Embavi

Package leaflet: Information for the user

Embavi, 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 you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What Embavi is and what it is used for
2. Important information before taking Embavi
3. How to take Embavi
4. Possible side effects
5. How to store Embavi
6. 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 blocking factor Xa, which is an important component of the blood clotting process.
Embavi is used in adults:

• to prevent blood clots forming 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 flow to these organs (known as systemic embolism). Stroke can be life-threatening and requires immediate medical attention.
• to treat blood clots in the 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 the 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 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 (e.g. active or recently treated peptic ulcer of the stomach or intestines, recently experienced brain haemorrhage);
• if the patient has liver disease leading to an increased risk of bleeding (liver 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 cannula and is receiving heparin through the cannula 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 this medicine, discuss with your doctor, pharmacist or nurse:

• if the patient has an increased risk of bleeding, for example:
  • bleeding disorders, including conditions with reduced platelet activity;
  • 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. Use of this medicine requires caution in patients with signs of liver function disorders.
• if the patient has a heart valve prosthesis;
• if the doctor considers the patient’s blood pressure to be unstable, or if other treatments or surgical procedures are 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 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 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 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 Embavi, while others may reduce its effectiveness.
The doctor will decide whether the patient should take Embavi while being treated 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 is taking acetylsalicylic acid, there may be an increased risk of bleeding;
• medicines used to treat high blood pressure or heart disease (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 become pregnant, 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 the doctor, pharmacist or nurse. They will advise whether it is better to stop 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 consult 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 exactly as instructed by your doctor or pharmacist.
If in doubt, consult your doctor, pharmacist, or nurse.
Dosage
Swallow the tablet with water. Embavi may be taken with or without food.
It is recommended to take the tablets at the same time each day to achieve optimal treatment results.
If you have difficulty swallowing the whole tablet, discuss alternative ways of taking Embavi with your doctor.
The tablet may be crushed immediately before administration and mixed with water, 5% aqueous glucose solution, apple juice, or apple puree.
Instructions for crushing tablets:

• Crush the tablet with a mortar and pestle.
• Carefully transfer the entire powder to a suitable container and mix it with a small amount, 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 and 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% aqueous glucose solution via a nasogastric tube.
Embavi 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 Embavi 5 mg tablet twice daily.
The recommended dose is one Embavi 2.5 mg tablet twice daily if:

• the patient has severe renal impairment;
• 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 tablet 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 Embavi 5 mg tablets twice daily for the first 7 days, for example two tablets in the morning and two tablets in the evening.
After 7 days, the recommended dose is one Embavi 5 mg tablet twice daily, for example one tablet in the morning and one tablet in the evening.
Prevention of recurrence of blood clots after completion of 6-month treatment
The recommended dose is one Embavi 2.5 mg tablet twice daily, for example one tablet in the morning and one tablet 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 recurrence of 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 in doubt, consult your doctor, pharmacist, or nurse.
To achieve optimal treatment results, it is recommended to take the tablets at the same times 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 two Embavi 5 mg tablets twice daily for the first 7 days, for example two tablets in the morning and two tablets in the evening.
After 7 days, the recommended dose is one Embavi 5 mg tablet twice daily, for example one tablet in the morning and one tablet in the evening.
For parents and caregivers: monitor the child to ensure the full dose has been taken.
Follow scheduled doctor visits, as dose adjustments may be necessary depending on changes in the child's body weight.
Your doctor may change anticoagulant treatment as follows:

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

Use in patients undergoing cardioversion
If a procedure called cardioversion is required to restore normal heart rhythm due to irregular heartbeat, the medicine should be taken at strictly defined times as instructed by your doctor to prevent formation of blood clots in blood vessels of the brain and other blood vessels in the body.
Taking more Embavi than recommended
If you have taken more Embavi than recommended, you should immediately contact your doctor.
Take the medicine packaging with you, even if no tablets remain inside.
If you take more Embavi than recommended, your risk of bleeding may increase. If bleeding occurs, surgical treatment, blood transfusion, or other treatment to reverse the factor Xa effect may be required.
Missed dose of Embavi

• If you miss the morning dose, take it as soon as possible and you may take it together with the 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 from the next day.

If you have any doubts about using the 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 most common general side effect of this medicine is bleeding, which may potentially
be life-threatening and may require immediate medical attention.

The following side effects are known to occur when taking Embavi 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 the urine;
  • from the nose;
  • from the gums;
  • subcutaneous haemorrhages (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 show:
  • increased gamma-glutamyl transferase (GGT) activity.

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

• bleeding:
  • into the brain or spinal canal;
  • in the mouth or presence of blood in sputum when coughing;
  • in the abdominal cavity or from the vagina;
  • presence of bright/red blood in stool;
  • bleeding after surgery, including subcutaneous haemorrhages (bruising), swelling, and leakage of blood or fluid from the surgical wound/incision site (wound discharge) or injection site;
  • from haemorrhoids;
  • test results showing blood in stool or urine;
• 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 product of 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 advice.

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

• skin rash, which may develop blisters and appears as 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)

• inflammation of blood vessels ( vasculitis ), which may cause skin rash or small, flat, red, circular spots beneath the skin surface or subcutaneous haemorrhages (bruising);
• bleeding in the kidneys, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following side effects are known to occur when taking Embavi to prevent recurrence of blood clots
in the legs and blood vessels of the lungs.

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

• bleeding, including:
  • from the nose;
  • from the gums;
  • blood in the urine;
  • subcutaneous haemorrhages (bruising) and swelling;
  • from the stomach, intestines, or 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-glutamyl transferase (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;
  • test results showing blood in stool or urine;
  • bleeding after surgery, including subcutaneous haemorrhages (bruising) and swelling, and 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 advice.
• blood test results may show:
  • abnormal liver function;
  • increased activity of certain liver enzymes;
  • increased bilirubin levels, a product of destroyed red blood cells, which may cause yellowing of the skin and eyes.

Rare side effects (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 in the abdominal cavity or retroperitoneal space;
• skin rash, which may develop blisters and appears as small target-like lesions (dark spots surrounded by a lighter area, with a dark ring at the edge) (erythema multiforme);
• inflammation of blood vessels ( vasculitis ), which may cause skin rash or small, flat, red, circular spots beneath the skin surface or subcutaneous haemorrhages (bruising);
• bleeding in the kidneys, sometimes with blood in the 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 are observed:

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

Generally, side effects observed in children and adolescents treated with Embavi were similar to those seen 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;
  • from the nose.

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

• Bleeding, including:
  • from the gums;
  • blood in the urine;
  • subcutaneous haemorrhages (bruising) and swelling;
  • from the intestines or rectum;
  • bright/red blood in stool;
  • bleeding after surgery, including subcutaneous haemorrhages (bruising) and swelling, and 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 blood clotting);
• nausea;
• skin rash;
• itching;
• low blood pressure, which may lead to 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 sputum when coughing;
  • into the brain or spinal canal;
  • into the lungs;
  • into muscles;
• skin rash, which may develop blisters and appears as small target-like lesions (dark spots surrounded by a lighter area, with a dark ring at the edge) (erythema multiforme);
• inflammation of blood vessels ( vasculitis ), which may cause skin rash or small, flat, red, circular spots beneath the skin surface or subcutaneous haemorrhages (bruising);
• blood test results may show:
  • increased gamma-glutamyl transferase (GGT) activity;
  • presence of blood in stool or urine.
• bleeding in the kidneys, sometimes with blood in the 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 at 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 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 pack after EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines should not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This 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 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 sulphate, and magnesium stearate.
  • Coating: monohydrate lactose (see section 2. Embavi contains lactose (a type of sugar) and sodium), hypromellose type 2910 (E464), titanium dioxide (E171), triacetin, iron oxide red (E172).

What Embavi looks like and contents of the pack
Oval, pink, biconvex film-coated tablets, embossed with "C" on one side and "74" on the other, approximately 9.95 mm in length and 5.35 mm in width.
This medicine is available in blisters made of Aluminium/PVC/PVdC, 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 Warning Card: information for use
Inside the Embavi packaging, in addition to the package leaflet, a Patient Warning Card is included. A similar card may also be provided to the patient by the physician.
The Patient Warning 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 carried on the person.

1. Take the card.
2. If necessary, detach the card in your language (perforated edges make this easier).
3. Complete the following sections, or ask your doctor to fill them in:
   • Name and surname:
   • Date of birth:
   • Indication:
   • Dose: ........mg twice daily
   • Name and surname of physician:
   • Physician's telephone number:
4. 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 for sale in 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