Package leaflet: Information for the user

Treftenin, 2.5 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, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

What Treftenin is and what it is used for
What you need to know before taking Treftenin
How to take Treftenin
Possible side effects
How to store Treftenin
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 known as anticoagulants.
This medicine helps prevent the formation of blood clots by inhibiting factor Xa, which is an important component in the blood clotting process.
Treftenin is used in adults:

To prevent the formation of blood clots (deep vein thrombosis, DVT) after hip or knee replacement surgery. After hip or knee surgery, patients 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 the formation of blood clots in the heart in patients with irregular heartbeat (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 supply to these organs (also known as systemic embolism). Stroke may be life-threatening and requires immediate medical intervention.
To treat existing 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. Important information before using Treftenin

When not to take Treftenin:

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

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

increased risk of bleeding, for example:
- conditions involving bleeding, including cases leading to reduced platelet function
- very high blood pressure not controlled with medication
- patient's age – over 75 years
- patient's body weight – 60 kg or less
severe kidney disease or the patient is on dialysis,
liver function disorders or history of such disorders; Treftenin should be used with caution in patients showing signs of impaired liver function,
if the patient has had a tube (catheter) or spinal injection (anaesthetic or pain-relieving) – in such a case, the doctor will advise taking Treftenin 5 or more hours after catheter removal,
if the patient has a heart valve prosthesis,
if the doctor finds that the patient's blood pressure is unstable or if another treatment or surgical procedure to remove a blood clot from the lungs is planned.

Special caution is required when using Treftenin:

If the patient has a condition 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 associated with bleeding is required, 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
Treftenin is not recommended for use in children and adolescents under 18 years of age.

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

The following medicines may enhance the effect of Treftenin 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 in patients over 75 years of age taking acetylosalicylic acid, the risk of unwanted bleeding may be increased.
medicines used for high blood pressure or heart problems (e.g. diltiazem),
antidepressants known as selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs).

The following medicines may reduce Treftenin's ability to prevent blood clots:

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 become pregnant, she should consult her doctor, pharmacist or nurse before taking this medicine.
The effect of apixaban on pregnancy and the unborn child is unknown. Treftenin should not be taken during pregnancy. If a patient becomes pregnant while taking Treftenin, she should contact her doctor immediately.
It is not known whether apixaban passes into human milk. Consult your doctor, pharmacist or nurse before taking this medicine during breastfeeding. The patient may be advised to stop breastfeeding, or to discontinue or not start taking Treftenin.

Driving and operating machinery
Apixaban has no influence on the ability to drive or operate machinery.

Treftenin contains lactose (a type of sugar) and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should contact the doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Treftenin

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. Treftenin may 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
administration methods with their doctor. The tablet may be crushed immediately before
administration and mixed with water or a 5% aqueous dextrose 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, then 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, a doctor may administer crushed Treftenin tablets mixed with 60 mL of water or
5% aqueous dextrose solution via a nasogastric tube.
Treftenin 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 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, tablets are usually taken for 32 to 38 days.
If the patient has undergone major knee surgery, tablets are usually taken for 10 to 14 days.
Prevention of blood clots in the heart in patients with irregular heartbeat 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:

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, e.g., 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 5 mg tablets twice daily for the first 7 days, e.g., two tablets in the morning and two in the evening.
After 7 days, the recommended dose is one 5 mg tablet twice daily, e.g., one tablet in the morning and one in the evening.
Prevention of recurrent blood clots after completing 6 months of treatment
The recommended dose is one 2.5 mg tablet twice daily, e.g., 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 Treftenin to anticoagulant medicines Discontinue Treftenin. Start anticoagulant therapy (e.g., heparin) at the time the next tablet was scheduled to be taken.
Switching from anticoagulant medicines to Treftenin Discontinue anticoagulant medicines. Start Treftenin at the time the next dose of anticoagulant medicine was scheduled to be taken, then continue regular dosing.
Switching from anticoagulant therapy including a vitamin K antagonist (e.g., warfarin) to Treftenin Discontinue the vitamin K antagonist-containing medicine. The doctor must perform blood tests and will inform the patient when to start taking Treftenin.
Switching from Treftenin to anticoagulant therapy including a vitamin K antagonist (e.g., warfarin) If the doctor informs the patient to start taking a vitamin K antagonist-containing medicine, continue taking Treftenin 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 Treftenin.

Patients undergoing cardioversion
Patients who require cardioversion to restore normal heart rhythm should take Treftenin at the times
specified by their doctor to prevent the formation of blood clots in the blood vessels of the brain and
other blood vessels in the body.
Taking more Treftenin than recommended
If a patient takes more Treftenin than recommended, contact a doctor immediately.
Bring the medicine packaging, even if it is empty.
If a patient takes more Treftenin than recommended, the risk of bleeding may increase. 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 Treftenin
Take the missed dose as soon as remembered and:

take the next dose at the usual time,
then continue taking the medicine as before.

If in doubt about use of the medicine or if more than one dose is missed, consult a doctor, pharmacist, or nurse.
Stopping Treftenin
DO NOT stop taking Treftenin without consulting a doctor, as the risk of developing a blood clot may be higher if treatment is stopped prematurely.
If there are any further questions about the use of this medicine, consult a doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Treftenin can be used for three different medical conditions. Known adverse reactions and their frequency of occurrence may differ for each of these medical conditions and are listed separately below. In these conditions, the most common general adverse reaction associated with apixaban is bleeding, which may potentially be life-threatening and may require immediate medical attention.

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

Common adverse reactions (may occur in up to 1 in 10 people)

Anaemia, which may cause fatigue or paleness
Bleeding including:
- bruising and swelling
Nausea.

Uncommon adverse reactions (may occur in up to 1 in 100 people)

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

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

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, contact a doctor immediately.
Bleeding:
- into muscle
- into the eyes
- from gums and coughing up blood
- from the rectum
Hair loss.

Frequency not known (cannot be estimated from available data)

Bleeding:
- into the brain or spinal canal
- in the lungs or throat
- in the mouth
- into the abdominal cavity or retroperitoneal space
- from haemorrhoids
- test results indicating presence of blood in stool or urine
Skin rash, which may develop blisters and appear as small target-like lesions (dark center surrounded by a lighter ring, with a dark ring at the edge) (erythema multiforme);
Vasculitis (inflammation of blood vessels), which may cause skin rash or raised, flat, red, circular spots beneath the skin surface or bruising;
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following adverse reactions 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 adverse reactions (may occur in up to 1 in 10 people)

Bleeding, including:
- into the eyes
- into the stomach or intestine
- from the rectum – blood in urine
- from the nose
- from gums
- bruising 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 adverse reactions (may occur in up to 1 in 100 people)

Bleeding:
- into the brain or spinal canal
- in the mouth or coughing up blood
- into the abdominal cavity or from the vagina
- 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
- 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:
- liver function abnormalities
- 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, contact a doctor immediately.

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

Bleeding:
- in the lungs or throat
- into retroperitoneal space
- into muscle.

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

Skin rash, which may develop blisters and appear as small target-like lesions (dark center surrounded by a lighter ring, with a dark ring at 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, circular spots beneath the skin surface or bruising;
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following adverse reactions may occur when taking apixaban for the treatment or prevention of recurrent blood clots in the deep veins of the legs and blood clots in the blood vessels of the lungs.

Common adverse reactions (may occur in up to 1 in 10 people)

Bleeding, including:
- from the nose
- from gums
- blood in urine
- bruising and swelling
- in the stomach, intestines, or from the rectum
- in the mouth
- from the vagina
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 (ALT) activity.

Uncommon adverse reactions (may occur in 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
- presence of blood in stool or urine detected in laboratory tests
- postoperative bleeding, including bruising and swelling, leakage of blood or fluid from the surgical wound/incision site (wound discharge) or injection site
- from haemorrhoids
- into muscle
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, contact a doctor immediately.
Blood test results may indicate:
- liver function abnormalities
- 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 adverse reactions (may occur in up to 1 in 1,000 people)

Bleeding:
- into the brain or spinal canal
- in the lungs.

Frequency not known (cannot be estimated from available data)

Bleeding:
- into the abdominal cavity or retroperitoneal space.
Skin rash, which may develop blisters and appear as small target-like lesions (dark center surrounded by a lighter ring, with a dark ring at the edge) (erythema multiforme);
Vasculitis (inflammation of blood vessels), which may cause skin rash or raised, flat, red, circular spots beneath the skin surface or bruising;
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

Reporting of adverse reactions
If any adverse reactions occur in a patient, including any adverse reactions not listed in this leaflet, inform a doctor, pharmacist, or nurse.
Adverse reactions 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, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl .
Adverse reactions can also be reported to the marketing authorization holder. Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Treftenin

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box and blister after: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions apply 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. Such measures 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 croscarmellose, sodium lauryl sulfate, magnesium stearate.
- Tablet coating: monohydrate lactose (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 types and 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 with cotton.

Blister packs and bottles are packed in cardboard boxes with a patient leaflet inside the box.
Not all pack sizes may be marketed.

Patient warning card: information on handling
Inside the Treftenin packaging, together with the patient leaflet, there is a Patient Warning Card, or a similar card may be issued by the physician.
The Patient Warning Card contains information that will be helpful for the patient and may serve as a warning to other physicians that the patient is taking Treftenin. You should always carry this card with you.

Remove the card.
Fill in the following details or ask your doctor to complete them:
- Name:
- Date of birth:
- Indication:
- Dose: ...... mg twice daily
- Name of doctor:
- Doctor's telephone number:
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
The 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 European Economic Area (EEA) under the following names:
Germany: Treftenin 2.5 mg Filmtabletten
Poland: Treftenin