Package leaflet: Information for the user

Modylan, 2.5 mg, coated tablets
Apixabanum
Please read carefully the entire leaflet before taking the medicine, as it contains important information for the patient.

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

Table of contents

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

1. What Modylan is and what it is used for

Modylan 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.
This medicine is used in adults:

to prevent the formation of blood clots (deep vein thrombosis) following 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 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 blood vessels of 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 experienced peptic ulcer of the stomach or intestines, recently experienced intracranial haemorrhage);
if the patient has liver disease associated with 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 is receiving 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 has current or past liver disease. Use of this medicine requires caution in patients with signs of liver dysfunction.
if the patient has had a catheter inserted or a spinal injection (for anaesthesia or pain treatment), the doctor will recommend taking this medicine at least 5 hours after catheter removal;
if the patient has a heart valve prosthesis;
if the doctor considers that the patient's blood pressure is unstable, or if other treatment or surgical procedure is planned to remove a blood clot from the lungs.

When to exercise particular caution when using Modylan

if the patient has a condition called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), 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 under 18 years of age.
Modylan and other medicines
Tell your doctor, pharmacist or nurse about all medicines currently taken, recently taken, or planned to be taken.
Some medicines may enhance the effect of Modylan, while others may reduce its effect. The doctor will decide whether the patient should take Modylan during treatment with other medicines and how the patient should be monitored.
The following medicines may enhance the effect of Modylan and increase the risk of
unwanted bleeding:

certain antifungal medicines (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 and 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 conditions (e.g. diltiazem);
antidepressants known as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors.

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

antiepileptic medicines (e.g. phenytoin and others);
St John's wort (an herbal supplement used for depression);
medicines used to treat tuberculosis or other infections (e.g. rifampicin).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor, pharmacist or nurse before using this medicine.
The effect of Modylan on pregnancy and the unborn child is unknown. This medicine should not be used during pregnancy. If a patient becomes pregnant while taking this medicine, she should contact her doctor immediately.
It is not known whether this medicine passes into human milk. Before using this medicine during breastfeeding, consult your 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 using machines
It has not been established that Modylan affects the ability to drive or operate machinery.

Modylan 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 Modylan

This medicine should always be taken as directed by your doctor or pharmacist. If you are
unsure, consult your doctor, pharmacist, or nurse.
Dosage
The tablet should be swallowed with water. This medicine may 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, discuss alternative methods of taking Modylan with your doctor. Just before administration, the tablet may be crushed and mixed with
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, 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 Modylan tablets mixed with
60 mL of water or 5% glucose solution via a nasogastric tube.
Modylan 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 Modylan tablet twice daily, for example in the morning and evening. The first dose should be taken 12 to 24 hours after surgery.
- After major hip surgery, patients usually take the medicine for 32 to 38 days.
- After major knee surgery, patients usually take the medicine 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 Modylan tablet twice daily.

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

the patient has severe kidney function impairment;
at least two of the following criteria are met:
- blood test results indicate reduced kidney function (serum creatinine concentration ≥1.5 mg/dL (133 μmol/L));
- 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 5 mg Modylan 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 Modylan tablet twice daily, for example one tablet in the morning and one in the evening.
Prevention of recurrent blood clots after completing 6 months of treatment The recommended dose is one 2.5 mg Modylan 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.
Your doctor may change your anticoagulant therapy as follows:
- Switching from Modylan to another anticoagulant Stop taking Modylan. At the time when the next scheduled dose would have been due, start treatment with another anticoagulant (e.g., heparin).
- Switching from another anticoagulant to Modylan Stop taking the current anticoagulant. At the time when the next scheduled dose of the anticoagulant would have been due, start treatment with Modylan and continue taking it as usual.
- Switching from vitamin K antagonist therapy (e.g., warfarin) to Modylan Stop taking the vitamin K antagonist medicine. Your doctor will order blood tests and advise when you may start taking Modylan.
- Switching from Modylan to vitamin K antagonist therapy (e.g., warfarin) If your doctor advises you to start taking a vitamin K antagonist medicine, continue taking Modylan 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 Modylan.

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 precisely scheduled times as directed by your doctor to prevent blood clots in the brain's blood vessels and other blood vessels in the body.
Taking more than the recommended dose of Modylan
If you have taken more than the recommended dose of Modylan, contact your doctor immediately. Bring the medicine packaging with you, even if no tablets remain.
Taking more than the recommended dose of Modylan may increase the risk of bleeding. If bleeding occurs, surgical treatment, blood transfusion, or other treatments to reverse the effect of factor Xa inhibition may be required.
Missed dose of Modylan
Take the missed dose as soon as you remember and:

take the next dose at your usual time
continue taking the medicine as normal. If you have any doubts about using this medicine or if you miss more than one dose, consult your doctor, pharmacist, or nurse.

Stopping Modylan
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 adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Modylan can be used for three different medical conditions. Known adverse effects and their frequency of occurrence may differ for each of these conditions and are listed separately.
In these conditions, the most common general adverse effect of this medicine is bleeding, which may potentially be life-threatening and may require immediate medical attention.

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

Common adverse 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 (feeling sick).

Uncommon adverse 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;
- presence of 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;
itching.

Rare adverse effects (may occur in up to 1 in 1,000 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 a doctor immediately.
bleeding:
- into muscle tissue;
- into the eyes;
- from gums, 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 column;
- 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 include blistering and resembles 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 pinpoint, flat, red, round spots under the skin or bruising.

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

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

bleeding, including:
- into the eyes;
- into the stomach or intestines;
- from the rectum;
- presence of blood in urine;
- nosebleeds;
- from gums;
- bruising and swelling;
anaemia, which may cause fatigue or paleness;
low blood pressure, which may lead to fainting or rapid heartbeat;
nausea (feeling sick);
blood tests showing increased gamma-glutamyl transferase (GGTP) activity.

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

bleeding:
- into the brain or spinal column;
- 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 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 adverse effects (may occur in up to 1 in 1,000 people)

bleeding:
- into the lungs or throat;
- into the retroperitoneal space;
- into muscles.

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

skin rash, which may include blistering 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)

inflammation of blood vessels ( vasculitis ), which may cause skin rash or pinpoint, flat, red, round spots under the skin or bruising.

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

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

bleeding, including:
- nosebleeds;
- from gums;
- presence of 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 (feeling sick);
skin rash;
blood tests may show increased gamma-glutamyl transferase (GGTP) or alanine aminotransferase (AlAT) activity.

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

low blood pressure, which may lead to fainting or rapid heartbeat;
bleeding:
- into the eyes;
- in the mouth, 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 adverse effects (may occur in up to 1 in 1,000 people)

bleeding:
- into the brain or spinal column;
into the lungs.

Frequency not known (cannot be estimated from available data)

bleeding into the abdominal cavity or retroperitoneal space.
skin rash, which may include blistering and resembles 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 pinpoint, flat, red, round spots under the skin or bruising.

Reporting of adverse effects
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Adverse effects can 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
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Modylan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack after:
EXP. The expiry date refers to the last day of the mentioned month.
No special storage instructions apply.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack 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: monohydrate lactose (see section 2. Modylan contains lactose (a type of sugar) and sodium), microcrystalline cellulose (E 460), Povidone K-30, Crospovidone (type A), sodium lauryl sulphate and sodium stearyl fumarate
- Coating: monohydrate lactose (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, film-coated tablets with a diameter of 6.1 mm.
This medicine is available in aluminium/PVC/PVdC foil blisters or in single-dose perforated blister packs contained in cardboard boxes.
Pack sizes: 7, 10, 14, 20, 28, 30, 56, 60 or 100 film-coated tablets (in blisters)
Pack 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 film-coated tablets (in single-dose perforated blister packs)
Not all pack sizes may be marketed.

Patient warning card: user information
Inside the Modylan packaging, in addition to the package leaflet, there is a patient warning card. A similar card may also be provided to the patient by the physician.
The patient warning card contains information useful for the patient and alerts other physicians that the patient is taking Modylan. You should always carry this card with you.

Take the card.
Fill in the following details or ask your doctor to complete them:
- Name and surname:
- Date of birth:
- Indication:
- Dose: ........mg twice daily
- Doctor's name:
- Doctor's telephone number:
Fold the card and keep 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
Adalvo Limited
Malta Life Sciences Park, Building 1, Level 4, Sir Temi Zammit Buildings,
San Gwann SGN 3000
Malta

This medicinal product is authorised 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 further information about this medicinal product, 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