Lixiana

Package leaflet: Information for the user

Lixiana 15 mg film-coated tablets, 30 mg film-coated tablets, 60 mg film-coated tablets

edoxaban
Please read this leaflet carefully before you start taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Lixiana is and what it is used for
2. What you need to know before taking Lixiana
3. How to take Lixiana
4. Possible side effects
5. How to store Lixiana
6. Contents of the pack and other information

1. What Lixiana is and what it is used for

Lixiana contains the active substance edoxaban and belongs to a group of medicines called
anticoagulants. This medicine helps to prevent the formation of blood clots. It works by
blocking the activity of factor Xa, an important component in blood clotting.
Lixiana is used in adults:

• to prevent the formation of blood clots in the brain (stroke) and in other blood vessels of the body in the presence of a heart rhythm disorder called non-valvular atrial fibrillation and at least one additional risk factor, such as heart failure, previous stroke or high blood pressure;
• 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 blood clots from recurring in the blood vessels of the legs and/or lungs.

2. What you should know before taking Lixiana

Do not take Lixiana

• if you are allergic to edoxaban or to any of the other ingredients of this medicine (listed in section 6);
• if you have active bleeding;
• if you have a disease or condition that increases the risk of serious bleeding (e.g. stomach ulcers, lesions or bleeding in the brain, or recent brain or eye surgery);
• if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, rivaroxaban, apixaban, or heparins), except when switching from one anticoagulant therapy to another or when receiving heparin through a venous or arterial catheter to keep it open;
• if you have a liver disease that increases the risk of bleeding;
• if you have uncontrolled high blood pressure;
• during pregnancy or breastfeeding.

Warnings and precautions
Talk to your doctor or pharmacist before taking Lixiana

• if you have an increased risk of bleeding, such as in the presence of any of the following conditions:
  • advanced kidney disease or if you are on dialysis;
  • severe liver disease;
  • coagulation disorders;
  • blood vessel disorders in the back of the eye (retinopathy);
  • recent bleeding in the brain (intracranial or intracerebral haemorrhage);
  • problems with blood vessels in the brain or spinal cord;
• if you have a mechanical heart valve.

Lixiana 15 mg should only be used when switching from Lixiana 30 mg to a vitamin K antagonist (e.g. warfarin) (see section 3, How to take Lixiana).
Pay special attention with Lixiana

• if you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether a change in therapy is necessary.

If you are scheduled for surgery,

• it is very important to take Lixiana exactly as directed by your doctor before and after the procedure. If possible, Lixiana should be stopped at least 24 hours before surgery. Your doctor will decide when to restart treatment with Lixiana. In emergency situations, your doctor will determine the appropriate actions regarding Lixiana.

Children and adolescents
Lixiana is not recommended for children and adolescents under 18 years of age.
Other medicines and Lixiana
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
If you are taking any of the following:

• certain antifungal medicines (e.g. ketoconazole);
• medicines for heart rhythm disorders (e.g. dronedarone, quinidine, verapamil);
• other medicines to reduce blood clotting (e.g. heparin, clopidogrel, or vitamin K antagonists such as warfarin, acenocoumarol, phenprocoumon, or dabigatran, rivaroxaban, apixaban);
• antibiotics (e.g. erythromycin, clarithromycin);
• medicines to prevent organ rejection after transplantation (e.g. cyclosporine);
• anti-inflammatory and pain-relieving medicines (e.g. naproxen or acetylsalicylic acid);
• antidepressants known as selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.

If any of the conditions described above apply to you, inform your doctor before taking Lixiana, because
these medicines may increase the effects of Lixiana and the risk of unwanted bleeding. Your doctor will decide whether you should be treated with Lixiana and whether you need to be monitored.
If you are taking any of the following:

• certain medicines for epilepsy (e.g. phenytoin, carbamazepine, phenobarbital);
• St John’s wort, a herbal medicine used for the treatment of anxiety and mild depression;
• rifampicin, an antibiotic medicine.

If any of the conditions described above apply to you, inform your doctor before taking Lixiana, because
the effects of Lixiana may be reduced. Your doctor will decide whether you should be treated with Lixiana and whether you need to be monitored.
Pregnancy and breastfeeding
Do not take Lixiana if you are pregnant or breastfeeding. If there is a possibility that you could become pregnant, use a reliable method of contraception during treatment with Lixiana. If you become pregnant while taking Lixiana, inform your doctor immediately, who will decide on the appropriate course of action.
Driving and using machines
Lixiana does not affect or has a negligible effect on the ability to drive or operate machinery.

3. How to take Lixiana

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Dosage
The recommended dose is one 60 mg tablet once daily.

• If renal function is impaired, your doctor may decide to reduce the dose to one 30 mg tablet once daily;
• If body weight is 60 kg or less, the recommended dose is one 30 mg tablet once daily;
• If your doctor has prescribed medicines known as P-gp inhibitors: cyclosporine, dronedarone, erythromycin, or ketoconazole, the recommended dose is one 30 mg tablet once daily.

How to take the tablet
Swallow the tablet, preferably with water.
Lixiana can be taken with or without food.
If you have difficulty swallowing the tablet whole, consult your doctor for alternative ways to take Lixiana. The tablet may be crushed and mixed with water or apple puree immediately before administration. If necessary, your doctor may administer crushed Lixiana tablets via a nasogastric tube or gastric tube.

Your doctor may adjust your anticoagulant treatment as follows:

Switching from vitamin K antagonists (VKA) (e.g. warfarin) to Lixiana
Stop treatment with the vitamin K antagonist (e.g. warfarin). Your doctor will perform blood tests and advise you when to start taking Lixiana.

Switching from oral anticoagulants other than VKAs (e.g. dabigatran, rivaroxaban, or apixaban) to Lixiana
Stop the previous anticoagulant (e.g. dabigatran, rivaroxaban, or apixaban) and start taking Lixiana at the time the next dose would have been due.

Switching from parenteral anticoagulants (e.g. heparin) to Lixiana
Stop the parenteral anticoagulant (e.g. heparin) and start taking Lixiana at the time the next dose of the parenteral anticoagulant would have been due.

Switching from Lixiana to vitamin K antagonists (e.g. warfarin)
If you are taking Lixiana 60 mg:
Your doctor will ask you to reduce the dose of Lixiana to one 30 mg tablet once daily and to take it together with a vitamin K antagonist (e.g. warfarin). Your doctor will perform blood tests and advise you when to stop taking Lixiana.
If you are taking Lixiana 30 mg (reduced dose):
Your doctor will ask you to reduce the dose of Lixiana to one 15 mg tablet once daily and to take it together with a vitamin K antagonist (e.g. warfarin). Your doctor will perform blood tests and advise you when to stop taking Lixiana.

Switching from Lixiana to oral anticoagulants other than VKAs (e.g. dabigatran, rivaroxaban, or apixaban)
Stop taking Lixiana and start taking the non-VKA oral anticoagulant (e.g. dabigatran, rivaroxaban, or apixaban) at the time the next dose of Lixiana would have been due.

Switching from Lixiana to parenteral anticoagulants (e.g. heparin)
Stop taking Lixiana and start the parenteral anticoagulant (e.g. heparin) at the time the next dose of Lixiana would have been due.

Patients undergoing cardioversion:
If an abnormal heartbeat is to be restored to normal rhythm by a procedure called cardioversion, take Lixiana according to your doctor's instructions to prevent blood clots in the brain and other blood vessels in the body.

If you take more Lixiana than you should
Inform your doctor immediately if you have taken too many Lixiana tablets.
If you have taken more Lixiana than recommended, your risk of bleeding may be increased.

If you forget to take Lixiana
Take the missed tablet as soon as you remember, then continue the next day with your usual once-daily dosing. Do not take a double dose on the same day to make up for a forgotten tablet.

If you stop taking Lixiana
Do not stop taking Lixiana without first consulting your doctor, as Lixiana is used to treat and prevent serious diseases.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Like other similar medicines (medicines that reduce blood clotting), Lixiana can cause bleeding, which may be fatal. In some cases, bleeding may not be obvious.
If you experience any bleeding that does not resolve on its own, or if you develop signs of excessive bleeding (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), consult your doctor immediately.
Your doctor may decide to monitor you closely or to change your treatment.

General list of possible side effects:

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

• stomach ache;
• abnormal liver function tests;
• bleeding from or under the skin;
• anaemia (low levels of red blood cells);
• nosebleeds;
• vaginal bleeding;
• skin rash;
• bleeding in the intestine;
• bleeding from the mouth and/or throat;
• presence of blood in the urine;
• bleeding following injury (puncture);
• bleeding in the stomach;
• dizziness;
• feeling unwell;
• headache;
• itching sensation.

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

• bleeding in the eyes;
• bleeding from a wound following surgery;
• coughing up blood;
• bleeding in the brain;
• other types of bleeding;
• reduced number of platelets in the blood (which may affect blood clotting);
• allergic reaction;
• hives.

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

• bleeding into muscles;
• bleeding into joints;
• bleeding in the abdomen;
• bleeding in the heart;
• bleeding inside the skull;
• bleeding following surgical procedure;
• anaphylactic shock;
• swelling in any part of the body due to allergic reaction.

Not known (frequency cannot be estimated from available data)

• bleeding in the kidney, sometimes with blood in the urine, leading to the kidneys being unable to function properly (anticoagulant-related nephropathy).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Lixiana

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton or bottle after
Exp. and on each blister after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Lixiana contains

• The active substance is edoxaban (as tosylate).

Lixiana 15 mg film-coated tablets
Each tablet contains 15 mg of edoxaban (as tosylate).
Lixiana 30 mg film-coated tablets
Each tablet contains 30 mg of edoxaban (as tosylate).
Lixiana 60 mg film-coated tablets
Each tablet contains 60 mg of edoxaban (as tosylate).

• The other components are:

Lixiana 15 mg film-coated tablets
Tablet core: mannitol (E421), pregelatinized starch, crospovidone (E1202),
hydroxypropylcellulose (E463), magnesium stearate (E470b).
Film coating: hypromellose (E464), macrogol (8000), titanium dioxide (E171), talc (E553b),
carnauba wax, red iron oxide (E172), yellow iron oxide (E172).
Lixiana 30 mg film-coated tablets
Tablet core: mannitol (E421), pregelatinized starch, crospovidone (E1202),
hydroxypropylcellulose (E463), magnesium stearate (E470b).
Film coating: hypromellose (E464), macrogol (8000), titanium dioxide (E171), talc (E553b),
carnauba wax, red iron oxide (E172).
Lixiana 60 mg film-coated tablets
Tablet core: mannitol (E421), pregelatinized starch, crospovidone (E1202),
hydroxypropylcellulose (E463), magnesium stearate (E470b).
Film coating: hypromellose (E464), macrogol (8000), titanium dioxide (E171), talc (E553b),
carnauba wax, yellow iron oxide (E172).

Description of the appearance of Lixiana and contents of the pack
Lixiana 15 mg film-coated tablets are orange-colored, round tablets (6.7 mm in diameter) with "DSC L15" engraved on one side.
They are supplied in blisters in cardboard packs containing 10 film-coated tablets, or in unit-dose divisible blisters in cardboard packs containing 10 × 1 film-coated tablets.

Lixiana 30 mg film-coated tablets are pink-colored, round tablets (8.5 mm in diameter) with "DSC L30" engraved on one side.
They are supplied in blisters in cardboard packs containing 10, 14, 28, 30, 56, 60, 84, 90, 98 or 100 film-coated tablets, or in unit-dose divisible blisters in cardboard packs containing 10 × 1, 50 × 1 or 100 × 1 film-coated tablets, or in bottles containing 90 film-coated tablets.

Lixiana 60 mg film-coated tablets are yellow-colored, round tablets (10.5 mm in diameter) with "DSC L60" engraved on one side.
They are supplied in blisters in cardboard packs containing 10, 14, 28, 30, 56, 60, 84, 90, 98 or 100 film-coated tablets, or in unit-dose divisible blisters in cardboard packs containing 10 × 1, 50 × 1 or 100 × 1 film-coated tablets, or in bottles containing 90 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder
Daiichi Sankyo Europe GmbH
Zielstattstrasse 48
81379 Munich
Germany

Manufacturer
Daiichi Sankyo Europe GmbH
Luitpoldstrasse 1
85276 Pfaffenhofen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Daiichi Sankyo Belgium N.V.-S.A UAB “SERVIER PHARMA”
Tél/Tel: +32-(0) 2 227 18 80 Tel: +370 (5) 2 63 86 28

България Luxembourg/Luxemburg
Daiichi Sankyo Europe GmbH Daiichi Sankyo Belgium N.V.-S.A
Tel: +49-(0) 89 7808 0 Tél/Tel: +32-(0) 2 227 18 80

Česká republika Magyarország
Organon Czech Republic s.r.o. Organon Hungary Kft.
Tel: +420 233 010 300 Tel.: +36 1 766 1963

Danmark Malta
Organon Denmark ApS Daiichi Sankyo Europe GmbH
Tlf: +45 4484 6800 Tel: +49-(0) 89 7808 0

Deutschland Nederland
Daiichi Sankyo Deutschland GmbH Daiichi Sankyo Nederland B.V.
Tel. +49-(0) 89 7808 0 Tel: +31-(0) 20 4 07 20 72

Eesti Norge
Servier Laboratories OÜ Organon Norway AS
Tel: +372 664 5040 Tlf: +47 24 14 56 60

Ελλάδα Österreich
Daiichi Sankyo Europe GmbH Daiichi Sankyo Austria GmbH
Τηλ: +49-(0) 89 7808 0 Tel: +43-(0) 1 485 86 42 0

España Polska
Daiichi Sankyo España, S.A. Daiichi Sankyo Europe GmbH
Tel: +34 91 539 99 11 Tel: +49-(0) 89 7808 0

France Portugal
Daiichi Sankyo France S.A.S. Daiichi Sankyo Portugal, Unip. LDA
Tél: +33-(0) 1 55 62 14 60 Tel: +351 21 4232010

Hrvatska România
Daiichi Sankyo Europe GmbH Daiichi Sankyo Europe GmbH
Tel: +49-(0) 89 7808 0 Tel: +49-(0) 89 7808 0

Ireland Slovenija
Daiichi Sankyo Ireland Ltd Daiichi Sankyo Europe GmbH
Tel: +353-(0) 1 489 3000 Tel: +49-(0) 89 7808 0

Ísland Slovenská republika
Vistor hf. Organon Slovakia s. r. o.
Sími: +354 535 7000 Tel: +421 2 44 88 98 88

Italia Suomi/Finland
Daiichi Sankyo Italia S.p.A. Organon Finland Oy
Tel: +39-06 85 2551 Puh/Tel: +358 (0) 29 170 3520

Κύπρος Sverige
Daiichi Sankyo Europe GmbH Organon Sweden AB
Τηλ: +49-(0) 89 7808 0 Tel: +46 8 502 597 00

Latvija United Kingdom (Northern Ireland)
SIA Servier Latvia Daiichi Sankyo Europe GmbH
Tel: +371 67502039 Tel: +49-(0) 89 7808 0

Other sources of information
More detailed information about this medicinal product is available by scanning the QR code with a smartphone.
The same information is also available at the following website: www.dspatient.eu.
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More detailed information about this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu/.