5 mg hard capsules consist of hard gelatin capsules, size 0 (approximate length 21.7 mm), with an opaque orange cap and an opaque white body, which are printed with the legend "AAR 100/40/5" and contain: 2 film-coated tablets, white or off-white in color, with 50 mg of acetylsalicylic acid, with the letters "AS" engraved; 2 film-coated tablets, pink in color, with 20 mg of atorvastatin, with the letters "AT" engraved; 1 film-coated tablet, pale yellow in color, with 5 mg of ramipril, with the letters "R5" engraved.

Trinomia 100 mg/40 mg/5 mg hard capsules are marketed in blister packs, in boxes containing 7, 14, 28, 56, 84, or 98 capsules.

Only certain package sizes may be marketed.

Marketing authorization holderand manufacturer

You can request more information about this medicine by contacting the marketing authorization holder.

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

Belgium: Trinomia 100 mg/40 mg/5 mg capsules

Bulgaria: Trinomia 100 mg/40 mg/5 mg ?????? ???????

Germany: Iltria 100 mg/40 mg/5 mg hard capsules

Finland: Trinomia 100 mg/40 mg/5 mg capsule, hard

France: Iltria 100 mg/40 mg/5 mg capsules

Greece: Trinomia 100 mg/40 mg/5 mg καψ?κια σκληρ?

Ireland: Trinomia 100 mg/40 mg/5 mg hard capsules

Italy: Trinomia 100 mg/40 mg/5 mg capsule rigide

Austria: Trinomia 100 mg/40 mg/5 mg hard capsules

Poland: Trinomia 100 mg/40 mg/5 mg kapsulki twarde

Portugal: Trinomia 100 mg/40 mg/5 mg capsules

Romania: Trinomia 100 mg/40 mg/5 mg capsule

Spain: Trinomia 100 mg/40 mg/5 mg hard capsules

Sweden: Trinomia 100 mg/40 mg/5 mg capsules, hard

Czech Republic: Trinomia 100 mg/40 mg/5 mg tvrdé tobolky

Date of last revision of this prospectus:March 2023

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/