TREFTENIN 2.5 mg Tablets

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Treftenin, 2.5 mg, film-coated tablets
   1. Read all of this leaflet carefully before taking this medicine because it contains important information for you.
   2. Contents of the pack and other information
3. What Treftenin is and what it is used for
4. What you need to know before you take Treftenin
   1. Do not take Treftenin:
   2. Warnings and precautions
   3. Children and adolescents
   4. Other medicines and Treftenin
   5. Pregnancy and breast-feeding
   6. Driving and using machines
   7. Treftenin contains lactose and sodium
5. How to take Treftenin
   1. Dose
   2. Instructions for crushing the tablets:
   3. Take Treftenin as follows:
   4. Patients undergoing cardioversion
   5. If you take more Treftenin than you should
   6. If you forget to take Treftenin
   7. If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.
6. Possible side effects
   1. Common side effects (may affect up to 1 in 10 people)
   2. Uncommon side effects (may affect up to 1 in 100 people)
   3. Rare side effects (may affect up to 1 in 1,000 people)
   4. Frequency not known (frequency cannot be estimated from the available data)
   5. Common side effects (may affect up to 1 in 10 people)
   6. Uncommon side effects (may affect up to 1 in 100 people)
   7. Rare side effects (may affect up to 1 in 1,000 people)
   8. Frequency not known (frequency cannot be estimated from the available data)
   9. Common side effects (may affect up to 1 in 10 people)
   10. Uncommon side effects (may affect up to 1 in 100 people)
   11. Rare side effects (may affect up to 1 in 1,000 people)
   12. Frequency not known (frequency cannot be estimated from the available data)
   13. Reporting of side effects
7. How to store Treftenin
8. Contents of the pack and other information
   1. What Treftenin contains
   2. What Treftenin looks like and contents of the pack
   3. Patient Alert Card: information for action
   4. Marketing Authorisation Holder
   5. Importer
   6. This medicinal product is authorised in the Member States of the European Economic Area (EEA) under the following names:
   7. Date of last revision of the leaflet:

Package Leaflet: Information for the User

Treftenin, 2.5 mg, film-coated tablets

Apixaban

Read all of 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

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

1. What Treftenin is and what it is used for

Treftenin contains the active substance apixaban and belongs to a group of medicines called anticoagulants. It helps to prevent blood clots from forming by blocking factor Xa, which is an important factor in blood clotting.

Treftenin is used in adults to:

• prevent blood clots from forming after hip or knee replacement surgery. After hip or knee surgery, you are at a higher risk of forming blood clots in the veins of your legs. This can lead to swelling of your legs, with or without pain. If a blood clot breaks loose from your leg, it can travel to your lungs, which can be life-threatening and requires immediate medical attention.
• prevent blood clots from forming in the heart in patients with irregular heart rhythm (atrial fibrillation) and at least one additional risk factor. Blood clots can break loose and travel to the brain, causing a stroke, or to other organs, reducing blood flow to those organs.
• 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 blood clots from forming again in the deep veins of the legs and/or lungs.

2. What you need to know before you take Treftenin

Do not take Treftenin:

• if you are allergic to apixaban or any of the other ingredients of this medicine (listed in section 6),
• if you have active bleeding,
• if you have a liver disease that increases the risk of bleeding (hepatic coagulopathy),
• if you are taking other medicines to prevent blood clotting (e.g., warfarin, rivaroxaban, dabigatran, or heparin), except when switching from these medicines to Treftenin under the guidance of your doctor.

Warnings and precautions

Before taking Treftenin, tell your doctor if you have any of the following conditions:

• increased risk of bleeding, such as:
• bleeding disorders, including those that affect platelet function
• uncontrolled high blood pressure
• age 75 years or older
• body weight 60 kg or less
• severe kidney disease or kidney dialysis,
• liver disease or liver function abnormalities; Treftenin should be used with caution in patients with signs of liver dysfunction.
• if you have had a tube or injection into your spine (epidural or spinal anaesthesia); your doctor will advise you when to take Treftenin after the procedure.
• if you have a prosthetic heart valve,
• if your doctor has told you that you have unstable blood pressure or if you are scheduled for another treatment or surgery to remove a blood clot from your lungs.

Be careful when taking Treftenin:

• If you have antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), you should inform your doctor, who will decide whether to change your treatment.

If you need to have surgery or a procedure that may cause bleeding, your doctor may ask you to stop taking Treftenin for a short time. If you are unsure whether a procedure may cause bleeding, ask your doctor.

Children and adolescents

Treftenin should not be used in children and adolescents under 18 years of age.

Other medicines and Treftenin

Tell your doctor, pharmacist, or nurse about all medicines you are taking, have recently taken, or might take, including those you have bought without a prescription.

Some medicines may increase the effect of Treftenin and increase the risk of bleeding:

• certain medicines used to treat fungal infections (e.g., ketoconazole),
• certain antiviral medicines used to treat HIV/AIDS (e.g., ritonavir),
• other medicines used to reduce blood clotting (e.g., enoxaparin),
• anti-inflammatory or pain-relieving medicines (e.g., aspirin or naproxen). Especially if you are over 75 years old and taking aspirin, you may be at increased risk of bleeding.
• medicines used to treat high blood pressure or heart problems (e.g., diltiazem),
• antidepressant medicines called selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).

Some medicines may reduce the ability of Treftenin to prevent blood clots:

• medicines used to prevent seizures or fits (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 and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor, pharmacist, or nurse for advice before taking this medicine.

The effect of apixaban on pregnancy and the unborn child is not known. Do not take Treftenin if you are pregnant. If you become pregnant while taking Treftenin, tell your doctor immediately.

It is not known whether apixaban passes into breast milk. If you are breast-feeding or plan to breast-feed, ask your doctor, pharmacist, or nurse for advice before taking Treftenin. You may be advised to stop breast-feeding, stop taking Treftenin, or not start taking Treftenin.

Driving and using machines

Apixaban has no effect on the ability to drive or use machines.

Treftenin contains lactose and sodium

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, which is essentially sodium-free.

3. How to take Treftenin

Always take this medicine exactly as your doctor, pharmacist, or nurse has told you. If you are not sure, ask your doctor, pharmacist, or nurse.

Dose

Swallow the tablet whole with water. You can take Treftenin with or without food.

To get the best results from your treatment, take your tablets at the same time every day.

If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take Treftenin. You can crush the tablet and mix it with water, 5% glucose solution, apple juice, or apple puree immediately before taking it.

Instructions for crushing the tablets:

• Crush the tablet with a pestle in a mortar.
• Carefully transfer the powder to a suitable container, then mix it with a small amount (e.g., 30 mL or 2 tablespoons) of water or another liquid mentioned above to make a mixture.
• Swallow the mixture.
• Rinse the pestle and mortar used to crush the tablets and the container with a small amount of water or another liquid (e.g., 30 mL or 2 tablespoons) and swallow the rinse liquid.

If necessary, your doctor may give you a crushed Treftenin tablet mixed with 60 mL of water or 5% glucose solution through a nasogastric tube.

Take Treftenin as follows:

Prevention of blood clots after hip or knee replacement surgery.

The recommended dose is one 2.5 mg tablet twice daily.

For example, one tablet in the morning and one in the evening.

Take the first tablet 12 to 24 hours after surgery.

If you have had major hip surgery, you will usually take the tablets for 32 to 38 days.

If you have had major knee surgery, you will usually take the tablets 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 5 mg tablet twice daily.

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

• you have severe kidney problems
• you meet two or more of the following conditions:
• your blood test results show reduced kidney function (creatinine level in the blood of 1.5 mg/dL (133 micromole/L) or more)
• you are 80 years old or older
• your body weight is 60 kg or less

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

Treatment of blood clots in the deep veins of the legs and blood clots in the lungs.

The recommended dose is two 5 mg tablets twice daily for the first 7 days.

After 7 days, the recommended dose is one 5 mg tablet twice daily.

Prevention of further blood clots after completing 6 months of treatment.

The recommended dose is one 2.5 mg tablet twice daily.

Your doctor will decide how long you should continue treatment.

Changing your anticoagulant treatment:

• Changing from Treftenin to other anticoagulants.Stop taking Treftenin. Start taking the other anticoagulant (e.g., heparin) when the next Treftenin tablet is due.
• Changing from other anticoagulants to Treftenin.Stop taking the other anticoagulant. Start taking Treftenin when the next dose of the other anticoagulant is due.
• Changing from treatment with a vitamin K antagonist (e.g., warfarin) to Treftenin.Stop taking the vitamin K antagonist. Your doctor will perform blood tests and tell you when to start taking Treftenin.
• Changing from Treftenin to treatment with a vitamin K antagonist (e.g., warfarin).If your doctor tells you to start taking a vitamin K antagonist, continue taking Treftenin for at least 2 days after the first dose of the vitamin K antagonist. Your doctor will perform blood tests and tell you when to stop taking Treftenin.

Patients undergoing cardioversion

Patients who need to undergo a procedure to restore a normal heart rhythm (cardioversion) should take Treftenin at the times specified by their doctor to prevent blood clots from forming in the blood vessels of the brain and other parts of the body.

If you take more Treftenin than you should

If you take more Treftenin than you should, tell your doctor immediately. Take the package with you, even if it is empty.

If you take more Treftenin than you should, you may be at increased risk of bleeding. If you experience bleeding, you may need surgical treatment, blood transfusion, or other treatment to reverse the effect of apixaban.

If you forget to take Treftenin

Take the missed dose as soon as you remember, and then:

• take the next dose at the usual time
• continue taking your tablets as before

If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Treftenin can cause side effects, although not everybody gets them.

Treftenin can be used in three different medical conditions. The known side effects and their frequency may vary depending on the condition and are listed separately below. In these conditions, the most common side effect of apixaban is bleeding, which can be life-threatening and may require immediate medical attention.

The following side effects may occur when taking apixaban to prevent blood clots after hip or knee replacement surgery.

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

• Anaemia, which can cause tiredness or pale skin
• Bleeding, including:
• bruising and swelling
• Nausea (feeling sick).

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

• Reduced platelet count (which can affect blood clotting)
• Bleeding:
• after surgery, including bruising and swelling, bleeding or fluid from the wound or injection site
• from the stomach or intestines, or black stools
• blood in the urine
• from the nose
• from the vagina
• Low blood pressure, which can cause dizziness or fainting
• Blood test results may show:
• liver problems
• increased activity of certain liver enzymes
• increased bilirubin levels - a breakdown product of red blood cells that can cause yellowing of the skin and eyes
• Itching.

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

• Allergic reactions (hypersensitivity), which can cause swelling of the face, lips, mouth, tongue, and/or throat, and difficulty breathing. If you experience any of these symptoms, tell your doctor immediately.
• Bleeding:
• into the muscle
• into the eyes
• from the gums and coughing up blood
• from the anus
• Hair loss.

Frequency not known (frequency cannot be estimated from the available data)

• Bleeding:
• into the brain or spinal cord
• into the lungs or throat
• into the mouth
• into the abdominal cavity or the space behind the abdominal cavity
• from haemorrhoids
• blood in the stool or urine detected by laboratory tests
• Skin rash, which can cause blisters and looks like small targets (a dark spot in the centre surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme);
• Vasculitis (inflammation of blood vessels), which can cause skin rash or raised, flat, red, round patches under the skin or bruising.

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

• Bleeding, including:
• into the eyes
• from the stomach or intestines
• from the anus - blood in the urine
• from the nose
• from the gums
• bruising and swelling
• Anaemia, which can cause tiredness or pale skin
• Low blood pressure, which can cause dizziness or fainting
• Nausea (feeling sick)
• Blood test results may show:
• increased gamma-glutamyltransferase (GGT) activity

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

• Bleeding:
• into the brain or spinal cord
• into the mouth or coughing up blood
• into the abdominal cavity or from the vagina
• black stools
• blood in the urine detected by laboratory tests
• bleeding after surgery, including bruising and swelling, bleeding or fluid from the wound or injection site
• from haemorrhoids
• Reduced platelet count (which can affect blood clotting)
• Blood test results may show:
• liver problems
• increased activity of certain liver enzymes
• increased bilirubin levels - a breakdown product of red blood cells that can cause yellowing of the skin and eyes
• Skin rash
• Itching
• Hair loss
• Allergic reactions (hypersensitivity), which can cause swelling of the face, lips, mouth, tongue, and/or throat, and difficulty breathing. If you experience any of these symptoms, tell your doctor immediately.

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

• Bleeding:
• into the lungs or throat
• into the abdominal cavity
• into the muscle

Frequency not known (frequency cannot be estimated from the available data)

• Vasculitis (inflammation of blood vessels), which can cause skin rash or raised, flat, red, round patches under the skin or bruising.

The following side effects may occur when taking apixaban to treat or prevent blood clots in the deep veins of the legs and blood clots in the lungs.

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

• Bleeding, including:
• from the nose
• from the gums
• blood in the urine
• bruising and swelling
• from the stomach or intestines
• from the anus
• from the vagina
• Anaemia, which can cause tiredness or pale skin
• Reduced platelet count (which can affect blood clotting)
• Nausea (feeling sick)
• Skin rash
• Blood test results may show:
• increased gamma-glutamyltransferase (GGT) or alanine aminotransferase (ALT) activity

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

• Low blood pressure, which can cause dizziness or fainting
• Bleeding:
• into the eyes
• into the mouth or coughing up blood
• black stools
• blood in the urine detected by laboratory tests
• bleeding after surgery, including bruising and swelling, bleeding or fluid from the wound or injection site
• from haemorrhoids
• into the muscle
• Itching
• Hair loss
• Allergic reactions (hypersensitivity), which can cause swelling of the face, lips, mouth, tongue, and/or throat, and difficulty breathing. If you experience any of these symptoms, tell your doctor immediately.
• Blood test results may show:
• liver problems
• increased activity of certain liver enzymes
• increased bilirubin levels - a breakdown product of red blood cells that can cause yellowing of the skin and eyes

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

• Bleeding:
• into the brain or spinal cord
• into the lungs

Frequency not known (frequency cannot be estimated from the available data)

• Bleeding:
• into the abdominal cavity or the space behind the abdominal cavity
• Skin rash, which can cause blisters and looks like small targets (a dark spot in the centre surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme);
• Vasculitis (inflammation of blood vessels), which can cause skin rash or raised, flat, red, round patches under the skin or bruising.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet.

Side effects can be reported to the national reporting system listed in the website: https://smz.ezdrowie.gov.pl . Side effects can also be reported to the marketing authorisation holder.

5. How to store Treftenin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.

No special storage precautions are required.

Medicines should 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 Treftenin contains

• The active substance is apixaban. Each tablet contains 2.5 mg of apixaban.
• The other ingredients are:
• Tablet core: lactose (see section 2), microcrystalline cellulose, sodium lauryl sulfate, magnesium stearate.
• Tablet coating: lactose monohydrate (see section 2), hypromellose (E 464), titanium dioxide (E 171), macrogol 3350, triacetin, yellow iron oxide (E 172), red iron oxide (E 172).

What Treftenin looks like and contents of the pack

Light yellow, round, film-coated tablets with "TV" engraved on one side and "G1" on the other side. Dimensions: diameter 5.9-6.5 mm, thickness 3.0-3.6 mm.

Treftenin is available in the following pack sizes:

• Unit dose blisters containing 10 x 1, 14 x 1, 20 x 1, 30 x 1, 56 x 1, 60 x 1, 100 x 1, 120 x 1, 168 x 1, or 200 x 1 film-coated tablets.
• Bottles containing 180, 200, or 500 film-coated tablets, and
• bottles containing 180, 200, or 500 film-coated tablets and cotton.

The blisters and bottles are packed in a cardboard box with a leaflet inside the box.

Not all pack sizes may be marketed.

Patient Alert Card: information for action

Inside the pack of Treftenin, together with the patient leaflet, you will find a Patient Alert Card or your doctor may give you a similar card.

The Patient Alert Card contains information that will be useful for you and may serve as a warning to other doctors that you are taking Treftenin. Always carry this card with you.

• 1. Remove the card
• 2. You or your doctor should fill in the following:
• Name:
• Date of birth:
• Indication:
• Dose: ...... mg twice daily
• Doctor's name:
• Doctor's phone number:
• 3. Fold the card and always carry it with you.

Marketing Authorisation Holder

Day Zero ehf

Reykjavíkurvegi 62

220 Hafnarfjördur

Iceland

Tel. +354 659 4144

Importer

Balkanpharma Dupnitsa AD

3 Samokovsko Shosse Str.

2600, Dupnitsa

Bulgaria

Teva Pharma B.V.

Swensweg 5

2031 GA Haarlem

Netherlands

Actavis International Ltd

4, Sqaq tal-Gidi off Valletta Road

Luqa LQA 6000

Malta

Actavis Group PTC ehf.

Dalshraun 1

IS-220 Hafnarfjördur

Iceland

This medicinal product is authorised in the Member States of the European Economic Area (EEA) under the following names:

Germany:

Treftenin 2.5 mg Filmtabletten

Poland:

Treftenin

Date of last revision of the leaflet: