Package Leaflet: Information for the User

Lixiana 15 mg Film-Coated Tablets

Lixiana 30 mg Film-Coated Tablets

Lixiana 60 mg Film-Coated Tablets

edoxaban

Read this package leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this package leaflet, as 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 they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist. See section 4.

Lixiana contains the active ingredient 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 element in blood coagulation.

Lixiana is used in adults:

• to prevent the formation of a blood clot in the brain(stroke)and in other blood vessels of the bodyif they have a type of irregular heart rhythm called non-valvular atrial fibrillation and at least one additional risk factor, such as heart failure, having had a stroke before or hypertension;
• to treat blood clots in the veins of the legs(deep vein thrombosis) andin the blood vessels of the lungs(pulmonary embolism), andto prevent these blood clots from coming backin the blood vessels of the legs and/or lungs.

Do not take Lixiana

• if you are allergic to edoxaban or any of the other ingredients of this medicine (listed in section 6);
• if you are bleeding actively;
• if you have a condition or disease that increases the risk of severe bleeding (for example, stomach ulcer, injury or bleeding in the brain or recent surgery in the brain or eyes);
• if you are taking other medicines to prevent blood clotting (e.g., warfarin, dabigatrán, rivaroxabán, apixabán or heparin), except when changing from one anticoagulant treatment to another or while receiving heparin through a central venous or arterial catheter, to prevent blockage;
• if you have liver disease that may increase the risk of bleeding;
• if you have uncontrolled high blood pressure;
• if you are pregnant or breastfeeding.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Lixiana,

• if you have an increased risk of bleeding, such as in the case of the following conditions:
• • terminal renal disease or if you are on dialysis;
  • severe liver disease;
  • bleeding disorders;
  • problems with blood vessels in the back of the eyes (retinopathy);
  • recent bleeding in the brain (intracranial or intracerebral hemorrhage);
  • problems with blood vessels in the brain or spinal cord;
• if you have a mechanical heart valve.

Lixiana 15 mg is only indicated when switching from Lixiana 30 mg to a vitamin K antagonist (e.g., warfarin) (see section 3. How to take Lixiana).

Be especially careful with Lixiana,

• if you know you have a condition called antiphospholipid syndrome (a disorder of the immune system that increases the risk of blood clots), inform your doctor so that they can decide if your treatment needs to be modified.

If you need surgery,

• it is very important to take Lixiana exactly as indicated by your doctor before and after the operation. If possible, stop taking Lixiana at least 24 hours before surgery. Your doctor will determine when to restart Lixiana.

In emergency situations, your doctor will contribute to determining the necessary actions regarding Lixiana.

Children and adolescents

Lixiana is not recommended for children and adolescents under 18 years

Other medicines and Lixiana

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine.

If you are taking any of the following:

• any medicine for a fungal infection (e.g., ketoconazol);
• medicines to treat abnormal heart rhythm (e.g., dronedarona, quinidina, verapamilo);
• other medicines to reduce blood clotting (e.g., heparin, clopidogrel or vitamin K antagonists, such as warfarin, acenocumarol, fenprocumon or dabigatrán, rivaroxabán, apixabán);
• antibiotics (e.g., eritromicina, claritromicina);
• medicines to prevent organ rejection after a transplant (e.g., ciclosporina);
• anti-inflammatory and pain-relieving medicines (e.g., naproxeno or ácido acetilsalicílico);
• antidepressants called selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors.

If any of the above circumstances apply to you, inform your doctorbefore taking Lixiana because these medicines may increase the effects of Lixiana and the risk of unwanted bleeding. Your doctor will decide if you should be treated with Lixiana and if you should be monitored.

If you are taking any of the following:

• any medicine for the treatment of epilepsy (e.g., fenitoína, carbamazepina, fenobarbital);
• St. John's Wort, a medicinal herb used for anxiety and mild depression;
• rifampicina, an antibiotic.

If any of the above circumstances apply to you, inform your doctorbefore taking Lixiana, because the effect of Lixiana may be reduced. Your doctor will decide if you should be treated with Lixiana and if you should be monitored.

Pregnancy and breastfeeding

Do not take Lixiana if you are pregnant or breastfeeding. If there is any possibility of becoming pregnant, use effective contraception while taking Lixiana. If you become pregnant while taking Lixiana, inform your doctor immediately, who will decide how to treat you.

Driving and operating machines

The influence of Lixiana on the ability to drive and operate machines is negligible or insignificant.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

What dose to take

The recommended dose is a tablet of60 mgonce a day.

• If you have renal insufficiency, your doctor may reduce your dose to a tablet of30 mgonce a day.
• If you weigh 60 kg or less, the recommended dose is a tablet of30 mgonce a day.
• If your doctor has prescribed you medications known as P-gp inhibitors:ciclosporina, dronedarona, eritromicina or ketoconazol, the recommended dose is a tablet of30 mgonce a day.

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 entire tablet, talk to your doctor about other ways to take Lixiana. The tablet can be crushed and mixed with water or apple sauce immediately before taking it. If necessary, your doctor may also administer the crushed Lixiana tablet through a tube into your nose (nasogastric tube) or into your stomach (gastric feeding tube).

Your doctor may change your anticoagulant treatment as follows:

Switch from vitamin K antagonists (e.g., warfarin) to Lixiana

Stop taking the vitamin K antagonist (e.g., warfarin). Your doctor will have to do a blood test and tell you when to start taking Lixiana.

Switch from oral anticoagulants that are not vitamin K antagonists (dabigatrán, rivaroxabán or apixabán) to Lixiana

Stop taking the previous medications (e.g., dabigatrán, rivaroxabán or apixabán) and start taking Lixiana at the time of the next scheduled dose of the anticoagulant.

Switch from parenteral anticoagulants (e.g., heparina) to Lixiana

Stop taking the anticoagulant (e.g., heparina) and start taking Lixiana at the time of the next scheduled dose of the anticoagulant.

Switch from Lixiana to vitamin K antagonists (e.g., warfarina)

If you are currently taking60 mg of Lixiana:

Your doctor will tell you to reduce the dose of Lixiana to a tablet of 30 mg once a day and take it with a vitamin K antagonist (e.g., warfarina). Your doctor will have to do a blood test and tell you when to stop taking Lixiana.

If you are currently taking30 mg (reduced dose) of Lixiana:

Your doctor will tell you to reduce the dose of Lixiana to a tablet of 15 mg once a day and take it with a vitamin K antagonist (e.g., warfarina). Your doctor will have to do a blood test and tell you when to stop taking Lixiana.

Switch from Lixiana to oral anticoagulants that are not vitamin K antagonists (dabigatrán, rivaroxabán or apixabán)

Stop taking Lixiana and start the non-vitamin K antagonist oral anticoagulant (e.g., dabigatrán, rivaroxabán or apixabán) at the time of the next scheduled dose of Lixiana.

Switch from Lixiana to parenteral anticoagulants (e.g., heparina)

Stop taking Lixiana and start the parenteral anticoagulant (e.g., heparina) at the time of the next scheduled dose of Lixiana.

Patients undergoing cardioversion:

If you need your abnormal heart rhythm to be restored to normal through a procedure called cardioversion, take Lixiana at the times indicated by your doctor to prevent the formation of blood clots in your brain and other blood vessels of your body.

If you take more Lixiana than you should

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

If you forget to take Lixiana

You should take the tablet immediately and continue with your usual daily tablet once a day. Do not take a double dose on the same day to compensate for the missed dose.

If you interrupt treatment with Lixiana

Do not stop treatment with Lixiana without first talking to your doctor, as Lixiana treats and prevents serious diseases.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Like other similar medicines (blood-thinning medicines), Lixiana may cause bleeding, which can be life-threatening. In some cases, the bleeding may not be apparent.

If you experience an episode of bleeding that does not stop on its own or if you experience signs of excessive bleeding (exceptional weakness, fatigue, pallor, dizziness, headache, or unexplained swelling), consult your doctor immediately.

Your doctor will decide whether to keep you under closer observation or change your treatment.

General list of possible side effects:

Common(may affect up to 1 in 10 people)

• Abdominal pain;
• Abnormal liver function test results in blood tests;
• Bleeding from the skin or under the skin;
• Anemia (low red blood cell count);
• Nasal bleeding;
• Vaginal bleeding;
• Skin rash;
• Bleeding from the intestines;
• Bleeding from the mouth and/or throat;
• Blood in the urine;
• Bleeding after a puncture;
• Stomach bleeding;
• Dizziness;
• Nausea;
• Headache;
• Itching.

Uncommon(may affect up to 1 in 100 people)

• Bleeding in the eyes;
• Bleeding from a surgical wound after surgery;
• Blood in the saliva when coughing;
• Bleeding in the brain;
• Other types of bleeding;
• Decreased platelet count in the blood (which can affect coagulation);
• Allergic reaction;
• Urticaria.

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

• Bleeding in the muscles;
• Bleeding in the joints;
• Bleeding in the abdomen
• Bleeding in the heart;
• Bleeding in the cranial cavity;
• Bleeding after surgery;
• Severe allergic shock;
• Swelling of any part of the body due to allergic reaction.

Unknown frequency(cannot be estimated from available data)

• Bleeding in the kidney, sometimes with blood in the urine, which can cause the kidneys to malfunction (anticoagulation-related nephropathy).

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly throughtheSpanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box or bottle after CAD and on each blister pack after EXP. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Lixiana

• The active ingredient is edoxaban (as tosilate).

Lixiana 15 mg film-coated tablets

Each tablet contains 15 mg of edoxaban (as tosilate).

Lixiana 30 mg film-coated tablets

Each tablet contains 30 mg of edoxaban (as tosilate).

Lixiana 60 mg film-coated tablets

Each tablet contains 60 mg of edoxaban (as tosilate).

• The other components are:

Lixiana 15 mg film-coated tablets

Core of the tablet: mannitol (E421), pregelatinized starch, crospovidone (E1202), hydroxypropylcellulose (E463), magnesium stearate (E470b).

Film coating: hypromellose (E464), macrogol (8000), titanium dioxide (E171), talc (E553b), carnauba wax, iron oxide red (E172), iron oxide yellow (E172).

Lixiana 30 mg film-coated tablets

Core of the tablet: mannitol (E421), pregelatinized starch, crospovidone (E1202), hydroxypropylcellulose (E463), magnesium stearate (E470b).

Film coating: hypromellose (E464), macrogol (8000), titanium dioxide (E171), talc (E553b), carnauba wax, iron oxide red (E172).

Lixiana 60 mg film-coated tablets

Core of the tablet: mannitol (E421), pregelatinized starch, crospovidone (E1202), hydroxypropylcellulose (E463), magnesium stearate (E470b).

Film coating: hypromellose (E464), macrogol (8000), titanium dioxide (E171), talc (E553b), carnauba wax, iron oxide yellow (E172).

Appearance of the product and contents of the pack

Lixiana 15 mg film-coated tablets are orange in color and round (6.7 mm in diameter) with “DSC L15” engraved on one side.

They are presented in blisters in packs of 10 film-coated tablets or in single-dose blisters in packs of 10 x 1 film-coated tablets.

Lixiana 30 mg film-coated tablets are pink in color and round (8.5 mm in diameter) with “DSC L30” engraved on one side.

They are presented in blisters in packs of 10, 14, 28, 30, 56, 60, 84, 90, 98 or 100 film-coated tablets or in single-dose blisters in packs of 10 x 1, 50 x 1 or 100 x 1 film-coated tablets or in bottles of 90 film-coated tablets.

Lixiana 60 mg film-coated tablets are yellow in color and round (10.5 mm in diameter) and with “DSC L60” engraved on one side.

They are presented in blisters in packs of 10, 14, 28, 30, 56, 60, 84, 90, 98 or 100 film-coated tablets or in single-dose blisters in packs of 10 x 1, 50 x 1 or 100 x 1 film-coated tablets or in bottles of 90 film-coated tablets.

Only some 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:

Last update of this leaflet:12/2024.

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.