Package leaflet: Information for the user

Voziberin, 5 mg, coated tablets
Apixabanum
Please 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 a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same as yours.
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet contents

What Voziberin is and what it is used for
What you need to know before taking Voziberin
How to take Voziberin
Possible side effects
How to store Voziberin
Contents of the pack and other information

1. What Voziberin is and what it is used for

Voziberin contains the active substance apixaban and belongs to a group of medicines called anticoagulants. This medicine helps prevent blood clots by inhibiting factor Xa, an important component in the blood clotting process.
Voziberin is used in adults:

to prevent 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 flow to these organs (also known as systemic embolism). Stroke can be life-threatening and requires immediate medical attention.
to treat blood clots in the deep veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), as well as to prevent recurrence of blood clots in the blood vessels of the legs and (or) lungs.

Voziberin is used in children from 28 days to below 18 years of age for the treatment of blood clots and prevention of recurrence of blood clots in veins or in the blood vessels of the lungs.
The recommended dose adjusted for body weight is given in section 3.

2. Important information before taking Voziberin

When not to take Voziberin

if the patient is allergic to apixaban or any of the other ingredients of this medicine (listed in section 6);
if the patient has excessive bleeding;
if the patient has an organ disease that increases the risk of major bleeding (such as active or recently diagnosed peptic ulcer of the stomach or intestine, recently experienced 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 when switching anticoagulant therapy, when an intravenous or intra-arterial line has been inserted 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 this medicine, discuss with your 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 activity;
very high blood pressure not controlled by medication;
if the patient is over 75 years of age;
if the patient's body weight is 60 kg or less;
severe kidney disease or if the patient is on dialysis;
liver problems or history of liver problems;
This medicine should be used with caution in patients showing signs of liver function abnormalities.
a tube (catheter) or injection into the spine (anaesthetic or pain relief). In such a 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 if other treatment or a surgical procedure to remove a blood clot from the lungs is planned.

When to exercise particular caution when taking Voziberin

if the patient has a condition called antiphospholipid syndrome (an autoimmune 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, consult the doctor.
Children and adolescents
This medicine is not recommended for use in children and adolescents weighing less than 35 kg.
Voziberin 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 Voziberin, while others may reduce it. The doctor will decide whether the patient should receive Voziberin while taking other medicines and how closely monitoring should be performed.
The following medicines may enhance the effect of Voziberin 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 when the patient is over 75 years of age 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 the ability of Voziberin 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 is planning to have a baby, she should consult her doctor, pharmacist, or nurse before taking this medicine.
The effect of apixaban 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 passes into human milk. Consult your doctor, pharmacist, or nurse before taking this medicine during breastfeeding. The patient may be advised to discontinue breastfeeding, or to discontinue or not start taking this medicine.
Driving and using machines
Apixaban has not been shown to affect the ability to drive or operate machinery.
Voziberin 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; therefore, this medicine is considered "sodium-free".

3. How to take Voziberin

This medicine should always be taken exactly as instructed by your doctor or pharmacist. If you are not sure, ask your doctor, pharmacist or nurse.
Dosage
Swallow the tablet with water. Apixaban may be taken with or without food.
To achieve the best treatment results, it is recommended to take the tablets at the same time each day.
If you have difficulty swallowing the tablets whole, talk to your doctor about other ways of taking apixaban. 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 entire powder into a suitable container and mix it with a small amount, e.g. 30 mL (2 tablespoons), of water or another liquid mentioned 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 then swallow the rinsing liquid.

If necessary, your doctor may administer crushed Voziberin tablets mixed with 60 mL of water or 5% aqueous glucose solution through a nasogastric tube.
Voziberin should be taken as recommended for the following indications:
Prevention of blood clots in the heart in patients with irregular heartbeat and at least one additional risk factor
The recommended dose is one Voziberin 5 mg tablet twice daily.
The recommended dose is one Voziberin 2.5 mg tablet twice daily if:

the patient has severe kidney function 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 in the morning and one in the evening.
Your doctor will decide how long treatment should continue.
Treatment of blood clots in the legs and blood clots in blood vessels of the lungs
The recommended dose is two tablets of Voziberin 5 mg twice daily for the first 7 days, for example two in the morning and two in the evening.
After 7 days, the recommended dose is one tablet of Voziberin 5 mg twice daily, for example one in the morning and one in the evening.
Prevention of recurrent blood clots after completion of 6-month treatment
The recommended dose is one Voziberin 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.
Use in children and adolescents
Treatment of blood clots and prevention of recurrent blood clots in veins or blood vessels of the lungs.
This medicine should always be taken or administered exactly as instructed by your doctor or pharmacist. If you are not sure, ask your doctor, pharmacist or nurse.
To achieve the best treatment results, try to take or administer the dose at the same time each day.
The dose of Voziberin depends on body weight and will be calculated by your doctor. The recommended dose for children and adolescents with body weight of at least 35 kg is two tablets of Voziberin 5 mg , taken twice daily for the first 7 days, for example two in the morning and two in the evening.
After 7 days, the recommended dose is one tablet of Voziberin 5 mg , taken twice daily, for example one in the morning and one in the evening.
For parents and caregivers: observe the child to ensure the full dose has been taken.
It is important to attend scheduled doctor's appointments, as dose adjustments may be necessary as the patient's body weight changes.
Your doctor may change anticoagulant treatment as follows:

Switching from Voziberin to anticoagulant medicines Discontinue taking Voziberin. Start treatment with anticoagulant medicines (e.g. heparin) at the time the next tablet was scheduled to be taken.
Switching from anticoagulant medicines to Voziberin Discontinue taking anticoagulant medicines. Start treatment with Voziberin at the time the next dose of anticoagulant medicine was scheduled to be taken, then continue taking it as usual.
Switching from anticoagulant treatment including a vitamin K antagonist (e.g. warfarin) to Voziberin Discontinue the vitamin K antagonist medicine. Your doctor will order blood tests and inform you when to start taking Voziberin.
Switching from Voziberin to anticoagulant treatment including a vitamin K antagonist (e.g. warfarin) If your doctor instructs you to start taking a vitamin K antagonist medicine, continue taking Voziberin for at least 2 days after taking the first dose of the vitamin K antagonist medicine. Your doctor will order blood tests and inform you when to stop taking Voziberin.

Patients undergoing cardioversion
Patients who require cardioversion to restore normal heart rhythm should take this medicine at the times specified by their doctor to prevent formation of blood clots in blood vessels of the brain and other blood vessels in the body.
Taking more Voziberin than recommended
If you have taken more Voziberin than recommended, contact your doctor immediately . Take the medicine packaging with you, even if no tablets remain.
If you have taken more than the recommended dose of Voziberin, your risk of bleeding may be increased. In case of bleeding, surgical treatment, blood transfusion or other treatment to reverse the effect of factor Xa inhibition may be necessary.
Missing a dose of Voziberin

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

If you have any doubts about taking the medicine or if you miss more than one dose , contact your doctor, pharmacist or nurse.
Stopping Voziberin
Do not stop taking this medicine without consulting your doctor, as stopping treatment prematurely may increase the risk of developing blood clots.
If you have any further questions about the use of this medicine, contact your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The most common general adverse reaction with Voziberin is bleeding, which may
potentially be life-threatening and may require immediate medical attention.
The following adverse reactions may occur when taking Voziberin to
prevent blood clots in the heart in patients with irregular heartbeat 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 the gums;
subcutaneous haemorrhages 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 show:
increased gamma-glutamyltransferase (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 presence of blood in coughed-up sputum;
in the abdominal cavity or from the vagina;
bright red blood in stool;
bleeding following surgery, including subcutaneous haemorrhages 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 blood clotting);
Blood test results may show:
abnormal liver function;
increased activity of certain liver enzymes;
increased bilirubin levels – a breakdown product of red blood cells, which may cause yellowing of the skin and eyes;
Skin rash;
Itching;
Hair loss;
Allergic (hypersensitivity) reactions, 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 reactions (may occur in up to 1 in 1,000 people)

Bleeding:
into the lungs or throat;
into the retroperitoneal space (area behind the abdominal cavity);
into muscles.

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

Skin rash with blister formation, resembling small target-like lesions (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) ( erythema multiforme ).

Frequency not known (cannot be estimated from available data)

Vasculitis (inflammation of blood vessels), which may cause skin rash or raised, flat, red, circular spots beneath the skin surface or subcutaneous haemorrhages;
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

The following adverse reactions may occur when taking Voziberin for
the treatment or prevention of recurrent venous blood clots in the legs and
pulmonary embolism (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 the gums;
blood in urine;
subcutaneous haemorrhages and swelling;
in the stomach, intestine, or 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 show:
increased gamma-glutamyltransferase (GGT) or alanine aminotransferase (AlAT) 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 presence of blood in coughed-up sputum;
bright red blood in stool;
test results indicating blood in stool or urine;
bleeding following surgery, including subcutaneous haemorrhages and swelling, leakage of blood or fluid from the surgical wound, incision site (wound discharge), or injection site;
from haemorrhoids;
into muscles;
Itching;
Hair loss;
Allergic (hypersensitivity) reactions, 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 show:
abnormal liver function;
increased activity of certain liver enzymes;
increased bilirubin levels – a breakdown product of red blood cells, which may cause yellowing of the skin and eyes.

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

Bleeding:
into the brain or spinal canal;
into the lungs.

Frequency not known (cannot be estimated from available data)

Bleeding:
into the abdominal cavity or retroperitoneal space;
Skin rash with blister formation, resembling small target-like lesions (dark spots in the center 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, circular spots beneath the skin surface or subcutaneous haemorrhages;
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

Additional adverse reactions in children and adolescents
If any of the following symptoms occur, seek immediate medical advice:

Allergic (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and/or throat, and breathing difficulties. The frequency of these adverse reactions is classified as common (may occur in up to 1 in 10 people).

In general, adverse reactions observed in children and adolescents treated with apixaban
were similar to those seen in adults and were mostly mild or moderate in severity.
Adverse reactions occurring more frequently in children and adolescents include nosebleeds and
unusual vaginal bleeding.
Very common adverse reactions (may occur in more than 1 in 10 people)

Bleeding, including:
from the vagina;
from the nose.

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

Bleeding, including:
from the gums;
blood in urine;
subcutaneous haemorrhages and swelling;
from the intestine or rectum;
bright red blood in stool;
bleeding following surgery, including subcutaneous haemorrhages and swelling, leakage of blood or fluid from the surgical wound, incision site (wound discharge), or injection site;
Hair loss;
Anaemia, which may cause fatigue or paleness;
Decreased platelet count (which may affect blood clotting);
Nausea;
Skin rash;
Itching;
Low blood pressure, which may cause fainting or rapid heartbeat in the child;
Blood test results may show:
abnormal liver function;
increased activity of certain liver enzymes;
increased alanine aminotransferase (AlAT) activity.

Frequency not known (cannot be estimated from available data)

Bleeding:
into the abdominal cavity or retroperitoneal space;
into the stomach;
into the eyes;
in the mouth;
from haemorrhoids;
in the mouth or presence of blood in coughed-up sputum;
into the brain or spinal canal;
into the lungs;
into muscles;
Skin rash with blister formation, resembling small target-like lesions (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) ( erythema multiforme );
Vasculitis, which may cause skin rash or raised, flat, red, circular spots beneath the skin surface or subcutaneous haemorrhages;
Blood test results may show:
increased gamma-glutamyltransferase (GGT) activity;
presence of blood in stool or urine;
Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the 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 reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store the medicine Voziberin

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 following:
EXP. The expiry date refers to the last day of the stated month.
No special storage instructions apply 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 will help
protect the environment.

6. Contents of the pack and other information

What Voziberin contains

The active substance is apixaban. Each tablet contains 5 mg of apixaban.
The other ingredients are:
- Tablet core: lactose monohydrate (see section 2), microcrystalline cellulose (E 460), sodium croscarmellose (E 468), sodium lauryl sulfate (E 487), magnesium stearate (E 470b);
- Tablet coating: lactose monohydrate (see section 2), hypromellose (E 464), titanium dioxide (E 171), triacetin, iron oxide red (E 172).

What Voziberin looks like and contents of the pack
Voziberin tablets are pink, oval-shaped (approximately 10 x 5 mm), biconvex, film-coated tablets, with the imprint "M" on one side and "5" on the other.
Voziberin is available in blister packs contained in cardboard cartons of 14, 20, 28, 56, 60, 168 and 200 film-coated tablets.
Not all pack sizes may be marketed.

Patient Card: information for use
Inside the Voziberin packaging, alongside the patient leaflet, a Patient Card is included, or your doctor may provide you with a similar card.
The Patient Card contains helpful information for the patient and serves as a warning to other healthcare professionals that the patient is taking Voziberin. You should always carry this card with you.

Take the card.
Fill in the following details, or ask your doctor to complete them:
- Name:
- Date of birth:
- Indication:
- Dose: ........mg twice daily
- Doctor's name:
- Doctor's telephone number:
Fold the card and always keep it with you.

Marketing Authorisation Holder:
MSN Labs Europe Limited
KW20A Corradino Park
Paola, PLA 3000
Malta
Tel.: (+48) 699 711 147
{logo of the marketing authorisation holder}

Manufacturer/Importer:
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta
MSN Labs Europe Limited
KW20A Corradino Park
Paola, PLA 3000
Malta

This medicinal product is authorised for marketing in the European Economic Area under the following names:
Bulgaria: EN: Voziberin 5 mg film-coated tablets
BG: Voziberin 5 mg филмирани таблетки
Croatia: Voziberin 5 mg filmom obložene tablete
Czech Republic: Voziberin
Estonia: Voziberin
Lithuania: Voziberin 5 mg plėvele dengtos tabletės
Latvia: Voziberin 5 mg apvalkotās tabletes
Poland: Voziberin
Romania: Voziberin 5 mg comprimate filmate
Slovakia: Voziberin 5 mg
Slovenia: Voziberin 5 mg filmsko obložene tablete
Sweden: Voziberin 5 mg filmdragerade tabletter
Hungary: Voziberin 5 mg filmtabletta

The most up-to-date approved product information and educational materials for this medicinal product are available by scanning the QR code below with a smartphone. The same information is also accessible via the following website (URL): https://rejestry.ezdrowie.gov.pl/rpl/search/public
After accessing the website, enter the name of the medicinal product and then open "Materiały do pobrania" ("Downloadable materials").