Patient Information Leaflet

Embavi 2.5 mg film-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 them, 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.

Table of contents

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

1. What Embavi is and what it is used for

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

to prevent blood clots (deep vein thrombosis) after hip or knee replacement surgery. After hip or knee surgery, patients are at 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, causing breathlessness, which may or may not be accompanied by chest pain. This condition (pulmonary embolism) can be life-threatening and requires immediate medical attention.
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, blocking blood supply to these organs (known as systemic embolism). Stroke may 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), and to prevent recurrence of blood clots in the veins of the legs and/or lungs.

Embavi is used in children aged from 28 days to below 18 years for the treatment of blood clots and prevention of recurrence of blood clots in veins or pulmonary blood vessels.
The recommended dose adjusted by body weight is described in section 3.

2. Important information before taking Embavi

When not to take Embavi:

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 any organ that increases the risk of severe bleeding (for example, active or recently experienced peptic ulcer of the stomach or intestines, recently experienced intracranial bleeding);
if the patient has liver disease leading to an increased risk of bleeding (hepatic coagulopathy);
if the patient is taking anticoagulant medicines (such as warfarin, rivaroxaban, dabigatran, or heparin), except when switching from one anticoagulant to another, when the patient has a permanent intravenous or intra-arterial catheter and receives heparin through this catheter to maintain its patency, or when a catheter is inserted into a blood vessel (during catheter ablation) to treat irregular heartbeat (arrhythmia).

Warnings and precautions
Before starting to take this medicine, discuss with your doctor, pharmacist, or nurse:

if the patient has an increased risk of bleeding, for example:
- coagulation disorders, including conditions associated with reduced platelet function;
- very high, uncontrolled blood pressure;
- if the patient is over 75 years of age;
- if the patient's body weight is 60 kg or less;
if the patient has severe kidney disease or is on dialysis;
if the patient currently has or has had liver disease in the past. This medicine should be used with caution in patients showing signs of liver dysfunction.
if the patient has had a tube (catheter) inserted or an injection (injection) into the spine (for anaesthesia or pain treatment), the doctor will recommend taking this medicine at least 5 hours after removal of the catheter;
if the patient has a heart valve prosthesis;
if the doctor considers that the patient's blood pressure is unstable or if another treatment or surgical procedure is planned to remove a blood clot from the lungs.

When to exercise particular caution when using Embavi

if the patient has a condition called antiphospholipid syndrome (an autoimmune disorder causing an 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 to temporarily stop taking this medicine. If in doubt whether a given procedure may cause bleeding, consult the doctor.
Children and adolescents
This medicine is not recommended for use in children and adolescents with body weight below 35 kg.
Embavi with 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 Embavi, while others may reduce its effectiveness.
The doctor will decide whether the patient should take Embavi during treatment with other medicines and how the patient should be monitored.
The following medicines may enhance the effect of Embavi 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). Especially if the patient is over 75 years of age and taking acetylsalicylic acid, there may be an increased risk of bleeding;
medicines used to treat high blood pressure or heart diseases (e.g. diltiazem);
antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors.

The following medicines may reduce the ability of Embavi 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 have a child, she should consult her doctor, pharmacist, or nurse before taking this medicine.
The effect of Embavi on pregnancy and the unborn child is unknown. This medicine should not be used during pregnancy. If the patient becomes pregnant while taking this medicine, she should contact her doctor immediately.
It is not known whether Embavi passes into human milk. Before taking this medicine during breastfeeding, consult a doctor, pharmacist, or nurse. They will advise whether it is better to discontinue breastfeeding or to stop/avoid starting treatment with this medicine.
Driving and operating machinery
No effects of Embavi on the ability to drive and operate machinery have been observed.
Embavi 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 Embavi

This medicine should always be taken according to the instructions given by your doctor or pharmacist. If you are unsure, you should consult your doctor, pharmacist, or nurse.

Dosage

The tablet should be swallowed with water. Embavi can be taken with or without food. It is recommended to take the tablets at the same time each day to achieve the best treatment results.

If you have difficulty swallowing the whole tablet, speak to your doctor about alternative ways of taking Embavi. The tablet may be crushed and mixed with water immediately before administration, using either water, 5% glucose solution, apple 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 of liquid—for example, 30 mL (2 tablespoons)—of water or one of the liquids listed above to form a mixture.
Swallow (drink) the resulting mixture.
Rinse the pestle and mortar used for crushing the tablet, as well as the container used to prepare the mixture, with a small amount of water or one of the liquids listed above (e.g., 30 mL). Then swallow (drink) the rinsing liquid.

If necessary, your doctor may administer crushed Embavi tablets mixed with 60 mL of water or 5% glucose solution via a nasogastric tube.

Embavi should be taken as directed for the following indications:

Prevention of blood clots after hip or knee replacement surgery

The recommended dose is one 2.5 mg Embavi 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.

After major hip replacement surgery, patients usually take the tablets for 32 to 38 days.
After major knee replacement surgery, patients usually take the tablets 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 Embavi tablet twice daily.

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

the patient has severe kidney function impairment; or
at least two of the following criteria are met:
- blood test results indicate reduced kidney function (serum creatinine level 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 legs and blood clots in the blood vessels of the lungs

The recommended dose is two 5 mg Embavi 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 Embavi 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 Embavi 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

For the 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 according to the instructions given by your doctor or pharmacist. If you are unsure, consult your doctor, pharmacist, or nurse.

To achieve the best treatment results, it is recommended to take or administer the tablets at the same time each day.

The Embavi dose depends on body weight and will be calculated by the doctor.

The recommended dose for children and adolescents with body weight of at least 35 kg is four 2.5 mg Embavi tablets 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 Embavi tablets twice daily—for example, two tablets in the morning and two in the evening.

For parents and caregivers: observe the child to ensure the full dose has been taken.

Follow scheduled doctor visits, as dose adjustments may be necessary due to changes in the child’s body weight.

Your doctor may change anticoagulant treatment as follows:

Switching from Embavi to another anticoagulant Discontinue taking Embavi. At the time when the next scheduled dose would have been taken, start treatment with another anticoagulant (e.g., heparin).
Switching from another anticoagulant to Embavi Discontinue taking the anticoagulant. At the time when the next scheduled dose of the anticoagulant would have been taken, start treatment with Embavi and continue taking it as usual.
Switching from vitamin K antagonist anticoagulant treatment (e.g., warfarin) to Embavi Discontinue taking the vitamin K antagonist medicine. Your doctor will order blood tests and advise when you can start taking Embavi.
Switching from Embavi to vitamin K antagonist anticoagulant treatment (e.g., warfarin) If your doctor advises you to start taking a vitamin K antagonist medicine, continue taking Embavi for at least 2 days after taking the first dose of the vitamin K antagonist medicine. Your doctor will order blood tests and advise when to stop taking Embavi.

Use in patients undergoing cardioversion

If you require a procedure called cardioversion to restore normal heart rhythm due to irregular heartbeat, you must take this medicine at strictly defined times as instructed by your doctor to prevent blood clots in the brain’s blood vessels and other blood vessels in the body.

Taking more Embavi than you should

If you take more Embavi than recommended, you must contact your doctor immediately. Bring the medicine packaging with you, even if it is empty.

Taking more Embavi than recommended may increase the risk of bleeding. If bleeding occurs, surgical treatment, blood transfusion, or other treatment to reverse the effect of factor Xa inhibition may be necessary.

Missed dose of Embavi

If you miss your morning dose, take it as soon as possible, 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 the twice-daily dosing schedule as recommended the following day.

If you have any doubts about using this medicine or if you miss more than one dose, consult your doctor, pharmacist, or nurse.

Stopping Embavi

Do not stop taking this medicine without consulting your doctor, as stopping treatment prematurely may increase the risk of blood clots.

If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The medicine Embavi can be used for three different medical conditions. The known side effects and
their frequency of occurrence in each of these conditions may differ and are listed separately.
The most common general side effect of this medicine in these conditions is bleeding, which
may potentially be life-threatening and may require immediate medical attention.

The following side effects are known to occur when Embavi is used to prevent blood clots after hip or knee replacement surgery:

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

Anaemia, which may cause fatigue or paleness;
Bleeding, including bruising (subcutaneous haemorrhage) and swelling;
Nausea.

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

Decrease in platelet count (which may affect blood clotting);
Bleeding:
- Occurring after surgery, including bruising (subcutaneous haemorrhage) and swelling, or leakage of blood or fluid from the surgical wound/incision site (wound discharge) or injection site;
- From the stomach or intestines, or presence of bright/red blood in stool;
- Blood in urine;
- Nosebleeds;
- From the vagina;
Low blood pressure, which may lead to fainting or rapid heartbeat;
Blood tests may show:
- Abnormal liver function;
- 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 (jaundice);
Itching.

Rare side effects (may occur in up to 1 in 1000 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 your doctor immediately.
Bleeding:
- Into muscle tissue;
- Into the eyes;
- From gums, or presence of blood in sputum when coughing;
- From the rectum;
Hair loss.

Frequency not known (cannot be estimated from available data)

Bleeding:
- Into the brain or spinal cord;
- Into the lungs or throat;
- In the mouth;
- Into the abdominal cavity or retroperitoneal space;
- From haemorrhoids;
- Tests showing presence of blood in stool or urine;
Skin rash, which may develop blisters and resembles small target-like lesions (dark spots surrounded by a lighter area, with a dark ring at the edge) (erythema multiforme);
Vasculitis (inflammation of blood vessels), which may cause skin rash or small, flat, red, round spots under the skin surface or subcutaneous haemorrhages (bruising);
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following side effects are known when Embavi is used to prevent blood clots in the heart in patients with irregular heartbeat and at least one additional risk factor:

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

Bleeding, including:
- Into the eyes;
- Into the stomach or intestines;
- From the rectum;
- Blood in urine;
- Nosebleeds;
- From gums;
- Subcutaneous haemorrhage (bruising) and swelling;
Anaemia, which may cause fatigue or paleness;
Low blood pressure, which may lead to fainting or rapid heartbeat;
Nausea;
Blood tests may show:
- Increased gamma-glutamyltransferase (GGT) activity.

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

Bleeding:
- Into the brain or spinal cord;
- In the mouth or presence of blood in sputum when coughing;
- Into the abdominal cavity or from the vagina;
- Presence of bright/red blood in stool;
- Bleeding occurring after surgery, including bruising (subcutaneous haemorrhage) and swelling, or leakage of blood or fluid from the surgical wound/incision site (wound discharge) or injection site;
From haemorrhoids;
Tests showing presence of blood in stool or urine;
- Decrease in blood platelet count (which may affect clotting);
- Blood tests may show:
  - Abnormal liver function;
  - 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;
- 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 immediate medical attention.

Rare side effects (may occur in up to 1 in 1000 people)

Bleeding:
- Into the lungs or throat;
- Into the retroperitoneal space;
- Into muscles.

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

Skin rash, which may develop blisters and resembles small target-like lesions (dark spots surrounded by a lighter area, 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 small, flat, red, round spots under the skin surface or subcutaneous haemorrhages (bruising);
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following side effects are known when Embavi is used to prevent recurrence of blood clots in the legs and in the blood vessels of the lungs:

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

Bleeding, including:
- Nosebleeds;
- From gums;
- Blood in urine;
- Subcutaneous haemorrhage (bruising) and swelling;
- From stomach, intestines, rectum;
- In the mouth;
- From the vagina;
Anaemia, which may cause fatigue or paleness;
Decrease in platelet count (which may affect clotting);
Nausea;
Skin rash;
Blood tests may show:
- Increased gamma-glutamyltransferase (GGT) or alanine aminotransferase (AlAT) activity.

Uncommon side 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 presence of blood in sputum when coughing;
- Presence of bright/red blood in stool;
- Tests showing presence of blood in stool or urine;
- Bleeding occurring after surgery, including bruising (subcutaneous haemorrhage) and swelling, or leakage of blood or fluid from the surgical wound/incision site (wound discharge) or injection site;
- From haemorrhoids;
- 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 immediate medical attention;
Blood tests may show:
- Abnormal liver function;
- 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.

Rare side effects (may occur in up to 1 in 1000 people)

Bleeding:
- Into the brain or spinal cord;
- Into 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 resembles small target-like lesions (dark spots surrounded by a lighter area, with a dark ring at the edge) (erythema multiforme);
Vasculitis (inflammation of blood vessels), which may cause skin rash or small, flat, red, round spots under the skin surface or subcutaneous haemorrhages (bruising);
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

Additional side effects in children and adolescents
Contact your doctor immediately if any of the following symptoms occur:

Allergic reactions (hypersensitivity), which may cause: swelling of the face, lips, mouth, tongue and/or throat, and breathing difficulties. These are common side effects (may occur in up to 1 in 10 people).

In general, side effects observed in children and adolescents treated with Embavi were similar to those observed in adults and were mostly mild to moderate in severity. Side effects observed more frequently in children and adolescents include nosebleeds and unusual vaginal bleeding.

Very common side effects (may occur in more than 1 in 10 people)

Bleeding, including:
- From the vagina;
- Nosebleeds.

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

Bleeding, including:
- From gums;
- Blood in urine;
- Subcutaneous haemorrhage (bruising) and swelling;
- From intestines or rectum;
- Bright/red blood in stool;
- Bleeding occurring after surgery, including bruising (subcutaneous haemorrhage) and swelling, or leakage of blood from the surgical wound/incision site (wound discharge) or injection site;
Hair loss;
Anaemia, which may cause fatigue or paleness;
Decreased platelet count in the child (which may affect clotting);
Nausea;
Skin rash;
Itching;
Low blood pressure, which may lead to fainting or rapid heartbeat in the child;
Blood tests 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 sputum when coughing;
- Into the brain or spinal cord;
- Into the lungs;
- Into muscles;
Skin rash, which may develop blisters and resembles small target-like lesions (dark spots surrounded by a lighter area, with a dark ring at the edge) (erythema multiforme);
Vasculitis (inflammation of blood vessels), which may cause skin rash or small, flat, red, round spots under the skin surface or subcutaneous haemorrhages (bruising);
Blood tests may show:
- Increased gamma-glutamyltransferase (GGT) activity;
- Presence of blood in stool or urine;
Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy).

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can also 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
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store the medicine Embavi

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label, carton, and blister after: EXP. The expiry date refers to the last day of the stated month.
No special storage instructions apply.
Medicines must not be disposed of via the sewage system 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 Embavi contains

The active substance is apixaban. Each coated tablet contains 2.5 mg of apixaban.
The other ingredients are:
- Tablet core: anhydrous lactose (see section 2. Embavi contains lactose (a type of sugar) and sodium), microcrystalline cellulose, sodium croscarmellose, sodium lauryl sulfate, and magnesium stearate (E470b).
- Coating: monohydrate lactose (see section 2. Embavi contains lactose (a type of sugar) and sodium), hypromellose type 2910 (E464), titanium dioxide (E171), triacetin, yellow iron oxide (E172).

What Embavi looks like and contents of the pack
Round, yellow, biconvex, film-coated tablets with an embossed "C" on one side and "73" on the other,
approximately 6.1 mm in diameter and about 3.0 mm thick.
This medicine is available in aluminum/PVC/PVdC foil blisters packed in cardboard boxes.
Pack sizes: 10, 14, 15, 20, 28, 56, 60, 100, 168 or 200 film-coated tablets.
Not all pack sizes may be marketed.

Patient Alert Card: information for users
Inside the Embavi medicine package, together with the Patient Leaflet, there is a Patient Alert Card.
A similar card may also be issued to the patient by the physician.
The Patient Alert Card contains information that may be helpful for the patient and may serve as a warning to other physicians that the patient is taking Embavi. The card should always be kept on hand.

Take the card.
If necessary, detach the card in your language (perforated edges make this easier).
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 carry it with you at all times.

Marketing Authorisation Holder:
Egis Pharmaceuticals PLC
Keresztúri út 30-38
1106 Budapest
Hungary

Importer:
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola PLA 3000
Malta

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Germany Embavi 2.5 mg, 5 mg film tablets
Bulgaria Ембави 2.5 mg, 5 mg филмирани таблетки
Embavi 2.5 mg, 5 mg film-coated tablets
Czech Republic Embavi
Hungary Embavi 2.5 mg, 5 mg filmtabletta
Lithuania Embavi 2.5 mg, 5 mg plėvele dengtos tabletės
Latvia Embavi 2.5 mg, 5 mg apvalkotās tabletes
Poland Embavi
Romania Embavi 2.5 mg, 5 mg comprimate filmate
Slovakia Embavi 2.5 mg, 5 mg

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
EGIS Polska Sp. z o.o.
ul. Komitetu Obrony Robotników 45D
02-146 Warsaw
Tel.: +48 22 417 92 00