Label: information for the user

Eliquis 2.5mg film-coated tablets

apixaban

Read this label carefully before starting to take this medicine because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section4.

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

Eliquis is used in adults:

• to prevent the formation of blood clots (deep vein thrombosis [DVT]) after a hip or knee replacement surgery. After a hip or knee replacement surgery, you may be at a higher risk of developing blood clots 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 blood flow, 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, move to the brain, and cause a stroke, or move to other organs and prevent proper blood flow (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.

Eliquis is used in children from 28 days to less than 18 years of age to treat blood clots and to prevent these blood clots from recurring in the veins and blood vessels of the lungs.

For the recommended dose based on body weight, see section 3.

Do not take Eliquis if

• you are allergicto apixaban or to any of the other components of this medication (listed in section6);
• you bleed excessively;
• you have acondition in an organof the body that increases the risk of severe bleeding (such asan active or recent stomach or intestinal ulcer,or recent cerebral hemorrhage);
• you have aliver diseasethat increases the risk of bleeding (hepatic coagulopathy);
• you aretaking medications to prevent blood coagulation(e.g., warfarin, rivaroxaban, dabigatrán or heparin), except when changing anticoagulant treatment, while having an arterial or venous catheter and being treated with heparin to keep that catheter open, or when a catheter is inserted into a blood vessel (catheter ablation) to treat an irregular heart rhythm (arrhythmia).

Warnings and precautions

Inform your doctor, pharmacist or nurse before taking this medication if you have any of the following conditions:

• ahigher 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 are75years or older;
• you weigh60kg or less;
• asevere kidney disease or if you are undergoing dialysis;
• aliver problem or a history of liver problems;
• This medication will be used with caution in patients with signs of liver function alteration
• you had a catheter or received an injection in the spinal column(for anesthesia or pain relief), your doctor will instruct you to wait at least 5hours after removing the catheter before taking this medication;
• you have aheart 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 a blood clot from your lungs.

Be especially careful with Eliquis

• 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 so they can decide if your treatment needs to be modified.

If you need 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 if a procedure may cause bleeding, consult your doctor.

Children and adolescents

This medication is not recommended for use in children and adolescents with a body weight of less than 35kg.

Use of Eliquis with other medications

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

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

The following medications may increase the effects of Eliquis and increase the risk of an unwanted bleeding:

• someantifungal medications(e.g., ketoconazol, etc.);
• someantiviral medications for HIV/AIDS(e.g., ritonavir);
• othermedications to prevent blood coagulation(e.g., enoxaparina, etc.);
• anti-inflammatoryorpain-relieving medications(e.g., acetylsalicylic acid or naproxeno). Especially if you are 75years or older and take acetylsalicylic acid, there is a higher risk of bleeding;
• medications for high blood pressure or heart problems(e.g., diltiazem);
• antidepressantscalledselective serotonin reuptake inhibitorsorserotonin-norepinephrine reuptake inhibitors‑noradrenaline.

The following medications may reduce the ability of Eliquis to prevent blood clots:

• medications for the treatment of epilepsy or seizures(e.g., phenytoin, etc.);
• St. John's Wort(a plant-based medication for the treatment of depression);
• medications to treat tuberculosisorother infections(e.g., rifampicina).

Pregnancy and breastfeeding

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

The effects of Eliquis on pregnancy and the fetus are unknown. Do not take this medication if you are pregnant.Inform your doctor, pharmacist or nurse immediatelyif you become pregnant while taking this medication.

The excretion of Eliquis in human milk is unknown. Ask your doctor or pharmacist before taking this medication during breastfeeding. They will instruct you to either stop breastfeeding or to stop or not start taking this medication.

Driving and operating machinery

Eliquis has no influence on the ability to drive or operate machinery.

Eliquis contains lactose (a type of sugar) and sodium

If your doctor has told you that you have an intolerance to certain sugars, speak with them before taking this medication.

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

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

Dosage

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

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

If you have difficulty swallowing the entire tablet, talk to your doctor about other possible ways to take Eliquis. 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 to a suitable container, mixing the powder with a small amount, e.g., 30 ml (2 tablespoons), of water or any of the liquids mentioned to make the mixture.
• Take the mixture.
• Clean the mortar and hand that were used to crush the tablet and the packaging with a small amount of water or one of the other liquids (e.g., 30 ml), and take that liquid.

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

Take Eliquis according to the following recommendations:

To prevent the formation of blood clots in operations of hip or knee replacement.

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

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

If you have undergone major surgery of the hip, you will generally take the tablets for a period of 32 to 38 days.

If you have undergone major surgery of the knee, you will generally take the tablets for a period of 10 to 14 days.

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

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

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

• You have severely impaired renal function;
• You have two or more of the following factors:
• • Your blood test results suggest poor kidney function (serum creatinine value is 1.5 mg/dl (133 micromoles/l) or higher);
  • You are 80 years of age 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 another in the evening. Your doctor will tell you for how long you should continue the treatment.

To treat blood clots in the veins of the legs and in the pulmonary blood vessels.

The recommended dose is two tablets of Eliquis 5 mg 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 tablet of Eliquis 5 mg twice a day, for example, one tablet in the morning and another in the evening.

To prevent blood clots from recurring after 6 months of treatment.

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

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

Use in children and adolescents.

To treat blood clots and to prevent these blood clots from recurring in the veins and pulmonary blood vessels.

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

Try to take or administer the dose at the same time every day to achieve a better effect of the treatment.

The dose of Eliquis depends on the child's body weight and will be calculated by the doctor.

The recommended dose for children and adolescents with a weight of at least 35 kg is four tablets of Eliquis 2.5 mg twice a day for the first 7 days, for example, four tablets in the morning and four tablets in the evening.

After 7 days, the recommended dose is two tablets of Eliquis 2.5 mg twice a day, for example, two tablets in the morning and two tablets in the evening.

For parents and caregivers: observe the child to ensure that the entire dose is taken.

It is essential to respect scheduled doctor visits, as the dose may need to be adjusted based on changes in weight.

Your doctor may change your anticoagulant treatment as indicated below:

• Change from Eliquis to anticoagulant medications

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

• Change from anticoagulant medications to Eliquis

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

• Change from an anticoagulant treatment containing vitamin K antagonists (e.g., warfarin) to Eliquis

Stop taking the medication containing a vitamin K antagonist. Your doctor will need to perform blood tests and tell you when to start taking Eliquis.

• Change from Eliquis to an anticoagulant treatment containing a vitamin K antagonist (e.g., warfarin).

If your doctor tells you to start taking a medication containing a vitamin K antagonist, continue taking Eliquis 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 tell you when to stop taking Eliquis.

Patients undergoing cardioversion

If your heart rhythm 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 of the body.

If you take more Eliquis than you should

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

If you take more Eliquis 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.

If you forget to take Eliquis

• If you forget a morning dose, take it as soon as you remember and take it with the evening dose.
• If you forget an evening dose, you can only take it that night. Do not take two doses the next morning, but instead take the medication as usual the next day, twice a day as recommended.

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 the treatment with Eliquis

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

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

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

The following side effects have been reported when taking Eliquis to prevent the formation of blood clots in operations for hip or knee replacement.

Frequent side effects (may affect up to 1 in 10 people)

• Anemia, which can cause fatigue or paleness;
• Bleeding that includes:

• hematoma and swelling;

• Nausea (general discomfort).

Less frequent side effects (may affect up to 1 in 100 people)

• Decrease in the number of platelets in the blood (which can affect coagulation);
• Bleeding:

• after your operation that includes hematoma and swelling, secretion of blood or liquid from the wound/surgical incision (suppuration), or at the injection site;
• from the stomach, intestine or red/bright blood in the stool;
• blood in the urine;
• from the nose;
• vaginal;

• Low blood pressure that can cause dizziness or a faster heart rate;
• The blood tests may show:

• abnormal liver function;
• increase in some liver enzymes;
• increase in bilirubin, a product derived from red blood cells in the blood, which can cause yellow discoloration of the skin and eyes;

• Itching.

Rare side 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 immediatelyif you experience any of these symptoms.
• Bleeding:

• in a muscle;
• in the eyes;
• from the gums and coughing up blood;
• from the rectum;
• Loss of hair.

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 that show blood in the stool or urine;

• Skin rash that can form blisters and resemble small dots (dark centers surrounded by a lighter area, with a dark ring around them) (erythema multiforme);
• Inflammation of blood vessels (vasculitis) that can cause skin rash, appearance of red, round and smooth points under the skin surface or hematomas.

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

Frequent side effects (may affect up to 1 in 10 people)

• Bleeding that includes:

• 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 dizziness or a faster heart rate;
• Nausea (general discomfort);
• The blood tests may show:
• an increase in gamma glutamil transferase (GGT).

Less frequent side 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;
• red/bright blood in the stool;
• Bleeding after your operation that includes hematoma and swelling, secretion of blood or liquid from the wound/surgical incision (suppuration) or at the injection site;
• hemorrhoidal;
• tests that show blood in the stool or urine;
• Decrease in the number of platelets in the blood (which can affect coagulation);
• The blood tests may show:
• abnormal liver function;
• increase in some liver enzymes;
• increase in bilirubin, a product derived from red blood cells in the blood, which can cause yellow discoloration of the skin and eyes;
• Skin rash;
• Itching;
• Loss of hair;
• 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 side effects (may affect up to 1 in 1,000 people)

• Bleeding:

• in the lungs;
• inside the space behind the abdominal cavity;
• in a muscle.

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

• Skin rash that can form blisters and resemble small dots (dark centers surrounded by a lighter area, with a dark ring around them) (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 points under the skin surface or hematomas.

The following side effects have been reported when taking Eliquis to treat or prevent the formation of blood clots in the veins of the legs and in the blood vessels of the lungs.

Frequent side effects (may affect up to 1 in 10 people)

• Bleeding that includes:

• 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;

• The blood tests may show:

• an increase in gamma glutamil transferase (GGT) or alanine aminotransferase (GPT).

Less frequent side effects (may affect up to 1 in 100 people)

• Low blood pressure that can cause dizziness or a faster heart rate

• Bleeding:

• in the eyes;
• in the mouth or coughing up blood;
• red/bright blood in the stool;
• tests that show blood in the stool or urine;
• Bleeding after your operation, that includes hematoma and swelling, secretion of blood or liquid from the wound/surgical incision (suppuration) or at the injection site;
• hemorrhoidal;
• in a muscle;

• Itching;
• Loss of hair;
• Allergic reactions (hypersensitivity) that can cause: swelling of the face, lips, mouth, tongue and/or throat, and difficulty breathing.Contact your doctor immediatelyif you experience any of these symptoms.
• The blood tests may show:

• abnormal liver function;
• increase in some liver enzymes;
• increase in bilirubin, a product derived from red blood cells in the blood, which can cause yellow discoloration of the skin and eyes.

Rare side 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;
• in the stomach;
• in the eyes;
• in the mouth;
• hemorrhoidal;
• in the mouth or coughing up blood;
• in the brain or spinal cord;
• in the lungs;
• in a muscle;

• Skin rash that can form blisters and resemble small dots (dark centers surrounded by a lighter area, with a dark ring around them) (erythema multiforme);
• Inflammation of blood vessels (vasculitis) that can cause skin rash, appearance of red, round and smooth points under the skin surface or;
• The blood tests may show:

• an increase in gamma glutamil transferase (GGT);
• tests that show blood in the stool or urine.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational reporting system included in theAppendixV. 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.

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

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. By doing so, you will help protect the environment.

Composition of Eliquis

• Tablet core: lactose (see section 2 "Eliquis contains lactose (a type of sugar) and sodium"), microcrystalline cellulose, sodium croscarmellose (see section 2 "Eliquis contains lactose (a type of sugar) and sodium"), sodium lauryl sulfate, magnesium stearate (E470b);
• Coating: lactose monohydrate , (see section 2 "Eliquis contains lactose (a type of sugar) and sodium"), hypromellose (E464), titanium dioxide (E171), triacetin, yellow iron oxide (E172).

Appearance of the product and contents of the package

The film-coated tablets are round (6 mm in diameter), yellow in color, and have "893" engraved on one side and "2½" on the other.

• They are presented in blisters within cartons containing 10, 20, 60, 168, and 200 film-coated tablets.
• Single-dose blisters are also available and are presented in clinical packs containing 60 x 1 and 100 x 1 film-coated tablets.

Only some package sizes may be marketed.

Patient Information Leaflet: handling information

Inside the Eliquis package, along with the leaflet, you will find a Patient Information Leaflet or your doctor may give you a similar leaflet.

This Patient Information Leaflet includes useful information for you and will inform other doctors that you are being treated with Eliquis. You must keep this leaflet with you at all times.

1. Take the leaflet.
2. Separate the language you need (this is facilitated through the perforated edges).
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:

1. Fold the leaflet and keep it with you at all times

Marketing Authorization Holder

Bristol-Myers Squibb/Pfizer EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Responsible Person for Manufacturing

CATALENT ANAGNI S.R.L.

Loc. Fontana del Ceraso snc

Strada Provinciale Casilina, 41

03012 Anagni (FR)

Italy

Pfizer Manufacturing Deutschland GmbH

Mooswaldallee 1

79108 Freiburg Im Breisgau

Germany

Swords Laboratories Unlimited Company T/A Bristol-Myers Squibb Pharmaceutical Operations, External Manufacturing

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Pfizer Ireland Pharmaceuticals

Little Connell Newbridge

Co. Kildare

Ireland

Last update of this leaflet {MM/YYYY}

The detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu /.