MODYLAN 2.5 mg Tablets

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Modylan, 2.5 mg, coated tablets
   1. Read the leaflet carefully before taking the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
3. What is Modylan and what is it used for
4. Important information before taking Modylan
   1. When not to take Modylan:
   2. Warnings and precautions
   3. Children and adolescents
   4. Modylan and other medicines
   5. The following medicines may enhance the effect of Modylan and increase the risk of unwanted bleeding:
   6. The following medicines may reduce the ability of Modylan to prevent blood clots:
   7. Pregnancy and breastfeeding
   8. Driving and using machines
   9. Modylan contains lactose (a type of sugar) and sodium
5. How to take Modylan
   1. Dose
   2. Instructions for crushing tablets:
   3. Modylan should be taken as directed in the following indications:
   4. Use in patients undergoing cardioversion
   5. Taking a higher dose of Modylan than recommended
   6. Missing a dose of Modylan
   7. In case of doubts about taking the medicine or if more than one doseis missed
   8. Stopping Modylan treatment
6. Possible side effects
   1. The following side effects are known to occur when taking Modylan to prevent blood clots after hip or knee replacement surgery:
   2. Common side effects (may occur in up to 1 in 10 people)
   3. Uncommon side effects (may occur in up to 1 in 100 people)
   4. Rare side effects (may occur in up to 1 in 1,000 people)
   5. Frequency not known (cannot be estimated from the available data)
   6. The following side effects are known to occur when taking Modylan to prevent blood clots in the heart in patients with irregular heart rhythm and at least one additional risk factor.
   7. Common side effects (may occur in up to 1 in 10 people)
   8. Uncommon side effects (may occur in up to 1 in 100 people)
   9. Rare side effects (may occur in up to 1 in 1,000 people)
   10. Very rare side effects (may occur in up to 1 in 10,000 people)
   11. Frequency not known (cannot be estimated from the available data)
   12. The following side effects are known to occur when taking Modylan to prevent recurrent blood clots in the legs and blood vessels of the lungs.
   13. Common side effects (may occur in up to 1 in 10 people)
   14. Uncommon side effects (may occur in up to 1 in 100 people)
   15. Rare side effects (may occur in up to 1 in 1,000 people)
   16. Frequency not known (cannot be estimated from the available data)
   17. Reporting side effects
7. How to store Modylan
8. Contents of the packaging and other information
   1. What Modylan contains
   2. What Modylan looks like and contents of the pack
   3. Patient alert card: information for use
   4. Marketing authorization holder:
   5. Importer:
   6. This medicine is authorized in the Member States of the European Economic Area under the following names:
   7. Date of last revision of the leaflet:

Leaflet accompanying the packaging: information for the user

Modylan, 2.5 mg, coated tablets

Apixaban

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed to a specific person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Modylan and what is it used for
• 2. Important information before taking Modylan
• 3. How to take Modylan
• 4. Possible side effects
• 5. How to store Modylan
• 6. Contents of the packaging and other information

1. What is Modylan and what is it used for

Modylan 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 element in the blood clotting process.

This medicine is used in adults:

• to prevent the formation of blood clots (deep vein thrombosis) after hip or knee replacement surgery. After hip or knee surgery, the patient may be at higher risk of developing blood clots in the legs. This can lead to swelling of the legs, with or without pain. If a blood clot moves from the leg to the lungs, it can block blood flow, causing shortness of breath, 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 the formation of blood clots in the heart in patients with irregular heart rhythm (atrial fibrillation) and at least one additional risk factor. Blood clots can break loose and travel to the brain, leading to a stroke, or to other organs, preventing blood flow to those organs (known as systemic embolism). A stroke can be life-threatening and requires immediate medical attention.
• to treat blood clots in the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism) and to prevent the recurrence of blood clots in the legs and/or lungs.

2. Important information before taking Modylan

When not to take Modylan:

• 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 severe bleeding (e.g., active or recently active stomach or intestinal ulcer disease, recent bleeding into the brain);
• if the patient has liver disease that increases the risk of bleeding (hepatic coagulopathy);
• if the patient is taking medicines that prevent blood clotting (such as warfarin, rivaroxaban, dabigatran, or heparin), except in situations where one anticoagulant is being switched for another, when the patient has a permanent venous or arterial catheter and is receiving heparin through the catheter to maintain its patency, or when a catheter is being inserted into a blood vessel (during catheter ablation) to treat irregular heart rhythm (arrhythmia).

Warnings and precautions

Before starting treatment, the patient should discuss the following with their doctor, pharmacist, or nurse:

• if the patient has an increased risk of bleeding, such as:
• bleeding disorders, including conditions with decreased platelet activity;
• very high, uncontrolled blood pressure;
• if the patient is over 75 years old;
• 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 has current or past liver disease. The use of this medicine requires caution in patients with signs of liver function disorders.
• if the patient has had a catheter inserted or an injection into the spine (for anesthesia or pain treatment), the doctor will advise the patient to take this medicine at least 5 hours after the catheter is removed;
• if the patient has a heart valve replacement;
• if the doctor considers that the patient's blood pressure is unstable or if treatment to remove a blood clot from the lungs is planned.

When to be particularly careful when taking Modylan

• if the patient has a disease called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), they should inform their doctor, who will decide if a change in treatment is needed.
• if the patient needs to undergo surgery or a procedure that may involve bleeding, the doctor may ask them to temporarily stop taking this medicine. If in doubt whether a procedure may cause bleeding, the patient should ask their doctor.

Children and adolescents

This medicine is not recommended for use in children and adolescents under 18 years of age.

Modylan and other medicines

The patient should tell their doctor, pharmacist, or nurse about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.

Some medicines may enhance the effect of Modylan, while others may reduce its effect. The doctor will decide whether the patient should take Modylan while being treated with other medicines and how closely they should be monitored.

The following medicines may enhance the effect of Modylan 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 (e.g., ritonavir);
• other medicines used to reduce blood clotting (e.g., enoxaparin and others);
• anti-inflammatory and pain-relieving medicines (e.g., acetylsalicylic acid or naproxen). Especially if the patient is over 75 years old and taking acetylsalicylic acid, they may be at higher risk of bleeding;
• medicines used to treat high blood pressure or heart disease (e.g., diltiazem);
• antidepressant medicines called selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors.

The following medicines may reduce the ability of Modylan to prevent blood clots:

• medicines used to prevent seizures or convulsions (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, thinks they may be pregnant, or plans to have a child, they should consult their doctor, pharmacist, or nurse before taking this medicine.

The effect of Modylan 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, they should contact their doctor immediately.

It is not known whether this medicine passes into breast milk. Before taking this medicine while breastfeeding, the patient should consult their doctor, pharmacist, or nurse. They will advise whether to stop breastfeeding or stop/take this medicine.

Driving and using machines

No effects on the ability to drive and use machines have been observed with Modylan.

Modylan contains lactose (a type of sugar) and sodium

If the patient has been diagnosed with intolerance to some sugars, they should consult their doctor before taking this medicine.

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means it is considered "sodium-free".

3. How to take Modylan

This medicine should always be taken as directed by the doctor or pharmacist. In case of doubts, the patient should consult their doctor, pharmacist, or nurse.

Dose

The tablet should be swallowed with water. This medicine can be taken with or without food.

It is recommended to take the tablets at the same time every day to achieve the best treatment results.

In case of difficulty swallowing the whole tablet, the patient should discuss other ways of taking Modylan with their doctor. The tablet can be crushed just before taking and mixed with water, 5% aqueous 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 to a suitable container and then mix it with a small amount of water or one of the above-mentioned liquids to obtain a mixture.
• Swallow (drink) the resulting mixture.
• Rinse the pestle and mortar used to crush the tablet and the container in which the mixture was prepared with a small amount of water or one of the above-mentioned liquids and swallow (drink) the rinse liquid.

If necessary, the doctor may administer a crushed Modylan tablet mixed with 60 mL of water or 5% aqueous glucose solution through a nasogastric tube.

Modylan should be taken as directed in the following indications:

• -Prevention of blood clots after hip or knee replacement surgeryThe recommended dose is one 2.5 mg Modylan tablet twice a day. For example, in the morning and evening. The first tablet should be taken 12 to 24 hours after surgery.
• After major hip replacement surgery, the patient will usually take the medicine for 32 to 38 days.
• After major knee replacement surgery, the patient will usually take the medicine for 10 to 14 days.
• -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 Modylan tablet twice a day.

The recommended dose is one 2.5 mg Modylan tablet twice a day if:

• the patient has severe kidney function disorders;
• at least 2 of the following criteria are met:
• the patient's blood test results indicate decreased kidney function (serum creatinine level of 1.5 mg/dL (133 μmol/L) or higher);
• the patient is 80 years old or older;
• the patient's body weight is 60 kg or less.

The recommended dose is one tablet twice a day, for example, one tablet in the morning and one tablet in the evening. The doctor will decide how long the treatment should be continued.

• -Treatment of blood clots in the legs and blood clots in the lungsThe recommended dose is two 5 mg Modylan tabletstwice a day 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 5 mg Modylan tablettwice a day, for example, one tablet in the morning and one tablet in the evening.
• -Prevention of recurrent blood clots after 6 months of treatmentThe recommended dose is one 2.5 mg Modylan tablet twice a day, for example, one tablet in the morning and one tablet in the evening. The doctor will decide how long the treatment should be continued.
• -The doctor may change the anticoagulant treatment as follows:
• •Switching from Modylan to other anticoagulantsThe patient should stop taking Modylan. At the time when the next scheduled dose of Modylan would be taken, the patient should start taking another anticoagulant (e.g., heparin).
• •Switching from other anticoagulants to ModylanThe patient should stop taking the other anticoagulant. At the time when the next scheduled dose of the other anticoagulant would be taken, the patient should start taking Modylan and continue with its usual administration.
• •Switching from treatment with a vitamin K antagonist (e.g., warfarin) to ModylanThe patient should stop taking the vitamin K antagonist. The doctor will order blood tests and tell the patient when to start taking Modylan.
• •Switching from Modylan to treatment with a vitamin K antagonist (e.g., warfarin)If the doctor advises the patient to start taking a vitamin K antagonist, the patient should continue taking Modylan for at least 2 days after taking the first dose of the vitamin K antagonist. The doctor will order blood tests and tell the patient when to stop taking Modylan.

Use in patients undergoing cardioversion

If a procedure called cardioversion is needed to restore a normal heart rhythm, the medicine should be taken at the times specified by the doctor to prevent the formation of blood clots in the blood vessels of the brain and other blood vessels in the body.

Taking a higher dose of Modylan than recommended

If the patient has taken a higher dose of Modylan than recommended, they should immediatelyinform their doctor. They should take the packaging with them, even if there are no tablets left.

If the patient has taken a higher dose of Modylan than recommended, they may be at increased risk of bleeding. If bleeding occurs, surgical treatment, blood transfusion, or other treatment to reverse the effect of factor Xa inhibition may be necessary.

Missing a dose of Modylan

The patient should take the missed dose as soon as they remember and:

• take the next dose of Modylan at the usual time
• continue with the normal administration of the medicine.

In case of doubts about taking the medicine or if more than one doseis missed

The patient should consult their doctor, pharmacist, or nurse.

Stopping Modylan treatment

The patient should not stop taking this medicine without consulting their doctor, as stopping treatment too early may increase the risk of developing a blood clot.

In case of any further doubts about taking this medicine, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Modylan can cause side effects, although not everybody gets them.

Modylan can be used in three different medical conditions. The known side effects and their frequency may vary in each of these conditions and are listed separately.

In these conditions, the most common overall side effect of this medicine is bleeding, which can be life-threatening and may require immediate medical attention.

The following side effects are known to occur when taking Modylan to prevent blood clots after hip or knee replacement surgery:

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

• anemia, which can cause fatigue or pale skin;
• bleeding, including bruising and swelling;
• nausea (vomiting).

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

• decreased platelet count, which can affect blood clotting;
• bleeding:
• after surgery, including bruising and swelling, as well as bleeding or fluid leakage from the wound or surgical incision site;
• from the stomach or intestines, or the presence of bright red or black blood in the stool;
• in the urine;
• from the nose;
• from the vagina;
• low blood pressure, which can lead to fainting or rapid heartbeat;
• blood tests may show:
• abnormal liver function;
• increased activity of certain liver enzymes;
• increased bilirubin levels, a product of destroyed red blood cells, which can cause yellowing of the skin and eyes;
• itching

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

• allergic reactions (hypersensitivity), which can cause: swelling of the face, lips, mouth, tongue, and/or throat, as well as difficulty breathing. If any of these symptoms occur, the patient should immediatelycontact their doctor.
• bleeding:
• into a muscle;
• into the eyes;
• from the gums, presence of blood in sputum when coughing;
• from the rectum;
• hair loss.

Frequency not known (cannot be estimated from the 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 hemorrhoids;
• blood tests showing blood in the stool or urine;
• rash, which can cause blisters and looks like small targets (dark spots surrounded by a lighter area, with a dark border on the edge) (erythema multiforme);
• vasculitis (inflammation of blood vessels), which can cause a rash or small, flat, round, red spots under the skin surface or bruising.

The following side effects are known to occur when taking Modylan to prevent blood clots in the heart in patients with irregular heart rhythm and at least one additional risk factor.

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

• bleeding, including:
• into the eyes;
• from the stomach or intestines;
• from the rectum;
• in the urine;
• from the nose;
• from the gums;
• bruising and swelling;
• anemia, which can cause fatigue or pale skin;
• low blood pressure, which can lead to fainting or rapid heartbeat;
• nausea (vomiting);
• blood tests showing increased gamma-glutamyltransferase (GGTP) 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;
• in the abdominal cavity or from the vagina;
• presence of bright red or black blood in the stool;
• bleeding after surgery, including bruising and swelling, as well as bleeding or fluid leakage from the wound or surgical incision site;
• from hemorrhoids;
• blood tests showing blood in the stool or urine;
• decreased platelet count, which can affect blood clotting;
• blood tests may show:
• abnormal liver function;
• increased activity of certain liver enzymes;
• increased bilirubin levels, a product of destroyed red blood cells, which can cause yellowing of the skin and eyes;
• rash;
• itching;
• hair loss;
• allergic reactions (hypersensitivity), which can cause: swelling of the face, lips, mouth, tongue, and/or throat, as well as difficulty breathing. If any of these symptoms occur, the patient should immediatelycontact their doctor.

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

• bleeding:
• into the lungs or throat;
• into the retroperitoneal space;
• into a muscle.

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

• rash, which can cause blisters and looks like small targets (dark spots surrounded by a lighter area, with a dark border on the edge) (erythema multiforme).

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

• vasculitis (inflammation of blood vessels), which can cause a rash or small, flat, round, red spots under the skin surface or bruising.

The following side effects are known to occur when taking Modylan to prevent recurrent 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;
• in the urine;
• bruising and swelling;
• from the stomach, intestines, or rectum;
• in the mouth;
• from the vagina;
• anemia, which can cause fatigue or pale skin;
• decreased platelet count, which can affect blood clotting;
• nausea (vomiting);
• rash;
• blood tests may show increased gamma-glutamyltransferase (GGTP) or alanine aminotransferase (AlAT) activity.

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

• low blood pressure, which can 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 or black blood in the stool;
• blood tests showing blood in the stool or urine;
• bleeding after surgery, including bruising and swelling, as well as bleeding or fluid leakage from the wound or surgical incision site;
• from hemorrhoids;
• into a muscle;
• itching;
• hair loss;
• allergic reactions (hypersensitivity), which can cause: swelling of the face, lips, mouth, tongue, and/or throat, as well as difficulty breathing. If any of these symptoms occur, the patient should immediatelycontact their doctor.
• blood tests may show:
• abnormal liver function;
• increased activity of certain liver enzymes;
• increased bilirubin levels, a product of destroyed red blood cells, which can 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 cord;
• into the lungs.

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

• bleeding in the abdominal cavity or retroperitoneal space.
• rash, which can cause blisters and looks like small targets (dark spots surrounded by a lighter area, with a dark border on the edge) (erythema multiforme);
• vasculitis (inflammation of blood vessels), which can cause a rash or small, flat, round, red spots under the skin surface or bruising.

Reporting side effects

If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring 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 authorization holder.

Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Modylan

The medicine should be stored out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging and blister after:

EXP. The expiry date refers to the last day of the month stated.

No special precautions for storage are necessary.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Modylan contains

• The active substance is apixaban. Each tablet contains 2.5 mg of apixaban.
• The other ingredients are:
• Tablet core: lactose monohydrate (see section 2. Modylan contains lactose (a type of sugar) and sodium), microcrystalline cellulose (E 460), povidone K-30, crospovidone (type A), sodium lauryl sulfate, and sodium stearyl fumarate
• Coating: lactose monohydrate (see section 2. Modylan contains lactose (a type of sugar) and sodium), hypromellose, titanium dioxide (E171), triacetin (E 1518), yellow iron oxide (E172).

What Modylan looks like and contents of the pack

Yellow, round, coated tablets with a diameter of 6.1 mm.

This medicine is available in blisters of aluminum/PVC/PVdC or in single-dose blisters with perforations, packaged in cardboard boxes.

Package sizes: 7, 10, 14, 20, 28, 30, 56, 60, or 100 coated tablets (in blisters)

Package sizes: 7 x 1, 10 x 1, 14 x 1, 20 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, or 100 x 1 coated tablets (in single-dose blisters with perforations)

Not all package sizes may be marketed.

Patient alert card: information for use

Inside the Modylan packaging, in addition to the leaflet, there is a patient alert card. A similar card may be provided by the doctor.

The patient alert card contains information that will be useful for the patient and will inform other doctors that the patient is taking Modylan. The patient should always carry this card with them.

• 1. Take the card.
• 2. Fill in the following points or ask the doctor to fill them in:
• Name and surname:
• Date of birth:
• Indication:
• Dose: ........mg twice a day
• Doctor's name:
• Doctor's phone number:
• 3. Fold the card and carry it with you at all times.

Marketing authorization holder:

Egis Pharmaceuticals PLC

Keresztúri út 30-38

1106 Budapest

Hungary

Importer:

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola PLA 3000

Malta

Adalvo Limited

Malta Life Sciences Park, Building 1, Level 4, Sir Temi Zammit Buildings,

San Gwann SGN 3000

Malta

This medicine is authorized in the Member States of the European Economic Area under the following names:

Finland

Modylan

Bulgaria

Modylan 2.5 mg, 5 mg film-coated tablets

Модилан 2.5 mg, 5 mg филмирани таблетки

Czech Republic

Modylan

Lithuania

Modylan 2.5 mg, 5 mg plėvele dengtos tabletės

Latvia

Modylan 2.5 mg, 5 mg apvalkotās tabletes

Poland

Modylan

Romania

Modylan 2.5 mg, 5 mg comprimate filmate

Slovakia

Modylan

For more information about this medicine, the patient should contact the local representative of the marketing authorization holder:

EGIS Polska Sp. z o.o.

ul. Komitetu Obrony Robotników 45D

02-146 Warsaw

Tel.: +48 22 417 92 00

Date of last revision of the leaflet: