Package leaflet: Information for the user

AXIPIO, 5 mg, coated tablets
Apixabanum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your doctor, pharmacist or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

1. What A is and what it is used for

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

To prevent blood clots forming 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 to other organs, impairing blood flow to these organs (also known as systemic embolism). Stroke may 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 recurrence of blood clots in the blood vessels of the legs and (or) lungs.

2. Information before using drug A

When not to use drug 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 a disease of an organ 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 the case of switching anticoagulant therapy, when a venous 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

Talk to your doctor, pharmacist or nurse before taking this medicine if the patient has any of the following conditions:

increased risk of bleeding, for example:
- conditions involving bleeding, including those resulting in reduced platelet activity
- very high blood pressure not controlled 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 liver function impairment
heart valve prosthesis
if the doctor determines that the patient's blood pressure is unstable or if other treatment or a surgical procedure to remove a blood clot from the lungs is planned.

When to exercise particular caution when using drug 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 particular 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.

Drug 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 drug A, while others may reduce its effect. The doctor will decide whether the patient should receive drug A while taking other medicines and how closely monitoring should be performed.

The following medicines may enhance the effect of drug 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 old 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 (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs).

The following medicines may reduce the ability of drug 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, thinks 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. The patient should consult her doctor, pharmacist or nurse before using this medicine during breastfeeding. The patient may be advised to discontinue breastfeeding or to stop/avoid starting treatment with this medicine.

Driving and operating machinery

Drug A has no or negligible influence on the ability to drive motor vehicles and operate machinery.

Drug A contains lactose and sodium

Lactose: If the patient has been previously diagnosed with intolerance to certain sugars, the patient should consult the doctor before taking this medicine.

Sodium: This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. the medicine is considered "sodium-free".

3. How to take medicine A

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor, pharmacist, or nurse.
Dosage
The tablet should be swallowed with water. Medicine A can be taken regardless of meals. To
achieve the best treatment outcomes, it is recommended to take the tablets at the same time
every day.
If a patient has difficulty swallowing the tablet whole, they should speak with their doctor about
alternative ways of taking medicine A. The tablet may be crushed immediately before administration and
mixed with water or a 5% aqueous glucose solution, juice, or apple puree.
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 rinsing liquid. If necessary, a doctor may administer crushed medicine A tablets mixed with 60 mL of water or 5% aqueous glucose solution via a nasogastric tube.

Medicine A should be taken as directed for the following indications:
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 renal impairment, or
two or more of the following conditions are met:
- blood test results suggest reduced kidney function (serum creatinine level is 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 switch anticoagulant therapy as follows:

Switching from medicine A to anticoagulant medicines Discontinue taking medicine A. Start treatment with anticoagulant medicines (e.g., heparin) at the time the next tablet was scheduled to be taken.
Switching from anticoagulant medicines to medicine A Discontinue taking anticoagulant medicines. Begin treatment with medicine A at the time the next dose of anticoagulant medicine was scheduled, then continue taking it regularly.
Switching from anticoagulant therapy including a vitamin K antagonist (e.g., warfarin) to medicine A Discontinue the medicine containing the vitamin K antagonist. 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 informs the patient that they should start taking a medicine containing a vitamin K antagonist, then medicine A should be continued for at least 2 days after taking the first dose of the vitamin K antagonist-containing medicine. The doctor must perform blood tests and inform the patient when to stop taking 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 blood
vessels of the brain and other blood vessels in the body.
Taking more than the recommended dose of medicine A
If a patient has taken more than the recommended dose of this medicine, contact a doctor immediately. Bring the medicine packaging with you, even if it is empty.
If a patient has taken more than the recommended dose of medicine A, there may be an increased risk
of bleeding. In case of bleeding, surgical treatment, blood transfusion, or other treatment to reverse
the effect directed against factor Xa may be necessary.
Missing a 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 how to take the medicine or if more than one dose has been missed,
consult a doctor, pharmacist, or nurse.
Stopping medicine A
Do not stop taking this medicine without consulting a doctor, as stopping medicine A prematurely may increase the risk of blood clots.
If there are any further doubts about using this medicine, consult a doctor, pharmacist, or nurse.

4. Possible side effects

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

The following side effects may occur when taking apixaban to
prevent blood clots in the heart in patients with irregular heart rhythm 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
- skin bruising and swelling
anaemia, which may cause tiredness or paleness
low blood pressure, which may lead to fainting or rapid heartbeat
nausea (feeling sick)
blood test results may show:
- increased gamma-glutamyl transferase (GGT) activity

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

bleeding:
- into the brain or spinal cord
- in the mouth or 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 in the blood (which may affect blood clotting)
blood test results may show:
- 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 (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and breathing difficulties. If any of these symptoms occur, you must contact your doctor immediately.

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

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

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

skin rash, which may develop blisters and 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 the available data):

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 the urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

The following side effects may occur when taking apixaban to
treat or prevent recurrence of blood clots in the veins of the lower limbs
and blood clots in blood vessels in the lungs.

Common (may affect up to 1 in 10 people):

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

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 (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and breathing difficulties. If any of these symptoms occur, you must contact your doctor immediately.
- blood test results may show:
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

Not known (frequency cannot be estimated from the available data):

bleeding:
- into the abdominal cavity or into the space located in the back of the abdominal cavity
skin rash, which may develop blisters and 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 the urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

Reporting of side effects
If you experience any side effects, including any not listed in
this leaflet, tell your doctor, pharmacist or nurse. Side 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
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store medicine A

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and the cardboard box
after: EXP. The expiry date refers to the last day of the stated month.
No special storage instructions apply for this medicine.
Medicines must not be disposed of via the sewage system 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 packaging and other information

What the medicine A contains
The active substance is apixaban. Each tablet contains 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 pink): hypromellose 2910, 15 mPa·s, monohydrate lactose, titanium dioxide (E 171), macrogol 3350, iron oxide red (E 172), iron oxide yellow (E 172)

What the medicine A looks like and contents of the pack
The coated tablets are pink, oval-shaped, with a score line on one side.

Blister packs in cardboard cartons containing 56, 60 or 90 coated tablets.
Perforated unit dose blisters in cardboard cartons containing 56 x 1, 60 x 1 or 90 x 1 coated tablets.

Not all pack sizes may be marketed.
Patient Alert Card: information on use
Inside the packaging of medicine A, next to the patient leaflet, there is a Patient Alert Card,
or your doctor may give you a similar card.
The Patient Alert Card contains helpful information for the patient and warns other doctors
that the patient is taking medicine A. You should always carry this card with you.

Take the card
If necessary, detach the section written in the language used by the patient (this is facilitated by perforated edges)
Complete the following items or ask your doctor to complete them:
- Name:
- Date of birth:
- Indication:
- Dose: ........ mg twice daily
- Doctor’s name:
- 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 on 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 in the countries of the European Economic Area under the following names:
Germany: A
Croatia: A 2.5 mg / 5 mg filmom
obložene tablete
Greece: A
Poland: A

Axipio