Modylan

Package leaflet: Information for the user

Modylan, 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.

Leaflet contents

1. What Modylan is and what it is used for
2. What you need to know before taking Modylan
3. How to take Modylan
4. Possible side effects
5. How to store Modylan
6. 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 blocking factor Xa, which is an important component of the blood clotting process.
This medicine 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 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 any organ that increases the risk of severe bleeding (for example, active or recently experienced peptic ulcer of the stomach or intestines, or bleeding into the brain);
• if the patient has liver disease associated with 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 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 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 blood pressure that is not controlled by medication;
  • 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 impairment.
• if the patient has a heart valve prosthesis;
• if the doctor considers the patient’s blood pressure to be unstable, or if other treatment or surgical procedure is planned to remove a blood clot from the lungs.

When to exercise special 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 needed.
• 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 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 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 used to treat epilepsy or seizures (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 during pregnancy and on 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 this medicine passes into human milk. Before using this medicine during breastfeeding, consult a doctor, pharmacist, or nurse. They will advise whether it is better to stop breastfeeding or to stop/not start taking this medicine.

Driving and operating machinery
No effects of Modylan on the ability to drive or operate machinery have been observed.

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 exactly as directed 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. Modylan 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, you should discuss alternative ways of taking
Modylan with your doctor. The tablet may be crushed and mixed with water, 5% glucose solution,
apple juice, or apple puree just before administration.
Instructions for crushing tablets:

• Crush the tablet with a pestle in a mortar.
• 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, 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 through a nasogastric tube.
Modylan should be taken as directed 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 Modylan 5 mg tablet twice daily.

The recommended dose is one Modylan 2.5 mg 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 Modylan 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 Modylan 5 mg tablet twice daily, for example one tablet in the morning and one tablet in the evening.
• Prevention of recurrent blood clots after completing 6 months of treatment The recommended dose is one Modylan 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.
• Your doctor may change your anticoagulant therapy as follows:
  • Switching from Modylan to another anticoagulant medicine Stop taking Modylan. At the time when the next scheduled dose would have been taken, start treatment with another anticoagulant (e.g. heparin).
  • Switching from another anticoagulant medicine to Modylan Stop taking the anticoagulant medicine. At the time when the next scheduled dose of the anticoagulant would have been taken, 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 inform you when you can 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 inform you 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 specific times as directed by your doctor to prevent formation of blood clots in the blood vessels of the brain and other parts of the body.
Taking more Modylan than prescribed
If you have taken more Modylan than prescribed, you should contact your doctor immediately.
Take the medicine packaging with you, even if there are no tablets left in it.
Taking more Modylan than prescribed 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 necessary.
Missed dose of Modylan
Take the missed dose as soon as you remember and:

• take the next dose of Modylan at your usual time
• continue taking the medicine as normal. If you have any doubts about how to take the medicine or if you have missed 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 developing a blood clot.
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 everybody 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 have been reported with the use of Modylan
for the prevention of 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;
  • 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-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 blood in the stool;
  • bleeding occurring after surgery, including subcutaneous haemorrhages (bruising) and swelling, and leakage of blood or fluid from the surgical wound/incision site or injection site (wound discharge);
  • from haemorrhoids;
  • tests showing presence of blood in stool or urine;
• decrease in platelet count (which may affect blood clotting);
• blood tests may show:
  • abnormal liver function;
  • increased activity of certain liver enzymes;
  • increased bilirubin levels, a product from destroyed red blood cells, which may cause yellowing of the skin and eyes;
• skin rash;
• itching;
• hair loss;
• allergic (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and/or throat, and breathing difficulties. If any of these symptoms occur, seek immediate medical advice from a doctor.

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 involve blistering and appears as small target-like lesions (dark spots surrounded by a lighter area, with a dark ring at the edge) (erythema multiforme).

Unknown frequency (cannot be estimated from available data)

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

The following side effects have been reported with the use of Modylan
for the prevention of recurrence of blood clots in the leg veins 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, rectum;
  • in the mouth;
  • from the vagina;
• anaemia, which may cause fatigue or paleness;
• decrease in platelet count (which may affect blood clotting);
• nausea (feeling sick);
• skin 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 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 the stool;
  • tests showing presence of blood in stool or urine;
  • bleeding occurring after surgery, including subcutaneous haemorrhages (bruising) and swelling, and leakage of blood or fluid from the surgical wound/incision site or injection site (wound discharge);
  • from haemorrhoids;
  • into muscles;
• itching;
• hair loss;
• allergic (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and/or throat, and breathing difficulties. If any of these symptoms occur, seek immediate medical advice from a doctor;
• blood tests may show:
  • abnormal liver function;
  • increased activity of certain liver enzymes;
  • increased bilirubin levels, a product from 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 cord;
  • into the lungs.

Unknown frequency (cannot be estimated from available data)

• bleeding into the abdominal cavity or retroperitoneal space (area behind the abdominal cavity);
• skin rash, which may involve blistering 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, round spots under the skin surface or bruising.

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform 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 Modylan

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack following:
EXP. The expiry date refers to the last day of the stated month.
No special storage conditions apply.
Medicines must not be disposed of via wastewater 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 Modylan contains

• The active substance is apixaban. Each tablet contains 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 sulfate, 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), and red iron oxide (E172).

What Modylan looks like and contents of the pack
Pink, film-coated, elongated tablets, 5.2 mm wide and 10.3 mm long.
This medicine is available in aluminum/PVC/PVdC blisters or in unit-dose blister packs with perforations, packed 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 perforated unit-dose blisters)
Not all pack sizes may be marketed.

Patient warning card: information on use
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 that will be useful for the patient and will inform other physicians that the patient is taking Modylan. You should always carry this card with you.

1. Take the card.
2. Fill in the following details yourself or ask your doctor to complete them:
   • Name:
   • Date of birth:
   • Indication:
   • Dose: ........mg twice daily
   • Doctor's name:

• Doctor's telephone number: 3. 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
Adalvo Limited
Malta Life Sciences Park, Building 1, Level 4, Sir Temi Zammit Buildings,
San Gwann SGN 3000
Malta

This medicine is authorized for sale in 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 on 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