Apixaban orion

Patient Information Leaflet

Apixaban Orion, 5 mg, film-coated tablets
apixaban
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm someone else, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Leaflet Contents

1. What Apixaban Orion is and what it is used for
2. What you need to know before taking Apixaban Orion
3. How to take Apixaban Orion
4. Possible side effects
5. How to store Apixaban Orion
6. Contents of the pack and other information

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

Apixaban Orion 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.
Apixaban Orion 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 off and travel to the brain, causing stroke, or to other organs, impairing blood flow to those organs (also known as systemic embolism). 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), as well as to prevent recurrence of blood clots in blood vessels.

Apixaban Orion is used in children from 28 days of life to below 18 years of age for the treatment of venous blood clots and to prevent recurrence of blood clots in the venous system or in the blood vessels of the lungs.
The recommended dose depending on body weight is given in section 3.

2. Important information before taking Apixaban Orion

When not to take Apixaban Orion

• 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 serious 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 the patient has an intravenous or intra-arterial line placed and heparin is administered through this line to maintain its patency, or when the patient is undergoing catheter ablation (a catheter is inserted into a vein) due to irregular heartbeat (arrhythmia).

Warnings and precautions
Before starting treatment with Apixaban Orion, discuss with your doctor or pharmacist
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 with 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 abnormalities
• a tube (catheter) or spinal injection (anaesthetic or painkiller), in which case the doctor will advise taking this medicine at least 5 hours after catheter removal
• if the patient has a heart valve prosthesis
• if the doctor determines that the patient's blood pressure is unstable or other treatment or a surgical procedure to remove a blood clot from the lungs is planned.

When to exercise particular caution when using Apixaban Orion

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

If surgery or a procedure associated with bleeding is required, the doctor may ask the patient to temporarily stop taking this medicine for a short period. If unsure whether a procedure may involve bleeding, ask the doctor.
Children and adolescents
This medicine is not recommended for use in children and adolescents weighing less than 35 kg.
Apixaban Orion and other medicines
Tell your doctor or pharmacist 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 Apixaban Orion, while others may reduce its effect.
The doctor will decide whether the patient should receive Apixaban Orion while taking other medicines and how closely monitoring should be.
The following medicines may enhance the effect of Apixaban Orion and increase the risk of unwanted bleeding:

• certain medicines used to treat fungal infections (e.g. ketoconazole and others)
• certain antiviral medicines used to treat HIV/AIDS infection (e.g. ritonavir)
• other medicines used to reduce blood clotting (e.g. enoxaparin and others)
• anti-inflammatory or pain-relieving medicines (e.g. acetylsalicylic acid or naproxen), especially if the patient is over 75 years old and taking acetylsalicylic acid, which may increase the risk of unwanted bleeding
• 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 Apixaban Orion to prevent clot formation:

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

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before taking this medicine.
The effect of Apixaban Orion 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.
It is not known whether Apixaban Orion passes into human milk. The patient should consult her doctor or pharmacist before using this medicine during breastfeeding. The patient may be advised to discontinue breastfeeding or to discontinue/avoid starting treatment with this medicine.
Driving and operating machinery
Apixaban Orion has no or negligible effect on the ability to drive or operate machinery.
Apixaban Orion contains lactose
This medicine contains 97 mg of lactose. If the patient has been previously diagnosed with intolerance to certain sugars, the patient should contact the doctor before taking this medicine.
Other excipients
The medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to take Apixaban Orion

This medicine should always be taken as prescribed by your doctor or pharmacist. If you have any doubts,
please consult your doctor or pharmacist.
Dosage
The tablet should be swallowed with water. Apixaban Orion can be taken with or without food.
To achieve the best treatment outcomes, it is recommended to take the tablets at the same times
each day.
If a patient has difficulty swallowing the tablets whole, they should discuss alternative methods of
taking Apixaban Orion with their 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, your doctor may administer crushed Apixaban Orion tablets mixed with 60 mL of
water or 5% aqueous glucose solution via a nasogastric tube.
Apixaban Orion should be taken as directed for the following indications:
Prevention of blood clots in the heart in patients with irregular heart rhythm (atrial fibrillation)
and at least one additional risk factor
The recommended dose is one tablet of Apixaban Orion 5 mg twice daily.
The recommended dose is one tablet of Apixaban Orion 2.5 mg twice daily if:

• the patient has severe renal impairment
• two or more of the following conditions are met :
• blood test results indicate reduced kidney function (serum creatinine level 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. Your doctor will decide how long treatment should continue.
Treatment of blood clots in the veins of the lower limbs and blood clots in the blood vessels of the lungs
The recommended dose is two tablets of Apixaban Orion 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 Apixaban Orion 5 mg twice daily, for
example, one tablet in the morning and one in the evening.
Prevention of recurrent blood clots after completing 6-month treatment
The recommended dose is one tablet of Apixaban Orion 2.5 mg twice daily, for example, one
tablet in the morning and one in the evening. Your doctor will decide how long treatment should continue.
Use in children and adolescents
Treatment of blood clots and prevention of recurrent blood clots in the veins or in the blood vessels of the lungs
This medicine should always be taken or administered as prescribed by your doctor or pharmacist. If you have
any doubts, please consult your doctor or pharmacist.
To achieve the best treatment outcomes, it is recommended to take the tablets at the same times
each day.
The dose of Apixaban Orion depends on body weight and will be calculated by the doctor.
The recommended dose for children and adolescents with body weight of at least 35 kg is two tablets of
Apixaban Orion 5 mg taken 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 Apixaban Orion 5 mg twice daily,
for example, one tablet in the morning and one tablet in the evening.
Advice for parents and caregivers: observe the child and ensure they have taken the full
dose.
It is important to attend scheduled doctor's appointments, as dose adjustment may be necessary if the
child's body weight changes.
Your doctor may change anticoagulant treatment as follows:
Switching from Apixaban Orion to other anticoagulant medicines
Stop taking Apixaban Orion. Treatment with other anticoagulant medicines (e.g., heparin) should begin at the
time the next tablet was scheduled to be taken.
Switching from other anticoagulant medicines to Apixaban Orion
Stop taking the other anticoagulant medicines. Begin treatment with Apixaban Orion at the time the next
dose of the previous anticoagulant was scheduled, then continue regular dosing.
Switching from vitamin K antagonist anticoagulant therapy (e.g., warfarin) to Apixaban Orion
Discontinue the vitamin K antagonist medicine. Your doctor must perform blood tests and will inform you
when to start taking Apixaban Orion.
Switching from Apixaban Orion to vitamin K antagonist anticoagulant therapy (e.g., warfarin)
If your doctor informs you that you should start taking a vitamin K antagonist medicine, continue taking
Apixaban Orion for at least 2 days after taking the first dose of the vitamin K antagonist medicine. Your
doctor must perform blood tests and inform you when to stop taking Apixaban Orion.
Patients undergoing cardioversion
Patients who require a cardioversion procedure to restore normal heart rhythm should take this medicine
at the times specified by their doctor to prevent the formation of blood clots in the blood vessels of the
brain and other parts of the body.
Taking more than the recommended dose of Apixaban Orion
If you have taken more than the recommended dose of this medicine, you must contact your doctor immediately.
Bring the medicine packaging with you, even if it is empty.
If you have taken more than the recommended dose of Apixaban Orion, your risk of bleeding may increase.
In case of bleeding, surgical treatment, blood transfusion, or other treatments to reverse the effect of the
factor Xa inhibitor may be necessary.
Missed dose of Apixaban Orion

• If you miss a morning dose, take it as soon as you remember, and you may take it together with your evening dose.
• A missed evening dose may only be taken that same evening. Do not take two doses the next morning; instead, continue taking the medicine the next day as directed, twice daily.

If you have any doubts about how to take the medicine or if you miss more than one dose,
please consult your doctor or pharmacist.
Stopping Apixaban Orion
Do not stop taking this medicine without consulting your doctor, as stopping Apixaban Orion
prematurely may increase the risk of developing blood clots.
If you have any further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.
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 Orion
to prevent blood clots in the heart in patients with irregular heartbeat
and at least one additional risk factor:
Common ( may occur in up to 1 in 10 people ):

• bleeding into the eye, stomach or intestine, from the rectum, blood in urine, nosebleeds, bleeding from gums, subcutaneous haemorrhage and swelling
• anaemia, which may cause fatigue or paleness
• low blood pressure, which may lead to fainting or rapid heartbeat
• nausea
• blood tests may show increased gamma-glutamyl transferase (GGT) activity.

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

• bleeding into the brain or spinal canal, in the mouth or haemoptysis, intra-abdominal bleeding or vaginal bleeding, bright red blood in stool, postoperative bleeding including bruising and swelling, leakage of blood or fluid from the surgical wound/incision site (wound discharge) or injection site, bleeding from haemorrhoids, presence of blood in stool or urine detected in laboratory tests
• decreased platelet count (which may affect blood clotting)
• blood tests 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 reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and breathing difficulties. If any of these symptoms occur, seek immediate medical advice.

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

• bleeding in the lungs or throat, into the retroperitoneal space, or into muscles.

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

• skin rash with blister formation resembling target-like lesions (dark spots in the centre 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
• kidney bleeding, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following adverse effects may occur when taking Apixaban Orion
for the treatment or prevention of recurrent venous thrombosis in the lower limbs
and pulmonary embolism:

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

• nosebleeds, bleeding from gums, blood in urine, subcutaneous haemorrhage and swelling, bleeding in the stomach, intestine or rectum, oral bleeding, vaginal bleeding
• anaemia, which may cause fatigue or paleness
• decreased platelet count (which may affect blood clotting)
• nausea
• skin rash
• blood tests may show increased gamma-glutamyl transferase (GGT) or alanine aminotransferase (AlAT) activity.

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

• low blood pressure, which may lead to fainting or rapid heartbeat
• bleeding into the eye, in the mouth or haemoptysis, bright red blood in stool, laboratory evidence of blood in stool or urine, postoperative bleeding including bruising and swelling, leakage of blood or fluid from the surgical wound/incision site (wound discharge) or injection site, bleeding from haemorrhoids, bleeding 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 occur, seek immediate medical advice.
• blood tests 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 occur in up to 1 in 1,000 people ):

• bleeding into the brain or spinal canal, or into the lungs.

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

• bleeding into the abdominal cavity or retroperitoneal space
• skin rash with blister formation resembling target-like lesions (dark spots in the centre 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
• kidney bleeding, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

Additional adverse effects occurring in children and adolescents
Seek immediate medical advice if any of the following symptoms occur in a child:

• allergic reaction (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and shortness of breath. These adverse effects are common (may occur
  in up to 1 in 10 people).
  In general, adverse effects observed in children and adolescents treated with Apixaban
  Orion were similar to those in adults, and were mostly mild or moderate in severity. Adverse effects observed more frequently in children and adolescents included nosebleeds and abnormal vaginal bleeding.
  Very common ( may occur in more than 1 in 10 people ):

• vaginal bleeding, nosebleeds.

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

• bleeding from gums, blood in urine, subcutaneous haemorrhages and swelling, intestinal or rectal bleeding, bright red blood in stool; postoperative bleeding including bruising and swelling, leakage of blood or other fluid from surgical wound/incision (wound discharge) or injection site
• hair loss
• anaemia, which may cause fatigue or paleness
• decreased platelet count (which may affect blood clotting)
• nausea
• skin rash
• itching
• low blood pressure, which may lead to fainting or rapid heartbeat
• blood tests may show liver function abnormalities, increased activity of certain liver enzymes, increased alanine aminotransferase (AlAT) activity.

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

• bleeding into the abdominal cavity or retroperitoneal space, into the stomach, eye, mouth, or haemoptysis during coughing, from haemorrhoids, into the brain or spinal canal, lungs, or muscles
• skin rash with blister formation resembling target-like lesions (dark spots in the centre 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
• blood tests may show increased gamma-glutamyl transferase (GGT) activity, presence of blood in stool or urine
• kidney bleeding, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

Reporting of adverse effects
If any adverse effects occur, including any not listed
in this leaflet, inform your doctor or pharmacist. Adverse effects can
be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, phone: +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.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Apixaban Orion

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and blister after "EXP". The expiry date refers to the last day of the stated month.
The batch number is indicated on the carton and blister after "Lot".
No special storage conditions are required for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

What Apixaban Orion contains

• The active substance is apixaban. Each tablet contains 5 mg of apixaban.
• The other ingredients are:
  Tablet core: lactose, microcrystalline cellulose (102), sodium croscarmellose, magnesium stearate, sodium lauryl sulfate.
  Tablet coating: hypromellose (HPMC 2910) - 5 mPas, monohydrate lactose, titanium dioxide (E 171), triacetin, iron oxide red (E 172).

What Apixaban Orion looks like and contents of the pack
Pink, oval, biconvex coated tablets, 10 mm in length and 5 mm in width,
with the imprint "I2" on one side and plain on the other.
Pack sizes:
Blister packs: 14, 20, 28, 56, 60, 100, 168 and 200 coated tablets.
HDPE bottle with child-resistant closure: 30, 200 and 500 coated tablets.
Not all pack sizes may be marketed.

Patient Warning Card: information for use
Inside the Apixaban Orion package, next to the patient leaflet, there is a Patient Warning Card, or the treating physician may provide the patient with a similar card.
The Patient Warning Card contains helpful information for the patient and warns other physicians that the patient is taking Apixaban Orion. You should always carry this card with you.

1. Take the card and separate the appropriate language section.
2. Complete the following sections, or ask your doctor to complete them:
   • Name:
   • Date of birth:
   • Indication:
   • Dose: mg twice daily
   • Doctor’s name:
   • Doctor’s telephone number:
3. Fold the card and always carry it with you.

Marketing Authorisation Holder
Orion Corporation
Orionintie 1
02200 Espoo
Finland

Manufacturer/Importer
Orion Corporation Orion Pharma
Orionintie 1
02200 Espoo
Finland
Orion Corporation Orion Pharma
Joensuunkatu 7
24100 Salo
Finland

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Orion Pharma Poland Sp. z o.o.
[email protected]