XARELTO 2.5 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Xarelto 2.5 mg film-coated tablets

rivaroxaban

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

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

1. What is Xarelto and what is it used for

You have been prescribed Xarelto because

• you have been diagnosed with acute coronary syndrome (a group of conditions that include heart attack and unstable angina, a type of severe chest pain) and your blood tests have shown high levels of certain heart tests.

Xarelto reduces the risk of having another heart attack in adults, or reduces the risk of death due to heart disease or blood vessel disease.

You will be prescribed Xarelto together with another medicine. Your doctor will also tell you to take:

• aspirin, or
• aspirin plus clopidogrel or ticlopidine

or

• you have been diagnosed with a high risk of blood clot formation due to coronary artery disease or peripheral artery disease that causes symptoms. Xarelto reduces the risk of blood clot formation (atherothrombotic events) in adults.

You will be prescribed Xarelto together with another medicine. Your doctor will also tell you to take aspirin.

In some cases, if you are given Xarelto after a procedure to open a narrowed or blocked artery in your leg to restore blood flow, your doctor may also prescribe clopidogrel for you to take in addition to aspirin for a short period of time.

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

2. What you need to know before you take Xarelto

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 have bleeding problems
• if you have a disease or condition that increases the risk of major bleeding (such as stomach ulcer, brain injury or recent brain or eye surgery)
• if you are taking medicines to prevent blood clots (e.g. warfarin, dabigatran, apixaban or heparin), except when switching to another anticoagulant treatment or while being given heparin through a vein or artery to prevent blockage
• 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 bleeding in the brain (stroke) or blockage of small arteries that supply blood to the deep tissues of the brain (lacunar stroke) or have had a blood clot in the brain (non-lacunar ischemic stroke) in the last month
• if you have liver disease that may increase the risk of bleeding
• if you are pregnant or breastfeeding.

Do not take Xarelto and inform your doctorif any of these circumstances apply to you.

Warnings and precautions

Consult your doctor or pharmacist before starting Xarelto.

Xarelto should not be used in combination with other medicines that reduce blood clotting, other than aspirin or clopidogrel/ticlopidine, such as prasugrel or ticagrelor.

Be careful with Xarelto

• if you have an increased risk of bleeding, such as in the following situations:
• • severe kidney problems, as kidney function may affect the amount of medicine that works in your body
  • if you are taking other medicines to prevent blood clots (e.g. warfarin, dabigatran, apixaban or heparin), when switching to another anticoagulant treatment or while receiving heparin through a vein or artery to prevent blockage (see section "Other medicines and Xarelto")
  • bleeding disorders
  • very high blood pressure, not controlled by medical treatment
  • stomach or intestinal diseases that may cause bleeding, such as stomach or intestinal inflammation, esophageal inflammation (e.g. due to gastroesophageal reflux disease), or tumors in the stomach, intestines, genital or urinary tract
  • a problem with the blood vessels in the back of your eyes (retinopathy)
  • a lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or have had previous bleeding in the lungs
  • you are over 75 years old
  • if you weigh less than 60 kg
  • you have coronary artery disease with severe symptomatic heart failure.
• if you have a heart valve prosthesis
• if you know you have a disease called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor to decide if it may be necessary to modify the treatment.

Tell your doctor if you have any of these conditionsbefore taking 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 surgery

• It is very important to take Xarelto before and after the operation, exactly at the times indicated by your doctor.
• If your operation requires the insertion of a catheter or injection into the spine (e.g. for epidural or spinal anesthesia, or pain relief):
• • It is very important to take Xarelto, before and after the injection or removal of the catheter, exactly at the times indicated by your doctor.
  • Tell your doctor immediately if you experience numbness or weakness in your legs or problems with your intestines or bladder after anesthesia, as urgent attention is needed.

Children and adolescents

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

Other medicines and Xarelto

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines, including those obtained without a prescription.

• If you are taking
• • any medicine for a fungal infection (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless it is only applied to the skin
  • tablets with ketoconazole (used to treat Cushing's syndrome, in which the body produces too much cortisol)
  • any medicine for bacterial infections (e.g. clarithromycin, erythromycin)
  • any antiviral medicine for HIV/AIDS (e.g. ritonavir)
  • other medicines to reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists, such as warfarin or acenocoumarol, prasugrel and ticagrelor (see section "Warnings and precautions"))
  • anti-inflammatory and pain-relieving medicines (e.g. naproxen or aspirin)
  • dronedarone, a medicine for the treatment of irregular heartbeat
  • certain medicines for the treatment of depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs))

If any of these circumstances apply to you, tell your doctorbefore taking Xarelto, as 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 considers that you have a higher risk of developing a stomach or intestinal ulcer, he may also recommend a preventive treatment.

• If you are taking
• • any medicine for the treatment of epilepsy (phenytoin, carbamazepine, phenobarbital)
  • St. John's Wort (Hypericum perforatum) a herbal medicine for the treatment of depression
  • rifampicin, an antibiotic

If any of these circumstances apply to you, tell your doctorbefore taking Xarelto, as 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 breastfeeding

Do not take Xarelto if you are pregnant or breastfeeding. If there is a possibility that you may become pregnant, use a reliable contraceptive while taking Xarelto. If you become pregnant while taking Xarelto, 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"). Do not drive, ride a bicycle or use tools or machines if you are affected by these symptoms.

Xarelto contains lactose and sodium

If your doctor has told you that you have an intolerance to some sugars, consult him before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take Xarelto

Follow exactly the instructions of administration of this medicine indicated by your doctor. If you are in doubt, consult your doctor or pharmacist again.

What dose to take

The recommended dose is one 2.5 mg tablet twice a day. Take Xarelto at the same time every day (e.g. 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, consult your doctor about other ways to take Xarelto. The tablet can be crushed and mixed with water or apple sauce, immediately before taking it.

If necessary, your doctor may also administer the crushed Xarelto tablet through a gastric tube.

You will be prescribed Xarelto together with another medicine.

Your doctor will also tell you to take aspirin. If you receive Xarelto after an acute coronary syndrome, your doctor may also tell you to take clopidogrel or ticlopidine.

If you are given Xarelto after a procedure to open a narrowed or blocked artery in your leg to restore blood flow, your doctor may also prescribe clopidogrel for you to take in addition to aspirin for a short period of time.

Your doctor will tell you the dose to take (usually between 75 and 100 mg of aspirin per day, or a dose of 75 to 100 mg of aspirin plus a daily dose of 75 mg of clopidogrel or a standard daily dose of ticlopidine).

When to start treatment with Xarelto

Treatment with Xarelto after an acute coronary syndrome should be started as soon as possible, once the acute coronary syndrome has been stabilized, i.e. from 24 hours after hospital admission and at the time when parenteral anticoagulant treatment (by injection) would be discontinued.

Your doctor will tell you when to start treatment with Xarelto if you have been diagnosed with coronary artery disease or peripheral artery disease.

The doctor will decide how long you should continue taking the treatment.

If you take more Xarelto than you should

Call 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 more than one tablet in one day to make up for a forgotten dose. If you forget to take a dose, take the next tablet at the usual time.

If you stop taking Xarelto

Take Xarelto regularly for the time indicated by your doctor.

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

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

4. Possible side effects

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

Like other similar medicines to reduce blood clotting, Xarelto can cause bleeding that can put your life at risk. Excessive bleeding can cause a sudden drop in blood pressure (shock). In some cases, the bleeding may not be visible.

Tell your doctor immediately if you experience any of the following symptoms:

• Signs of bleeding

• bleeding in the brain or inside the skull (symptoms may include headache, weakness on one side of the body, vomiting, seizures, decreased level of consciousness and stiffness of the neck. This is a serious medical emergency. Go to the doctor immediately!)
• prolonged or excessive bleeding
• exceptional weakness, fatigue, paleness, dizziness, headache, unexplained swelling, difficulty breathing, chest pain or angina

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

?

• severe skin rash that spreads, blisters or lesions on the mucous membranes, e.g. in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
• drug reaction that causes rash, fever, inflammation of internal organs, blood abnormalities and systemic disease (DRESS syndrome).

The frequency of these side effects is very rare (up to 1 in 10,000 people).

?

• swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives and difficulty breathing; 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 edema; may affect up to 1 in 100 people).

General List of Possible Adverse Effects

Frequent(may affect up to 1 in 10 people)

• decrease in red blood cells that can cause paleness and weakness or difficulty breathing
• bleeding from the stomach or intestine, urogenital hemorrhage (including blood in the urine and heavy menstrual bleeding), nasal bleeding, bleeding from the gums
• bleeding in the eye (including bleeding in the white part of the eye)
• bleeding into a tissue or cavity of the body (hematoma, bruising)
• coughing up blood
• bleeding from the skin or under the skin
• bleeding after surgery
• oozing of blood or fluid from a surgical wound
• swelling of the limbs

• pain in the limbs
• alteration of kidney function (may be seen in tests performed by the doctor)
• fever
• stomach pain, indigestion, dizziness or feeling of dizziness, constipation, diarrhea
• low blood pressure (symptoms may be dizziness or fainting when standing up)
• general decrease in strength and energy (weakness, fatigue), headache, dizziness
• rash, itching of the skin
• blood tests may show an increase in some liver enzymes

Infrequent(may affect up to 1 in 100 people)

• bleeding in the brain or inside the skull (see above, signs of bleeding)
• bleeding in a joint, causing pain and swelling
• thrombocytopenia (low platelet count, cells that help blood clot)
• allergic reaction, including skin allergic reaction
• alteration of liver function (may be seen in tests performed by the doctor)
• blood tests may show an increase in bilirubin, some pancreatic or liver enzymes, or platelet count
• fainting
• feeling of discomfort
• increased heart rate
• dry mouth
• hives

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

• bleeding in a muscle
• cholestasis (decrease in bile flow), hepatitis, including traumatic hepatocellular injury (inflammation or liver damage)
• yellowing of the skin and eyes (jaundice)
• localized swelling
• blood accumulation (hematoma) in the groin as a complication after heart surgery in which a catheter is inserted into the leg artery (pseudoaneurysm)

Very Rare(may affect up to 1 in 10,000 people)

• accumulation of eosinophils, a type of granulocytic white blood cell that causes inflammation in the lung (eosinophilic pneumonia)

Frequency Not Known(frequency cannot be estimated from available data)

• kidney failure after severe bleeding
• bleeding in the kidney, sometimes with blood in the urine, which causes the kidneys to malfunction (anticoagulant-related nephropathy)
• increase in pressure in the muscles of the legs or arms after bleeding, causing pain, swelling, altered sensation, numbness, or paralysis (compartment syndrome after bleeding)

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report it directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Xarelto

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the packaging and on each blister or bottle after "CAD" or "EXP". The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Crushed tablets

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

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Xarelto Composition

• The active ingredient is rivaroxaban. Each tablet contains 2.5 mg of rivaroxaban.
• The other components are:

Tablet core: microcrystalline cellulose, sodium croscarmellose, lactose monohydrate, hypromellose (2910), sodium lauryl sulfate, magnesium stearate. See section 2 "Xarelto contains lactose and sodium".

Tablet film coating: macrogol (3350), hypromellose (2910), titanium dioxide (E 171), yellow iron oxide (E 172).

Product Appearance and Package Contents

Xarelto 2.5 mg film-coated tablets are pale yellow, round, biconvex, and have the Bayer cross engraved on one side, and "2.5" and a triangle on the other.

They are packaged

• in blisters, in boxes of 14, 20, 28, 30, 56, 60, 98, 168, or 196 film-coated tablets, or
• in single-dose blisters, in packs of 10 x 1 or 100 x 1, or
• in multiple packs containing 10 boxes, 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 flap of the box 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

You can request more information about this medication from the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:

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