PACKAGE LEAFLET

Package leaflet: information for the patient

Apixaban HCS 2.5 mg film-coated tablets

apixaban
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Apixaban HCS is and what it is used for
What you need to know before taking Apixaban HCS
How to take Apixaban HCS
Possible side effects
How to store Apixaban HCS
Contents of the pack and other information

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

Apixaban HCS contains the active substance apixaban and belongs to a group of medicines called
anticoagulants. This medicine helps prevent the formation of blood clots by inhibiting Factor Xa, an important component in blood coagulation.
Apixaban HCS 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 surgery, you may be at increased risk of developing blood clots in the veins of the legs. This can cause swelling of the legs, with or without pain. If a blood clot travels from the leg to the lungs, it can block blood flow, causing shortness of breath, with or without chest pain. This condition (pulmonary embolism) can be life-threatening and requires immediate medical attention.
to prevent the formation of blood clots in the heart in patients with irregular heartbeat (atrial fibrillation) and at least one additional risk factor. Blood clots can break loose and travel to the brain, causing a stroke, or reach other organs, blocking normal blood supply to these organs (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 the recurrence of blood clots in the blood vessels of the legs and/or lungs.

Apixaban HCS is used in children aged 28 days up to but less than 18 years to treat blood clots and to prevent the recurrence of blood clots in the veins or blood vessels of the lungs.
For the recommended dose according to body weight, see section 3.

2. What you need to know before taking Apixaban HCS

Do not take Apixaban HCS if

you are allergic to apixaban or to any of the other ingredients of this medicine (listed in section 6);
you have excessive bleeding;
you have a disease in an organ of the body that leads to an increased risk of serious bleeding (such as an active or recent ulcer of the stomach or intestine, or a recent bleeding in the brain);
you have a liver disease that leads to an increased risk of bleeding (hepatic coagulopathy);
you are taking medicines to prevent blood clotting (e.g., warfarin, rivaroxaban, dabigatran, or heparin), except when switching from one anticoagulant treatment to another, while you have a venous or arterial catheter and are receiving heparin through that catheter to keep it open, or if a catheter is inserted into one of your blood vessels (transcatheter ablation) to treat an irregular heartbeat (arrhythmia).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking this medicine if you have any of the following conditions:

an increased risk of bleeding, such as:
- bleeding disorders, including conditions leading to reduced platelet function
- very high blood pressure not controlled by medical treatment
- if you are over 75 years old
- if you weigh 60 kg or less
severe kidney disease or if you are on dialysis;
liver problems or a history of liver problems; This medicine will be used with caution in patients showing signs of impaired liver function.
you have had a tube (catheter) or an injection in your spine (for anaesthesia or pain relief). Your doctor will instruct you to take this medicine at least 5 hours or more after removal of the catheter;
you have a prosthetic heart valve;
if your doctor finds that your blood pressure is unstable, or if another treatment or surgical procedure to remove a blood clot from the lungs is planned.

Take special care with Apixaban HCS

if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether a change in therapy is needed.

If you are scheduled for surgery or any procedure that may cause bleeding, your doctor may ask you to temporarily stop taking this medicine for a short period. If you are unsure whether a procedure might cause bleeding, ask your doctor.

Children and adolescents
This medicine is not recommended for children and adolescents weighing less than 35 kg.

Other medicines and Apixaban HCS
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Some medicines can increase the effects of Apixaban HCS, while others can reduce them. Your doctor will decide whether you should be treated with Apixaban HCS when taking these medicines and how closely you should be monitored.
The following medicines may increase the effects of Apixaban HCS and increase the risk of unwanted bleeding:

certain medicines for fungal infections (e.g., ketoconazole, etc.);
certain antiviral medicines for HIV/AIDS (e.g., ritonavir);
other medicines used to reduce blood clotting (e.g., enoxaparin, etc.);
anti-inflammatory drugs or painkillers (e.g., acetylsalicylic acid or naproxen). In particular, if you are over 75 years old and taking acetylsalicylic acid, your risk of bleeding may be higher;
medicines for high blood pressure or heart problems (e.g., diltiazem);
antidepressants known as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).

The following medicines may reduce the effectiveness of Apixaban HCS in helping to prevent blood clots:

medicines used to prevent epilepsy or seizures (e.g., phenytoin, etc.);
St. John’s wort (a herbal remedy used for depression);
medicines used to treat tuberculosis or other infections (e.g., rifampicin).

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, consult your doctor, pharmacist, or nurse before taking this medicine.
The effects of Apixaban HCS on pregnancy and the unborn child are unknown. You must not take this medicine if you are pregnant. Contact your doctor immediately if you become pregnant while taking this medicine.
It is not known whether Apixaban HCS passes into breast milk. Consult your doctor, pharmacist, or nurse before taking this medicine during breastfeeding. They will advise you whether to stop breastfeeding or to stop or not start treatment with this medicine.

Driving and using machines
Apixaban HCS has not shown any effects on the ability to drive or operate machinery.

Apixaban HCS contains lactose and sodium.
If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. How to take Apixaban HCS

Take this medicine exactly as your doctor or pharmacist has told you. If you have any doubts, consult your doctor, pharmacist, or nurse.

Dose
Swallow the tablet with a glass of water. Apixaban HCS may be taken with or without food. Try to take the tablets at the same time each day to get the best effect from treatment.

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

Instructions for crushing the tablet:

Crush the tablets using a mortar and pestle.
Carefully transfer all the powder into a suitable container and then mix the powder with a small amount, e.g., 30 ml (2 tablespoons), of water or one of the other liquids listed above to prepare a mixture.
Swallow the mixture.
Rinse the mortar and pestle used to crush the tablet and the container with a small amount of water (e.g., 30 ml) or one of the other liquids, and swallow the rinse.

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

Take Apixaban HCS as recommended:

To prevent blood clots after hip or knee replacement surgery:
The recommended dose is one Apixaban HCS 2.5 mg tablet twice daily, for example, one in the morning and one in the evening.
You should take the first tablet 12 to 24 hours after surgery.
If you have had hip surgery, you will usually take the tablets for 32 to 38 days.
If you have had knee surgery, you will usually take the tablets for 10 to 14 days.

To prevent blood clots in the heart in patients with irregular heartbeat (atrial fibrillation) and at least one additional risk factor:
The recommended dose is one Apixaban HCS 5 mg tablet twice daily.
The recommended dose is one Apixaban HCS 2.5 mg tablet twice daily if:
‐ you have severely reduced kidney function;
‐ you meet two or more of the following conditions:

blood test results suggest poor kidney function (serum creatinine level is 1.5 mg/dL (133 micromoles/L) or higher);
you are 80 years of age or older;
your body weight is 60 kg or less.

The recommended dose is one tablet twice daily, for example, one in the morning and one in the evening. Your doctor will decide how long you should continue treatment.

To treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism):
The recommended dose is two tablets of Apixaban HCS 5 mg twice daily for the first 7 days, for example, two in the morning and two in the evening.
After 7 days, the recommended dose is one tablet of Apixaban HCS 5 mg twice daily, for example, one in the morning and one in the evening.

To prevent recurrence of blood clots after completing 6 months of treatment:
The recommended dose is one Apixaban HCS 2.5 mg tablet twice daily, for example, one in the morning and one in the evening.
Your doctor will decide how long you should continue treatment.

Use in children and adolescents
For the treatment of blood clots and to prevent recurrence of blood clots in the veins or in the blood vessels of the lungs:
Always take or administer this medicine exactly as your doctor, pharmacist, or the child's doctor has instructed. Consult your doctor, pharmacist, or nurse if you are unsure.
Try to take or administer the dose at the same time each day to achieve the best treatment effect.
The dose of apixaban depends on body weight and will be calculated by the doctor.

The recommended dose for children and adolescents weighing at least 35 kg is four tablets of Apixaban HCS 2.5 mg twice daily for the first 7 days, for example, four in the morning and four in the evening. After 7 days, the recommended dose is two tablets of Apixaban HCS 2.5 mg twice daily, for example, two in the morning and two in the evening.

For parents or caregivers: Observe the child to ensure the full dose is taken.
It is important to keep scheduled medical appointments, as the dose may need to be adjusted due to changes in body weight.

Your doctor may modify your anticoagulant treatment as follows:

Switching from Apixaban HCS to another anticoagulant medicine
Stop taking Apixaban HCS. Start treatment with the new anticoagulant medicine (e.g., heparin) at the time you would have taken your next Apixaban HCS tablet.
Switching from another anticoagulant medicine to Apixaban HCS
Stop taking the current anticoagulant medicine. Start treatment with Apixaban HCS at the time you would have taken your next dose of the previous anticoagulant, then continue taking it as directed.
Switching from a vitamin K antagonist anticoagulant (e.g., warfarin) to Apixaban HCS
Stop taking the vitamin K antagonist medicine. Your doctor will need to perform blood tests and advise you on when to start Apixaban HCS treatment.
Switching from Apixaban HCS to a vitamin K antagonist anticoagulant (e.g., warfarin)
If your doctor instructs you to start taking a vitamin K antagonist medicine, continue taking Apixaban HCS for at least 2 days after the first dose of the vitamin K antagonist. Your doctor will need to perform blood tests and advise you on when to stop Apixaban HCS.

Patients undergoing cardioversion
If your abnormal heart rhythm needs to be restored to normal by a procedure called cardioversion, take this medicine exactly as your doctor instructs, to prevent blood clots in the blood vessels of the brain and elsewhere in your body.

If you take more Apixaban HCS than you should
Contact your doctor immediately if you have taken more than the prescribed dose of this medicine. Bring the medicine pack with you, even if no tablets are left.
If you take more Apixaban HCS than recommended, your risk of bleeding may be higher. If bleeding occurs, you may require surgery, a blood transfusion, or other treatments that can reverse the anticoagulant effect on factor Xa.

If you forget to take Apixaban HCS

If you miss a morning dose, take it as soon as you remember, and it may be taken together with your evening dose.
A missed evening dose may only be taken on the same evening. Do not take two doses the following morning; continue with your regular twice-daily dosing schedule the next day.

If you are unsure what to do or if you have missed more than one dose, consult your doctor, pharmacist, or nurse.

If you stop taking Apixaban HCS
Do not stop taking this medicine without first talking to your doctor, as your risk of developing a blood clot may be higher if you stop treatment too early.
If you have any questions about using this medicine, speak to your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Apixaban HCS may be given for three different medical conditions. The known side effects and their frequency may differ and are listed separately below. For these conditions, the most common general side effect with this medicine is bleeding, which can potentially be life-threatening and requires immediate medical attention.

The following side effects are known to occur when Apixaban HCS is taken to prevent blood clots after hip or knee replacement surgery.

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

Anaemia, which may cause tiredness or pale skin
Bleeding, including:
- bruising and swelling
- nausea (feeling unwell)

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

Reduction in the number of platelets in the blood (which may affect blood clotting)
Bleeding:
- occurring after surgery, including bruising and swelling, leakage of blood or fluids from the surgical wound/incision (wound discharge) or from the injection site
- in the stomach, intestines, or clear/red blood in stools
- in the urine
- from the nose
- from the vagina
Low blood pressure, which may cause you to feel faint or have a rapid heartbeat
Blood tests may show:
- abnormal liver function
- increased liver enzymes
- increased bilirubin, a product of red blood cell breakdown, which may cause yellowing of the skin and eyes
Itching

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

Allergic reactions (hypersensitivity) which may 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.
Bleeding:
- in the muscle
- in the eyes
- from the gums and blood in sputum when coughing
- from the rectum
Hair loss

Not known (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 in the space behind the abdominal cavity
- from haemorrhoids
- tests showing blood in stools or urine
Skin rash that may form blisters and appear as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme)
Inflammation of blood vessels (vasculitis), which may present as skin rashes or small, flat, red, round spots under the skin surface or bruising
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy)

The following side effects are known to occur when Apixaban HCS is taken to prevent blood clots in the heart in patients with irregular heartbeat and at least one additional risk factor.

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

Bleeding, including:
- in the eyes
- in the stomach or intestines
- from the rectum
- in the urine
- from the nose
- from the gums
- bruising and swelling
Anaemia, which may cause tiredness or pale skin
Low blood pressure, which may cause you to feel faint or have a rapid heartbeat
Nausea (feeling unwell)
Blood tests may show:
- increased gamma-glutamyltransferase (GGT)

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

Bleeding:
- in the brain or spinal cord
- in the mouth or blood in sputum when coughing
- in the abdomen or from the vagina
- clear/red blood in stools
- occurring after surgery, including bruising and swelling, leakage of blood or fluids from the surgical wound/incision (wound discharge) or from the injection site
- from haemorrhoids
- tests showing blood in stools or urine
Reduction in the number of platelets in the blood (which may affect blood clotting)
Blood tests may show:
- abnormal liver function
- increased liver enzymes
- increased bilirubin, a product of red blood cell breakdown, which may cause yellowing of the skin and eyes
Skin rash
Itching
Hair loss
Allergic reactions (hypersensitivity) which may 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.

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

Bleeding:
- in the lungs or throat
- in the space behind the abdominal cavity
- in the muscle

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

Skin rash that may form blisters and appear as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme)

Not known (frequency cannot be estimated from available data)

Inflammation of blood vessels (vasculitis), which may present as skin rashes or small, flat, red, round spots under the skin surface or bruising
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy)

The following side effects are known to occur when Apixaban HCS is taken to treat or prevent recurrence of blood clots in the legs and blood vessels of the lungs.

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

Bleeding, including:
- from the nose
- from the gums
- in the urine
- bruising and swelling
- in the stomach, intestines, or from the rectum
- in the mouth
- from the vagina
Anaemia, which may cause tiredness or pale skin
Reduction in the number of platelets in the blood (which may affect blood clotting)
Nausea (feeling unwell)
Skin rash
Blood tests may show:
- increased gamma-glutamyltransferase (GGT) or alanine aminotransferase (ALT)

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

Low blood pressure, which may cause weakness or a rapid heartbeat
Bleeding:
- in the eyes
- in the mouth or blood in sputum when coughing
- clear/red blood in stools
- tests showing blood in stools or urine
- occurring after surgery, including bruising and swelling, leakage of blood or fluids from the surgical wound/incision (wound discharge) or from the injection site
- from haemorrhoids
- in the muscle
Itching
Hair loss
Allergic reactions (hypersensitivity) which may 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
- increased liver enzymes
- increased bilirubin, a product of red blood cell breakdown, which may cause yellowing 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

Not known (frequency cannot be estimated from available data)

Bleeding:
- in the abdomen or in the space behind the abdominal cavity
Skin rash that may form blisters and appear as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme)
Inflammation of blood vessels (vasculitis), which may present as skin rashes or small, flat, red, round spots under the skin surface or bruising
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy)

Additional side effects in children and adolescents

Contact your paediatrician immediately if you notice any of these symptoms:

Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat, and breathing difficulties. The frequency of these side effects is common (may affect up to 1 in 10 people).

In general, the side effects observed in children and adolescents treated with apixaban were similar in type to those observed in adults and were mainly mild to moderate in severity. The most frequently observed side effects in children and adolescents were nosebleeds and abnormal vaginal bleeding.

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

Bleeding, including:
- from the vagina
- from the nose

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

Bleeding, including:
- from the gums
- in the urine
- bruising and swelling
- from the intestine or rectum
- bright red blood in stools
- bleeding after surgery, including bruising and swelling, leakage of blood from the surgical wound/incision (wound discharge) or from the injection site
Hair loss
Anaemia, which may cause tiredness or paleness
Reduced number of platelets in the child’s blood (which may affect clotting)
Nausea (feeling unwell)
Skin rash
Itching
Low blood pressure, which may make the child feel weak or have a rapid heartbeat
Blood tests may show:
- abnormal liver function
- increased liver enzymes
- increased alanine aminotransferase (ALT)

Not known (frequency cannot be estimated from available data)

Bleeding:
- in the abdomen or in the space behind the abdominal cavity
- in the stomach
- in the eyes
- in the mouth
- from a haemorrhoid
- in the mouth or blood in sputum when coughing
- in the brain or spinal cord
- in the lungs
- in a muscle
Skin rash that may form blisters and appear as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme)
Inflammation of blood vessels (vasculitis), which may cause skin rash or small, flat, red, round spots under the skin surface or bruising
Blood tests may show:
- increased gamma-glutamyltransferase (GGT)
- tests showing blood in stools or urine
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy)

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Apixaban HCS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after Exp. The expiry
date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Apixaban HCS contains

The active substance is apixaban. Each film-coated tablet contains 2.5 mg of apixaban.
The other components (excipients) are: microcrystalline cellulose (E460), monohydrate lactose, sodium croscarmellose (E468), sodium lauryl sulfate, hydroxyethylcellulose, magnesium stearate (E470b) in the tablet core and hypromellose (E464), propylene glycol (E1520), titanium dioxide (E171) and talc (E553b) in the coating. See section 2 “Apixaban HCS contains lactose and sodium”.

Description of the appearance of Apixaban HCS and package contents
White, round, biconvex, film-coated tablets (tablets), with "2.5" engraved on one side of the tablet.
Tablet size: diameter of approximately 6 mm.
Apixaban HCS is available in packs containing:

10, 14, 20, 28, 56, 60, 100, 168 and 200 film-coated tablets in non-divisible blisters.
10 x 1, 14 x 1, 20 x 1, 28 x 1, 56 x 1, 60 x 1, 100 x 1 and 168 x 1 film-coated tablets in unit-dose divisible blisters.
168 film-coated tablets in an HDPE bottle with a child-resistant tamper-evident PP closure.

Not all pack sizes may be marketed.
Patient Card: information management
Inside the Apixaban HCS package, together with the package leaflet, you will find a Patient Card or your doctor may provide you with a similar one.
This Patient Card includes information that may be useful to you and alerts other doctors that you are taking Apixaban HCS. You must always carry this card with you.

Take the card.
Separate the text in your language as needed (this will be facilitated by the pre-perforated edge).
Complete the following sections or ask your doctor to do so:
- Name:
- Date of birth:
- Indication:
- Weight (for the paediatric population)
- Dose: ......mg twice daily
- Doctor’s name:
- Doctor’s telephone number:
Fold the card and always keep it with you.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
HCS BV, H Kennisstraat 53, B 2650, Edegem, Belgium
Local representative for Italy
KRKA Farmaceutici Milano S.r.l. – Italy
Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
This medicinal product is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Member State Name	Medicinal Product Name
Croatia	Apiksaban Krka
Belgium, Denmark, Finland, France, Ireland, Iceland, Norway, Sweden, United Kingdom	Apixaban Krka
Austria, Italy, Netherlands	Apixaban HCS
Spain	Apixaban TAD
Portugal	Apixabano Krka

Patient information leaflet

Apixaban HCS 5 mg film-coated tablets

apixaban
Generic medicine
Please read this entire leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Apixaban HCS is and what it is used for
What you need to know before taking Apixaban HCS
How to take Apixaban HCS
Possible side effects
How to store Apixaban HCS
Contents of the pack and other information

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

Apixaban HCS contains the active substance apixaban and belongs to a group of medicines called
anticoagulants. This medicine helps prevent the formation of blood clots by blocking Factor Xa, an important component in blood coagulation.
Apixaban HCS is used in adults:

to prevent the formation of blood clots in the heart in patients with irregular heart rhythm (atrial fibrillation) and at least one additional risk factor. Blood clots may break loose and travel to the brain, causing stroke, or reach other organs, blocking normal blood flow to these organs (also known as systemic embolism). A stroke can be life-threatening and requires immediate medical attention.
to treat blood clots in the deep veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent the recurrence of blood clots in the blood vessels of the legs and/or lungs.

Apixaban HCS is used in children aged from 28 days up to but less than 18 years of age to treat blood clots and to prevent the recurrence of blood clots in the veins or blood vessels of the lungs.
For the recommended dose according to body weight, see section 3.

2. What you need to know before taking Apixaban HCS

Do not take Apixaban HCS if

you are allergic to apixaban or to any of the other ingredients of this medicine (listed in section 6);
you have excessive bleeding;
you have a disease in a body organ that leads to an increased risk of serious bleeding (such as an active or recent ulcer of the stomach or intestine, or recent bleeding in the brain);
you have a liver disease that leads to an increased risk of bleeding (hepatic coagulopathy);
you are taking medicines to prevent blood clotting (e.g., warfarin, rivaroxaban, dabigatran, or heparin), except when switching from one anticoagulant treatment to another, while you have a venous or arterial catheter and are receiving heparin through it to keep it open, or if a catheter is inserted into one of your blood vessels (transcatheter ablation) to treat an irregular heartbeat (arrhythmia).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking this medicine if you have any of the following conditions:

an increased risk of bleeding, such as:
bleeding disorders, including conditions leading to reduced platelet function;
very high blood pressure not controlled by medical treatment;
if you are over 75 years old;
if 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 showing signs of impaired liver function.
you have a prosthetic heart valve;
if your doctor finds that your blood pressure is unstable, or if another treatment or surgical procedure to remove a blood clot from the lungs is planned.

Take special care with Apixaban HCS

if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether a change in therapy is necessary.

If you are scheduled for surgery or a procedure that may cause bleeding, your doctor may ask you to temporarily stop taking this medicine for a short period. If you are unsure whether a procedure might cause bleeding, ask your doctor.
Children and adolescents
This medicine is not recommended for children and adolescents with body weight below 35 kg.
Other medicines and Apixaban HCS
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Some medicines can increase the effects of Apixaban HCS, while others can reduce them. Your doctor will decide whether you should be treated with Apixaban HCS when taking these medicines and how closely you should be monitored.
The following medicines may increase the effects of Apixaban HCS and increase the risk of unwanted bleeding:

some medicines for fungal infections (e.g., ketoconazole, etc.);
some antiviral medicines for HIV/AIDS (e.g., ritonavir);
other medicines used to reduce blood clotting (e.g., enoxaparin, etc.);
anti-inflammatory medicines or painkillers (e.g., acetylsalicylic acid or naproxen). In particular, if you are over 75 years of age and taking acetylsalicylic acid, you may have an increased risk of bleeding;
medicines for high blood pressure or heart problems (e.g., diltiazem);
antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.

The following medicines may reduce the effects of Apixaban HCS in helping to prevent blood clots:

medicines to prevent epilepsy or seizures (e.g., phenytoin, etc.);
St. John’s wort (a herbal remedy used for depression);
medicines to treat tuberculosis or other infections (e.g., rifampicin).

Pregnancy and breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor, pharmacist, or nurse before taking this medicine.
The effects of Apixaban HCS during pregnancy and on the unborn child are unknown. You must not take this medicine if you are pregnant. Contact your doctor immediately if you become pregnant while taking this medicine.
It is not known whether Apixaban HCS passes into breast milk. Consult your doctor, pharmacist, or nurse before taking this medicine while breastfeeding. They will advise you whether to stop breastfeeding or to stop/avoid starting treatment with this medicine.
Driving and using machines
Apixaban has not shown effects on the ability to drive or use machines.
Apixaban HCS contains lactose and sodium.
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. How to take Apixaban HCS

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor, pharmacist, or nurse.

Dosage
Swallow the tablet with a glass of water. Apixaban HCS can be taken with or without food. Try to take the tablets at the same time each day to get the best effect from treatment.

If you have difficulty swallowing the tablet whole, ask your doctor about other ways to take Apixaban HCS. The tablet may be crushed and mixed with water, 5% glucose in water, apple juice, or apple puree, immediately before administration.

Instructions for crushing the tablet:

Crush the tablets using a mortar and pestle.
Carefully transfer all the powder into a suitable container and then mix the powder with a small amount, e.g., 30 ml (2 tablespoons), of water or one of the other liquids mentioned above to prepare a mixture.
Swallow the mixture.
Rinse the mortar and pestle used to crush the tablet, as well as the container, with a small amount of water (e.g., 30 ml) or one of the other liquids, and swallow the rinse solution.

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

Take Apixaban HCS as recommended:

For preventing blood clots in the heart in patients with irregular heartbeat and at least one additional risk factor.
The recommended dose is one tablet of Apixaban HCS 5 mg twice daily.

The recommended dose is one tablet of Apixaban HCS 2.5 mg twice daily if:

‐ you have severely reduced kidney function;
‐ you meet two or more of the following conditions:

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 body weight is 60 kg or less.

The recommended dose is one tablet twice daily, for example, one in the morning and one in the evening.
Your doctor will decide how long you should continue treatment.

For treating blood clots in the veins of the legs and in the blood vessels of the lungs
The recommended dose is two tablets of Apixaban HCS 5 mg twice daily for the first 7 days, for example, two in the morning and two in the evening.
After 7 days, the recommended dose is one tablet of Apixaban HCS 5 mg twice daily, for example, one in the morning and one in the evening.

For preventing recurrence of blood clots after completing 6 months of treatment
The recommended dose is one tablet of Apixaban HCS 2.5 mg twice daily, for example, one in the morning and one in the evening.
Your doctor will decide how long you should continue treatment.

Use in children and adolescents
For the treatment of blood clots and to prevent recurrence of blood clots in the veins or in the blood vessels of the lungs.
Always take or administer this medicine exactly as directed by your doctor, pharmacist, or pediatrician. Consult your doctor, pharmacist, or nurse if you are unsure.
Try to take or administer the dose at the same time each day to achieve the best treatment effect.
The dose of apixaban depends on body weight and will be calculated by the doctor.

The recommended dose for children and adolescents weighing at least 35 kg is two tablets of Apixaban HCS 5 mg twice daily for the first 7 days, for example, two in the morning and two in the evening. After 7 days, the recommended dose is one tablet of Apixaban HCS 5 mg twice daily, for example, one in the morning and one in the evening.

For parents or caregivers: observe the child to ensure the full dose is taken.
It is important to attend scheduled medical appointments, as the dose may need to be adjusted due to changes in body weight.

Your doctor may modify your anticoagulant treatment as follows:

Switching from Apixaban HCS to another anticoagulant medicine
Stop taking Apixaban HCS. Start treatment with the other anticoagulant medicine (e.g., heparin) at the time you would have taken your next Apixaban HCS dose.
Switching from another anticoagulant medicine to Apixaban HCS
Stop taking the other anticoagulant medicine. Start treatment with Apixaban HCS at the time you would have taken your next dose of the previous anticoagulant, then continue taking it as directed.
Switching from a vitamin K antagonist anticoagulant (e.g., warfarin) to Apixaban HCS
Stop taking the vitamin K antagonist medicine. Your doctor will need to perform blood tests and advise you on when to start Apixaban HCS treatment.
Switching from Apixaban HCS to a vitamin K antagonist anticoagulant (e.g., warfarin)
If your doctor instructs you to start taking a vitamin K antagonist medicine, continue taking Apixaban HCS for at least 2 days after the first dose of the vitamin K antagonist. Your doctor will need to perform blood tests and advise you on when to stop Apixaban HCS treatment.

If you take more Apixaban HCS than you should
Contact your doctor immediately if you have taken more than the prescribed dose of Apixaban HCS. Bring the medicine pack with you, even if no tablets remain.
If you take more Apixaban HCS than recommended, you may have an increased risk of bleeding. If bleeding occurs, you may require surgery, a blood transfusion, or other treatments that can reverse the anticoagulant effect on factor Xa.

If you forget to take Apixaban HCS

If you miss a morning dose, take it as soon as you remember, and it may be taken together with your evening dose.
A missed evening dose may only be taken on the same evening. Do not take two doses the next morning; instead, continue with your regular twice-daily dosing schedule the following day.

If you are unsure what to do or if you have missed more than one dose, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The most common general side effect of this medicine is bleeding, which may potentially be life-threatening and requires immediate medical attention.

The following side effects are known to occur when Apixaban HCS is taken to prevent blood clots forming in the heart of patients with irregular heartbeat and at least one additional risk factor.

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

Bleeding, including:
in the eyes;
in the stomach or intestines;
from the rectum;
blood in the urine;
from the nose;
from the gums;
bruising and swelling;
Anaemia, which may cause tiredness or pale skin;
Low blood pressure, which may make you feel faint or have a racing heartbeat;
Nausea (feeling unwell);
Blood tests may show:
an increase in gamma-glutamyl transferase (GGT).

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

Bleeding:
in the brain or spinal cord;
in the mouth or blood in coughed-up mucus;
in the abdomen or from the vagina;
bright red blood in the stools;
bleeding occurring after surgery, including bruising and swelling, leakage of blood or fluids from the surgical wound/incision (wound discharge) or from the injection site;
from haemorrhoids;
tests showing blood in the stools or urine;
Decrease in the number of platelets in the blood (which may affect blood clotting);
Blood tests may show:
abnormal liver function;
increase in certain liver enzymes;
increase in bilirubin, a product of red blood cell breakdown, which may cause yellowing of the skin and eyes.
Skin rash;
Itching;
Hair loss;
Allergic reactions (hypersensitivity) which may 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.

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

Bleeding:
in the lungs or throat;
in the space behind the abdominal cavity (retroperitoneal space);
in the muscle.

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

Skin rash which may blister and appear as small target-like spots (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme).

Not known (frequency cannot be estimated from available data)

Inflammation of blood vessels (vasculitis), which may present as skin rashes or small, flat, red, round spots under the skin surface or bruising.
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following side effects are known to occur when Apixaban HCS is taken to treat or prevent recurrence of blood clots in the veins of the legs and in the blood vessels of the lungs.

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

Bleeding, including:
from the nose;
from the gums;
blood in the urine;
bruising and swelling;
in the stomach, intestines, or from the rectum;
in the mouth;
from the vagina;
Anaemia, which may cause tiredness or pale skin;
Decrease in the number of platelets in the blood (which may affect blood clotting);
Nausea (feeling unwell);
Skin rash;
Blood tests may show:
an increase in gamma-glutamyl transferase (GGT) or alanine aminotransferase (ALT).

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

Low blood pressure, which may cause weakness or a racing heartbeat;
Bleeding:
in the eyes;
in the mouth or blood in coughed-up mucus;
bright red blood in the stools;
tests showing blood in the stools or urine;
bleeding occurring after any surgery, including bruising and swelling, leakage of blood or fluids from the surgical wound/incision (wound discharge) or from the injection site;
from haemorrhoids;
in the muscle;
Itching;
Hair loss;
Allergic reactions (hypersensitivity) which may 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 certain liver enzymes;
increase in bilirubin, a product of red blood cell breakdown, which may cause yellowing 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.

Not known (frequency cannot be estimated from available data)

Bleeding:
in the abdomen or in the space behind the abdominal cavity (retroperitoneal space).
Skin rash which may blister and appear as small target-like spots (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme).
Inflammation of blood vessels (vasculitis), which may present as skin rashes or small, flat, red, round spots under the skin surface or bruising.
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy).

Additional side effects in children and adolescents
Inform your paediatrician immediately if you observe any of the following symptoms:

Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat and breathing difficulties. The frequency of these side effects is common (may affect up to 1 in 10 people).

In general, the side effects observed in children and adolescents treated with apixaban were similar in type to those seen in adults and were mainly mild to moderate in severity. The most frequently observed side effects in children and adolescents were nosebleeds and abnormal vaginal bleeding.

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

Bleeding, including:
from the vagina;
from the nose.

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

Bleeding, including:
from the gums;
blood in the urine;
bruising and swelling;
from the intestine or rectum;
bright red blood in the stools;
bleeding after surgery, including bruising and swelling, leakage of blood from the surgical wound/incision (wound discharge) or from the injection site;
hair loss;
anaemia, which may cause tiredness or paleness;
reduced number of platelets in the child’s blood (which may affect clotting);
nausea (feeling unwell);
skin rash;
itching;
low blood pressure, which may make the child feel weak or have a racing heartbeat;
blood tests may show:
abnormal liver function;
increase in certain liver enzymes;
increase in alanine aminotransferase (ALT).

Not known (frequency cannot be estimated from available data)

Bleeding:
in the abdomen or in the space behind the abdominal cavity (retroperitoneal space);
in the stomach;
in the eyes;
in the mouth;
from a haemorrhoid;
in the mouth or blood in spit when coughing;
in the brain or spinal cord;
in the lungs;
in a muscle;
Skin rash which may blister and appear as small target-like spots (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme);
Inflammation of blood vessels (vasculitis) which may cause skin rash or small, flat, red, round spots under the skin surface or bruising;
Blood tests may show:
increase in gamma-glutamyl transferase (GGT);
tests showing blood in the stools or urine.
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy).

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Apixaban HCS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Apixaban HCS contains
The active substance is apixaban. Each film-coated tablet contains 5 mg of apixaban.
The other components (excipients) are: microcrystalline cellulose (E460), monohydrate lactose,
sodium croscarmellose (E468), sodium lauryl sulfate, hydroxyethylcellulose, magnesium stearate
(E470b) in the tablet core; hypromellose (E464), propylene glycol (E1520), titanium dioxide (E171),
talc (E553b) and yellow iron oxide (E172) in the coating.
See section 2 “Apixaban HCS contains lactose and sodium”.

Description of the appearance of Apixaban HCS and contents of the pack
Brown-yellow, oval, biconvex film-coated tablets with the number "5" engraved on one side of the tablet.
Tablet dimensions: approximately 10.5 x 5.5 mm (length x width).
Apixaban HCS is available in packs containing:

10, 14, 20, 28, 56, 60, 100, 168 and 200 film-coated tablets in non-divisible blisters.
10 x 1, 14 x 1, 20 x 1, 28 x 1, 56 x 1, 60 x 1, 100 x 1 and 168 x 1 film-coated tablets in unit-dose divisible blisters.
100 or 168 film-coated tablets in HDPE bottles with child-resistant PP tamper-evident caps.

Not all pack sizes may be marketed.

Patient Card: managing information
Inside the Apixaban HCS package, together with the package leaflet, you will find a Patient Card or your doctor may provide you with a similar one.
This Patient Card includes information that may be useful to you and alerts other doctors that you are taking Apixaban HCS. You must always carry this card with you.

Take the card.
Separate the text in your language as needed (this will be facilitated by the pre-perforated edge).
Complete the following sections or ask your doctor to do so:
- Name:
- Date of birth:
- Indication:
- Weight (for pediatric population)
- Dose: ......mg twice daily
- Doctor’s name:
- Doctor’s telephone number:
Fold the card and always keep it with you.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
HCS BV, H Kennisstraat 53, B 2650, Edegem, Belgium
Local representative for Italy
KRKA Farmaceutici Milano S.r.l. – Italy
Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Member State Name	Medicinal Product Name
Croatia	Apiksaban Krka
Belgium, Denmark, Finland, France, Ireland, Iceland, Norway, Sweden, United Kingdom	Apixaban Krka
Austria, Italy, Netherlands	Apixaban HCS
Spain	Apixaban TAD
Portugal	Apixabano Krka