APIXABAN NORMOGEN 2.5 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Apixaban Normogen 2.5 mg film-coated tablets EFG

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Apixaban Normogen and what is it used for
2. What you need to know before you take Apixaban Normogen
3. How to take Apixaban Normogen
4. Possible side effects
5. Storage of Apixaban Normogen
6. Contents of the pack and other information

1. What is Apixaban Normogen and what is it used for

Apixaban Normogen contains the active substance apixaban and belongs to a group of medicines called anticoagulants. This medicine helps to prevent the formation of blood clots by blocking Factor Xa, an important component of blood clotting.

Apixaban Normogen is used in adults:

• to prevent the formation of blood clots (deep vein thrombosis [DVT]) after hip or knee replacement surgery. After hip or knee replacement surgery, you may have a higher risk of blood clots forming in the veins of your legs. This can cause swelling in your legs, with or without pain. If a blood clot travels from your leg to your lungs, it can block the flow of blood, causing difficulty breathing, with or without chest pain. This medical condition (pulmonary embolism) can be life-threatening and requires immediate medical attention.

• to prevent the formation of a blood clot in the heart in patients with an irregular heartbeat (atrial fibrillation) and at least one additional risk factor. Blood clots can break loose, travel to the brain, and cause a stroke, or travel to other organs and prevent proper irrigation of the organ (also known as systemic embolism). A stroke can be life-threatening and requires immediate medical attention.

• to treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent these blood clots from recurring in the blood vessels of the legs and/or lungs.

2. What you need to know before you take Apixaban Normogen

Do not take Apixaban Normogen if

• you are allergicto apixaban or any of the other ingredients of this medicine (listed in section 6);

• you have excessive bleeding;
• you have an organ diseasethat increases the risk of severe bleeding (such as an active or recent stomach or intestinal ulcer, or recent brain hemorrhage);

• you have a liver diseasethat increases the risk of bleeding (hepatic coagulopathy);
• you are taking medicines to prevent blood clotting(e.g., warfarin, rivaroxaban, dabigatran, or heparin), except when switching treatment, while having an arterial or venous line and being treated with heparin to keep the line open, or when having a tube inserted into a blood vessel (catheter ablation) to treat an irregular heartbeat (arrhythmia).

Warnings and precautions

Tell your doctor, pharmacist, or nurse before taking this medicine if you have any of these conditions:

• an increased risk of bleeding, such as:
• • bleeding disorders, including situations that result in a decrease in platelet activity;
  • very high blood pressure, not controlled by medical treatment;
  • you are over 75 years old;
  • you weigh 60 kg or less;
• severe kidney disease or if you are on dialysis;
• a liver problem or history of liver problems;
• • This medicine will be used with caution in patients with signs of altered liver function
• you have had a catheter or received an injection in your spine(for anesthesia or pain relief), your doctor will tell you to wait at least 5 hours after removing the catheter before taking this medicine;
• you have a heart valve prosthesis;
• if your doctor determines that your blood pressure is unstable or you are scheduled to receive another treatment or undergo surgery to remove the blood clot from your lungs.

Be careful with Apixaban Normogen

• if you know you have a disease called antiphospholipid syndrome (a disorder of the immune system that increases the risk of blood clots), inform your doctor to decide if it may be necessary to modify the treatment.

If you need to have surgery or a procedure that may cause bleeding, your doctor will tell you to temporarily stop taking this medicine for a period of time. If you are not sure if a procedure may cause bleeding, ask your doctor.

Children and adolescents

This medicine is not recommended for use in children and adolescents under 18 years of age.

Using Apixaban Normogen with other medicines

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use other medicines.

Some medicines may increase the effects of Apixaban Normogen and some medicines may decrease its effects. Your doctor will decide if you should be treated with Apixaban Normogen if you are taking these medicines and if you should be kept under closer observation.

The following medicines may increase the effects of Apixaban Normogen and increase the risk of unwanted bleeding:

• some antifungal medicines(e.g., ketoconazole, etc.);
• some antiviral medicines for HIV/AIDS(e.g., ritonavir);
• other medicines to reduce blood clotting(e.g., enoxaparin, etc.);
• anti-inflammatory medicinesor medicines to relieve pain(e.g., acetylsalicylic acid or naproxen). Especially if you are over 75 years old and taking acetylsalicylic acid, there is a higher likelihood of bleeding;
• medicines for high blood pressure or heart problems(e.g., diltiazem);
• antidepressantscalled selective serotonin reuptake inhibitorsor serotonin-noradrenaline reuptake inhibitors.

The following medicines may reduce the ability of Apixaban Normogen to prevent blood clots:

• medicines for the treatment of epilepsy or convulsions(e.g., phenytoin, etc.);
• St. John's Wort(a herbal medicine for the treatment of depression);
• medicines to treat tuberculosisor other infections(e.g., rifampicin).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor, pharmacist, or nurse for advice before taking this medicine.

The effects of Apixaban Normogen on pregnancy and the fetus are not known. You should not take this medicine if you are pregnant. Tell your doctor, pharmacist, or nurse immediatelyif you become pregnant while taking this medicine.

It is not known if Apixaban Normogen is excreted in human milk. Ask your doctor or pharmacist before taking this medicine during breastfeeding. They will tell you whether to stop breastfeeding or whether to stop or not start taking this medicine.

Driving and using machines

Apixaban Normogen has no influence on the ability to drive or use machines.

Apixaban Normogen contains lactose (a type of sugar) and sodium

If your doctor has told you that you have an intolerance to certain sugars, talk to them before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which is essentially "sodium-free".

3. How to take Apixaban Normogen

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, ask your doctor, pharmacist, or nurse.

Dosage

Take the tablet with water. Apixaban Normogen can be taken with or without food. Try to take the tablets at the same time each day to achieve a better effect of the treatment.

If you have difficulty swallowing the tablet whole, talk to your doctor about other possible ways to take Apixaban Normogen. The tablet can be crushed and mixed with water, 5% glucose in water, apple juice, or apple puree, immediately before taking it.

Instructions for crushing:

• Crush the tablets with a mortar.
• Transfer all the powder carefully into a suitable container, mixing the powder with a small amount, e.g., 30 ml (2 tablespoons), of water or one of the other liquids mentioned to make the mixture.
• Take the mixture.
• Rinse the mortar and pestle used to crush the tablet and the container with a small amount of water or one of the other liquids (e.g., 30 ml), and take that liquid.

If necessary, your doctor may also administer the crushed Apixaban Normogen tablet mixed in 60 ml of water or 5% glucose in water through a nasogastric tube.

Take Apixaban Normogen according to the following recommendations:

For preventing the formation of blood clots in hip or knee replacement surgery.

The recommended dose of Apixaban Normogen is one 2.5 mg tablet twice a day. For example, take one tablet in the morning and one in the evening.

You should take the first tablet between 12 and 24 hours after surgery.

If you have had major hipsurgery, you will usually take the tablets for a period of 32 to 38 days.

If you have had major kneesurgery, you will usually take the tablets for a period of 10 to 14 days.

For preventing the formation of a blood clot in the heart in patients with an irregular heartbeat and at least one additional risk factor.

The recommended dose of Apixaban Normogen is one 5 mg tablet twice a day.

The recommended dose is one 2.5 mg tablet twice a day if:

• you have severely decreased kidney function;
• you have two or more of the following factors:
• • your blood test results suggest poor kidney function (the serum creatinine value is 1.5 mg/dl (133 micromoles/l) or higher);
  • you are 80 years old or older;
  • your weight is 60 kg or less.

The recommended dose is one tablet twice a day, for example, take one tablet in the morning and one in the evening.

Your doctor will tell you how long you should continue the treatment.

For treating blood clots in the veins of the legs and in the blood vessels of the lungs.

The recommended dose is two 5 mg tabletsof Apixaban Normogen twice a day for the first 7 days, for example, two tablets in the morning and two tablets in the evening.

After 7 days, the recommended dose is one 5 mg tabletof Apixaban Normogen twice a day, for example, one tablet in the morning and one in the evening.

For preventing blood clots from recurring after 6 months of treatment.

The recommended dose is one 2.5 mg tablet of Apixaban Normogen twice a day, for example, one tablet in the morning and one in the evening.

Your doctor will tell you how long you should continue the treatment.

Your doctor may change your anticoagulant treatment as follows:

• Changing from Apixaban Normogen to anticoagulant medicines

Stop taking Apixaban Normogen. Start treatment with anticoagulant medicines (e.g., heparin) at the time you would take the next Apixaban Normogen tablet.

• Changing from anticoagulant medicines to Apixaban Normogen

Stop taking anticoagulant medicines. Start treatment with Apixaban Normogen at the time you would take the next dose of an anticoagulant medicine, and then continue as usual.

• Changing from treatment with anticoagulants that contain vitamin K antagonists (e.g., warfarin) to Apixaban Normogen

Stop taking the medicine that contains a vitamin K antagonist. Your doctor will need to perform blood tests and tell you when to start taking Apixaban Normogen.

• Changing from Apixaban Normogen to treatment with anticoagulants that contain vitamin K antagonists (e.g., warfarin)

If your doctor tells you to start taking a medicine that contains a vitamin K antagonist, continue taking Apixaban Normogen for at least 2 days after your first dose of the medicine that contains a vitamin K antagonist. Your doctor will need to perform blood tests and tell you when to stop taking Apixaban Normogen.

Patients undergoing cardioversion

If your heartbeat needs to be restored through a process called cardioversion, take this medicine at the times your doctor tells you to prevent blood clots in the blood vessels of the brain and other blood vessels in the body.

If you take more Apixaban Normogen than you should

Tell your doctor immediatelyif you have taken a higher dose of this medicine than prescribed. Take the package of the medicine to your doctor, even if there are no tablets left.

If you take more Apixaban Normogen than the recommended dose, you may increase the risk of bleeding. If bleeding occurs, surgery, blood transfusions, or other treatments that can reverse the anti-factor Xa activity may be necessary.

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 medicine and the amount taken.

If you forget to take Apixaban Normogen

• Take the dose as soon as you remember and:
• • take the next dose of Apixaban Normogen at the usual time
  • then continue taking the medicine as usual.

If you are unsure what to do or if you forget to take more than one dose, ask your doctor, pharmacist, or nurse.

If you stop taking Apixaban Normogen

Do not stop taking this medicine without talking to your doctor first, because the risk of developing a blood clot may be higher if you stop the treatment too soon.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Apixabán Normogen can be administered in three different diseases. The known adverse effects and the frequency with which they occur may be different and, therefore, are indicated separately below. For those conditions, the most frequent adverse effect of this medicine is bleeding, which can put the patient's life at risk and requires immediate medical attention.

The following adverse effects have been reported when taking Apixabán Normogen to prevent the formation of blood clots in hip or knee replacement surgeries.

Frequent Adverse Effects (may affect up to 1 in 10 people)

• Anemia, which can cause fatigue or paleness;
• Bleeding, including:
• • hematoma and swelling;
• Nausea (general discomfort).

Uncommon Adverse Effects (may affect up to 1 in 100 people)

• Decrease in the number of platelets in the blood (which can affect coagulation);
• Bleeding:
• • after surgery, including hematoma and swelling, bleeding or fluid secretion from the wound/surgical incision (suppuration), or at the injection site;
  • from the stomach, intestine, or blood in the stool;
  • blood in the urine;
  • from the nose;
  • vaginal;
• Low blood pressure that can cause fainting or a faster heart rate;
• Blood tests may show:
• • abnormal liver function;
  • increased liver enzymes;
  • increased bilirubin, a byproduct of red blood cells, which can cause yellowing of the skin and eyes;
  • Itching.

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

• Allergic reactions (hypersensitivity) that can cause: swelling of the face, lips, mouth, tongue, and/or throat, and difficulty breathing. Inform your doctor immediately if you experienceany of these symptoms.
• Bleeding:
• in a muscle;
• in the eyes;
• from the gums and coughing up blood;
• from the rectum;
• Hair loss.

Unknown Frequency (cannot be estimated from available data)

• Bleeding:
• in the brain or spinal cord;
• in the lungs or throat;
• in the mouth;
• in the abdomen or the space behind the abdominal cavity;
• hemorrhoidal;
• tests showing blood in the stool or urine;
• Skin rash that can form blisters and resemble small targets (dark spots in the center surrounded by a paler area, with a dark ring around) (erythema multiforme);
• Inflammation of the blood vessels (vasculitis) that can cause skin rash, appearance of red, round, and smooth spots under the skin surface or hematomas.

The following adverse effects have been reported when taking Apixabán Normogen to prevent the formation of blood clots in the heart in patients with irregular heartbeats and at least one additional risk factor.

Frequent Adverse Effects (may affect up to 1 in 10 people)

• Bleeding, including:
• in the eyes;
• in the stomach or intestine;
• from the rectum;
• blood in the urine;
• from the nose;
• from the gums;
• hematoma and swelling;
• Anemia, which can cause fatigue or paleness;
• Low blood pressure that can cause fainting or a faster heart rate;
• Nausea (general discomfort);
• Blood tests may show:
• an increase in gamma glutamyl transferase (GGT).

Uncommon Adverse Effects (may affect up to 1 in 100 people)

• Bleeding:
• in the brain or spinal cord;
• in the mouth or coughing up blood;
• in the abdomen or vagina;
• bright/red blood in the stool;
• bleeding after surgery, including hematoma and swelling, bleeding or fluid secretion from the wound/surgical incision (suppuration), or at the injection site;
• hemorrhoidal;
• tests showing blood in the stool or urine;
• Decrease in the number of platelets in the blood (which can affect coagulation);
• Blood tests may show:
• abnormal liver function;
• increased liver enzymes;
• increased bilirubin, a byproduct of red blood cells, which can cause yellowing of the skin and eyes;
• Skin rash;
• Itching;
• Hair loss;
• Allergic reactions (hypersensitivity) that can cause: swelling of the face, lips, mouth, tongue, and/or throat, and difficulty breathing. Inform your doctor immediately if you experienceany of these symptoms.

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

• Bleeding:
• in the lungs or throat;
• within the space behind the abdominal cavity;
• in a muscle.

Very Rare Adverse Effects (may affect up to 1 in 10,000 people)

• Skin rash that can form blisters and resemble small targets (dark spots in the center surrounded by a paler area, with a dark ring around) (erythema multiforme).

Unknown Frequency (cannot be estimated from available data)

• Inflammation of the blood vessels (vasculitis) that can cause skin rash, appearance of red, round, and smooth spots under the skin surface or hematomas.

The following adverse effects have been reported when taking Apixabán Normogen to treat or prevent blood clots from recurring in the veins of the legs and in the blood vessels of the lungs.

Frequent Adverse Effects (may affect up to 1 in 10 people)

• Bleeding, including:
• from the nose;
• from the gums;
• blood in the urine;
• hematoma and swelling;
• from the stomach, intestine, or rectum;
• in the mouth;
• vaginal;
• Anemia, which can cause fatigue or paleness;
• Decrease in the number of platelets in the blood (which can affect coagulation);
• Nausea (general discomfort);
• Skin rash;
• Blood tests may show:
• an increase in gamma glutamyl transferase (GGT) or alanine aminotransferase (GPT).

Uncommon Adverse Effects (may affect up to 1 in 100 people)

• Low blood pressure that can cause fainting or a faster heart rate
• Bleeding:
• in the eyes;
• in the mouth or coughing up blood;
• bright/red blood in the stool;
• tests showing blood in the stool or urine;
• bleeding after surgery, including hematoma and swelling, bleeding or fluid secretion from the wound/surgical incision (suppuration); or at the injection site;
• hemorrhoidal;
• in a muscle;
• Itching;
• Hair loss;
• Allergic reactions (hypersensitivity) that can cause: swelling of the face, lips, mouth, tongue, and/or throat, and difficulty breathing. Contact your doctor immediately if you experienceany of these symptoms.
• Blood tests may show:
• abnormal liver function;
• increased liver enzymes;
• increased bilirubin, a byproduct of red blood cells, which can cause yellowing of the skin and eyes.

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

Bleeding:

• in the brain or spinal cord;
• in the lungs.

Unknown Frequency (cannot be estimated from available data)

• Bleeding:
• in the abdomen or the space behind the abdominal cavity.
• Skin rash that can form blisters and resemble small targets (dark spots in the center surrounded by a paler area, with a dark ring around) (erythema multiforme);
• Inflammation of the blood vessels (vasculitis) that can cause skin rash, appearance of red, round, and smooth spots under the skin surface or hematomas.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Apixabán Normogen

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging and on each blister, after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be disposed of through wastewater or household waste. 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 Apixabán Normogen

• The active ingredient is apixaban. Each tablet contains 2.5 mg of apixaban.
• The other components (excipients) are:

Tablet core:anhydrous lactose; microcrystalline cellulose (type 14); microcrystalline cellulose (type 101); sodium croscarmellose; sodium lauryl sulfate; magnesium stearate. See section 2 "Apixabán Normogen contains lactose (a type of sugar) and sodium".

Tablet coating:lactose monohydrate; hypromellose (E464); titanium dioxide (E171); triacetin; yellow iron oxide (E172).

Appearance and Package Contents

The film-coated tablets are yellow and round, with a diameter of 6.0 mm ± 0.2 mm.

They are presented in blisters within cartons containing 20 and 60 film-coated tablets.

Only some pack sizes may be marketed.

Patient Information Card: Information Management

Inside the packaging of Apixabán Normogen, along with the prospectus, you will find a Patient Information Card or your doctor may give you a similar card.

This Patient Information Card includes useful information for you and will alert other doctors that you are being treated with Apixabán Normogen. You must keep this card with you at all times.

1. Take the card.
2. Separate the language you need (this is facilitated through the perforated ends).
3. Complete the following sections or ask your doctor to complete them:
   • Name:
   • Date of birth:
   • Indication:
   • Dose: ____ mg twice a day
   • Doctor's name:
   • Doctor's phone number:
4. Fold the card and carry it with you at all times.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Manufacturer

Atlantic Pharma – Produções Farmacêuticas, S.A.

Rua da Tapada Grande, n.º 2

Abrunheira, 2710-089 Sintra

Portugal

This medicine is authorized in the EEA member states under the following names:

Spain, Apixabán Normogen 2.5 mg film-coated tablets EFG

Portugal, Apixabano Normogen

Date of the last revision of this prospectus:

December 2022

Other Sources of Information

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