Treftenin

Package leaflet: Information for the user

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

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

Table of contents

1. What Treftenin is and what it is used for
2. Important information before taking 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.
This medicine helps prevent blood clots by inhibiting Factor Xa, a key component in the blood clotting process.
Treftenin is used in adults:

• 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 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, DVT) 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 stomach or intestinal ulcer, recently diagnosed bleeding into the brain),
• 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 a venous or arterial line has been inserted and heparin is administered through this line to maintain its patency, or when the patient is undergoing catheter ablation (a catheter is inserted into the vein) due to irregular heartbeat (arrhythmia).

Warnings and precautions
Before starting treatment, discuss with a doctor, pharmacist, or nurse 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 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 a heart valve prosthesis,
• if the doctor determines that the patient's blood pressure is unstable or if other treatment or a surgical procedure to remove a blood clot from the lungs is planned.

Special caution is required when using Treftenin:

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

If the patient needs to undergo surgery or a procedure that may involve bleeding, the doctor may ask the patient to temporarily stop taking this medicine for a short period. If in doubt whether a particular procedure may involve bleeding, consult 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 the 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 effectiveness. 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 if the patient is over 75 years old and taking acetylsalicylic acid, the risk of unwanted bleeding may be increased.
• medicines used for high blood pressure or heart problems (e.g. diltiazem),
• antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors.

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 plans to become pregnant, she should consult a doctor, pharmacist, or nurse before using 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 breast milk. Before using this medicine while breastfeeding, consult a doctor, pharmacist, or nurse. The patient may be advised to stop breastfeeding, discontinue, or not start taking Treftenin.
Driving and operating machinery
Apixaban has no effect 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 consult a 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 exactly as directed by your doctor or pharmacist. If you have any doubts,
you should consult your doctor, pharmacist or nurse.
Dosage
The tablet should be swallowed with water. Treftenin can be taken with or without food.
To achieve the best treatment results, it is recommended to take the tablets at the same times each day.
If a patient has difficulty swallowing tablets whole, they should discuss alternative methods of taking Treftenin with their doctor. The tablet may be crushed immediately before administration and mixed with water or 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 to crush 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 Treftenin tablets mixed with 60 mL of water or 5% aqueous dextrose solution via a nasogastric tube.
Treftenin should be taken as directed for the following indications:
Prevention of blood clots in the heart in patients with irregular heart rhythm and at least one
additional risk factor.
The recommended dose is one 5 mg tablet twice daily.
The recommended dose is one 2.5 mg tablet twice daily if:

• the patient has severe renal impairment, or
• two or more of the following conditions are met:
  • blood test results suggest reduced kidney function (serum creatinine 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. Your 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, for example, two tablets in the morning and two in the evening.
After 7 days, the recommended dose is one 5 mg tablet 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 twice daily, for example, one tablet in the morning and one in the evening.
Your doctor will decide how long treatment should continue.
Your doctor may change anticoagulant therapy as follows:

• Switching from Treftenin to anticoagulant medicines Discontinue Treftenin. Start anticoagulant treatment (e.g., heparin) at the time the next tablet was scheduled to be taken.

• Switching from anticoagulant medicines to Treftenin Discontinue anticoagulant medicines. Begin Treftenin at the time the next dose of anticoagulant medicine was scheduled to be taken, then continue taking it as usual.

• Switching from anticoagulant therapy including a vitamin K antagonist (e.g., warfarin) to Treftenin Discontinue the vitamin K antagonist-containing medicine. Your doctor must perform blood tests and will inform you when to start taking Treftenin.

• Switching from Treftenin to anticoagulant therapy including a vitamin K antagonist (e.g., warfarin) If your doctor informs you that you should start taking a vitamin K antagonist-containing medicine, you should continue taking Treftenin for at least 2 days after taking the first dose of the vitamin K antagonist-containing medicine.
  Your doctor must perform blood tests and will inform you when to discontinue 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 formation of blood clots in the blood vessels of the brain and other blood vessels in the body.
  Taking more Treftenin than recommended
  If you have taken more Treftenin than recommended, you must inform your doctor immediately.
  Bring the medicine packaging with you, even if it is empty.
  If you have taken more Treftenin than recommended, your risk of bleeding may be increased. In case of bleeding, surgical treatment, blood transfusion or other treatment to reverse the effect directed against factor Xa may be required.
  Missing a dose of Treftenin
  Take the missed dose as soon as you remember and:

• take the next dose at the usual time,

• then continue taking the medicine as before.

If you have any doubts about taking this medicine or if you miss more than one dose, you should consult your doctor, pharmacist or nurse.
Stopping Treftenin
DO NOT stop taking Treftenin without consulting your doctor, as the risk of developing a blood clot may be higher if treatment is stopped prematurely.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist or nurse.

4. Possible adverse effects

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

The following adverse effects may occur when taking apixaban to prevent blood clots in the heart in patients with irregular heartbeat and at least one additional risk factor.

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

• Bleeding, including:
  • into the eyes
  • into the stomach or intestine
  • from the rectum
  • blood in the urine
  • from the nose
  • from the 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 activity of gamma-glutamyl transferase (GGT)

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

• Bleeding:
  • into the brain or spinal canal
  • in the mouth or coughing up blood
  • in the abdominal cavity or from the vagina
  • bright red blood in the stool
  • bleeding occurring after surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/tissue 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 blood 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 that 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 your doctor immediately.

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

• Bleeding:
  • in the lungs or throat
  • into the retroperitoneal space (area at the back of the abdominal cavity)
  • into muscle tissue

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

• Skin rash with blister formation, resembling small bullseyes (dark spot in the center surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme).

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

• Inflammation of blood vessels (vasculitis), which may cause skin rash or raised, flat, red, round spots under the skin surface or bruising;
• Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy).

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

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

• Bleeding, including:
  • from the nose
  • from the gums
• Blood in the urine
• Bruising and swelling
• In the stomach, intestine, from the rectum
• In the mouth
• From the vagina
  • Anaemia, which may cause fatigue or paleness
  • Decreased platelet count (which may affect blood clotting)
  • Nausea
  • Skin rash
  • Blood test results may indicate:
    • increased activity of gamma-glutamyl transferase (GGT) or alanine aminotransferase (ALT)

Uncommon adverse effects (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 the stool
  • presence of blood in stool or urine detected in laboratory tests
  • bleeding occurring after surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/tissue incision site (wound discharge) or injection site
  • from haemorrhoids
  • into muscle tissue
• 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 your 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 that may cause yellowing of the skin and eyes

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

• Bleeding:
  • into the brain or spinal canal
  • in the lungs

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

• Bleeding:
  • into the abdominal cavity or retroperitoneal space
• Skin rash with blister formation, resembling small bullseyes (dark spot in the center surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme)
• Inflammation of blood vessels (vasculitis), which may cause skin rash or raised, flat, red, round spots under the skin surface or bruising
• Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy)

Reporting of adverse effects
If any adverse effects occur in the patient, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist or nurse.
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 181C, 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 Treftenin

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack after: EXP. The expiry date refers to the last day of the stated month.
There are no special storage instructions for this medicine.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Treftenin contains

• The active substance is apixaban. Each tablet contains 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, iron oxide red (E 172).

What Treftenin looks like and contents of the pack
Light pink, modified oval-shaped film-coated tablets, embossed with the code "TV" on one side and "G2" on the other side. Dimensions: length: 9.9 – 10.5 mm, width: 5.0 – 5.6 mm, thickness: 4.2 – 4.8 mm.
Treftenin is available in the following pack types and sizes:

• Unit dose blisters containing 10 x 1, 14 x 1, 20 x 1, 28 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.

Blisters and bottles are packed in cardboard boxes with a leaflet inside the box.
Not all pack sizes may be marketed.
Patient Alert Card: Information on what to do
Inside the Treftenin packaging, together with the patient leaflet, there is a Patient Alert Card, or a similar card may be issued by the physician.
The Patient Alert 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.

1. Remove the card
2. Fill in the following details or ask your doctor to complete them:
   • First name and surname:
   • 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
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) member states under the following names:
Germany: Treftenin 5 mg Filmtabletten
Poland: Treftenin