rivaroxaban: package leaflet

You have been given Xarelto because
- you have been diagnosed with an acute coronary syndrome (a group of conditions that includes heart attack and unstable angina, a severe type of chest pain) and have been shown to have had an increase in certain cardiac blood tests.
Xarelto reduces the risk in adults of having another heart attack or reduces the risk of dying from a disease related to your heart or your blood vessels.
Xarelto will not be given to you on its own. Your doctor will also tell you to take either:
- acetylsalicylic acid or
- acetylsalicylic acid plus clopidogrel or ticlopidine.

or

- you have been diagnosed with a high risk of getting a blood clot due to a coronary artery disease or peripheral artery disease which causes symptoms.
Xarelto reduces the risk in adults of getting blot clots (atherothrombotic events).
Xarelto will not be given to you on its own. Your doctor will also tell you to take acetylsalicylic acid.
In some cases, if you get Xarelto after a procedure to open a narrowed or closed artery of your leg to restore blood flow, your doctor may also prescribe clopidogrel for you to take in addition to acetylsalicylic acid for a short while.

Xarelto contains the active substance rivaroxaban and belongs to a group of medicines called antithrombotic agents. It works by blocking a blood clotting factor (factor Xa) and thus reducing the tendency of the blood to form clots.

Do not take Xarelto
- if you are allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6)

- if you are bleeding excessively
- if you have a disease or condition in an organ of the body that increases the risk of serious bleeding (e.g. stomach ulcer, injury or bleeding in the brain, recent surgery of the brain or eyes)
- if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open
- if you have an acute coronary syndrome and previously had a bleeding or a blood clot in your brain (stroke)
- if you have coronary artery disease or peripheral artery disease and previously had a bleeding in your brain (stroke) or where there was a blockage of the small arteries providing blood to the brain’s deep tissues (lacunar stroke) or if you had a blood clot in your brain (ischaemic, non- lacunar stroke) in the previous month
- if you have a liver disease which leads to an increased risk of bleeding
- if you are pregnant or breast-feeding
Do not take Xarelto and tell your doctor if any of these apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xarelto.
Xarelto should not be used in combination with certain other medicines which reduce blood clotting such as prasugrel or ticagrelor other than acetylsalicylic acid and clopidogrel/ticlopidine.

Take special care with Xarelto
- if you have an increased risk of bleeding, as could be the case in situations such as:
▪ severe kidney disease, since your kidney function may affect the amount of medicine that works in your body ▪ if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open (see section “Other medicines and Xarelto”) ▪ bleeding disorders ▪ very high blood pressure, not controlled by medical treatment ▪ diseases of your stomach or bowel that might result in bleeding, e.g. inflammation of the bowels or stomach, or inflammation of the oesophagus (gullet), e.g. due to gastroesophageal reflux disease (disease where stomach acid goes upwards into the oesophagus) or tumours located in the stomach or bowels or genital tract or urinary tract ▪ a problem with the blood vessels in the back of your eyes (retinopathy) ▪ a lung disease where your bronchi are widened and filled with pus (bronchiectasis), or previous bleeding from your lung ▪ you are older than 75 years ▪ you weigh less than 60 kg ▪ you have a coronary artery disease with severe symptomatic heart failure
- if you have a prosthetic heart valve
- if you know that you have a disease called antiphospholipid syndrome (a disorder of the immune system that causes an increased risk of blood clots), tell your doctor who will decide if the treatment may need to be changed.

If any of the above apply to you, tell your doctor before you take Xarelto. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.

If you need to have an operation
- it is very important to take Xarelto before and after the operation exactly at the times you have been told by your doctor.
- If your operation involves a catheter or injection into your spinal column (e.g. for epidural or spinal anaesthesia or pain reduction):
▪ it is very important to take Xarelto before and after the injection or removal of the catheter exactly at the times you have been told by your doctor

▪ tell your doctor immediately if you get numbness or weakness of your legs or problems with your bowel or bladder after the end of anaesthesia, because urgent care is necessary.

Children and adolescents
Xarelto 2.5 mg tablets are not recommended for people under 18 years of age. There is not enough information on their use in children and adolescents.

Other medicines and Xarelto
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
- If you are taking
▪ some medicines for fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are only applied to the skin ▪ ketoconazole tablets (used to treat Cushing’s syndrome - when the body produces an excess of cortisol) ▪ some medicines for bacterial infections (e.g. clarithromycin, erythromycin) ▪ some anti-viral medicines for HIV / AIDS (e.g. ritonavir) ▪ other medicines to reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists such as warfarin and acenocoumarol, prasugrel and ticagrelor (see section “Warnings and Precautions”)) ▪ anti-inflammatory and pain relieving medicines (e.g. naproxen or acetylsalicylic acid) ▪ dronedarone, a medicine to treat abnormal heart beat ▪ some medicines to treat depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs))

If any of the above apply to you, tell your doctor before taking Xarelto, because the effect of Xarelto may be increased. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.
If your doctor thinks that you are at increased risk of developing stomach or bowel ulcers, he may also use a preventative ulcer treatment.

- If you are taking
▪ some medicines for treatment of epilepsy (phenytoin, carbamazepine, phenobarbital) ▪ St John’s Wort (Hypericum perforatum), a herbal product used for depression ▪ rifampicin, an antibiotic If any of the above apply to you, tell your doctor before taking Xarelto, because the effect of Xarelto may be reduced. Your doctor will decide, if you should be treated with Xarelto and if you should be kept under closer observation.

Pregnancy and breast---feeding
Do not take Xarelto if you are pregnant or breast-feeding. If there is a chance that you could become pregnant, use a reliable contraceptive while you are taking Xarelto. If you become pregnant while you are taking this medicine, tell your doctor immediately, who will decide how you should be treated.

Driving and using machines
Xarelto may cause dizziness (common side effect) or fainting (uncommon side effect) (see section 4, ”Possible side effects”). You should not drive, ride a bicycle or use any tools or machines if you are affected by these symptoms.

Xarelto contains lactose and sodium
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ”sodium- free”.

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

How much to take
The recommended dose is one 2.5 mg tablet twice a day. Take Xarelto around the same time every day (for example, one tablet in the morning and one in the evening). This medicine can be taken with or without food.

If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take Xarelto. The tablet may be crushed and mixed with water or apple puree immediately before you take it.
If necessary, your doctor may also give you the crushed Xarelto tablet through a stomach tube.

Xarelto will not be given to you on its own.
Your doctor will also tell you to take acetylsalicylic acid.
If you get Xarelto after an acute coronary syndrome, your doctor may tell you to also take clopidogrel or ticlopidine.
If you get Xarelto after a procedure to open a narrowed or closed artery of your leg to restore blood flow, your doctor may also prescribe clopidogrel for you to take in addition to acetylsalicylic acid for a short while.

Your doctor will tell you how much of these to take (usually between 75 to 100 mg acetylsalicylic acid daily or a daily dose of 75 to 100 mg acetylsalicylic acid plus a daily dose of either 75 mg clopidogrel or a standard daily dose of ticlopidine).

When to start Xarelto
Treatment with Xarelto after an acute coronary syndrome should be started as soon as possible after stabilisation of the acute coronary syndrome, at the earliest 24 hours after admission to hospital and at the time when parenteral (via injection) anticoagulation therapy would normally be stopped.
Your doctor will tell you when to start treatment with Xarelto if you have been diagnosed with coronary artery disease or peripheral artery disease.
Your doctor will decide how long you must continue treatment.

If you take more Xarelto than you should
Contact your doctor immediately if you have taken too many Xarelto tablets. Taking too much Xarelto increases the risk of bleeding.

If you forget to take Xarelto
Do not take a double dose to make up for a missed dose. If you miss a dose, take your next dose at the usual time.

If you stop taking Xarelto
Take Xarelto on a regular basis and for as long as your doctor keeps prescribing it.

Do not stop taking Xarelto without talking to your doctor first. If you stop taking this medicine, it may increase your risk of having another heart attack or stroke or dying from a disease related to your heart or your blood vessels.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

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

Like other similar medicines to reduce the formation of blood clots, Xarelto may cause bleeding which may potentially be life threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). In some cases the bleeding may not be obvious.

Tell your doctor immediately if you experience any of the following side effects:
- Signs of bleeding
- bleeding into the brain or inside the skull (symptoms can include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness.
A serious medical emergency. Seek medical attention immediately!)
- long or excessive bleeding
- exceptional weakness, tiredness, paleness, dizziness, headache, unexplained swelling, breathlessness, chest pain or angina pectoris

Your doctor may decide to keep you under closer observation or change the treatment.

- Signs of severe skin reactions
- spreading intense skin rash, blisters or mucosal lesions, e.g. in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
- a drug reaction that causes rash, fever, inflammation of internal organs, blood abnormalities and systemic illness (DRESS syndrome).
The frequency of these side effects is very rare (up to 1 in 10,000 people).

- Signs of severe allergic reactions
- swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives and breathing difficulties; sudden drop in blood pressure.
The frequencies of severe allergic reactions are very rare (anaphylactic reactions, including anaphylactic shock; may affect up to 1 in 10,000 people) and uncommon (angioedema and allergic oedema; may affect up to 1 in 100 people).

Overall list of possible side effects

Common (may affect up to 1 in 10 people)
- reduction in red blood cells which can make the skin pale and cause weakness or breathlessness
- bleeding in the stomach or bowel, urogenital bleeding (including blood in the urine and heavy menstrual bleeding), nose bleed, bleeding in the gum
- bleeding into the eye (including bleeding from the whites of the eyes)
- bleeding into tissue or a cavity of the body (haematoma, bruising)
- coughing up blood
- bleeding from the skin or under the skin
- bleeding following an operation
- oozing of blood or fluid from surgical wound
- swelling in the limbs
- pain in the limbs
- impaired function of the kidneys (may be seen in tests performed by your doctor)
- fever
- stomach ache, indigestion, feeling or being sick, constipation, diarrhoea
- low blood pressure (symptoms may be feeling dizzy or fainting when standing up)
- decreased general strength and energy (weakness, tiredness), headache, dizziness
- rash, itchy skin
- blood tests may show an increase in some liver enzymes

Uncommon (may affect up to 1 in 100 people)
- bleeding into the brain or inside the skull (see above, signs of bleeding)
- bleeding into a joint causing pain and swelling
- thrombocytopenia (low number of platelets, which are cells that help blood to clot)
- allergic reactions, including allergic skin reactions
- impaired function of the liver (may be seen in tests performed by your doctor)

• blood tests may show an increase in bilirubin, some pancreatic or liver enzymes or in the number of platelets
• fainting
• feeling unwell
• faster heartbeat
• dry mouth
• hives

Rare (may affect up to 1 in 1,000 people)
- bleeding into a muscle
- cholestasis (decreased bile flow), hepatitis incl. hepatocellular injury (inflamed liver incl. liver injury)
- yellowing of the skin and eye (jaundice)
- localised swelling
- collection of blood (haematoma) in the groin as a complication of the cardiac procedure where a catheter is inserted in your leg artery (pseudoaneurysm)

Very rare (may affect up to 1 in 10,000 people)
- accumulation of eosinophils, a type of white granulocytic blood cells that cause inflammation in the lung (eosinophilic pneumonia)

Not known (frequency cannot be estimated from the available data)
- kidney failure after a severe bleeding
- bleeding in the kidney sometimes with presence of blood in urine leading to inability of the kidneys to work properly (anticoagulant-related nephropathy)
- increased pressure within muscles of the legs or arms after a bleeding, which leads to pain, swelling, altered sensation, numbness or paralysis (compartment syndrome after a bleeding)

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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 and on each blister or bottle after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Crushed tablets
Crushed tablets are stable in water or apple puree for up tp 4 hours.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Xarelto contains
- The active substance is rivaroxaban. Each tablet contains 2.5 mg of rivaroxaban.
- The other ingredients are:
Tablet core: microcrystalline cellulose, croscarmellose sodium, lactose monohydrate,

hypromellose (2910), sodium laurilsulfate, magnesium stearate. See section 2 “Xarelto contains lactose and sodium”.
Tablet film coat: macrogol (3350), hypromellose (2910), titanium dioxide (E 171), iron oxide yellow (E 172).

What Xarelto looks like and contents of the pack
Xarelto 2.5 mg film-coated tablets are light yellow, round, biconvex and marked with the BAYER- cross on one side and “2.5” and a triangle on the other side.
They come
- in blisters in cartons of 14, 20, 28, 30, 56, 60, 98, 168 or 196 film-coated tablets or
- in unit dose blisters in cartons of 10 x 1 or 100 x 1 or
- in multipacks comprising 10 cartons, each containing 10 x 1 film-coated tablets or
- in bottles of 100 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Bayer AG
51368 Leverkusen
Germany

Manufacturer

The manufacturer can be identified by the batch number printed on the side flap of the carton and on each blister or bottle:

- If the first and second characters are BX, the manufacturer is
Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany

- If the first and second characters are IT, the manufacturer is
Bayer HealthCare Manufacturing Srl.
Via delle Groane, 126
20024 Garbagnate Milanese
Italy

- If the first and second characters are BT, the manufacturer is
Bayer Bitterfeld GmbH
Ortsteil Greppin, Salegaster Chaussee 1
06803 Bitterfeld-Wolfen
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België / Belgique / Belgien
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Lietuva
UAB Bayer
Tel: +370-5-233 68 68

България
Байер България ЕООД
Тел: +359-(0)2-424 72 80

Luxembourg / Luxemburg
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Česká republika
Bayer s.r.o.
Tel: +420-266 101 111

Magyarország
Bayer Hungária KFT
Tel: +36-1-487 4100

Danmark
Bayer A/S
Tlf: +45-45 235 000

Malta
Alfred Gera and Sons Ltd.
Tel: +356-21 44 62 05

Deutschland
Bayer Vital GmbH
Tel: +49-(0)214-30 513 48

Nederland
Bayer B.V.
Tel: +31-23-799 1000

Eesti
Bayer OÜ
Tel: +372-655 85 65

Norge
Bayer AS
Tlf: +47-23 13 05 00

Ελλάδα
Bayer Ελλάς ΑΒΕΕ
Τηλ: +30-210-618 75 00

Österreich
Bayer Austria Ges. m. b. H.
Tel: +43-(0)1-711 460

España
Bayer Hispania S.L.
Tel: +34-93-495 65 00

Polska
Bayer Sp. z o.o.
Tel: +48-22-572 35 00

France
Bayer HealthCare
Tél (N° vert): +33-(0)800 87 54 54

Portugal
Bayer Portugal, Lda.
Tel: +351-21-416 42 00

Hrvatska
Bayer d.o.o.
Tel: + 385-(0)1-6599 900

România
SC Bayer SRL
Tel: +40-(0)21-529 59 00

Ireland
Bayer Limited
Tel: +353 1 216 3300

Slovenija
Bayer d. o. o.
Tel: +386-(0)1-58 14 400

Ísland
Icepharma hf.
Sími: +354-540 80 00

Slovenská republika
Bayer, spol. s r.o.
Tel: +421-(0)2-59 21 31 11

Italia
Bayer S.p.A.
Tel: +39-02-3978 1

Suomi/Finland
Bayer Oy
Puh/Tel: +358-(0)20-78521

Κύπρος
NOVAGEM Limited
Τηλ: +357-22-48 38 58

Sverige
Bayer AB
Tel: +46-(0)8-580 223 00

Latvija
SIA Bayer
Tel: +371-67 84 55 63

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency website:
http://www.ema.europa.eu.

Xarelto contains the active substance rivaroxaban and is used in adults to
- prevent blood clots in the veins after a hip or knee replacement operation. Your doctor has prescribed this medicine for you because after an operation you are at an increased risk of getting blood clots.
- treat blood clots in the veins of your legs (deep vein thrombosis) and in the blood vessels of your lungs (pulmonary embolism), and to prevent blood clots from re-occurring in the blood vessels of your legs and/or lungs.

Xarelto belongs to a group of medicines called antithrombotic agents. It works by blocking a blood clotting factor (factor Xa) and thus reducing the tendency of the blood to form clots.

Do not take Xarelto
- if you are allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6)
- if you are bleeding excessively
- if you have a disease or condition in an organ of the body that increases the risk of serious bleeding (e.g. stomach ulcer, injury or bleeding in the brain, recent surgery of the brain or eyes)
- if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open
- if you have a liver disease which leads to an increased risk of bleeding
- if you are pregnant or breast-feeding
Do not take Xarelto and tell your doctor if any of these apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xarelto.

Take special care with Xarelto
- if you have an increased risk of bleeding, as could be the case in situations such as:
▪ moderate or severe kidney disease, since your kidney function may affect the amount of medicine that works in your body ▪ if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open (see section “Other medicines and Xarelto”) ▪ bleeding disorders ▪ very high blood pressure, not controlled by medical treatment ▪ diseases of your stomach or bowel that might result in bleeding, e.g. inflammation of the bowels or stomach, or inflammation of the oesophagus (gullet), e.g. due to gastroesophageal reflux disease (disease where stomach acid goes upwards into the oesophagus) or tumours located in the stomach or bowels or genital tract or urinary tract ▪ a problem with the blood vessels in the back of your eyes (retinopathy) ▪ a lung disease where your bronchi are widened and filled with pus (bronchiectasis), or previous bleeding from your lung
- if you have a prosthetic heart valve
- if you know that you have a disease called antiphospholipid syndrome (a disorder of the immune system that causes an increased risk of blood clots), tell your doctor who will decide if the treatment may need to be changed.
- if your doctor determines that your blood pressure is unstable or another treatment or surgical procedure to remove the blood clot from your lungs is planned.

If any of the above apply to you, tell your doctor before you take Xarelto. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.

If you need to have an operation
- it is very important to take Xarelto before and after the operation exactly at the times you have been told by your doctor.
- If your operation involves a catheter or injection into your spinal column (e.g. for epidural or spinal anaesthesia or pain reduction):
▪ it is very important to take Xarelto exactly at the times you have been told by your doctor ▪ tell your doctor immediately if you get numbness or weakness of your legs or problems with your bowel or bladder after the end of anaesthesia, because urgent care is necessary.

Children and adolescents
Xarelto 10 mg tablets are not recommended for people under 18 years of age. There is not enough information on their use in children and adolescents.

Other medicines and Xarelto
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

- If you are taking
▪ some medicines for fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are only applied to the skin ▪ ketoconazole tablets (used to treat Cushing’s syndrome - when the body produces an excess of cortisol) ▪ some medicines for bacterial infections (e.g. clarithromycin, erythromycin) ▪ some anti-viral medicines for HIV / AIDS (e.g. ritonavir) ▪ other medicines to reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists such as warfarin and acenocoumarol) ▪ anti-inflammatory and pain relieving medicines (e.g. naproxen or acetylsalicylic acid) ▪ dronedarone, a medicine to treat abnormal heart beat ▪ some medicines to treat depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs))

If any of the above apply to you, tell your doctor before taking Xarelto, because the effect of Xarelto may be increased. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.
If your doctor thinks that you are at increased risk of developing stomach or bowel ulcers, he may also use a preventative ulcer treatment.

- If you are taking
▪ some medicines for treatment of epilepsy (phenytoin, carbamazepine, phenobarbital) ▪ St John’s Wort (Hypericum perforatum), a herbal product used for depression ▪ rifampicin, an antibiotic

If any of the above apply to you, tell your doctor before taking Xarelto, because the effect of Xarelto may be reduced. Your doctor will decide, if you should be treated with Xarelto and if you should be kept under closer observation.

Pregnancy and breast-feeding
Do not take Xarelto if you are pregnant or breast-feeding. If there is a chance that you could become pregnant, use a reliable contraceptive while you are taking Xarelto. If you become pregnant while you are taking this medicine, tell your doctor immediately, who will decide how you should be treated.

Driving and using machines
Xarelto may cause dizziness (common side effect) or fainting (uncommon side effect) (see section 4 ”Possible side effects”). You should not drive, ride a bicycle or use any tools or machines if you are affected by these symptoms.

Xarelto contains lactose and sodium
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium- free”.

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

How much to take
- To prevent blood clots in the veins after a hip or knee replacement operation
The recommended dose is one tablet Xarelto 10 mg once a day.

• To treat blood clots in the veins of your legs and blood clots in the blood vessels of your lungs, and for preventing blood clots from re-occurring

After at least 6 months blood clot treatment, the recommended dose is either one 10 mg tablet once a day or one 20 mg tablet once a day. Your doctor has prescribed you Xarelto 10 mg once a day.

Swallow the tablet preferably with water.
Xarelto can be taken with or without food.

If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take Xarelto. The tablet may be crushed and mixed with water or apple puree immediately before you take it.
If necessary, your doctor may also give you the crushed Xarelto tablet through a stomach tube.

When to take Xarelto
Take the tablet every day until your doctor tells you to stop.
Try to take the tablet at the same time every day to help you to remember it.
Your doctor will decide how long you must continue treatment.

To prevent blood clots in the veins after a hip or knee replacement operation:
Take the first tablet 6 - 10 hours after your operation.
If you have had a major hip operation you will usually take the tablets for 5 weeks.
If you have had a major knee operation you will usually take the tablets for 2 weeks.

If you take more Xarelto than you should
Contact your doctor immediately if you have taken too many Xarelto tablets. Taking too much Xarelto increases the risk of bleeding.

If you forget to take Xarelto
If you have missed a dose, take it as soon as you remember. Take the next tablet on the following day and then carry on taking a tablet once a day as normal.
Do not take a double dose to make up for a forgotten tablet.

If you stop taking Xarelto
Do not stop taking Xarelto without talking to your doctor first, because Xarelto prevents the development of a serious condition.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

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

Like other similar medicines to reduce the formation of blood clots, Xarelto may cause bleeding which may potentially be life threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). In some cases the bleeding may not be obvious.

Tell your doctor immediately if you experience any of the following side effects:
- Signs of bleeding
- bleeding into the brain or inside the skull (symptoms can include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness.
A serious medical emergency. Seek medical attention immediately!)
- long or excessive bleeding
- exceptional weakness, tiredness, paleness, dizziness, headache, unexplained swelling, breathlessness, chest pain or angina pectoris

Your doctor may decide to keep you under closer observation or change the treatment.

- Signs of severe skin reactions
- spreading intense skin rash, blisters or mucosal lesions, e.g. in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
- a drug reaction that causes rash, fever, inflammation of internal organs, blood abnormalities and systemic illness (DRESS syndrome).
The frequency of these side effects is very rare (up to 1 in 10,000 people).

- Signs of severe allergic reactions
- swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives and breathing difficulties; sudden drop in blood pressure.
The frequencies of severe allergic reactions are very rare (anaphylactic reactions, including anaphylactic shock; may affect up to 1 in 10,000 people) and uncommon (angioedema and allergic oedema; may affect up to 1 in 100 people).

Overall list of possible side effects
Common (may affect up to 1 in 10 people)
- reduction in red blood cells which can make the skin pale and cause weakness or breathlessness
- bleeding in the stomach or bowel, urogenital bleeding (including blood in the urine and heavy menstrual bleeding), nose bleed, bleeding in the gum
- bleeding into the eye (including bleeding from the whites of the eyes)
- bleeding into tissue or a cavity of the body (haematoma, bruising)
- coughing up blood
- bleeding from the skin or under the skin
- bleeding following an operation
- oozing of blood or fluid from surgical wound
- swelling in the limbs
- pain in the limbs
- impaired function of the kidneys (may be seen in tests performed by your doctor)
- fever
- stomach ache, indigestion, feeling or being sick, constipation, diarrhoea
- low blood pressure (symptoms may be feeling dizzy or fainting when standing up)
- decreased general strength and energy (weakness, tiredness), headache, dizziness
- rash, itchy skin
- blood tests may show an increase in some liver enzymes

Uncommon (may affect up to 1 in 100 people)
- bleeding into the brain or inside the skull (see above, signs of bleeding)
- bleeding into a joint causing pain and swelling
- thrombocytopenia (low number of platelets, which are cells that help blood to clot)
- allergic reactions, including allergic skin reactions
- impaired function of the liver (may be seen in tests performed by your doctor)
- blood tests may show an increase in bilirubin, some pancreatic or liver enzymes or in the number of platelets
- fainting
- feeling unwell
- faster heartbeat
- dry mouth
- hives

Rare (may affect up to 1 in 1,000 people)
- bleeding into a muscle
- cholestasis (decreased bile flow), hepatitis incl. hepatocellular injury (inflamed liver incl. liver injury)
- yellowing of the skin and eye (jaundice)
- localised swelling
- collection of blood (haematoma) in the groin as a complication of the cardiac procedure where a catheter is inserted in your leg artery (pseudoaneurysm)

Very rare (may affect up to 1 in 10,000 people)
- accumulation of eosinophils, a type of white granulocytic blood cells that cause inflammation in the lung (eosinophilic pneumonia)

Not known (frequency cannot be estimated from the available data)
- kidney failure after a severe bleeding
- bleeding in the kidney sometimes with presence of blood in urine leading to inability of the kidneys to work properly (anticoagulant-related nephropathy)
- increased pressure within muscles of the legs or arms after a bleeding, which leads to pain, swelling, altered sensation, numbness or paralysis (compartment syndrome after a bleeding)

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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 and on each blister or bottle after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Xarelto contains
- The active substance is rivaroxaban. Each tablet contains 10 mg of rivaroxaban.
- The other ingredients are:
Tablet core: microcrystalline cellulose, croscarmellose sodium, lactose monohydrate, hypromellose (2910), sodium laurilsulfate, magnesium stearate. See section 2 “Xarelto contains lactose and sodium”.
Tablet film coat: macrogol (3350), hypromellose (2910), titanium dioxide (E 171), iron oxide red (E 172).

What Xarelto looks like and contents of the pack
Xarelto 10 mg film-coated tablets are light red, round, biconvex and marked with the BAYER-cross on one side and “10” and a triangle on the other side.
They come
- in blisters in cartons of 5, 10, 14, 28, 30 or 98 film-coated tablets or
- in unit dose blisters in cartons of 10 x 1 or 100 x 1 or
- in multipacks comprising 10 cartons, each containing 10 x 1 film-coated tablets or
- in bottles of 100 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Bayer AG
51368 Leverkusen
Germany

Manufacturer

The manufacturer can be identified by the batch number printed on the side flap of the carton and on each blister or bottle:

- If the first and second characters are BX, the manufacturer is
Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany

- If the first and second characters are IT, the manufacturer is
Bayer HealthCare Manufacturing Srl.
Via delle Groane, 126
20024 Garbagnate Milanese
Italy

- If the first and second characters are BT, the manufacturer is
Bayer Bitterfeld GmbH
Ortsteil Greppin, Salegaster Chaussee 1
06803 Bitterfeld-Wolfen
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België / Belgique / Belgien
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Lietuva
UAB Bayer
Tel: +370-5-233 68 68

България
Байер България ЕООД
Тел: +359-(0)2-424 72 80

Luxembourg / Luxemburg
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Česká republika
Bayer s.r.o.
Tel: +420-266 101 111

Magyarország
Bayer Hungária KFT
Tel: +36-1-487 4100

Danmark
Bayer A/S
Tlf: +45-45 235 000

Malta
Alfred Gera and Sons Ltd.
Tel: +356-21 44 62 05

Deutschland
Bayer Vital GmbH
Tel: +49-(0)214-30 513 48

Nederland
Bayer B.V.
Tel: +31-23-799 1000

Eesti
Bayer OÜ
Tel: +372-655 85 65

Norge
Bayer AS
Tlf: +47-23 13 05 00

Ελλάδα
Bayer Ελλάς ΑΒΕΕ
Τηλ: +30-210-618 75 00

Österreich
Bayer Austria Ges. m. b. H.
Tel: +43-(0)1-711 460

España
Bayer Hispania S.L.
Tel: +34-93-495 65 00

Polska
Bayer Sp. z o.o.
Tel: +48-22-572 35 00

France
Bayer HealthCare
Tél (N° vert): +33-(0)800 87 54 54

Portugal
Bayer Portugal, Lda.
Tel: +351-21-416 42 00

Hrvatska
Bayer d.o.o.
Tel: + 385-(0)1-6599 900

România
SC Bayer SRL
Tel: +40-(0)21-529 59 00

Ireland
Bayer Limited
Tel: +353 1 216 3300

Slovenija
Bayer d. o. o.
Tel: +386-(0)1-58 14 400

Ísland
Icepharma hf.
Sími: +354-540 80 00

Slovenská republika
Bayer, spol. s r.o.
Tel: +421-(0)2-59 21 31 11

Italia
Bayer S.p.A.
Tel: +39-02-3978 1

Suomi/Finland
Bayer Oy
Puh/Tel: +358-(0)20-78521

Κύπρος
NOVAGEM Limited
Τηλ: +357-22-48 38 58

Sverige
Bayer AB
Tel: +46-(0)8-580 223 00

Latvija
SIA Bayer
Tel: +371-67 84 55 63

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency website:
http://www.ema.europa.eu.

Xarelto contains the active substance rivaroxaban.
Xarelto is used in adults to:
- prevent blood clots in brain (stroke) and other blood vessels in your body if you have a form of irregular heart rhythm called non-valvular atrial fibrillation.
- treat blood clots in the veins of your legs (deep vein thrombosis) and in the blood vessels of your lungs (pulmonary embolism), and to prevent blood clots from re-occurring in the blood vessels of your legs and/or lungs.
Xarelto is used in children and adolescents below 18 years and with a body weight of 30 kg or more to:
- treat blood clots and prevent re-occurrence of blood clots in the veins or in the blood vessels of the lungs, following initial treatment of at least 5 days with injectable medicines used to treat blood clots.

Xarelto belongs to a group of medicines called antithrombotic agents. It works by blocking a blood clotting factor (factor Xa) and thus reducing the tendency of the blood to form clots.

Do not take Xarelto
- if you are allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6)
- if you are bleeding excessively
- if you have a disease or condition in an organ of the body that increases the risk of serious bleeding (e.g. stomach ulcer, injury or bleeding in the brain, recent surgery of the brain or eyes)
- if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open.
- if you have a liver disease which leads to an increased risk of bleeding
- if you are pregnant or are breast-feeding
Do not take Xarelto and tell your doctor if any of these apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xarelto.

Take special care with Xarelto
- if you have an increased risk of bleeding, as could be the case in situations such as:
▪ severe kidney disease for adults, and moderate or severe kidney disease for children and adolescents, since your kidney function may affect the amount of medicine that works in your body ▪ if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open (see section “Other medicines and Xarelto”) ▪ bleeding disorders ▪ very high blood pressure, not controlled by medical treatment ▪ diseases of your stomach or bowel that might result in bleeding, e.g. inflammation of the bowels or stomach, or inflammation of the oesophagus (gullet), e.g. due to gastroesophageal reflux disease (disease where stomach acid goes upwards into the oesophagus) or tumours located in the stomach or bowels or genital tract or urinary tract ▪ a problem with the blood vessels in the back of your eyes (retinopathy) ▪ a lung disease where your bronchi are widened and filled with pus (bronchiectasis), or previous bleeding from your lung
- if you have a prosthetic heart valve
- if you know that you have a disease called antiphospholipid syndrome (a disorder of the immune system that causes an increased risk of blood clots), tell your doctor who will decide if the treatment may need to be changed.
- if your doctor determines that your blood pressure is unstable or another treatment or surgical procedure to remove the blood clot from your lungs is planned

If any of the above apply to you, tell your doctor before you take Xarelto. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.

If you need to have an operation
- it is very important to take Xarelto before and after the operation exactly at the times you have been told by your doctor.
- If your operation involves a catheter or injection into your spinal column (e.g. for epidural or spinal anaesthesia or pain reduction):
▪ it is very important to take Xarelto before and after the injection or removal of the catheter exactly at the times you have been told by your doctor ▪ tell your doctor immediately if you get numbness or weakness of your legs or problems with your bowel or bladder after the end of anaesthesia, because urgent care is necessary.

Children and adolescents
Xarelto tablets are not recommended for children with a body weight below 30 kg.
There is not enough information on the use of Xarelto in children and adolescents in the adult indications.

Other medicines and Xarelto
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
- If you are taking
▪ some medicines for fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are only applied to the skin ▪ ketoconazole tablets (used to treat Cushing’s syndrome - when the body produces an excess of cortisol) ▪ some medicines for bacterial infections (e.g. clarithromycin, erythromycin) ▪ some anti-viral medicines for HIV / AIDS (e.g. ritonavir) ▪ other medicines to reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists such as warfarin and acenocoumarol) ▪ anti-inflammatory and pain relieving medicines (e.g. naproxen or acetylsalicylic acid) ▪ dronedarone, a medicine to treat abnormal heart beat ▪ some medicines to treat depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs))

If any of the above apply to you, tell your doctor before taking Xarelto, because the effect of Xarelto may be increased. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.
If your doctor thinks that you are at increased risk of developing stomach or bowel ulcers, he may also use a preventative ulcer treatment.

- If you are taking
▪ some medicines for treatment of epilepsy (phenytoin, carbamazepine, phenobarbital) ▪ St John’s Wort (Hypericum perforatum), a herbal product used for depression ▪ rifampicin, an antibiotic

If any of the above apply to you, tell your doctor before taking Xarelto, because the effect of Xarelto may be reduced. Your doctor will decide, if you should be treated with Xarelto and if you should be kept under closer observation.

Pregnancy and breast-feeding
Do not take Xarelto if you are pregnant or breast-feeding. If there is a chance that you could become pregnant, use a reliable contraceptive while you are taking Xarelto. If you become pregnant while you are taking this medicine, tell your doctor immediately, who will decide how you should be treated.

Driving and using machines
Xarelto may cause dizziness (common side effect) or fainting (uncommon side effect) (see section 4, ”Possible side effects”). You should not drive, ride a bicycle or use any tools or machines if you are affected by these symptoms.

Xarelto contains lactose and sodium
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium- free”.

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

You must take Xarelto together with a meal.
Swallow the tablet(s) preferably with water.

If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take Xarelto. The tablet may be crushed and mixed with water or apple puree immediately before you take it. This mixture should be immediately followed by food.
If necessary, your doctor may also give you the crushed Xarelto tablet through a stomach tube.

How much to take
- Adults
▪
To prevent blood clots in brain (stroke) and other blood vessels in your body
The recommended dose is one tablet Xarelto 20 mg once a day.
If you have kidney problems, the dose may be reduced to one tablet Xarelto 15 mg once a day.

If you need a procedure to treat blocked blood vessels in your heart (called a percutaneous coronary intervention - PCI with an insertion of a stent), there is limited evidence to reduce the dose to one tablet Xarelto 15 mg once a day (or to one tablet Xarelto 10 mg once a day in case your kidneys are not working properly) in addition to an antiplatelet medicine such as clopidogrel.

▪
To treat blood clots in the veins of your legs and blood clots in the blood vessels of your lungs, and for preventing blood clots from re-occurring The recommended dose is one tablet Xarelto 15 mg twice a day for the first 3 weeks. For treatment after 3 weeks, the recommended dose is one tablet Xarelto 20 mg once a day.
After at least 6 months blood clot treatment your doctor may decide to continue treatment with either one 10 mg tablet once a day or one 20 mg tablet once a day.
If you have kidney problems and take one tablet Xarelto 20 mg once a day, your doctor may decide to reduce the dose for the treatment after 3 weeks to one tablet Xarelto 15 mg once a day if the risk for bleeding is greater than the risk for having another blood clot.

- Children and adolescents
The dose of Xarelto depends on the body weight, and will be calculated by the doctor.
▪
The recommended dose for children and adolescents with a body weight between 30 kg and less than 50 kg is one Xarelto 15 mg tablet once a day.
▪
The recommended dose for children and adolescents with a body weight of 50 kg or more is one Xarelto 20 mg tablet once a day.
Take each Xarelto dose with a drink (e.g. water or juice) during a meal. Take the tablets every day at approximately the same time. Consider setting an alarm to remind you.
For parents or caregivers: please observe the child to ensure the full dose is taken.

As the Xarelto dose is based on body weight it is important to keep scheduled doctor’s visits because the dose may need to be adjusted as the weight changes.
Never adjust the dose of Xarelto by yourself. The doctor will adjust the dose if necessary.

Do not split the tablet in an attempt to provide a fraction of a tablet dose. If a lower dose is required please use the alternative presentation of Xarelto granules for oral suspension.
For children and adolescents who are unable to swallow tablets whole, please use Xarelto granules for oral suspension.
If the oral suspension is not available, you may crush the Xarelto tablet and mix with water or apple puree immediately before taking. Take some food after taking this mixture. If necessary, your doctor may also give the crushed Xarelto tablet through a stomach tube.

If you spit up the dose or vomit
- less than 30 minutes after you have taken Xarelto, take a new dose.
- more than 30 minutes after you have taken Xarelto, do not take a new dose. In this case, take the next Xarelto dose at the usual time.

Contact the doctor if you repeatedly spit up the dose or vomit after taking Xarelto.

When to take Xarelto
Take the tablet(s) every day until your doctor tells you to stop.
Try to take the tablet(s) at the same time every day to help you to remember it.
Your doctor will decide how long you must continue treatment.

To prevent blood clots in the brain (stroke) and other blood vessels in your body:
If your heart beat needs to be restored to normal by a procedure called cardioversion, take Xarelto at the times your doctor tells you.

If you forget to take Xarelto
- Adults, children and adolescents:
If you are taking one 20 mg tablet or one 15 mg tablet once a day and have missed a dose, take it as soon as you remember. Do not take more than one tablet in a single day to make up for a forgotten dose. Take the next tablet on the following day and then carry on taking one tablet once a day.

- Adults:
If you are taking one 15 mg tablet twice a day and have missed a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in a single day. If you forget to take a dose you can take two 15 mg tablets at the same time to get a total of two tablets (30 mg) on one day.
On the following day you should carry on taking one 15 mg tablet twice a day.

If you take more Xarelto than you should
Contact your doctor immediately if you have taken too many Xarelto tablets. Taking too much Xarelto increases the risk of bleeding.

If you stop taking Xarelto
Do not stop taking Xarelto without talking to your doctor first, because Xarelto treats and prevents serious conditions.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

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

Like other similar medicines to reduce the formation of blood clots, Xarelto may cause bleeding which may potentially be life threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). In some cases the bleeding may not be obvious.

Tell your doctor immediately if you or the child experience any of the following side effects:
- Signs of bleeding
- bleeding into the brain or inside the skull (symptoms can include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness.
A serious medical emergency. Seek medical attention immediately!)
- long or excessive bleeding
- exceptional weakness, tiredness, paleness, dizziness, headache, unexplained swelling, breathlessness, chest pain or angina pectoris

Your doctor may decide to keep you under closer observation or change the treatment.

- Signs of severe skin reactions
- spreading intense skin rash, blisters or mucosal lesions, e.g. in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
- a drug reaction that causes rash, fever, inflammation of internal organs, blood abnormalities and systemic illness (DRESS syndrome).
The frequency of these side effects is very rare (up to 1 in 10,000 people).

- Signs of severe allergic reactions
- swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives and breathing difficulties; sudden drop in blood pressure.
The frequencies of severe allergic reactions are very rare (anaphylactic reactions, including anaphylactic shock; may affect up to 1 in 10,000 people) and uncommon (angioedema and allergic oedema; may affect up to 1 in 100 people).

Overall list of possible side effects found in adults, children and adolescents
Common (may affect up to 1 in 10 people)
- reduction in red blood cells which can make the skin pale and cause weakness or breathlessness
- bleeding in the stomach or bowel, urogenital bleeding (including blood in the urine and heavy menstrual bleeding), nose bleed, bleeding in the gum
- bleeding into the eye (including bleeding from the whites of the eyes)
- bleeding into tissue or a cavity of the body (haematoma, bruising)
- coughing up blood
- bleeding from the skin or under the skin
- bleeding following an operation
- oozing of blood or fluid from surgical wound
- swelling in the limbs
- pain in the limbs
- impaired function of the kidneys (may be seen in tests performed by your doctor)
- fever
- stomach ache, indigestion, feeling or being sick, constipation, diarrhoea
- low blood pressure (symptoms may be feeling dizzy or fainting when standing up)
- decreased general strength and energy (weakness, tiredness), headache, dizziness
- rash, itchy skin
- blood tests may show an increase in some liver enzymes

Uncommon (may affect up to 1 in 100 people)
- bleeding into the brain or inside the skull (see above, signs of bleeding)
- bleeding into a joint causing pain and swelling
- thrombocytopenia (low number of platelets, which are cells that help blood to clot)
- allergic reactions, including allergic skin reactions
- impaired function of the liver (may be seen in tests performed by your doctor)
- blood tests may show an increase in bilirubin, some pancreatic or liver enzymes or in the number of platelets
- fainting
- feeling unwell
- faster heartbeat
- dry mouth
- hives

Rare (may affect up to 1 in 1,000 people)
- bleeding into a muscle
- cholestasis (decreased bile flow), hepatitis incl. hepatocellular injury (inflamed liver incl. liver injury)
- yellowing of the skin and eye (jaundice)
- localised swelling
- collection of blood (haematoma) in the groin as a complication of the cardiac procedure where a catheter is inserted in your leg artery (pseudoaneurysm)

Very rare (may affect up to 1 in 10,000 people)
- accumulation of eosinophils, a type of white granulocytic blood cells that cause inflammation in the lung (eosinophilic pneumonia)

Not known (frequency cannot be estimated from the available data)
- kidney failure after a severe bleeding
- bleeding in the kidney sometimes with presence of blood in urine leading to inability of the kidneys to work properly (anticoagulant-related nephropathy)
- increased pressure within muscles of the legs or arms after a bleeding, which leads to pain, swelling, altered sensation, numbness or paralysis (compartment syndrome after a bleeding)

Side effects in children and adolescents
In general, the side effects observed in children and adolescents treated with Xarelto were similar in type to those observed in adults and were primarily mild to moderate in severity.

Side effects that were observed more often in children and adolescents:

Very common (may affect more than 1 in 10 people)
- headache
- fever
- nose bleeding
- vomiting
Common (may affect up to 1 in 10 people)
- raised heartbeat
- blood tests may show an increase in bilirubin (bile pigment)
- thrombocytopenia (low number of platelets which are cells that help blood to clot)
- heavy menstrual bleeding
Uncommon (may affect up to 1 in 100 people)
- blood tests may show an increase in a subcategory of bilirubin (direct bilirubin, bile pigment)

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system

listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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 and on each blister or bottle after EXP.
The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Xarelto contains
- The active substance is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban.
- The other ingredients are:
Tablet core: microcrystalline cellulose, croscarmellose sodium, lactose monohydrate, hypromellose (2910), sodium laurilsulfate, magnesium stearate. See section 2 “Xarelto contains lactose and sodium” Tablet film coat: macrogol (3350), hypromellose (2910), titanium dioxide (E 171), iron oxide red (E 172).

What Xarelto looks like and contents of the pack
Xarelto 15 mg film-coated tablets are red, round, biconvex and marked with the BAYER-cross on one side and “15” and a triangle on the other side.
They come
- in blisters in cartons of 10, 14, 28, 42 or 98 film-coated tablets or
- in unit dose blisters in cartons of 10 x 1 or 100 x 1 or
- in multipacks comprising 10 cartons, each containing 10 x 1 film-coated tablets or
- in bottles of 100 film-coated tablets.

Xarelto 20 mg film-coated tablets are brown-red, round, biconvex and marked with the BAYER-cross on one side and “20” and a triangle on the other.
They come
- in blisters in cartons of 10, 14, 28 or 98 film-coated tablets or
- in unit dose blisters in cartons of 10 x 1 or 100 x 1 or
- in multipacks comprising 10 cartons, each containing 10 x 1 film-coated tablets or
- in bottles of 100 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Bayer AG
51368 Leverkusen
Germany

Manufacturer

The manufacturer can be identified by the batch number printed on the side flap of the carton and on each blister or bottle:

- If the first and second characters are BX, the manufacturer is
Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany

- If the first and second characters are IT, the manufacturer is
Bayer HealthCare Manufacturing Srl.
Via delle Groane, 126
20024 Garbagnate Milanese
Italy

- If the first and second characters are BT, the manufacturer is
Bayer Bitterfeld GmbH
Ortsteil Greppin, Salegaster Chaussee 1
06803 Bitterfeld-Wolfen
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België / Belgique / Belgien
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Lietuva
UAB Bayer
Tel: +370-5-233 68 68

България
Байер България ЕООД
Тел: +359-(0)2-424 72 80

Luxembourg / Luxemburg
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Česká republika
Bayer s.r.o.
Tel: +420-266 101 111

Magyarország
Bayer Hungária KFT
Tel: +36-1-487 4100

Danmark
Bayer A/S
Tlf: +45-45 235 000

Malta
Alfred Gera and Sons Ltd.
Tel: +356-21 44 62 05

Deutschland
Bayer Vital GmbH
Tel: +49-(0)214-30 513 48

Nederland
Bayer B.V.
Tel: +31-23-799 1000

Eesti
Bayer OÜ
Tel: +372-655 85 65

Norge
Bayer AS
Tlf: +47-23 13 05 00

Ελλάδα
Bayer Ελλάς ΑΒΕΕ
Τηλ: +30-210-618 75 00

Österreich
Bayer Austria Ges. m. b. H.
Tel: +43-(0)1-711 460

España
Bayer Hispania S.L.
Tel: +34-93-495 65 00

Polska
Bayer Sp. z o.o.
Tel: +48-22-572 35 00

France
Bayer HealthCare
Tél (N° vert): +33-(0)800 87 54 54

Portugal
Bayer Portugal, Lda.
Tel: +351-21-416 42 00

Hrvatska
Bayer d.o.o.
Tel: + 385-(0)1-6599 900

România
SC Bayer SRL
Tel: +40-(0)21-529 59 00

Ireland
Bayer Limited
Tel: +353 1 216 3300

Slovenija
Bayer d. o. o.
Tel: +386-(0)1-58 14 400

Ísland
Icepharma hf.
Sími: +354-540 80 00

Slovenská republika
Bayer, spol. s r.o.
Tel: +421-(0)2-59 21 31 11

Italia
Bayer S.p.A.
Tel: +39-02-3978 1

Suomi/Finland
Bayer Oy
Puh/Tel: +358-(0)20-78521

Κύπρος
NOVAGEM Limited
Τηλ: +357-22-48 38 58

Sverige
Bayer AB
Tel: +46-(0)8-580 223 00

Latvija
SIA Bayer
Tel: +371-67 84 55 63

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency website:
http://www.ema.europa.eu.

Xarelto contains the active substance rivaroxaban and is used in adults to:
- treat blood clots in the veins of your legs (deep vein thrombosis) and in the blood vessels of your lungs (pulmonary embolism), and to prevent blood clots from re-occurring in the blood vessels of your legs and/or lungs.

Xarelto belongs to a group of medicines called antithrombotic agents. It works by blocking a blood clotting factor (factor Xa) and thus reducing the tendency of the blood to form clots.

Do not take Xarelto
- if you are allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6)
- if you are bleeding excessively
- if you have a disease or condition in an organ of the body that increases the risk of serious bleeding (e.g. stomach ulcer, injury or bleeding in the brain, recent surgery of the brain or eyes)
- if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open.
- if you have a liver disease which leads to an increased risk of bleeding
- if you are pregnant or breast-feeding
Do not take Xarelto and tell your doctor if any of these apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xarelto.

Take special care with Xarelto
- if you have an increased risk of bleeding, as could be the case in situations such as:
▪ severe kidney disease, since your kidney function may affect the amount of medicine that works in your body ▪ if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open (see section “Other medicines and Xarelto”) ▪ bleeding disorders ▪ very high blood pressure, not controlled by medical treatment ▪ diseases of your stomach or bowel that might result in bleeding, e.g. inflammation of the bowels or stomach, or inflammation of the oesophagus (gullet), e.g. due to gastroesophageal reflux disease (disease where stomach acid goes upwards into the oesophagus) or tumours located in the stomach or bowels or genital tract or urinary tract ▪ a problem with the blood vessels in the back of your eyes (retinopathy) ▪ a lung disease where your bronchi are widened and filled with pus (bronchiectasis), or previous bleeding from your lung
- if you have a prosthetic heart valve
- if you know that you have a disease called antiphospholipid syndrome (a disorder of the immune system that causes an increased risk of blood clots), tell your doctor who will decide if the treatment may need to be changed.
- if your doctor determines that your blood pressure is unstable or another treatment or surgical procedure to remove the blood clot from your lungs is planned

If any of the above apply to you, tell your doctor before you take Xarelto. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.

If you need to have an operation
- it is very important to take Xarelto before and after the operation exactly at the times you have been told by your doctor.
- If your operation involves a catheter or injection into your spinal column (e.g. for epidural or spinal anaesthesia or pain reduction):
▪ it is very important to take Xarelto before and after the injection or removal of the catheter exactly at the times you have been told by your doctor ▪ tell your doctor immediately if you get numbness or weakness of your legs or problems with your bowel or bladder after the end of anaesthesia, because urgent care is necessary.

Children and adolescents
Xarelto treatment initiation pack is not recommended for people under 18 years of age as it is specifically designed for initiation of treatment in adult patients and is not appropriate for use in children and adolescents.

Other medicines and Xarelto
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

- If you are taking
▪ some medicines for fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are only applied to the skin ▪ ketoconazole tablets (used to treat Cushing’s syndrome - when the body produces an excess of cortisol) ▪ some medicines for bacterial infections (e.g. clarithromycin, erythromycin) ▪ some anti-viral medicines for HIV / AIDS (e.g. ritonavir) ▪ other medicines to reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists such as warfarin and acenocoumarol) ▪ anti-inflammatory and pain relieving medicines (e.g. naproxen or acetylsalicylic acid) ▪ dronedarone, a medicine to treat abnormal heart beat ▪ some medicines to treat depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs)) If any of the above apply to you, tell your doctor before taking Xarelto, because the effect of Xarelto may be increased. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.
If your doctor thinks that you are at increased risk of developing stomach or bowel ulcers, he may also use a preventative ulcer treatment.

- If you are taking
▪ some medicines for treatment of epilepsy (phenytoin, carbamazepine, phenobarbital) ▪ St John’s Wort (Hypericum perforatum), a herbal product used for depression ▪ rifampicin, an antibiotic

If any of the above apply to you, tell your doctor before taking Xarelto, because the effect of Xarelto may be reduced. Your doctor will decide, if you should be treated with Xarelto and if you should be kept under closer observation.

Pregnancy and breast-feeding
Do not take Xarelto if you are pregnant or breast-feeding. If there is a chance that you could become pregnant, use a reliable contraceptive while you are taking Xarelto. If you become pregnant while you are taking this medicine, tell your doctor immediately, who will decide how you should be treated.

Driving and using machines
Xarelto may cause dizziness (common side effect) or fainting (uncommon side effect) (see section 4, ”Possible side effects”). You should not drive, ride a bicycle or use any tools or machines if you are affected by these symptoms.

Xarelto contains lactose and sodium
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium- free”.

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

You must take Xarelto together with a meal.
Swallow the tablet(s) preferably with water.

If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take Xarelto. The tablet may be crushed and mixed with water or apple puree immediately before you take it. This mixture should be immediately followed by food.
If necessary, your doctor may also give you the crushed Xarelto tablet through a stomach tube.

How much to take
The recommended dose is one tablet Xarelto 15 mg twice a day for the first 3 weeks. For treatment after 3 weeks, the recommended dose is one tablet Xarelto 20 mg once a day.
This Xarelto 15 mg and 20 mg treatment initiation pack is only for the first 4 weeks of treatment.
Upon completion of this pack, treatment will continue on Xarelto 20 mg once daily as your doctor has told you.
If you have kidney problems, your doctor may decide to reduce the dose for the treatment after 3 weeks to one tablet Xarelto 15 mg once a day if the risk for bleeding is greater than the risk for having another blood clot.

When to take Xarelto
Take the tablet(s) every day until your doctor tells you to stop.
Try to take the tablet(s) at the same time every day to help you to remember it.
Your doctor will decide how long you must continue treatment.

If you take more Xarelto than you should
Contact your doctor immediately if you have taken too many Xarelto tablets. Taking too much Xarelto increases the risk of bleeding.

If you forget to take Xarelto
- If you are taking one 15 mg tablet twice a day and have missed a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in a single day. If you forget to take a dose you can take two 15 mg tablets at the same time to get a total of two tablets (30 mg) on one day.
On the following day you should carry on taking one 15 mg tablet twice a day.

- If you are taking one 20 mg tablet once a day and have missed a dose, take it as soon as you remember. Do not take more than one tablet in a single day to make up for a forgotten dose.
Take the next tablet on the following day and then carry on taking one tablet once a day.

If you stop taking Xarelto
Do not stop taking Xarelto without talking to your doctor first, because Xarelto treats and prevents serious conditions.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

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

Like other similar medicines to reduce the formation of blood clots, Xarelto may cause bleeding which may potentially be life threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). In some cases the bleeding may not be obvious.

Tell your doctor immediately if you experience any of the following side effects:
- Signs of bleeding
- bleeding into the brain or inside the skull (symptoms can include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness.
A serious medical emergency. Seek medical attention immediately!)
- long or excessive bleeding
- exceptional weakness, tiredness, paleness, dizziness, headache, unexplained swelling, breathlessness, chest pain or angina pectoris

Your doctor may decide to keep you under closer observation or change the treatment.

- Signs of severe skin reactions
- spreading intense skin rash, blisters or mucosal lesions, e.g. in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
- a drug reaction that causes rash, fever, inflammation of internal organs, blood abnormalities and systemic illness (DRESS syndrome).
The frequency of these side effects is very rare (up to 1 in 10,000 people).

- Signs of severe allergic reactions
- swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives and breathing difficulties; sudden drop in blood pressure.
The frequencies of severe allergic reactions are very rare (anaphylactic reactions, including anaphylactic shock; may affect up to 1 in 10,000 people) and uncommon (angioedema and allergic oedema; may affect up to 1 in 100 people).

Overall list of possible side effects

Common (may affect up to 1 in 10 people)
- reduction in red blood cells which can make the skin pale and cause weakness or breathlessness
- bleeding in the stomach or bowel, urogenital bleeding (including blood in the urine and heavy menstrual bleeding), nose bleed, bleeding in the gum
- bleeding into the eye (including bleeding from the whites of the eyes)
- bleeding into tissue or a cavity of the body (haematoma, bruising)
- coughing up blood
- bleeding from the skin or under the skin
- bleeding following an operation
- oozing of blood or fluid from surgical wound
- swelling in the limbs
- pain in the limbs
- impaired function of the kidneys (may be seen in tests performed by your doctor)
- fever
- stomach ache, indigestion, feeling or being sick, constipation, diarrhoea
- low blood pressure (symptoms may be feeling dizzy or fainting when standing up)
- decreased general strength and energy (weakness, tiredness), headache, dizziness
- rash, itchy skin
- blood tests may show an increase in some liver enzymes

Uncommon (may affect up to 1 in 100 people)
- bleeding into the brain or inside the skull (see above, signs of bleeding)
- bleeding into a joint causing pain and swelling
- thrombocytopenia (low number of platelets, which are cells that help blood to clot)
- allergic reactions, including allergic skin reactions
- impaired function of the liver (may be seen in tests performed by your doctor)
- blood tests may show an increase in bilirubin, some pancreatic or liver enzymes or in the number of platelets
- fainting
- feeling unwell
- faster heartbeat
- dry mouth
- hives

Rare (may affect up to 1 in 1,000 people)
- bleeding into a muscle
- cholestasis (decreased bile flow), hepatitis incl. hepatocellular injury (inflamed liver incl. liver injury)
- yellowing of the skin and eye (jaundice)
- localised swelling

• collection of blood (haematoma) in the groin as a complication of the cardiac procedure where a catheter is inserted in your leg artery (pseudoaneurysm)

Very rare (may affect up to 1 in 10,000 people)
- accumulation of eosinophils, a type of white granulocytic blood cells that cause inflammation in the lung (eosinophilic pneumonia)

Not known (frequency cannot be estimated from the available data)
- kidney failure after a severe bleeding
- bleeding in the kidney sometimes with presence of blood in urine leading to inability of the kidneys to work properly (anticoagulant-related nephropathy)
- increased pressure within muscles of the legs or arms after a bleeding, which leads to pain, swelling, altered sensation, numbness or paralysis (compartment syndrome after a bleeding)

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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 and on each wallet after EXP.
The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Xarelto contains
- The active substance is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban, respectively.
- The other ingredients are:
Tablet core: microcrystalline cellulose, croscarmellose sodium, lactose monohydrate, hypromellose (2910), sodium laurilsulfate, magnesium stearate. See section 2 “Xarelto contains lactose and sodium”. Tablet film coat: macrogol (3350), hypromellose (2910), titanium dioxide (E 171), iron oxide red (E 172).

What Xarelto looks like and contents of the pack
Xarelto 15 mg film-coated tablets are red, round, biconvex and marked with the BAYER-cross on one side and “15” and a triangle on the other side.
Xarelto 20 mg film-coated tablets are brown-red, round, biconvex and marked with the BAYER-cross on one side and “20” and a triangle on the other.
First 4 weeks treatment initiation pack: each pack of 49 film-coated tablets for the first 4 weeks of treatment contains:

42 film-coated tablets of 15 mg rivaroxaban and 7 film-coated tablets of 20 mg rivaroxaban in a wallet.

Marketing Authorisation Holder

Bayer AG
51368 Leverkusen
Germany

Manufacturer

The manufacturer can be identified by the batch number printed on the side flap of the carton and on each blister or bottle:

- If the first and second characters are BX, the manufacturer is
Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany

- If the first and second characters are IT, the manufacturer is
Bayer HealthCare Manufacturing Srl.
Via delle Groane, 126
20024 Garbagnate Milanese
Italy

- If the first and second characters are BT, the manufacturer is
Bayer Bitterfeld GmbH
Ortsteil Greppin, Salegaster Chaussee 1
06803 Bitterfeld-Wolfen
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België / Belgique / Belgien
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Lietuva
UAB Bayer
Tel: +370-5-233 68 68

България
Байер България ЕООД
Тел: +359-(0)2-424 72 80

Luxembourg / Luxemburg
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Česká republika
Bayer s.r.o.
Tel: +420-266 101 111

Magyarország
Bayer Hungária KFT
Tel: +36-1-487 4100

Danmark
Bayer A/S
Tlf: +45-45 235 000

Malta
Alfred Gera and Sons Ltd.
Tel: +356-21 44 62 05

Deutschland
Bayer Vital GmbH
Tel: +49-(0)214-30 513 48

Nederland
Bayer B.V.
Tel: +31-23-799 1000

Eesti
Bayer OÜ
Tel: +372-655 85 65

Norge
Bayer AS
Tlf: +47-23 13 05 00

Ελλάδα
Bayer Ελλάς ΑΒΕΕ
Τηλ: +30-210-618 75 00

Österreich
Bayer Austria Ges. m. b. H.
Tel: +43-(0)1-711 460

España
Bayer Hispania S.L.
Tel: +34-93-495 65 00

Polska
Bayer Sp. z o.o.
Tel: +48-22-572 35 00

France
Bayer HealthCare
Tél (N° vert): +33-(0)800 87 54 54

Portugal
Bayer Portugal, Lda.
Tel: +351-21-416 42 00

Hrvatska
Bayer d.o.o.
Tel: + 385-(0)1-6599 900

România
SC Bayer SRL
Tel: +40-(0)21-529 59 00

Ireland
Bayer Limited
Tel: +353 1 216 3300

Slovenija
Bayer d. o. o.
Tel: +386-(0)1-58 14 400

Ísland
Icepharma hf.
Sími: +354-540 80 00

Slovenská republika
Bayer, spol. s r.o.
Tel: +421-(0)2-59 21 31 11

Italia
Bayer S.p.A.
Tel: +39-02-3978 1

Suomi/Finland
Bayer Oy
Puh/Tel: +358-(0)20-78521

Κύπρος
NOVAGEM Limited
Τηλ: +357-22-48 38 58

Sverige
Bayer AB
Tel: +46-(0)8-580 223 00

Latvija
SIA Bayer
Tel: +371-67 84 55 63

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency website:
http://www.ema.europa.eu.

Step 1.1: Preparation – Get ready

The preparation of the suspension is done once with every new package.
Before preparing the suspension:

a. Thoroughly wash your hands with soap and dry them afterwards.

b. Check the expiry date on the label provided on the box.
Do not use the medicine if the medicine has expired.

c. Obtain the following additional items:
▪
Container with at least 150 mL of water:
• Either fresh tap water or non-carbonated (still) mineral water
• Water should be at room temperature

▪
Tissue for soaking up any excess water

Step 1.2: Filling the required volume of water

Every time you start a new pack, use only the new materials contained in the new package.

a. Unpack the water syringe.

b. Dip the opening of the water syringe into the container with water.
c. Extract a volume of more than 100 mL.
To do this, pull the plunger rod towards you, and make sure that the opening of the water syringe stays below the water surface all the time. This will avoid air bubbles in the syringe.
d. Take the syringe out of the water.

e. Turn the water syringe in a way that the opening is facing upwards.

→ Any air bubbles will move to the top when holding the syringe upwards.

Tap it with your fingers to further move any air bubble to the top.

f. Push the plunger rod until the upper ring of the plunger reaches the 100 mL mark.
→ When pressing the plunger, water can come out of the tip of the water syringe. This waste water can be soaked up with a tissue.

Cautionary Information:
The upper ring of the black plunger must be precisely in line with the 100 mL mark to be able to achieve the correct concentration of the suspension.

Step 1.3: Adding water to the granules

a. If the granules in the bottle appear to be clumpy:
- Gently tap the bottle on your hand.
- Be careful since the bottle is made of glass.

b. Unscrew the child resistant cap of the bottle (push down and turn counterclockwise).

g. Continue to hold the water syringe with the opening facing upwards and check the water in the syringe carefully:
- for correct volume,
- for air bubbles.
Small air bubbles are uncritical, but big air bubbles are critical. See below for more explanation on what to do.

h. If the syringe is not loaded correctly or contains too much air:
- Empty the water syringe
- Repeat steps b. to h

c. Place the filled water syringe on the upper edge of the bottle opening

d. Hold the bottle firmly.
e. Press the plunger rod down slowly.

The full volume of water must be transferred to the bottle.
f. Dispose of the water syringe in household waste.

Step 1.4: Fitting the adapter and mixing the oral suspension

The adapter is used to fill the blue syringe with suspension.

a. Unpack the bottle adapter

b. Push the adapter completely into the neck of the bottle

c. Close the bottle tightly with the screw cap.

d. Shake the bottle gently for at least 60 seconds.
→ This is intended to provide a well-mixed suspension.

e. Check whether the suspension is thoroughly mixed:
- no clumps
- no deposit.

Cautionary Information:
To guarantee correct dose, the suspension must not contain any clumps or deposit.

f. If there are clumps or sediment repeat steps d. to f.

→ When no clumps or deposits are left, the suspension is ready for use.
Do not add more water to the bottle.
The suspension has a shelf life of 14 days at room temperature.

g. Write the date of expiry of the just prepared suspension on the label of the bottle.
Date of preparation + 14 days
The shown pictogram is only an example.

To prevent overdosing or underdosing an exact dose of suspension is required.
Before you take the first dose out of the bottle, the enclosed blue syringe must be set up in accordance with the dose prescribed by your child's doctor. This information can be found on the dedicated area of the box. If no information has been entered here check back with the child's doctor or pharmacist.
After setting the dose the same blue syringe can be used for all administrations from the bottle of suspension prepared in step 1.
Once the dose has been fixed on the blue syringe, it cannot be changed.

Step 2.1: Selecting a suitable blue syringe

Dosing devices with different capacities are included in this pack:

5 mL blue syringes for doses from 1 mL to 5 mL

10 mL blue syringes for doses from 5 mL to 10 mL

a. Select the suitable blue syringe based on the dose prescribed by your child's doctor.
The other blue syringes are not needed.
b. Unpack the blue syringe.
Note:
Do not remove the peelable label until you are prompted in the Instructions for Use.
The blue syringe features a red button to adjust the volume. This button is initially covered by a peelable label.
By pressing the red button the volume of the syringe is set, which can only be done once. Do not press the red button until the Instructions for Use tell you to do so.
Once the red button has been pressed, the volume can no longer be adjusted.

Step 2.2: Setting the required dose on new blue syringe
The blue syringe features a scale (mL).
The scale of the 5 mL blue syringe starts with 1 mL. The graduation marks are in increments of 0.2 mL.
The scale of the 10 mL blue syringe starts with 2 mL. The graduation marks are in increments of 0.5 mL.

a. Review the dose provided in the respective field on the outside of the box.
Note:
Use the 10 mL blue syringe for prescribed doses larger than
10 mL as follows:
Dose of 15 mL: 2 x 7.5 mL blue syringe
Dose of 20 mL: 2 x 10 mL blue syringe

b. If the information is not available:
Ask your pharmacist or doctor to provide it.

c. Hold the blue syringe with the opening pointing upwards

d. Pull the plunger rod slowly until the upper margin reaches the mark of the volume to be administered.
→ When moving the plunger rod, you can hear a “Click” for each adjustable volume step.

Cautionary Information:
The upper edge of the plunger must be exactly in line with the correct mark of the volume to be administered.

The shown pictogram is only an example. Your volume might be different.
Be careful, do not pull the plunger past the volume to be administered.
Be careful, do not press on the label when pulling the plunger.

e. Remove the label of the blue syringe completely.
→ You can now see the red button for setting the volume.
f. Check the position of the plunger again. Ensure the upper edge of the plunger is exactly in line with the correct mark of the volume to be administered.
g. If the position of the blue plunger does not match the required volume:
Adjust it accordingly

h. If the position of the blue plunger matches the required volume, push the red button to fix the adjustment.
→ The required dose is now set.
→ Pressing the red button will produce another clicking sound.
→ The clicking sound will not be audible afterwards.

Cautionary Information:
If you notice that the wrong dose has been selected (the red button has been pushed, when the plunger was in the wrong position) use the appropriate spare blue syringe.
Repeat steps a. to h. with a new blue syringe.

i. Push the plunger upwards in the blue syringe as far as it goes.
The blue syringe can now be used.

Follow the steps described below for each required administration.

Step 3.1: Mixing the oral suspension

Cautionary Information:
Allow the suspension to adjust to room temperature if it has been stored in the refrigerator.

a. Gently shake the bottle for at least 10 seconds before each dose.
→ This is intended to provide a well-mixed suspension.

b. Check whether the suspension is mixed thoroughly, i.e.:
• no clumps
• no deposit.
c. If there are clumps or deposit:
Repeat steps a. and b.

d. Shaking can lead to formation of foam.
Let the bottle stand until the foam dissolves.

e. Unscrew the bottle cap, but keep the adapter on the top of the bottle.
Note:
The larger opening visible on the adapter is used to connect the blue syringe.
The surface of the bottle adapter should be free of liquid.
f. If there is any liquid on the adapter:
Remove the liquid with a clean tissue

Step 3.2: Extracting the required dose

a. Keep the bottle in the upright position. Insert the tip of the blue syringe fully into the large opening of the adapter

b. Turn the bottle upside down.
c. Pull the blue plunger rod slowly until it stops (i.e. until the set dose is reached).

d. Carefully check for air in the blue syringe.
Smaller air bubbles are not critical.

Step 3.3: Administration of prescribed dose

e. If there are bigger air bubbles:
• Return the suspension to the bottle by pushing back the plunger rod into the blue syringe as far as possible.
• Repeat steps b. to e.
f. Return the bottle to the upright position.
g. Remove the blue syringe carefully from the adapter

h. Hold the blue syringe upright and check:
- that the tip of the blue syringe is filled
- whether the right dose has been filled into the blue syringe
- that no big air bubbles are present.

i. If there are bigger air bubbles or air in the tip:
• Insert the tip of the blue syringe again fully into the large opening of the adapter • Return the suspension to the bottle by pushing back the plunger rod into the blue syringe as far as it goes.
• Repeat steps b. to h. until no bigger air bubbles are visible.

j. Close the bottle with the screw cap.
Administer the suspension immediately after filling the blue syringe (step 3.3)

a. Place the blue syringe into the mouth of the patient.
b. Direct its tip into the cheek to allow for natural swallowing.
c. Push the plunger rod down slowly until the plunger stops (blue syringe is completely empty).
d. Ensure that the patient swallows the entire dose.

Cautionary Information:
The patient must swallow the full dose of medicine.
If the dose repeatedly is not completely swallowed or if the patient is vomiting, consult your doctor for further instructions.

e. Encourage the patient to drink one typical serving of liquid.
• For an infant of 6 months, for example, this may be 20 mL.
• This can also be breast-feeding.
• For an adolescent it may be a volume up to 240 mL

The blue syringe must be cleaned following every application.
Follow the steps listed below to clean the device. Altogether, three cycles of cleaning are necessary to ensure proper cleaning.

Before you start, you will need the following equipment for step 4.1:
- Get two containers (such as a cup or bowl) o one container filled with drinking water, o the other container empty

Step 4.1: Cleaning

a. Dip the tip of the blue syringe into the container of water.
b. Withdraw water until plunger rod stops.

c. Empty the blue syringe into the prepared empty container

d. Repeat steps a. to c. an additional two times.
e. After cleaning, push the plunger rod back in until it stops.
f. Dry the outer surface of the syringe with a clean tissue

Cautionary Information:
▪
Do not clean the blue syringe in the dish washer.
▪
Never boil the blue syringe.

Step 4.2: Storage

Store the blue syringe in a clean and dry place until next use, e.g. keep it in the box Xarelto was given to you.

Keep away from sunlight.

Cautionary Information:
The blue syringe can be used for up to 14 days.

Store the suspension below 30 °C.

Cautionary Information:
Do not freeze the suspension.
The prepared suspension is stable at room teperature for up to 14 days (preparation date plus 14 days).
Keep Xarelto out of the sight and reach of children.
Store the prepared suspension upright.

Any unused medicine or waste material, syringes, and adapter should be disposed of in accordance with local requirements.

Any serious incidents that occur in connection with the product should be reported to the manufacturer and the relevant authority in your country.