Apixaban orion

Package leaflet: Information for the user

Apixaban Orion, 2.5 mg, coated tablets
apixaban
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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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 blocking factor Xa, an important clotting factor.
Apixaban Orion is used in adults:

• to prevent 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) may be life-threatening and requires immediate medical attention.
• to prevent 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 to other organs, impairing blood flow to these organs (also known as systemic embolism). Stroke may be life-threatening and requires immediate medical intervention.
• 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.

Apixaban Orion is used in children from 28 days of age to below 18 years of age for the treatment of venous blood clots and to prevent recurrence of venous blood clots or blood clots 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 a disease that increases the risk of serious bleeding (such as active or recently diagnosed peptic ulcer of the stomach or intestine, recently diagnosed intracranial haemorrhage)
• 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 the patient has an intravenous or arterial line in place and heparin is administered through the 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 Apixaban Orion, discuss with a 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 not controlled 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
• spinal catheter or spinal injection (anaesthetic or pain relief), in which case the doctor will advise taking this medicine 5 or more hours after removal of the catheter
• 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 special caution when using Apixaban Orion

• 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 surgery or a procedure that may involve bleeding is required, the doctor may ask the patient to temporarily stop taking this medicine for a short period. If in doubt whether a procedure may involve bleeding, ask the doctor.
Children and adolescents
This medicine is not recommended for use in children and adolescents with body weight 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 performed.
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), particularly 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 (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs).

The following medicines may reduce the ability of Apixaban Orion to prevent blood clots:

• medicines used to prevent epilepsy or seizures (e.g. phenytoin and others)
• St John’s wort (a 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 plans to become pregnant, she should consult a 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. Consult a doctor or pharmacist before using this medicine during breastfeeding. The patient may be advised to stop breastfeeding or to discontinue/avoid starting this medicine.
Driving and operating machinery
Apixaban Orion has no effect or negligible effect on the ability to drive and operate machinery.
Apixaban Orion contains lactose
This medicine contains 48 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 directed by the doctor or pharmacist. If in doubt,
consult the doctor or pharmacist.
Dosage
The tablet should be swallowed with water. Apixaban Orion can be taken regardless of
meals. To achieve the best treatment outcomes, it is recommended to take the tablets at the
same times each day.
If the patient has difficulty swallowing the tablets whole, they should discuss alternative
administration methods with the doctor. The tablet may be crushed immediately before
administration and mixed with water or 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, the doctor may administer crushed Apixaban Orion tablets mixed with 60 mL of water or 5% aqueous glucose solution through a nasogastric tube.
Apixaban Orion should be taken as directed in the following indications:
Prevention of blood clots after hip or knee replacement surgery
The recommended dose is one 2.5 mg tablet of Apixaban Orion 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 has undergone major hip surgery, they will usually take the tablets for 32 to 38 days.
If the patient has undergone major knee surgery, they will usually take the tablets for 10 to 14 days.
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 5 mg tablet of Apixaban Orion twice daily.
The recommended dose is one 2.5 mg tablet of Apixaban Orion twice daily if:

• the patient has severe renal 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 veins of the lower limbs and blood clots in the blood vessels of the lungs
The recommended dose is two 5 mg tablets of Apixaban Orion 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 5 mg tablet of Apixaban Orion twice daily, for
example, one tablet in the morning and one in the evening.
Prevention of recurrence of blood clots after completion of 6-month treatment
The recommended dose is one 2.5 mg tablet of Apixaban Orion twice daily, for example, one
tablet in the morning and one in the evening. The doctor will decide how long treatment should continue.
Use in children and adolescents
Treatment and prevention of blood clots in the veins or in the blood vessels of the lungs
The medicine should always be taken or administered as directed by the doctor or pharmacist. If in
doubt, consult the 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 a body weight of at least 35 kg is four 2.5 mg tablets of Apixaban Orion taken twice daily for the first 7 days, for example, four tablets in the morning and four in the evening.
After 7 days, the recommended dose is two 2.5 mg tablets of Apixaban Orion twice daily,
for example, two tablets in the morning and two in the evening.
Advice for parents and caregivers: observe the child and ensure they have taken the full
dose.
It is important to attend medical appointments as recommended, because if the child's body weight changes, the dose of medicine may need to be adjusted.
The doctor may change anticoagulant treatment as follows:
Switching from Apixaban Orion to other anticoagulant medicines
Stop taking Apixaban Orion. Start treatment with anticoagulant medicines (e.g., heparin) at the time the next tablet was scheduled to be taken.
Switching from anticoagulant medicines to Apixaban Orion
Stop taking anticoagulant medicines. Begin treatment with Apixaban Orion at the time the next dose of anticoagulant medicine was scheduled to be taken, then continue regular dosing.
Switching from anticoagulant treatment including a vitamin K antagonist (e.g., warfarin) to Apixaban Orion
Discontinue the vitamin K antagonist medicine. The doctor must perform blood tests and will inform the patient when to start taking Apixaban Orion.
Switching from Apixaban Orion to anticoagulant treatment including a vitamin K antagonist (e.g., warfarin)
If the doctor informs the patient that they 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. The doctor must perform blood tests and will inform the patient when to stop taking Apixaban Orion.
Patients undergoing cardioversion
Patients who require cardioversion 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 Apixaban Orion than recommended
If the patient has taken more than the recommended dose of this medicine, they should contact the doctor immediately. Take the medicine packaging with them, even if it is empty.
If the patient has taken more than the recommended dose of Apixaban Orion, there may be an increased risk of bleeding. In case of bleeding, surgical treatment, blood transfusion, or other treatment capable of reversing the effect of factor Xa inhibitors may be necessary.
Missing a dose of Apixaban Orion

• If a morning dose is missed, take it as soon as remembered, and it may be taken together with the evening dose.
• A missed evening dose may be taken only on the same evening. Do not take two doses the next morning instead; continue taking the medicine the next day as directed, twice daily. If in doubt about use of the medicine or if more than one dose is missed, consult the doctor or pharmacist.

Stopping Apixaban Orion
Do not stop taking this medicine without consulting the doctor, as stopping Apixaban Orion prematurely may increase the risk of blood clots.
If there are any further doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although they do not occur in everyone.
Apixaban Orion can be used for three different medical conditions. Known adverse effects and their frequency of occurrence 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 Orion to prevent blood clots after hip or knee replacement surgery.

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

• Anaemia, which may cause fatigue or paleness
• Bleeding including subcutaneous haemorrhages and swelling
• Nausea.

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

• Decreased platelet count (which may affect blood clotting)
• Postoperative bleeding, including bruising and swelling, leakage of blood or other fluid from the surgical wound/incision site (wound discharge) or injection site, gastrointestinal bleeding, red blood in stool, blood in urine, nosebleeds, vaginal bleeding
• 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 occur in up to 1 in 1000 people):

• Bleeding into muscle, eye, gums, or coughing up blood, rectal bleeding
• Hair loss.

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

• Bleeding into the brain or spinal canal, lungs, throat, mouth, abdominal cavity, or retroperitoneal space; bleeding from haemorrhoids; test results indicating presence of blood in stool or urine
• Skin rash, which may develop blisters and resembles small target 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
• Bleeding in the kidneys, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

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.

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

• Bleeding into the eye, stomach or intestine, rectal bleeding, blood in urine, nosebleeds, gum bleeding, subcutaneous haemorrhage and swelling
• Anaemia, which may cause fatigue or paleness
• Low blood pressure, which may lead to fainting or rapid heartbeat
• Nausea
• Blood test results may indicate increased gamma-glutamyl transferase (GGT) activity.

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

• Bleeding into the brain or spinal canal, 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 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 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 occur, seek medical advice immediately.

Rare (may occur in up to 1 in 1000 people):

• Bleeding in the lungs or throat, retroperitoneal space, or muscles.

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

• Skin rash, which may develop blisters and resembles small target lesions (dark spots in the centre surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme).

Not known (frequency 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 kidneys, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

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

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

• Nosebleeds, gum bleeding, blood in urine, subcutaneous haemorrhage and swelling, bleeding in stomach, intestine, rectum, oral cavity, or vaginal bleeding
• Anaemia, which may cause fatigue or paleness
• Decreased platelet count (which may affect clotting)
• Nausea
• Skin rash
• Blood test results may indicate 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, mouth or coughing up blood, bright red blood in stool, test results indicating blood in stool or urine, postoperative bleeding including bruising and swelling, leakage of blood or fluid from 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 medical advice 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 occur in up to 1 in 1000 people):

• Bleeding into the brain or spinal canal, lungs.

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

• Bleeding into the abdominal cavity or retroperitoneal space
• Skin rash, which may develop blisters and resembles small target 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
• Bleeding in the kidneys, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

Additional adverse effects in children and adolescents
Inform your doctor immediately if a child develops any of the following symptoms:

• Allergic reaction (hypersensitivity), which may cause: swelling of the face, lips, mouth, tongue and/or throat, and shortness of breath. These adverse effects are frequent (may occur in up to 1 in 10 children).

Generally, adverse effects observed in children and adolescents treated with Apixaban Orion were similar to those seen in adults, and their severity was mild or moderate. Adverse effects observed more frequently in children and adolescents were nosebleeds and abnormal vaginal bleeding.

Very frequent (may occur in more than 1 in 10 people):

• Vaginal bleeding, nosebleeds.

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

• Gum bleeding, blood in urine, subcutaneous haemorrhages and swelling, intestinal or rectal bleeding, bright red blood in stool; postoperative bleeding including bruises and swelling, leakage of blood or other fluid from surgical wound/incision site (wound discharge) or injection site
• Hair loss
• Anaemia, which may cause fatigue or paleness
• Decreased platelet count (which may affect clotting)
• Nausea
• Skin rash
• Itching
• 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 alanine aminotransferase (AlAT) activity.

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

• Bleeding into the abdominal cavity or retroperitoneal space, stomach, eye, mouth or coughing up blood, from haemorrhoids, into the brain or spinal canal, lungs, or muscles
• Skin rash, which may develop blisters and resembles small target 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 test results may indicate increased gamma-glutamyl transferase (GGT) activity, presence of blood in stool or urine
• Bleeding in the kidneys, 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, 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.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Apixaban Orion

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box and blister pack following "EXP". The expiry date refers to the last day of the stated month.
The batch number is indicated on the box and blister pack following "Lot".
There are no special storage instructions 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 will help protect the environment.

6. Contents of the pack and other information

What Apixaban Orion contains

• The active substance is apixaban. Each tablet contains 2.5 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) - 5mPas, monohydrate lactose, titanium dioxide (E 171), triacetin, yellow iron oxide (E 172).

What Apixaban Orion looks like and contents of the pack
Yellow, round, biconvex coated tablets with a diameter of 6 mm, embossed with the mark "I1" on one side and smooth on the other.
Pack sizes:
Blister packs: 10, 20, 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 Alert Card: information on use
Inside the Apixaban Orion packaging, 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 Apixaban Orion. You should always carry this card with you.

1. Take the card and separate the appropriate language section.
2. Complete the following details, or ask your doctor to complete them:
   • Name:
   • Date of birth:
   • Indication:
   • Dose: mg twice daily
   • Name of physician:
   • Physician's telephone number:
3. Fold the card and always keep 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 about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Orion Pharma Poland Sp. z o.o.
[email protected]