Xarelto: detailed information

Package leaflet: Information for the user

Xarelto 2.5 mg film-coated tablets

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

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Xarelto is and what it is used for

Xarelto has been prescribed to you because

you have been diagnosed with acute coronary syndrome (a group of conditions that includes heart attack and unstable angina, a severe form of chest pain) and an increase in certain cardiac markers has been detected in blood tests. In adults, Xarelto reduces the risk of another heart attack or the risk of dying from a disease related to the heart or blood vessels. Xarelto will not be given to you alone. Your doctor will also prescribe:
- acetylsalicylic acid, or
- acetylsalicylic acid plus clopidogrel or ticlopidine.

you have been diagnosed with a high risk of developing blood clots due to coronary artery disease or peripheral artery disease causing symptoms. In adults, Xarelto reduces the risk of clot formation (atherothrombotic events). Xarelto will not be given to you alone. Your doctor will also prescribe acetylsalicylic acid. In some cases, if you are taking Xarelto following a procedure used to widen a narrowed or blocked artery in the leg to restore blood flow, your doctor may also prescribe clopidogrel, which you will need to take for a short period in combination with acetylsalicylic acid.

Xarelto contains the active substance rivaroxaban and belongs to a group of medicines called antithrombotic agents. It works by blocking a clotting factor (factor Xa), resulting in reduced tendency of the blood to clot.

2. What you should know before taking Xarelto

Do not take Xarelto

if you are allergic to rivaroxaban or to any of the other ingredients of this medicine (listed in section 6)
if you have excessive bleeding
if you have a disease or condition in any part of the body that increases the risk of serious bleeding (e.g. stomach ulcers, wounds or bleeding in the brain, recent brain or eye surgery)
if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban, or heparins), except when switching anticoagulant therapy or when receiving heparins through a venous or arterial catheter to keep it open
if you have acute coronary syndrome and have previously had bleeding or a blood clot in the brain (stroke)
if you have coronary artery disease or peripheral artery disease and have previously had a brain bleed (stroke), or if you have had a blockage of the small arteries supplying deep brain tissue (lacunar stroke) or a blood clot in the brain (non-lacunar ischemic stroke) within the previous month
if you have a liver disease that increases the risk of bleeding
during pregnancy or breastfeeding. Do not take Xarelto and inform your doctor if any of the conditions described above apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xarelto.
Xarelto must not be used in combination with certain medicines that reduce blood clotting, such as prasugrel or ticagrelor, except for acetylsalicylic acid and clopidogrel/ticlopidine.
Exercise particular caution with Xarelto

if you have an increased risk of bleeding, such as in the following cases:
severe kidney disease, because kidney function may affect the amount of active medicine in your body
if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban, or heparin), when switching anticoagulant therapy or when receiving heparins through a venous or arterial catheter to keep it open (see section “Other medicines and Xarelto”)
coagulation disorders
very high blood pressure not controlled by medication
stomach or intestinal diseases that may cause bleeding, for example inflammation of the intestine or stomach, or inflammation of the esophagus (e.g. due to gastroesophageal reflux disease [a condition in which stomach acid flows back into the esophagus]), or tumors in the stomach, intestine, genital tract, or urinary tract
a blood vessel disorder in the back of the eye (retinopathy)
a lung disease with dilated bronchi filled with pus (bronchiectasis), or a history of lung bleeding
if you are over 75 years old
if you weigh less than 60 kg
if you suffer from coronary artery disease with severe symptomatic heart failure
if you have a prosthetic heart valve
if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether a change in therapy is necessary.

If any of the conditions described above apply to you, inform your doctor before taking Xarelto. Your doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored.
If you are scheduled for surgery

it is very important to take Xarelto before and after surgery exactly as directed by your doctor.
If your surgery involves the use of a catheter or an injection into the spine (e.g. for epidural or spinal anesthesia for pain relief):
- it is very important to take Xarelto before and after the injection or catheter removal exactly as directed by your doctor
- inform your doctor immediately if you experience numbness or weakness in your legs or bowel or bladder problems after anesthesia, as urgent intervention may be required.

Children and adolescents
Xarelto 2.5 mg tablets are not recommended for people under 18 years of age. There is insufficient information available on its 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 those without a prescription.

If you are taking
certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are applied only to the skin
ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol)
certain antibacterial medicines (e.g. clarithromycin, erythromycin)
certain antiviral medicines for HIV/AIDS (e.g. ritonavir)
other medicines used to inhibit 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 used to treat atrial fibrillation
certain medicines used to treat depression (selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs])

If any of the conditions described above apply to you, inform your doctor before taking Xarelto, as the effect of Xarelto may be enhanced. Your doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored.
If your doctor believes you have an increased risk of developing stomach or intestinal ulcers, they may prescribe preventive ulcer treatment.

If you are taking
certain medicines for epilepsy (phenytoin, carbamazepine, phenobarbital)
St. John’s wort (Hypericum perforatum), a herbal medicine used for depression
rifampicin, an antibiotic
If any of the conditions described above apply to you, inform your doctor before taking Xarelto, as the effect of Xarelto may be reduced. Your doctor will decide whether you should be treated with Xarelto and whether you need to be closely monitored.

Pregnancy and breastfeeding
Do not take Xarelto during pregnancy or breastfeeding. If there is a possibility you could become pregnant, use a reliable method of contraception while taking Xarelto. If you become pregnant while taking this medicine, inform your doctor immediately, who will decide how to proceed with your treatment.
Driving and using machines
Xarelto may cause dizziness (a common side effect) or fainting (an uncommon side effect) (see section 4, “Possible side effects”). If you experience these symptoms, do not drive, ride a bicycle, or use tools or machines.
Xarelto contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Xarelto

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

What dose to take
The recommended dose is one 2.5 mg tablet twice daily. Take Xarelto at the same times each 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, ask your doctor how to take Xarelto in another way. The tablet can be crushed and mixed with a small amount of water or apple puree immediately before taking it.

If necessary, your doctor may administer crushed Xarelto tablets through a tube inserted into the stomach.

Xarelto will not be given to you alone.
Your doctor will also prescribe acetylsalicylic acid for you.

If you are taking Xarelto following an acute coronary syndrome, your doctor may also prescribe clopidogrel or ticlopidine.

If you are taking Xarelto after a procedure used to widen a narrowed or blocked leg artery to restore blood flow, your doctor may also prescribe clopidogrel, which you will take for a short period in combination with acetylsalicylic acid.

Your doctor will prescribe the correct dose of these medicines (usually 75 to 100 mg of acetylsalicylic acid per day, or a daily dose of 75–100 mg acetylsalicylic acid plus a daily dose of 75 mg clopidogrel, or a standard daily dose of ticlopidine).

When to start Xarelto
Treatment with Xarelto after an acute coronary syndrome should begin as soon as possible after stabilization of the acute coronary syndrome, but not earlier than 24 hours after hospital admission and at the time when parenteral anticoagulant therapy (by injection) would normally be discontinued.

If you have been diagnosed with coronary artery disease or peripheral artery disease, your doctor will tell you when to start treatment with Xarelto.
Your doctor will decide how long your treatment should continue.

If you take more Xarelto than you should
Contact your doctor immediately if you have taken too many Xarelto tablets. If you have taken an excessive amount of Xarelto, your risk of bleeding increases.

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

If you stop taking Xarelto
Take Xarelto regularly for the entire duration prescribed by your doctor.
Do not stop taking Xarelto without first talking to your doctor. If you stop taking this medicine, your risk of having another heart attack, stroke, or of dying from heart or blood vessel disease may increase.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Xarelto can cause side effects, although not everybody gets them.
Like other similar medicines used to reduce blood clot formation, Xarelto can cause bleeding which
may potentially be life-threatening. Massive bleeding can cause a sudden drop
in blood pressure (shock). In some cases, bleeding may not be obvious.
Inform your doctor immediately if you notice any of the following side effects:

Signs of bleeding
- bleeding in the brain or skull (symptoms may include headache, weakness on one side, vomiting, seizures, reduced level of consciousness, and neck stiffness. A serious medical emergency. Seek immediate medical help!)
- prolonged or excessive blood loss
- unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina pectoris. Your doctor may decide to monitor you closely or change your treatment.
Signs of severe skin reactions
- widespread and intense rash, blisters or mucosal lesions, for example in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
- a drug reaction causing rash, fever, inflammation of internal organs, blood abnormalities, and systemic illness (DRESS syndrome). The frequency of these side effects is very rare (may occur in 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 occur in up to 1 in 10,000 people) and uncommon (angioedema and allergic edema; may occur in up to 1 in 100 people).

Complete list of possible side effects
Common (may occur in up to 1 in 10 people)

reduction in red blood cells, which may cause pale skin, weakness or shortness of breath
bleeding in the stomach or intestines, urogenital bleeding (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding gums
bleeding in the eye (including bleeding in the white of the eye)
bleeding into tissues or body cavities (haematoma, bruising)
coughing up blood
bleeding from or under the skin
bleeding after surgery
blood or fluid leakage from surgical wound
swelling of limbs
limb pain
kidney dysfunction (may be detected through tests performed by your doctor)
fever
stomach ache, indigestion, feeling unwell, constipation, diarrhoea
low blood pressure (symptoms include dizziness or fainting when standing)
general loss of strength and energy (weakness, fatigue), headache, dizziness
rash, itchy skin
increased liver enzymes in blood tests

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

bleeding in the brain or within the skull (see above, signs of bleeding)
joint bleeding, causing pain and swelling
thrombocytopenia (reduction in platelet count; platelets are blood cells that help blood to clot)
allergic reactions, including allergic skin reactions
liver dysfunction (may be detected through tests performed by your doctor)
blood tests may show increased bilirubin, increased pancreatic or liver enzymes, or increased platelet count
fainting
feeling unwell
rapid heartbeat
dry mouth
hives

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

muscle bleeding
cholestasis (reduced flow of bile, a substance produced by the liver), hepatitis, including hepatocellular injury (liver inflammation including liver damage)
yellowing of the skin and eyes (jaundice)
localized swelling, formation of a blood collection (haematoma) in the groin as a complication of a heart procedure involving insertion of a catheter into the leg artery (pseudoaneurysm)

Very rare (may occur in up to 1 in 10,000 people)
accumulation of eosinophils, a type of granulocytic white blood cells causing lung inflammation
(eosinophilic pneumonia)
Frequency not known (frequency cannot be estimated from available data)

kidney failure following severe bleeding
kidney bleeding sometimes with blood in the urine leading to kidney dysfunction (Anticoagulant-related nephropathy)
increased pressure in the muscles of the arms or legs after bleeding, causing pain, swelling, altered sensation, numbness or paralysis (compartment syndrome following bleeding)

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

5. How to store Xarelto

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./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 dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Xarelto contains

The active substance is rivaroxaban. Each tablet contains 2.5 mg of rivaroxaban.
The other components are: Tablet core: microcrystalline cellulose, croscarmellose sodium, monohydrate lactose, hypromellose (2910), sodium lauryl sulfate, magnesium stearate. See section 2 “Xarelto contains lactose and sodium”. Film coating of the tablet: macrogol (3350), hypromellose (2910), titanium dioxide (E 171), yellow iron oxide (E 172).

Description of the appearance of Xarelto and package contents
The 2.5 mg film-coated tablets of Xarelto are light yellow, round, biconvex, with the BAYER cross imprint on one side and “2.5” and a triangle on the other side.
The tablets are supplied:

in blisters in packs of 14, 20, 28, 30, 56, 60, 98, 168 or 196 film-coated tablets, or
in unit-dose divisible blisters in packs of 10 x 1 or 100 x 1 film-coated tablets, or
in multiple packs comprising 10 packs each containing 10 x 1 film-coated tablets, or
in bottles of 100 film-coated tablets.

Not all pack sizes may be marketed.
Marketing Authorization Holder
Bayer AG
51368 Leverkusen
Germany
Manufacturer
The manufacturer can be identified by the batch number printed on the side of the packaging 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 S.r.l., 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 further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder.
België / Belgique / Belgien Lietuva
Bayer SA-NV UAB Bayer
Tél/Tel: +32-(0)2-535 63 11 Tel: +370-5-233 68 68
България Luxembourg / Luxemburg
Байер България ЕООД Bayer SA-NV
Тел: +359-(0)2-424 72 80 Tél/Tel: +32-(0)2-535 63 11
Česká republika Magyarország
Bayer s.r.o. Bayer Hungária KFT
Tel: +420-266 101 111 Tel: +36-1-487 4100
Danmark Malta
Bayer A/S Alfred Gera and Sons Ltd.
Tlf: +45-45 235 000 Tel: +356-21 44 62 05
Deutschland Nederland
Bayer Vital GmbH Bayer B.V.
Tel: +49-(0)214-30 513 48 Tel: +31-23-799 1000
Eesti Norge
Bayer OÜ Bayer AS
Tel: +372-655 85 65 Tlf: +47-23 13 05 00
Ελλάδα Österreich
Bayer Ελλάς ΑΒΕΕ Bayer Austria Ges. m. b. H.
Τηλ: +30-210-618 75 00 Tel: +43-(0)1-711 460
España Polska
Bayer Hispania S.L. Bayer Sp. z o.o.
Tel: +34-93-495 65 00 Tel: +48-22-572 35 00
France Portugal
Bayer HealthCare Bayer Portugal, Lda
Tél (N° vert): +33-(0)800 87 54 54 Tel: +351-21-416 42 00
Hrvatska România
Bayer d.o.o. SC Bayer SRL
Tel: +385-(0)1-6599 900 Tel: +40-(0)21-529 59 00
Ireland Slovenija
Bayer Limited Bayer d. o. o.
Tel: +353 1 216 3300 Tel: +386-(0)1-58 14 400
Ísland Slovenská republika
Icepharma hf. Bayer, spol. s r.o.
Sími: +354-540 80 00 Tel: +421-(0)2-59 21 31 11
Italia Suomi/Finland
Bayer S.p.A. Bayer Oy
Tel: +39-02-3978 1 Puh/Tel: +358-(0)20-78521
Κύπρος Sverige
NOVAGEM Limited Bayer AB
Τηλ: +357-22-48 38 58 Tel: +46-(0)8-580 223 00
Latvija United Kingdom (Northern Ireland)
SIA Bayer Bayer AG
Tel: +371-67 84 55 63 Tel: +44-(0)118 206 3000

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

Package leaflet: Information for the user

Xarelto 10 mg film-coated tablets

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

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

Contents of this leaflet:

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

1. What Xarelto is and what it is used for

Xarelto contains the active substance rivaroxaban and is used in adults to

prevent the formation of blood clots in the veins after hip or knee replacement surgery. Your doctor has prescribed this medicine because, after surgery, there is an increased risk of blood clots forming.
treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent the recurrence of blood clots in the blood vessels of the legs and/or the lungs.

Xarelto belongs to a group of medicines called antithrombotic agents. It works by blocking
a blood clotting factor (factor Xa), thereby reducing the tendency of the blood to clot.

2. What you should know before taking Xarelto

Do not take Xarelto

if you are allergic to rivaroxaban or to any of the other ingredients of this medicine (listed in section 6)
if you have excessive bleeding
if you have a disease or condition in any part of the body that increases the risk of serious bleeding (e.g. stomach ulcers, wounds or bleeding in the brain, recent brain or eye surgery)
if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban, or heparins), except when switching anticoagulant therapy or when receiving heparin through a venous or arterial catheter to keep it open
if you have a liver disease that increases the risk of bleeding
during pregnancy or breastfeeding Do not take Xarelto and inform your doctor if any of the conditions described above apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xarelto.
Be especially careful with Xarelto

if you have a high risk of bleeding, which may occur in situations such as:
moderate or severe kidney disease, because kidney function can affect the amount of active medicine in your body
if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban, or heparin), if you are switching anticoagulant therapy, or while receiving heparin through a venous or arterial catheter to keep it open (see section “Other medicines and Xarelto”)
disorders of blood coagulation
very high blood pressure that is not controlled with medication
diseases of the stomach or intestines that may cause bleeding, for example inflammation of the intestine or stomach, or inflammation of the esophagus, such as caused by gastroesophageal reflux disease (a condition in which stomach acid flows back into the esophagus), or tumors located in the stomach, intestine, genital tract, or urinary tract
a blood vessel disorder at the back of the eye (retinopathy)
a lung disease with dilated bronchi filled with pus (bronchiectasis), or a history of bleeding from your lungs
if you have a prosthetic heart valve
if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether a change in therapy is needed
if your doctor finds that your blood pressure is unstable or if another treatment or surgical procedure to remove blood clots from the lungs is planned.

If any of the conditions described above apply to you, inform your doctor before taking Xarelto. Your doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored.
If you are scheduled for surgery

it is very important to take Xarelto exactly as directed by your doctor before and after surgery.
If the surgical procedure involves the use of a catheter or an injection into the spinal column (e.g. for epidural or spinal anesthesia for pain relief):
- it is very important to take Xarelto exactly as directed by your doctor
- inform your doctor immediately if you experience numbness or weakness in your legs or bowel or bladder problems after the anesthesia, as urgent medical intervention may be required.

Children and adolescents
Xarelto 10 mg tablets are not recommended for patients under 18 years of age. There is insufficient information available on its use in children and adolescents.
Other medicines and Xarelto
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.

If you are taking
certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are applied only to the skin
ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol)
certain antibacterial medicines (e.g. clarithromycin, erythromycin)
certain antiviral medicines for HIV/AIDS (e.g. ritonavir)
other medicines used to inhibit 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 used to treat atrial fibrillation
certain medicines for the treatment of depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs))

If any of the conditions described above apply to you, inform your doctor before taking Xarelto, because the effect of Xarelto may be enhanced. Your doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored.
If your doctor considers that you have an increased risk of developing stomach or intestinal ulcers, they may prescribe preventive ulcer treatment.

If you are taking
certain medicines for epilepsy (phenytoin, carbamazepine, phenobarbital)
St. John’s wort ( Hypericum perforatum ), a herbal remedy for depression
rifampicin, an antibiotic

If any of the conditions described above apply to you, inform your doctor before taking Xarelto, as the effect of Xarelto may be reduced. Your doctor will decide whether you should be treated with Xarelto and whether you need to be closely monitored.
Pregnancy and breastfeeding
Do not take Xarelto during pregnancy or breastfeeding. If you could become pregnant, use a reliable method of contraception while taking Xarelto. If you become pregnant while taking this medicine, inform your doctor immediately, who will decide how to proceed with treatment.
Driving and using machines
Xarelto may cause dizziness (a common side effect) and fainting (an uncommon side effect) (see section 4, “Possible side effects”). If you experience these symptoms, do not drive, ride a bicycle, or operate tools or machinery.
Xarelto contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Xarelto

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

What dose to take

To prevent blood clots in veins after hip or knee replacement surgery: The recommended dose is one 10 mg Xarelto tablet once daily.
To treat blood clots in the leg veins and in the blood vessels of the lungs, and to prevent recurrence of clots: After at least 6 months of treatment for blood clots, the recommended dose is either one 10 mg tablet once daily or one 20 mg tablet once daily. Your doctor has prescribed Xarelto 10 mg once daily.

Swallow the tablet preferably with some water.
Xarelto can be taken regardless of meals.
If you have difficulty swallowing the tablet whole, ask your doctor how to take Xarelto in another way. The tablet can be crushed and mixed with water or apple puree immediately before administration.
If necessary, your doctor may administer crushed Xarelto tablets through a tube inserted into the stomach.

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

To prevent blood clots in veins after hip or knee replacement surgery:
Take the first tablet 6–10 hours after surgery.
If you had major hip surgery, you will generally need to take the tablets for 5 weeks.
If you had major knee surgery, you will generally need to take the tablets for 2 weeks.

If you forget to take Xarelto
If you forget a dose, take it as soon as you remember. Take the next tablet the following day, and then continue taking one tablet per day as before.
Do not take a double dose to make up for a forgotten tablet.

If you stop taking Xarelto
Do not stop taking Xarelto without first talking to your doctor, because Xarelto helps prevent serious conditions from occurring.

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

4. Possible side effects

Like all medicines, Xarelto can cause side effects, although not everyone experiences them.
As with other similar medicines used to reduce blood clot formation, Xarelto may cause bleeding, which
can potentially be life-threatening. Severe bleeding can cause a sudden drop in blood pressure (shock).
In some cases, bleeding may not be obvious.
Contact your doctor immediately if you notice any of the following side effects:

Signs of bleeding
- bleeding in the brain or skull (symptoms may include headache, weakness on one side of the body, vomiting, seizures, reduced level of consciousness, and neck stiffness. This is a serious medical emergency. Seek immediate medical help!)
- prolonged or excessive blood loss
unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina pectoris. Your doctor may decide to monitor you closely or change your treatment.
- Signs of severe skin reactions
widespread and intense rash, blisters or mucosal lesions, for example in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
a drug reaction causing rash, fever, internal organ inflammation, blood abnormalities, and systemic illness (DRESS syndrome). The frequency of these side effects is very rare (may occur in up to 1 in 10,000 people).
- Signs of severe allergic reactions
swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives; breathing difficulties; sudden drop in blood pressure. The frequencies of severe allergic reactions are very rare (anaphylactic reactions, including anaphylactic shock; may occur in up to 1 in 10,000 people) and not common (angioedema and allergic edema; may occur in up to 1 in 100 people).

Complete list of possible side effects
Common (may affect up to 1 in 10 people)

reduction in red blood cells, which may cause pale skin, weakness or shortness of breath
bleeding in the stomach or intestines, urogenital bleeding (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding gums
bleeding in the eye (including bleeding in the white part of the eye)
bleeding into tissues or body cavities (haematoma, bruising)
coughing up blood
bleeding from or under the skin
bleeding after surgery
blood or fluid leakage from the surgical wound
swelling in limbs
limb pain
kidney dysfunction (can be detected by blood tests performed by your doctor)
fever
stomach pain, indigestion, feeling unwell, constipation, diarrhoea
low blood pressure (symptoms include dizziness or fainting when standing up)
general loss of strength and energy (weakness, fatigue), headache, dizziness
skin rash, itchy skin
increased levels of certain liver enzymes in blood tests

Uncommon (may affect up to 1 in 100 people)

bleeding in the brain or within the skull (see above, signs of bleeding)
joint bleeding, causing pain and swelling
thrombocytopenia (reduced platelet count; platelets are blood cells that help blood to clot)
allergic reactions, including allergic skin reactions
liver dysfunction (can be detected by blood tests performed by your doctor)
blood tests may show increased bilirubin, increased levels of certain pancreatic or liver enzymes, or increased platelet count
fainting
feeling unwell
rapid heartbeat
dry mouth
hives

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

muscle bleeding
cholestasis (reduced flow of bile, a substance produced by the liver), hepatitis including hepatocellular injury (liver inflammation including liver damage)
yellowing of the skin and eyes (jaundice)
localized swelling
formation of a blood collection (haematoma) in the groin as a complication of a heart procedure involving insertion of a catheter into the leg artery (pseudoaneurysm)

Very rare (may affect up to 1 in 10,000 people)
accumulation of eosinophils, a type of granulocyte white blood cell causing lung inflammation (eosinophilic pneumonia)
Frequency not known (frequency cannot be estimated from the available data)

kidney impairment following severe bleeding
kidney bleeding sometimes with blood in the urine leading to kidney dysfunction (Anticoagulant-related nephropathy)
increased pressure in the muscles of the arms or legs after bleeding, causing pain, swelling, altered sensation, numbness or paralysis (compartment syndrome following bleeding)

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

5. How to store Xarelto

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on each blister or bottle after Exp./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 dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Xarelto contains

The active substance is rivaroxaban. Each tablet contains 10 mg of rivaroxaban.
Other components are: Tablet core: microcrystalline cellulose, croscarmellose sodium, lactose monohydrate, hypromellose (2910), sodium lauryl sulfate, magnesium stearate. See section 2 “Xarelto contains lactose and sodium”.
Film coating: macrogol (3350), hypromellose (2910), titanium dioxide (E 171), iron oxide red (E 172).

Description of the appearance of Xarelto and contents of the pack
The 10 mg film-coated tablets of Xarelto are round, biconvex, light red in colour, with the BAYER cross imprinted on one side and “10” and a triangle on the other side.
The tablets are supplied:

in blisters in packs of 5, 10, 14, 28, 30 or 98 film-coated tablets, or
in unit-dose divisible blisters in packs of 10 x 1 or 100 x 1 film-coated tablets, or
in multiple packs comprising 10 packs each containing 10 x 1 film-coated tablets, or
in bottles containing 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 of the packaging 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 S.r.l. 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 further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België / Belgique / Belgien Lietuva
Bayer SA-NV UAB Bayer
Tél/Tel: +32-(0)2-535 63 11 Tel: +370-5-233 68 68

България Luxembourg / Luxemburg
Байер България ЕООД Bayer SA-NV
Тел: +359-(0)2-424 72 80 Tél/Tel: +32-(0)2-535 63 11

Česká republika Magyarország
Bayer s.r.o. Bayer Hungária KFT
Tel: +420-266 101 111 Tel: +36-1-487 4100

Danmark Malta
Bayer A/S Alfred Gera and Sons Ltd.
Tlf: +45-45 235 000 Tel: +356-21 44 62 05

Deutschland Nederland
Bayer Vital GmbH Bayer B.V.
Tel: +49-(0)214-30 513 48 Tel: +31-23-799 1000

Eesti Norge
Bayer OÜ Bayer AS
Tel: +372-655 85 65 Tlf: +47-23 13 05 00

Ελλάδα Österreich
Bayer Ελλάς ΑΒΕΕ Bayer Austria Ges. m. b. H.
Τηλ: +30-210-618 75 00 Tel: +43-(0)1-711 460

España Polska
Bayer Hispania S.L. Bayer Sp. z o.o.
Tel: +34-93-495 65 00 Tel: +48-22-572 35 00

France Portugal
Bayer HealthCare Bayer Portugal, Lda
Tél (N° vert): +33-(0)800 87 54 54 Tel: +351-21-416 42 00

Hrvatska România
Bayer d.o.o. SC Bayer SRL
Tel: +385-(0)1-6599 900 Tel: +40-(0)21-529 59 00

Ireland Slovenija
Bayer Limited Bayer d. o. o.
Tel: +353 1 216 3300 Tel: +386-(0)1-58 14 400

Ísland Slovenská republika
Icepharmahf. Bayer, spol. s r.o.
Sími: +354-540 80 00 Tel: +421-(0)2-59 21 31 11

Italia Suomi/Finland
Bayer S.p.A. Bayer Oy
Tel: +39-02-3978 1 Puh/Tel: +358-(0)20-78521

Κύπρος Sverige
NOVAGEM Limited Bayer AB
Τηλ: +357-22-48 38 58 Tel: +46-(0)8-580 223 00

Latvija United Kingdom (Northern Ireland)
SIA Bayer Bayer AG
Tel: +371-67 84 55 63 Tel: +44-(0)118 206 3000

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

Package leaflet: information for the user

Xarelto 15 mg film-coated tablets, 20 mg film-coated tablets

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

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Xarelto and what is it used for?

Xarelto contains the active substance rivaroxaban.
Xarelto is used in adults to:

prevent the formation of blood clots in the brain (stroke) and in other blood vessels of the body if you have a type of irregular heartbeat called non-valvular atrial fibrillation.
treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent recurrence of blood clots in the blood vessels of the legs and/or lungs.

Xarelto is used in children and adolescents under 18 years of age and with body weight equal to or greater than 30 kg to:

treat blood clots and prevent their recurrence in the veins or in the blood vessels of the lungs, following an 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. Its action is due to
inhibition of a clotting factor (factor Xa), resulting in reduced tendency of the blood to form
clots.

2. What you should know before taking Xarelto

Do not take Xarelto

if you are allergic to rivaroxaban or to any of the other ingredients of this medicine (listed in section 6)
if you have excessive bleeding
if you have a disease or condition in any part of the body that increases the risk of serious bleeding (e.g. stomach ulcers, wounds or bleeding in the brain, recent brain or eye surgery)
if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparins), except when switching anticoagulant therapy or when receiving heparin through a venous or arterial catheter to keep it open
if you have a liver disease that increases the risk of bleeding
during pregnancy or breastfeeding Do not take Xarelto and inform your doctor if any of the conditions described above apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xarelto.
Be especially careful with Xarelto

if you have an increased risk of bleeding, such as:
severe kidney disease in adults or moderate to severe kidney disease in children and adolescents, because kidney function can affect the amount of active medicine in your body
if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), if you are switching anticoagulant therapy, or while receiving heparin through a venous or arterial catheter to keep it open (see section “Other medicines and Xarelto”)
disorders of blood clotting
very high blood pressure not controlled with medication
stomach or intestinal diseases that may cause bleeding, such as inflammation of the intestine or stomach, or inflammation of the esophagus, for example due to gastroesophageal reflux disease (a condition in which stomach acid flows back into the esophagus), or tumors in the stomach, intestine, genital tract, or urinary tract
a blood vessel disorder in the back of the eye (retinopathy)
a lung disease with dilated bronchi filled with pus (bronchiectasis), or a history of bleeding from the lungs
if you have a prosthetic heart valve
if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether therapy adjustment is needed
if your doctor finds that your blood pressure is unstable or if another treatment or surgical procedure to remove blood clots from the lungs is planned

it is very important to take Xarelto exactly at the times indicated by your doctor, both before and after surgery.
If the surgery involves using a catheter or an injection into the spinal column (e.g. for epidural or spinal anesthesia for pain relief):
- it is very important to take Xarelto exactly at the times indicated by your doctor, both before and after the injection or catheter removal
inform your doctor immediately if you experience numbness or weakness in your legs or bowel or bladder problems after anesthesia, as urgent medical intervention may be required.

Children and adolescents
Xarelto tablets are not recommended for children weighing less than 30 kg. There is insufficient information on the use of Xarelto in children and adolescents for 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 those without a prescription.

If you are taking
certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are applied only to the skin
ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol)
certain antibiotics (e.g. clarithromycin, erythromycin)
certain antiviral medicines for HIV/AIDS (e.g. ritonavir)
other medicines used to prevent 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 used to treat atrial fibrillation
certain antidepressants (selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs))

If you are taking
certain medicines for epilepsy (phenytoin, carbamazepine, phenobarbital)
St. John’s wort (Hypericum perforatum), a herbal medicine used for depression
rifampicin, an antibiotic

If any of the conditions described above apply to you, inform your doctor before taking Xarelto, as the effect of Xarelto may be reduced. Your doctor will decide whether you should be treated with Xarelto and whether you need to be closely monitored.
Pregnancy and breastfeeding
Do not take Xarelto during pregnancy or breastfeeding. If you could become pregnant, use a reliable method of contraception while taking Xarelto. If you become pregnant while taking this medicine, inform your doctor immediately, who will decide how to proceed with treatment.
Driving and using machines
Xarelto may cause dizziness (a common side effect) or fainting (an uncommon side effect) (see section 4, “Possible side effects”). If you experience these symptoms, do not drive, ride a bicycle, or operate tools or machinery.
Xarelto contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Xarelto

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Xarelto should be taken with food.
Swallow the tablet or tablets preferably with some water.
If you have difficulty swallowing the tablet whole, ask your doctor how to take Xarelto in another way. The tablet may be crushed and mixed with water or apple puree immediately before taking. The mixture should be followed immediately by eating food.
If necessary, your doctor may administer crushed Xarelto tablets through a tube inserted into the stomach.

What dose to take
Adults
o To prevent blood clots in the brain (stroke) and in other blood vessels of the body
The recommended dose is one 20 mg Xarelto tablet once daily.
If you have kidney problems, the dose may be reduced to one 15 mg Xarelto tablet once daily.
If you need to undergo a procedure to treat blocked blood vessels in your heart (called PCI – Percutaneous Coronary Intervention with stent placement), there is limited evidence supporting dose reduction to one 15 mg Xarelto tablet once daily (or one 10 mg Xarelto tablet if your kidneys are not functioning properly), in addition to an antiplatelet medicine such as clopidogrel.
o To treat blood clots in the veins of the legs and in the blood vessels of the lungs, and to prevent recurrence of clots
The recommended dose is one 15 mg Xarelto tablet twice daily for the first 3 weeks. After 3 weeks, the recommended dose is one 20 mg Xarelto tablet once daily.
After at least 6 months of treatment for blood clots, your doctor may decide to continue treatment with either one 10 mg tablet once daily or one 20 mg tablet once daily.
If you have kidney problems and are taking one 20 mg Xarelto tablet once daily, your doctor may decide to reduce the dose after 3 weeks to one 15 mg Xarelto tablet once daily if the risk of bleeding is greater than the risk of developing a new blood clot.

Children and adolescents
The dose of Xarelto depends on body weight and will be calculated by your doctor.

The recommended dose for children and adolescents with a body weight between 30 kg and 50 kg is one 15 mg Xarelto tablet once daily.
The recommended dose for children and adolescents with a body weight equal to or greater than 50 kg is one 20 mg Xarelto tablet once daily. Take each dose of Xarelto with a drink (e.g. water or juice) during a meal. Take the tablets at approximately the same time each day. Consider setting an alarm to remind yourself. For parents or caregivers: please observe the child to ensure the entire dose is taken.

Since the dose of Xarelto is based on body weight, it is important to attend scheduled appointments with your doctor, as the dose may need to be adjusted as weight changes.
Never adjust the dose of Xarelto on your own. If adjustment is needed, your doctor will do so.
Do not split the tablet in an attempt to divide the dose. If a lower dose is required, use the alternative formulation of Xarelto granules for oral suspension.
For children and adolescents who cannot swallow whole tablets, use Xarelto granules for oral suspension.
If the oral suspension is not available, the Xarelto tablet may be crushed and mixed with water or apple puree immediately before administration. After taking this mixture, eat food. If necessary, your doctor may also administer crushed Xarelto tablets via a gastric tube.

If you spit out the dose or vomit

Less than 30 minutes after taking Xarelto, take a new dose.
More than 30 minutes after taking Xarelto, do not take a new dose. In this case, take your next dose of Xarelto at the usual time.

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

When to take Xarelto
Take the tablet or tablets every day until your doctor tells you to stop.
Try to take the tablet or tablets at the same time each day to help you remember.
Your doctor will decide how long your treatment should continue.
To prevent formation of clots in the brain (stroke) and in other blood vessels in the body:
If your heartbeat is to be restored to normal through a procedure called cardioversion, take Xarelto exactly as your doctor has instructed.

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

Adults:
If you are taking one 15 mg tablet twice daily and have missed a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in one day. If you miss a dose, you may take two 15 mg tablets together to achieve a total of two tablets (30 mg) in one day. The following day, continue with one 15 mg tablet twice daily.

If you stop taking Xarelto
Do not stop taking Xarelto without first talking to your doctor, as Xarelto treats serious conditions and helps prevent their occurrence.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Xarelto can cause side effects, although not everybody gets them.
Like other similar medicines used to reduce blood clot formation, Xarelto can cause bleeding which
may potentially be life-threatening. Major bleeding can cause a sudden drop
in blood pressure (shock). In some cases, bleeding may not be obvious.
Contact your doctor immediately if you notice any of the following side effects:

Signs of bleeding
- bleeding in the brain or skull (symptoms may include headache, weakness on one side of the body, vomiting, seizures, reduced level of consciousness, and neck stiffness. A serious medical emergency. Seek immediate medical help!)
- prolonged or excessive bleeding
- unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina pectoris. Your doctor may decide to monitor you closely or change your treatment.
Signs of serious skin reactions
- widespread and severe rash, blisters or mucosal lesions, for example in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
- a drug reaction causing rash, fever, internal organ inflammation, blood abnormalities, and systemic illness (DRESS syndrome). The frequency of these side effects is very rare (may occur in up to 1 in 10,000 people).
Signs of serious 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 occur in up to 1 in 10,000 people) and uncommon (angioedema and allergic edema; may occur in up to 1 in 100 people).

Complete list of possible side effects observed in adults, children and adolescents
Common (may affect up to 1 in 10 people)

reduced number of red blood cells, which may cause pale skin, weakness or shortness of breath
bleeding in the stomach or intestines, urogenital bleeding (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding from the gums
bleeding in the eye (including bleeding in the white part of the eye)
bleeding into tissues or body cavities (haematoma, bruising)
coughing up blood
bleeding from or under the skin
bleeding after surgery
blood or fluid leaking from the surgical wound
swelling of limbs
limb pain
kidney dysfunction (can be detected by tests performed by your doctor)
fever
stomach ache, indigestion, feeling unwell, constipation, diarrhoea
low blood pressure (symptoms include dizziness or fainting when standing up)
general loss of strength and energy (weakness, fatigue), headache, dizziness
skin rash, itchy skin
increased levels of certain liver enzymes in blood tests

Uncommon (may affect up to 1 in 100 people)

bleeding in the brain or within the skull (see above, signs of bleeding)
joint bleeding, causing pain and swelling
thrombocytopenia (reduced number of platelets, which are the cells that help blood to clot)
allergic reactions, including allergic skin reactions
liver dysfunction (can be detected by tests performed by your doctor)
blood tests may show increased bilirubin, increased levels of certain pancreatic or liver enzymes, or increased platelet count
fainting
feeling unwell
rapid heartbeat
dry mouth
hives

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

muscle bleeding
cholestasis (reduced flow of bile, a substance produced by the liver), hepatitis including hepatocellular injury (liver inflammation including liver damage)
yellowing of the skin and eyes (jaundice)
localized swelling, formation of a blood collection (haematoma) in the groin as a complication of a heart procedure involving insertion of a catheter into the leg artery (pseudoaneurysm)

Very rare (may affect up to 1 in 10,000 people)
accumulation of eosinophils, a type of granulocyte white blood cell causing lung inflammation
(eosinophilic pneumonia)
Frequency not known (frequency cannot be estimated from the available data):

kidney failure following severe bleeding
kidney bleeding sometimes with blood in the urine leading to kidney dysfunction (Anticoagulant-related nephropathy)
increased pressure in the muscles of the arms or legs after bleeding, causing pain, swelling, altered sensation, numbness or paralysis (compartment syndrome following bleeding)

Side effects in children and adolescents
In general, the side effects observed in children and adolescents treated with Xarelto have been
similar to those observed in adults and have mainly been mild to moderate in severity.
Side effects observed more frequently in children and adolescents:
Very common (may affect more than 1 in 10 people)

headache
fever
nosebleeds
vomiting
Common (may affect up to 1 in 10 people)
increased heart rate
blood tests may show increased bilirubin (bile pigment)
thrombocytopenia (reduced platelets, which are the cells that help blood to clot)
heavy menstrual periods
Uncommon (may affect up to 1 in 100 people)
blood tests may show increased levels of a subcategory of bilirubin (direct bilirubin, bile pigment)

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

5. How to store Xarelto

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on each blister or bottle
after Exp./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 dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Xarelto contains

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

Description of the appearance of Xarelto and package contents
Xarelto 15 mg film-coated tablets are red, round, biconvex, with the BAYER cross imprinted on one side and “15” and a triangle on the other side.
The tablets are supplied

in blisters in packs of 10, 14, 28, 42 or 98 film-coated tablets or
in unit-dose divisible blisters in packs of 10 x 1 or 100 x 1 film-coated tablets or
in multiple packs containing 10 packs each with 10 x 1 film-coated tablets or
in bottles of 100 film-coated tablets.

Xarelto 20 mg film-coated tablets are red-brown, round, biconvex, with the BAYER cross imprinted on one side and “20” and a triangle on the other side.
The tablets are supplied

in blisters in packs of 10, 14, 28 or 98 film-coated tablets or
in unit-dose divisible blisters in packs of 10 x 1 or 100 x 1 film-coated tablets or
in multiple packs containing 10 packs each with 10 x 1 film-coated tablets or
in bottles of 100 film-coated tablets.

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 S.r.l. 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 further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder.
België / Belgique / Belgien Lietuva
Bayer SA-NV UAB Bayer
Tél/Tel: +32-(0)2-535 63 11 Tel: +370-5-233 68 68
България Luxembourg / Luxemburg
Байер България ЕООД Bayer SA-NV
Тел: +359-(0)2-424 72 80 Tél/Tel: +32-(0)2-535 63 11
Česká republika Magyarország
Bayer s.r.o. Bayer Hungária KFT
Tel: +420-266 101 111 Tel: +36-1-487 4100
Danmark Malta
Bayer A/S Alfred Gera and Sons Ltd.
Tlf: +45-45 235 000 Tel: +356-21 44 62 05
Deutschland Nederland
Bayer Vital GmbH Bayer B.V.
Tel: +49-(0)214-30 513 48 Tel: +31-23-799 1000
Eesti Norge
Bayer OÜ Bayer AS
Tel: +372-655 85 65 Tlf: +47-23 13 05 00
Ελλάδα Österreich
Bayer Ελλάς ΑΒΕΕ Bayer Austria Ges. m. b. H.
Τηλ: +30-210-618 75 00 Tel: +43-(0)1-711 460
España Polska
Bayer Hispania S.L. Bayer Sp. z o.o.
Tel: +34-93-495 65 00 Tel: +48-22-572 35 00
France Portugal
Bayer HealthCare Bayer Portugal, Lda.
Tél (N° vert): +33-(0)800 87 54 54 Tel: +351-21-416 42 00
Hrvatska România
Bayer d.o.o. SC Bayer SRL
Tel: + 385-(0)1-6599 900 Tel: +40-(0)21-529 59 00
Ireland Slovenija
Bayer Limited Bayer d. o. o.
Tel: +353 1 216 3300 Tel: +386-(0)1-58 14 400
Ísland Slovenská republika
Icepharma hf. Bayer, spol. s r.o.
Sími: +354-540 80 00 Tel: +421-(0)2-59 21 31 11
Italia Suomi/Finland
Bayer S.p.A. Bayer Oy
Tel: +39-02-3978 1 Puh/Tel: +358-(0)20-78521
Κύπρος Sverige
NOVAGEM Limited Bayer AB
Τηλ: +357-22-48 38 58 Tel: +46-(0)8-580 223 00
Latvija United Kingdom (Northern Ireland)
SIA Bayer Bayer AG
Tel: +371-67 84 55 63 Tel: +44-(0)118 206 3000
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

Package leaflet: information for the user

Xarelto 15 mg film-coated tablets, 20 mg film-coated tablets

Starting treatment pack
Not for use in children
rivaroxaban
Please read this leaflet carefully before taking this medicine because it contains important information for you.

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

Contents of this leaflet:

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

1. What Xarelto is and what it is used for

Xarelto contains the active substance rivaroxaban and is used in adults to:

treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent the recurrence of blood clots in the blood vessels of the legs and/or lungs.

Xarelto belongs to a group of medicines called antithrombotic agents. It works by blocking
a clotting factor (factor Xa), resulting in reduced tendency of the blood to form
clots.

2. What you should know before taking Xarelto

Do not take Xarelto

if you are allergic to rivaroxaban or to any of the other ingredients of this medicine (listed in section 6)
if you have excessive bleeding
if you have a disease or condition in any part of the body that increases the risk of serious bleeding (e.g. stomach ulcers, wounds or bleeding in the brain, recent brain or eye surgery)
if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparins), except when switching anticoagulant therapy or when receiving heparin through a venous or arterial catheter to keep it open.
if you have a liver disease that increases the risk of bleeding
during pregnancy or breastfeeding Do not take Xarelto and inform your doctor if any of the conditions described above apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xarelto.
Be especially careful with Xarelto

if you have an increased risk of bleeding, such as:
severe kidney disease, because kidney function may affect the amount of active medicine in your body
if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), if you are switching anticoagulant therapy, or while receiving heparin through a venous or arterial catheter to keep it open (see section “Other medicines and Xarelto”)
coagulation disorders
very high, uncontrolled blood pressure
stomach or intestinal diseases that may cause bleeding, such as inflammation of the intestine or stomach, or inflammation of the esophagus, for example caused by gastroesophageal reflux disease (a condition in which stomach acid flows back into the esophagus), or tumors in the stomach, intestine, genital tract, or urinary tract
a blood vessel disorder in the back of the eye (retinopathy)
a lung disease with dilated bronchi filled with pus (bronchiectasis), or a history of lung bleeding
if you have a prosthetic heart valve
if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether a change in therapy is needed
if your doctor finds that your blood pressure is unstable or if another treatment or surgical procedure to remove blood clots from the lungs is planned

it is very important to take Xarelto exactly at the times indicated by your doctor, both before and after surgery.
If the surgery involves using a catheter or an injection into the spine (e.g. for epidural or spinal anesthesia for pain relief):
- it is very important to take Xarelto exactly at the times indicated by your doctor, both before and after the injection or removal of the catheter
- inform your doctor immediately if you experience numbness or weakness in your legs or bowel or bladder problems after the anesthesia, as urgent medical intervention may be required.

Children and adolescents
The Xarelto starter pack is not recommended for people under 18 years of age, as it is specifically designed for initiating treatment in adult patients and is not suitable 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 those without a prescription.

If you are taking
certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are applied only to the skin
ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol)
certain antibiotics (e.g. clarithromycin, erythromycin)
certain antiviral medicines for HIV/AIDS (e.g. ritonavir)
other medicines used to prevent 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 used to treat atrial fibrillation
certain medicines used to treat depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs))

If any of the conditions described above apply to you, inform your doctor before taking Xarelto, as the effect of Xarelto may be increased. Your doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored.
If your doctor believes you have an increased risk of developing stomach or intestinal ulcers, they may prescribe preventive treatment for ulcers.

If you are taking
certain medicines for epilepsy (phenytoin, carbamazepine, phenobarbital)
St. John's wort (Hypericum perforatum), a herbal medicine used for depression
rifampicin, an antibiotic

If any of the conditions described above apply to you, inform your doctor before taking Xarelto, as the effect of Xarelto may be reduced. Your doctor will decide whether you should be treated with Xarelto and whether you need to be closely monitored.
Pregnancy and breastfeeding
Do not take Xarelto during pregnancy or breastfeeding. If you may become pregnant, use a reliable method of contraception while taking Xarelto. If you become pregnant while taking this medicine, inform your doctor immediately, who will decide how to proceed with treatment.
Driving and using machines
Xarelto may cause dizziness (a common side effect) or fainting (an uncommon side effect) (see section 4, “Possible side effects”). If you experience these symptoms, do not drive, ride a bicycle, or operate tools or machinery.
Xarelto contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Xarelto

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
Xarelto should be taken with food.
Swallow the tablet or tablets with some water.
If you have difficulty swallowing the tablet whole, ask your doctor how to take Xarelto in another way. The tablet may be crushed and mixed with water or apple puree immediately before administration. After taking the mixture, food should be taken immediately.
If necessary, your doctor may administer crushed Xarelto tablets through a tube inserted into the stomach.

What dose to take
The recommended dose is one 15 mg Xarelto tablet twice daily for the first 3 weeks.
After 3 weeks, the recommended dose is one 20 mg Xarelto tablet once daily.
This starter pack containing 15 mg and 20 mg Xarelto tablets is intended for use only during the first 4 weeks of treatment. Once this pack is finished, treatment will continue with Xarelto 20 mg once daily, as instructed by your doctor.
If you have kidney problems, your doctor may decide to reduce the dose after 3 weeks to one 15 mg Xarelto tablet once daily, if your risk of bleeding is greater than your risk of developing a new blood clot.

If you forget to take Xarelto
If you are taking one 15 mg tablet twice daily and you miss a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in one day. If you miss a dose, you may take two 15 mg tablets together to achieve a total of two tablets (30 mg) in one day. On the following day, continue with one 15 mg tablet twice daily.
If you are taking one 20 mg tablet once daily and you miss a dose, take it as soon as you remember. Do not take more than one tablet in one day to make up for the missed dose. Take your next tablet the following day and then continue with one tablet once daily.

If you stop taking Xarelto
Do not stop taking Xarelto without first talking to your doctor, because Xarelto treats serious conditions and helps prevent them from occurring.
If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Xarelto can cause side effects, although not everybody gets them.
Like other similar medicines used to reduce blood clot formation, Xarelto can cause bleeding which
may potentially be life-threatening. Severe bleeding can cause a sudden drop in
arterial pressure (shock). In some cases, bleeding may not be obvious.
Contact your doctor immediately if you notice any of the following side effects:

Signs of bleeding
- bleeding in the brain or skull (symptoms may include headache, weakness on one side of the body, vomiting, seizures, reduced level of consciousness, and neck stiffness. This is a serious medical emergency. Seek immediate medical help!)
- prolonged or excessive blood loss
- unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina pectoris. Your doctor may decide to monitor you closely or modify your treatment.
Signs of severe skin reactions
- widespread and intense rash, blisters or mucosal lesions, for example in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
- a drug reaction causing rash, fever, internal organ inflammation, blood abnormalities, and systemic illness (DRESS syndrome). The frequency of these side effects is very rare (may occur in up to 1 in 10,000 people).
Signs of severe allergic reactions
- swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives; breathing difficulties; sudden drop in blood pressure. The frequencies of severe allergic reactions are very rare (anaphylactic reactions, including anaphylactic shock; may occur in up to 1 in 10,000 people) and uncommon (angioedema and allergic edema; may occur in up to 1 in 100 people).

Complete list of possible side effects:
Common (may occur in up to 1 in 10 people):

reduction in red blood cells, which may cause pale skin, weakness or shortness of breath
bleeding in the stomach or intestines, urogenital bleeding (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding gums
bleeding in the eye (including bleeding into the white part of the eye)
bleeding into tissues or body cavities (hematoma, bruising)
coughing up blood
bleeding from or under the skin
bleeding after surgery
loss of blood or fluid from the surgical wound
swelling of limbs
limb pain
kidney dysfunction (may be detected by blood tests performed by your doctor)
fever
stomach pain, indigestion, feeling unwell, constipation, diarrhoea
low blood pressure (symptoms include dizziness or fainting when standing)
general decrease in strength and energy (weakness, fatigue), headache, dizziness
rash, itchy skin
increased levels of certain liver enzymes in blood tests

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

bleeding in the brain or within the skull (see above, signs of bleeding)
joint bleeding, causing pain and swelling
thrombocytopenia (reduction in platelet count; platelets are cells that help blood to clot)
allergic reactions, including allergic skin reactions
liver dysfunction (may be detected by blood tests performed by your doctor)
blood tests may show increased bilirubin, increased levels of certain pancreatic or liver enzymes, or increased platelet count
fainting
feeling unwell
rapid heartbeat
dry mouth
hives

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

muscle bleeding
cholestasis (reduced flow of bile, a substance produced by the liver), hepatitis including hepatocellular injury (liver inflammation including liver damage)
yellowing of the skin and eyes (jaundice)
localized swelling with formation of a blood collection (hematoma) in the groin as a complication of a heart procedure involving insertion of a catheter into the leg artery (pseudoaneurysm)

Very rare (may occur in up to 1 in 10,000 people):
accumulation of eosinophils, a type of granulocytic white blood cell, causing lung inflammation
(eosinophilic pneumonia)
Frequency not known (frequency cannot be estimated from the available data):

kidney failure following severe bleeding
kidney bleeding sometimes with blood in the urine leading to kidney dysfunction (Anticoagulant nephropathy)
increased pressure in the muscles of the arms or legs after bleeding, causing pain, swelling, altered sensation, numbness or paralysis (compartment syndrome following bleeding)

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

5. How to store Xarelto

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 wallet container after Scad./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 and apple puree for up to 4 hours.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Xarelto contains

The active substance is rivaroxaban. Each tablet contains either 15 mg or 20 mg of rivaroxaban.
The other components are:
Tablet core: microcrystalline cellulose, croscarmellose sodium, monohydrate lactose,
hypromellose (2910), sodium lauryl sulfate, magnesium stearate. See section 2 “Xarelto contains
lactose and sodium”.
Film coating of the tablet: macrogol (3350), hypromellose (2910), titanium dioxide
(E 171), iron oxide red (E 172).

Description of the appearance of Xarelto and contents of the pack
Xarelto 15 mg film-coated tablets are red, round, biconvex, with the BAYER cross imprinted on one side and “15” and a triangle on the other side.
Xarelto 20 mg film-coated tablets are red-brown, round, biconvex, with the BAYER cross imprinted on one side and “20” and a triangle on the other side.
Starter pack for the first 4 weeks of treatment: each pack containing 49 film-coated tablets for the first 4 weeks of treatment includes:
42 film-coated tablets containing 15 mg of rivaroxaban and 7 film-coated tablets containing 20 mg of rivaroxaban, in a wallet-style container.

Marketing Authorization Holder
Bayer AG
51368 Leverkusen
Germany

Manufacturer
The manufacturer can be identified by the batch number printed on the side of the package 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 S.r.l. 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 further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder.