Axipio: detailed information

Package leaflet: Information for the user

AXIPIO, 2.5 mg, coated tablets
Apixabanum
Please read this 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 further questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them, even if their symptoms are the same.
If you experience any side effects, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents

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

1. What A medicine is and what it is used for

A medicine contains the active substance apixaban and belongs to a group of medicines called anticoagulants.
This medicine helps prevent blood clots by inhibiting factor Xa, an important component in the blood clotting process.
A medicine is used in adults:

to prevent the formation of blood clots (deep vein thrombosis) after hip or knee replacement surgery. After hip or knee surgery, patients may have an increased risk of developing blood clots in the veins of the legs. This may lead to leg swelling, with or without pain. If a blood clot travels from the leg to the lungs, it may block blood flow through the lungs, causing breathlessness with or without chest pain. This condition (pulmonary embolism) can be life-threatening and requires immediate medical attention.
to prevent blood clots in the heart in patients with an irregular heart rhythm (atrial fibrillation) and at least one additional risk factor. Blood clots may break loose and travel to the brain, causing a stroke, or to other organs, impairing blood flow to these organs (also known as systemic embolism). A stroke may be life-threatening and requires immediate medical treatment.
to treat blood clots in the deep veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), as well as to prevent recurrence of blood clots in the blood vessels of the legs and/or lungs.

2. Important information before using medicine A

When not to use medicine A

if the patient is allergic to apixaban or any of the other ingredients of this medicine (listed in section 6)
if the patient has excessive bleeding
if the patient has an organ disease that increases the risk of severe bleeding (such as active or recently diagnosed peptic ulcer of the stomach or intestine, recently diagnosed intracranial bleeding)
if the patient has liver disease leading to an increased risk of bleeding (hepatic coagulopathy)
if the patient is taking anticoagulant medicines (e.g. warfarin, rivaroxaban, dabigatran or heparin), except in situations of switching anticoagulant therapy, when an intravenous or arterial line has been inserted and heparin is administered through this line to maintain its patency, or when the patient is undergoing catheter ablation (a catheter is inserted into the vein) due to irregular heartbeat (arrhythmia).

Warnings and precautions
Before starting to take this medicine, discuss with your doctor, pharmacist or nurse if the patient has any of the following conditions:

increased risk of bleeding, for example:
- conditions associated with bleeding, including those resulting in reduced platelet activity
- very high blood pressure uncontrolled by medication
- if the patient is over 75 years of age
- if the patient weighs 60 kg or less
severe kidney disease or if the patient is on dialysis
liver disease or history of liver disease
this medicine should be used with caution in patients showing signs of impaired liver function
a tube (catheter) or injection into the spine (anaesthetic or pain relief), in which case the doctor will advise taking this medicine 5 or more hours after removal of the catheter
heart valve prosthesis
if the doctor determines that the patient's blood pressure is unstable or if another treatment or surgical procedure to remove a blood clot from the lungs is planned.

When to exercise particular caution when using medicine A

if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots). The patient should inform the doctor, who will decide whether a change in treatment is necessary.

If the patient needs to undergo surgery or a procedure that may involve bleeding, the doctor may ask the patient to temporarily stop taking this medicine for a short period. If in doubt whether a given procedure may involve bleeding, ask the doctor.
Children and adolescents
This medicine is not recommended for use in children and adolescents under 18 years of age.
Medicine A and other medicines
Tell your doctor, pharmacist or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Some medicines may enhance the effect of medicine A, while others may reduce its effect. The doctor will decide whether the patient should receive medicine A while taking other medicines and how closely monitoring should be performed.
The following medicines may enhance the effect of medicine A and increase the risk of unwanted bleeding:

some medicines used to treat fungal infections (e.g. ketoconazole)
some antiviral medicines used to treat HIV/AIDS infection (e.g. ritonavir)
other medicines used to reduce blood clotting (e.g. enoxaparin)
anti-inflammatory or pain-relieving medicines (e.g. acetylsalicylic acid or naproxen). Especially when the patient is over 75 years of age and taking acetylsalicylic acid, the risk of unwanted bleeding may be increased
medicines used for high blood pressure or heart problems (e.g. diltiazem)
antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors.

The following medicines may reduce the ability of medicine A to prevent blood clots:

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

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant or is planning to have a baby, she should consult her doctor, pharmacist or nurse before using this medicine.
Pregnancy
The effect of apixaban on pregnancy and the unborn child is unknown. This medicine should not be taken during pregnancy. If the patient becomes pregnant while taking this medicine, she should contact her doctor immediately.
Breastfeeding
It is not known whether apixaban passes into human milk. Before using this medicine during breastfeeding, consult a doctor, pharmacist or nurse. The patient may be advised to discontinue breastfeeding or to discontinue/avoid starting this medicine.
Driving and operating machinery
Medicine A has no effect or a negligible effect on the ability to drive motor vehicles and operate machinery.
Medicine A contains lactose and sodium
Lactose: If the patient has previously been diagnosed with intolerance to certain sugars, the patient should contact the doctor before taking the medicine.
Sodium: This medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to take medicine A

This medicine should always be taken exactly as directed by the doctor or pharmacist. If in doubt,
consult your doctor, pharmacist, or nurse.
Dosage
The tablet should be swallowed whole with water. Medicine A may be taken regardless of meals.
To achieve the best treatment outcomes, it is recommended to take the tablets at the same times
every day.
If the patient has difficulty swallowing the tablets whole, discuss alternative ways of taking medicine A
with the doctor. The tablet may be crushed and mixed with water or 5% aqueous glucose solution, juice,
or apple puree immediately before administration.
Instructions for crushing tablets:

Crush the tablet with a pestle in a mortar.
Carefully transfer the powder to a suitable container and mix it with a small amount, e.g., 30 mL (2 tablespoons), of water or another liquid listed above to prepare a mixture.
Swallow the mixture.
Rinse the pestle and mortar used for crushing the tablets, as well as the container, with a small amount of water or another liquid (e.g., 30 mL), and swallow the rinse liquid. If necessary, the doctor may administer crushed medicine A tablets mixed with 60 mL of water or 5% aqueous glucose solution through a nasogastric tube.

Medicine A should be taken as directed in the following indications:
Prevention of blood clots after hip or knee replacement surgery
The recommended dose is one tablet of medicine A 2.5 mg twice daily. For example, one tablet in the morning
and one in the evening.
The first tablet should be taken 12 to 24 hours after surgery.
If the patient underwent major hip surgery, tablets are usually taken for 32 to 38 days.
If the patient underwent major knee surgery, tablets are usually taken for 10 to 14 days.
Prevention of blood clots in the heart in patients with irregular heart rhythm and at least one additional
risk factor
The recommended dose is one tablet of medicine A 5 mg twice daily.
The recommended dose is one tablet of medicine A 2.5 mg twice daily if:

the patient has severe kidney function impairment
two or more of the following conditions are met :
- blood test results suggest reduced kidney function (serum creatinine concentration of 1.5 mg/dL (133 micromoles/L) or higher)
- the patient is 80 years of age or older
- the patient's body weight is 60 kg or less.

The recommended dose is one tablet twice daily, for example, one tablet in the morning and one in the evening.
The doctor will decide how long treatment should continue.
Treatment of blood clots in the deep veins of the legs and blood clots in the blood vessels of the lungs
The recommended dose is two tablets of medicine A 5 mg twice daily for the first 7 days, for example,
two tablets in the morning and two in the evening.
After 7 days, the recommended dose is one tablet of medicine A 5 mg twice daily, for example, one
tablet in the morning and one in the evening.
Prevention of recurrent blood clots after completion of 6-month treatment
The recommended dose is one tablet of medicine A 2.5 mg twice daily, for example, one tablet
in the morning and one in the evening.
The doctor will decide how long treatment should continue.
The doctor may change anticoagulant therapy as follows:

Switching from medicine A to anticoagulant medicines Discontinue medicine A. Start anticoagulant treatment (e.g., heparin) at the time the next tablet was scheduled to be taken.
Switching from anticoagulant medicines to medicine A

Discontinue anticoagulant medicines. Start treatment with medicine A at the time the next dose of anticoagulant medicine was scheduled, then continue regular dosing.

Switching from anticoagulant therapy including a vitamin K antagonist (e.g., warfarin) to medicine A Discontinue the vitamin K antagonist-containing medicine. The doctor will perform blood tests and inform the patient when to start taking medicine A.
Switching from medicine A to anticoagulant therapy including a vitamin K antagonist (e.g., warfarin) If the doctor instructs the patient to start taking a vitamin K antagonist-containing medicine, continue taking medicine A for at least 2 days after the first dose of the vitamin K antagonist-containing medicine. The doctor must perform blood tests and inform the patient when to discontinue medicine A.

Patients undergoing cardioversion
Patients who require a cardioversion procedure to restore normal heart rhythm should take this medicine
at the times specified by the doctor to prevent the formation of blood clots in the brain's blood vessels
and other blood vessels in the body.
Taking more medicine A than recommended
If the patient has taken more than the recommended dose of this medicine, contact the doctor immediately.
Bring the medicine packaging with you, even if it is empty.
If the patient has taken more than the recommended dose of medicine A, the risk of bleeding may be increased.
In case of bleeding, surgical treatment, blood transfusion, or other treatment to reverse the effect directed
against factor Xa may be necessary.
Missed dose of medicine A

Take the missed dose as soon as the patient remembers and:
- take the next dose of medicine A at the usual time,
- then continue taking the medicine as usual.

If in doubt about taking the medicine or if more than one dose has been missed, consult the doctor, pharmacist, or nurse.
Stopping medicine A
Do not stop taking this medicine without consulting the doctor, as stopping medicine A prematurely may increase the risk of blood clots.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Medicine A can be used in three different medical conditions. Known adverse effects and their
frequency in each of these medical conditions may differ and are listed separately below. In these
conditions, the most common general adverse effect of this medicine is bleeding, which may
potentially be life-threatening and may require immediate medical attention.

The following adverse effects may occur when taking apixaban to prevent blood clots after hip or
knee replacement surgery.
Common (may affect up to 1 in 10 people):

anaemia, which may cause fatigue or paleness
bleeding including bruising and swelling
nausea (feeling sick)

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

reduced platelet count (which may affect blood clotting)
bleeding:
- after surgery, including bruising and swelling, leakage of blood or other fluid from the surgical wound or incision site (wound discharge) or injection site
- from the stomach, intestines, or bright red blood in stool
- blood in urine
- from the nose
- from the vagina
low blood pressure, which may lead to fainting or rapid heartbeat
blood test results may indicate:
- liver function abnormalities
- increased activity of certain liver enzymes
- increased bilirubin levels, a product formed from destroyed red blood cells, which may cause yellowing of the skin and eyes
itching

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

allergic (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and breathing difficulties. If any of these symptoms occur, contact your doctor immediately.
bleeding:
- into muscle
- into the eyes
- from the gums and coughing up blood
- from the rectum
hair loss

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

bleeding:
- into the brain or spinal cord
- in the lungs or throat
- in the mouth
- into the abdominal cavity or into the space located at the back of the abdominal cavity
- from haemorrhoids
- test results indicating presence of blood in stool or urine
skin rash, during which blisters may form and which resembles small target-like lesions (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) ( erythema multiforme )
inflammation of blood vessels (vasculitis), which may cause skin rash or raised, flat, red, round spots beneath the skin surface, or bruising.
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following adverse effects may occur when taking apixaban to prevent blood clots in the heart
in patients with irregular heartbeat and at least one additional risk factor.
Common (may affect up to 1 in 10 people):

bleeding:
- into the eye
into the stomach or intestine
from the rectum
blood in urine
from the nose
from the gums
bruising and swelling
- anaemia, which may cause fatigue or paleness
- low blood pressure, which may lead to fainting or rapid heartbeat
- nausea (feeling sick)
- blood test results may indicate:
increased activity of gamma-glutamyl transferase (GGT)

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

bleeding:
- into the brain or spinal cord
- in the mouth or haemoptysis (coughing up blood)
- in the abdominal cavity or from the vagina
- bright red blood in stool
- bleeding occurring after surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound or tissue incision site (wound discharge) or injection site
- from haemorrhoids
- presence of blood in stool or urine detected in laboratory tests
decreased platelet count (which may affect clotting)
blood test results may indicate:
- abnormal liver function
- increased activity of certain liver enzymes
- increased bilirubin levels – a breakdown product of red blood cells, 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 breathing difficulties. If any of these symptoms are observed, contact your doctor immediately.

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

bleeding:
- in the lungs or throat
- into the space located at the back of the abdominal cavity
- into muscles

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

skin rash, during which blisters may form and which resembles small target-like lesions (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) ( erythema multiforme ).

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

Vasculitis (inflammation of blood vessels), which may cause skin rash or raised, flat, red, round spots beneath the skin surface, or bruising.
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following adverse effects may occur when taking apixaban for the treatment or prevention of
recurrent blood clots in the deep veins of the legs and blood clots in the blood vessels of the lungs.
Common (may affect up to 1 in 10 people):

bleeding:
- from the nose
- from the gums
- blood in urine
- bruising and swelling
- in the stomach, intestines
- from the rectum
- in the mouth
- from the vagina
anaemia, which may cause fatigue or paleness
reduced platelet count (which may affect clotting)
nausea (feeling sick)
skin rash
blood test results may indicate:
- increased activity of gamma-glutamyl transferase (GGT) or alanine aminotransferase (AlAT)

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

low blood pressure, which may lead to fainting or rapid heartbeat
bleeding:
- into the eyes
- in the mouth or coughing up blood
- bright red blood in stool
- test results indicating blood in stool or urine
- bleeding occurring after surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound or tissue incision site (wound discharge) or injection site
- from haemorrhoids
- into muscles
itching
hair loss
allergic reactions (hypersensitivity), which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and breathing difficulties. If any of these symptoms are observed, contact your doctor immediately.
blood test results may indicate:
- abnormal liver function
- increased activity of certain liver enzymes
- increased bilirubin levels – a breakdown product of red blood cells, which may cause yellowing of the skin and eyes

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

bleeding:
- in the brain or spinal cord
- in the lungs

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

bleeding:
- into the abdominal cavity or into the space located at the back of the abdominal cavity
skin rash, during which blisters may form and which resembles small target-like lesions (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) ( erythema multiforme )
vasculitis (inflammation of blood vessels), which may cause skin rash or raised, flat, red, round spots beneath the skin surface, or bruising.
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function
(anticoagulant-related nephropathy).

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL-02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
By reporting adverse effects, additional information on the safety of the medicine can be collected.

5. How to store medicine A

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and outer cardboard box
following: EXP. The expiry date refers to the last day of the stated month.
No special storage instructions apply.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What A medicine contains
The active substance is apixaban. Each tablet contains 2.5 mg of apixaban.
Other components are:

Tablet core: microcrystalline cellulose (type 101), sodium croscarmellose, sodium docusate, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyvinyl acetate, polyethylene glycol, magnesium stearate
Coating (Opadry II yellow): hypromellose 2910, 15 mPa·s, lactose monohydrate, titanium dioxide (E 171), macrogol 3350, iron oxide yellow (E 172)

What A medicine looks like and contents of the pack
The coated tablets are yellow, round, and biconvex.

Blister packs in cardboard boxes containing 20, 60, or 90 coated tablets.
Perforated single-dose blisters in cardboard boxes containing 20 x 1, 60 x 1, or 90 x 1 coated tablets.

Not all pack sizes may be marketed.
Patient Alert Card: information for users
Inside the packaging of medicine A, alongside the patient leaflet, there is a Patient Alert Card,
or the treating physician may provide the patient with a similar card.
The Patient Alert Card contains helpful information for the patient and warns other physicians
that the patient is taking medicine A. The card should always be carried on the person.

Take the card
If necessary, detach the section written in the patient's language (facilitated by perforated edges)
Complete the following items or ask the doctor to complete them:
- Name and surname:
- Date of birth:
- Indication:
- Dose: ........ mg twice daily
- Doctor's name and surname:
- Doctor's telephone number:
Fold the card and always carry it with you

Marketing Authorisation Holder:
STADA Arzneimittel AG,
Stadastrasse 2-18,
61118 Bad Vilbel,
Germany
Manufacturer:
STADA Arzneimittel AG,
Stadastrasse 2-18,
61118 Bad Vilbel,
Germany
Centrafarm Services B.V.
Van de Reijtstraat 31 E
4814NE Breda
The Netherlands
For further information about this medicine, contact the local representative of the Marketing Authorisation Holder:
Stada Pharm Sp. z o.o.
ul. Krakowiaków 44
02-255 Warszawa
Tel. +48 22 737 79 20
This medicine is authorised for marketing in the European Economic Area countries under the following names:
Germany: A
Croatia: A 2,5 mg / 5 mg film-coated tablets
Greece: A
Poland: A