APIXABAN COMBIX 5 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Apixaban Combix 5 mg Film-Coated Tablets EFG

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, pharmacist, or nurse.
• 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, pharmacist, or nurse, even if they are not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Apixaban Combix and what is it used for
2. What you need to know before taking Apixaban Combix
3. How to take Apixaban Combix
4. Possible side effects
5. Storage of Apixaban Combix
6. Package Contents and Additional Information

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

Apixaban Combix contains the active substance apixaban and belongs to a group of medications called anticoagulants. This medication helps prevent the formation of blood clots by blocking Factor Xa, an important element in blood coagulation.

Apixaban is used in adults:

• 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, move to the brain, and cause a stroke, or move to other organs, preventing proper irrigation (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 taking Apixaban Combix

Do not takeApixaban Combix:

• if you are allergicto apixaban or any of the other components of this medication (listed in section 6)
• if you bleed excessively
• if you have an organ diseasethat increases the risk of severe bleeding (such as an active or recent stomach or intestinal ulcer, or recent cerebral hemorrhage)
• if you have a liver diseasethat increases the risk of bleeding (hepatic coagulopathy)
• if you are taking medications to prevent blood coagulation(e.g., warfarin, rivaroxaban, dabigatran, or heparin), except when switching to a different anticoagulant treatment, while having an arterial or venous line and being treated with heparin to keep the line open, or when a tube is inserted into a blood vessel (catheter ablation) to treat an irregular heartbeat (arrhythmia).

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting to take this medication if you have any of the following conditions:

• increased risk of bleeding, such as:
• • bleeding disorders, including situations that result in decreased platelet activity
  • uncontrolled high blood pressure
  • you are over 75 years old
  • you weigh 60 kg or less
• severe kidney disease or if you are on dialysis
• liver disease or history of liver problems
• • This medication will be used with caution in patients with signs of altered liver function
• if 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

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

If you need to undergo surgery or a procedure that may cause bleeding, your doctor will instruct you to temporarily stop taking this medication for a period of time. If you are unsure whether a procedure may cause bleeding, consult your doctor.

Children and Adolescents

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

Other Medications and Apixaban

Inform your doctor, pharmacist, or nurse if you are using, have recently used, or may need to use other medications.

Some medications may increase the effects of apixaban tablets, and some medications may decrease their effects. Your doctor will decide if you should be treated with apixaban tablets if you are taking these medications and if you should be monitored more closely.

The following medications may increase the effects of apixaban tablets and increase the risk of unwanted bleeding:

• some fungal infection medications(e.g., ketoconazole, etc.)
• some antiviral medications for HIV/AIDS(e.g., ritonavir)
• other medications to reduce blood coagulation(e.g., enoxaparin, etc.)
• anti-inflammatory or pain-relieving medications(e.g., acetylsalicylic acid or naproxen). In particular, if you are over 75 years old and taking acetylsalicylic acid, there is a higher likelihood of bleeding.
• medications for high blood pressure or heart problems(e.g., diltiazem)
• antidepressants called selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.

The following medications may reduce the ability of apixaban tablets to prevent blood clot formation:

• medications for the treatment of epilepsy or seizures(e.g., phenytoin, etc.)
• St. John's Wort(a plant-based supplement for the treatment of depression)
• medications to treat tuberculosis or other infections(e.g., rifampicin)

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor, pharmacist, or nurse before using this medication.

The effects of apixaban tablets on pregnancy and the fetus are unknown. You should not take this medication if you are pregnant and should contact your doctor immediatelyif you become pregnant while taking this medication.

It is unknown whether apixaban tablets are excreted in human milk. Ask your doctor, pharmacist, or nurse before taking this medication during breastfeeding. They will indicate whether to interrupt breastfeeding or whether to stop or not start taking this medication.

Driving and Using Machines

Apixaban tablets have not been shown to decrease the ability to drive or use machines.

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

This medication contains lactose. If your doctor has told you that you have an intolerance to certain sugars, talk to your doctor before taking this medication.

This medication contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially "sodium-free".

3. How to Take Apixaban Combix

Follow the administration instructions for this medication exactly as indicated by your doctor or pharmacist. If you are unsure, consult your doctor, pharmacist, or nurse again.

Dosage

Take the tablet with water. Apixaban tablets can be taken with or without food.

Try to take the tablets at the same time each day to achieve a better treatment effect.

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

Crushing Instructions:

• 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 any 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 tablet mixed in 60 ml of water or 5% glucose in water through a nasogastric tube.

Take apixaban tablets according to the following recommendations:

To prevent 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 is one apixaban 5 mgtablet twice a day.

The recommended dose is one apixaban 2.5 mgtablet twice a day if:

• you have severely impaired kidney function
• two or more of the following factors apply:
• • 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 indicate how long you should continue the treatment.

To treat blood clots in the veins of the legs and in the blood vessels of the lungs

The recommended dose is two tabletsof apixaban 5 mgtwice 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 tabletof apixaban 5 mgtwice a day, for example, one tablet in the morning and one tablet in the evening.

To prevent blood clots from recurring after 6 months of treatment

The recommended dose is one apixaban 2.5 mgtablet twice a day, for example, one tablet in the morning and one tablet in the evening.

Your doctor will indicate how long you should continue the treatment

Your doctor may change your anticoagulant treatment as follows:

• Switching from apixaban tablets to anticoagulant medications

Stop taking apixaban tablets. Start treatment with anticoagulant medications (e.g., heparin) at the time you would take the next apixaban tablet.

• Switching from anticoagulant medications to apixaban tablets

Stop taking anticoagulant medications. Start treatment with apixaban tablets at the time you would take the next dose of an anticoagulant medication, and then continue as usual.

• Switching from a treatment with anticoagulants containing vitamin K antagonists (e.g., warfarin) to apixaban tablets

Stop taking the medication containing a vitamin K antagonist. Your doctor will need to perform blood tests and indicate when to start taking apixaban tablets.

• Switching from apixaban tablets to a treatment with anticoagulants containing vitamin K antagonists (e.g., warfarin).

If your doctor indicates that you should start taking a medication containing a vitamin K antagonist, continue taking apixaban tablets for at least 2 days after your first dose of the medication containing a vitamin K antagonist. Your doctor will need to perform blood tests and indicate when to stop taking apixaban tablets.

Patients Undergoing Cardioversion

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

If you take more Apixaban Combix than you should

Inform your doctor immediatelyif you have taken a dose larger than the prescribed dose of this medication. Bring the medication package to your doctor, even if there are no tablets left.

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91562 04 20, indicating the medication and the amount ingested.

If you forget to take Apixaban Combix

• Take the dose as soon as you remember and:

• take the next apixaban dose at the usual time
• then continue taking the medication as usual.

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

If you interrupt treatment with Apixaban Combix

Do not interrupt treatment with this medication without first talking to your doctor, as the risk of developing a blood clot may be higher if treatment is interrupted too soon.

If you have any other questions about the use of this medication, 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. 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 apixaban tablets 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
• bruising and swelling

• Anemia, which can cause fatigue or paleness
• Low blood pressure that can cause fainting or a faster heartbeat
• Nausea (general discomfort)
• Blood tests may show:

• an increase in gamma glutamyl transferase (GGT)

Infrequent 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 bruising and swelling, discharge of blood or fluid 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
• increase in some liver enzymes
• increase in 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 immediatelyif you experience any of these symptoms.

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

• Bleeding:

• in the lungs or throat
• in 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 blood vessels (vasculitis) that can cause skin rash, appearance of red, round, and smooth spots under the skin surface, or bruising.
• Bleeding in the kidney, sometimes with blood in the urine, which can cause the kidneys to fail to function properly (anticoagulant-related nephropathy).

The following adverse effects have been reported when taking apixaban tablets to treat or prevent blood clots from recurring in the veins of the legs and 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
• bruising 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).

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

• Low blood pressure that can cause fainting or a faster heartbeat
• 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 bruising and swelling, discharge of blood or fluid 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 experience any of these symptoms.
• Blood tests may show:

• abnormal liver function
• increase in some liver enzymes
• increase in 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 blood vessels (vasculitis) that can cause skin rash, appearance of red, round, and smooth spots under the skin surface, or bruising.
• Bleeding in the kidney, sometimes with blood in the urine, which can cause the kidneys to fail to function properly (anticoagulant-related nephropathy).

Reporting 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 is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Apixaban Combix

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

Do not use this medicine after the expiration date that appears on the packaging and blister pack, 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. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. 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 Apixaban Combix 5 mg film-coated tablets

• The active ingredient is apixaban. Each tablet contains 5 mg of apixaban.
• The other ingredients are:
• Core of the tablet: hypromellose, stearic acid, anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate.
• Coating: lactose monohydrate, hypromellose, titanium dioxide (E171), triacetin, yellow iron oxide (E172), and red iron oxide (E172)

See section 2 "apixaban tablets contain lactose (a type of sugar) and sodium".

Appearance of the Product and Package Contents

Apixaban Combix 5 mg are film-coated tablets of beige color, oval, engraved with "1181" on one side and flat on the other. The length of the tablet is approximately 10.0 mm, and the width is approximately 5.3 mm.

• They are presented in blister packs in packages of 14, 20, 28, 56, 60, 168, and 200 film-coated tablets.
• They are also available in clinical blister packs containing 60x1 film-coated tablets.

Only some package sizes may be marketed.

Patient Information Card: Information Management

Inside the Apixaban Combix package, along with the leaflet, 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 apixaban. You should 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

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

Or

Pharmex Advanced Laboratories S.L.

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

Or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Or

Netpharmalab Consulting Services S.L.

Carretera de Fuencarral 22,

Alcobendas,

28108 Madrid

Spain

Date of the Last Revision of this Leaflet:

May 2025

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