Package Leaflet: Information for the User

Xarelto 2.5 mg Film-Coated Tablets

rivaroxaban

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

-Keep this leaflet, as you may need to read it again.

-If you have any questions, ask your doctor or pharmacist.

-This medicine has been prescribed for you only. Do not pass it on to others even if their symptoms are the same as yours. It may harm them.

-If you experience any side effects, talk to your doctor or pharmacist. This includes very rare side effects. Check the full list of side effects in section 4.

1.What Xarelto is and what it is 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 additional information

You have been prescribed Xarelto because

• you have been diagnosed with acute coronary syndrome (a group of disorders that includes myocardial infarction and unstable angina, a severe type of chest pain) and your blood test results show elevated levels in certain heart tests.

Xarelto reduces the risk of experiencing another myocardial infarction in adults, or reduces the risk of death due to heart disease or vascular disease.

Your doctor will prescribe Xarelto along with another medication. Your doctor will also instruct you to take:

• aspirin, or
• aspirin plus clopidogrel or ticlopidine

or

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

Xarelto contains the active ingredient rivaroxaban, which belongs to a group of medications called antithrombotic medications. It acts by blocking a clotting factor (factor Xa) and therefore, reducing the tendency of blood to form clots.

Do not take Xarelto

• if you are allergic to rivaroxaban or any of the other ingredients of this medication (listed in section6)
• if you bleed excessively
• if you have a disease or problem in an organ of the body that increases the risk of severe bleeding (for example, stomach ulcer, brain injury or bleeding, or recent surgery in the brain or eyes)
• if you are taking medications to prevent blood clot formation (e.g., warfarin, dabigatran, apixaban, or heparin), except when switching to another anticoagulant or while receiving heparin through a central venous or arterial catheter, to prevent blockage
• if you have an acute coronary syndrome and have previously had a bleeding or a blood clot in the brain (stroke)
• if you have coronary artery disease or peripheral artery disease and have previously had a bleeding in the brain (stroke) or obstruction of small arteries that supply deep brain tissues (lacunar stroke) or have had a blood clot in the brain (non-lacunar ischemic stroke) in the past 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 your case.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Xarelto.

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

Be especially careful with Xarelto

• if you have an increased risk of bleeding, which may occur in the following situations:

• severe kidney failure, as kidney function may affect the amount of medication that acts in your body
• if you are taking other medications to prevent blood clot formation (e.g., warfarin, dabigatran, apixaban, or heparin), when switching to another anticoagulant or while receiving heparin through a central venous or arterial catheter, to prevent blockage (see section “Other medications and Xarelto”)
• bleeding disorder
• uncontrolled high blood pressure
• stomach or intestinal diseases that may cause bleeding, such as stomach or intestinal inflammation, esophageal inflammation, for example due to gastroesophageal reflux disease (disease in which stomach acid rises up into the esophagus), or localized tumors in the stomach, intestines, genital tract, or urinary tract
• problem with blood vessels in the back of your eyes (retinopathy)
• lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or have previously had a bleeding in the lungs
• you are over 75years old
• you weigh less than 60kg
• you have severe symptomatic heart failure with coronary artery disease.

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

Inform your doctor if you experience any of these situationsbefore taking Xarelto.Your doctor will decide if you should be treated with this medication and if you should be under closer observation.

If you need surgery

• It is very important to take Xarelto before and after the operation, exactly at the hours indicated by your doctor.
• If your operation requires the placement of a catheter or injection in the spinal column (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 hours that your doctor has indicated.
• Inform your doctor immediately if you experience numbness or weakness in your legs or problems with your intestines or bladder after the anesthesia, as urgent attention is required.

Children and adolescents

Xarelto 2.5mg tabletsare not recommended for children and adolescents under 18years old.No sufficient information is available on its use in children and adolescents.

Other medications and Xarelto

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

• If you are taking

• any medication for a fungal infection (e.g., fluconazole, itraconazole, voriconazole, posaconazole), except when applied to the skin
• tablets with ketoconazole (used to treat Cushing's syndrome, in which the body produces an excess of cortisol)
• any medication for bacterial infections (e.g., clarithromycin, erythromycin)
• anyantiviral medication for HIV/SIDA (e.g., ritonavir)
• other medications to prevent 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 medications (e.g., naproxen or aspirin)
• dronedarone, a medication for the treatment of irregular heartbeat
• some medications for depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs))

If any of the above circumstances apply to you,inform your doctorbefore taking Xarelto, as the effect of Xarelto may be increased.Your doctor will decide if you should be treated with this medication and if you should be under closer observation.

If your doctor considers that you have a higher risk of developing a stomach or intestinal ulcer, they may recommend additional preventive treatment.

• If you are taking

• anymedication for the treatment of epilepsy(phenytoin, carbamazepine, phenobarbital)
• St. John's Wort (Hypericum perforatum)a medicinal plant for the treatment of depression
• rifampicin,a antibiotic

If any of the above circumstances apply to you, informe 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 under closer observation.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding,do not take Xarelto.If there is any possibility of becoming pregnant, use a reliable contraceptive while taking Xarelto. If you become pregnant while taking Xarelto, inform your doctor immediately, who will decide how you should be treated.

Driving and operating machinery

Xarelto may cause dizziness (common side effect) or fainting (rare side effect) (see section4, “Possible side effects”). Do not drive, ride a bike, 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 certain sugars, consult with them before taking this medication.

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of 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 (for example, one tablet in the morning and another at night). This medication can be taken with or without food.

If you have difficulty swallowing the entire tablet, 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 along with another medication.

Your doctor will also instruct you to take acetylsalicylic acid.

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

If you are administered Xarelto after an intervention to open a narrowed or blocked artery in the leg to restore blood flow, your doctor may prescribe clopidogrel for you to take in addition to acetylsalicylic acid for a short period of time.

Your doctor will instruct you on the dose to take (usually between 75 and 100 mg of acetylsalicylic acid per day, or a daily dose of 75 mg of clopidogrel or a standard daily dose of ticlopidine, in addition to acetylsalicylic acid).

When to start treatment with Xarelto

Treatment with Xarelto after an acute coronary syndrome should be initiated as soon as possible, once the acute coronary syndrome has stabilized, that is, from 24 hours after admission to the hospital and at the time when the parenteral anticoagulant treatment (by injection) would end.

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

Your doctor will decide for how long you should continue 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 a single day to make up for a missed dose. If you forget to take a dose, take the next tablet at the usual time.

If you interrupt treatment with Xarelto

Take Xarelto regularly for the time your doctor tells you.

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

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

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

Like other medicines similar to reduce blood clot formation, Xarelto may cause bleeding that can put the patient's life at risk. Excessive bleeding can cause a sudden drop in blood pressure (shock). In some cases, bleeding may not be evident.

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

• Bleeding signs

• Brain or intracranial bleeding (symptoms may include headache, weakness on one side of the body, vomiting, seizures, decreased level of consciousness, and neck stiffness.This is a serious medical emergency. Seek medical attention immediately!).
• Prolonged or excessive bleeding
• Exceptional weakness, fatigue, pallor, 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.

• Signs of severe skin reactions

• Intense skin eruptions that spread, blisters, or lesions on mucous membranes, e.g., in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
• Medication reaction that causes rash, fever, internal organ inflammation, blood abnormalities, and systemic disease (DRESS syndrome).

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

• Signs of severe allergic reactions

• Swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing; hives, and 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 infrequent (angioedema and allergic edema; may affect up to 1 in 100 people).

General list of possible side effects

Frequent(may affect up to 1 in 10 people)

• Decreased red blood cells that can cause pallor and weakness or difficulty breathing
• Stomach or intestinal bleeding, hematuria (including blood in the urine and heavy menstrual bleeding), nasal bleeding, gum bleeding
• Eye bleeding (including bleeding in the white part of the eye)
• Bleeding into a tissue or cavity of the body (hematoma, ecchymosis)
• Coughing up blood
• Bleeding under the skin
• Bleeding after surgery
• Suppuration of blood or fluid from a surgical wound
• Swelling of the extremities
• Pain in the extremities
• Alteration of kidney function (may be seen in tests performed by your doctor)
• Fever
• Stomach pain, indigestion, dizziness, or sensation 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 skin
• Lab tests may show an increase in some liver enzymes

Infrequent(may affect up to 1 in 100 people)

• Brain or intracranial bleeding (see above, bleeding signs)
• Bleeding into a joint, which causes pain and swelling
• Thrombocytopenia (low platelet count, cells that help blood clotting)
• Allergic reaction, including skin rash
• Alteration of liver function (may be seen in tests performed by your doctor)
• Lab tests may show an increase in bilirubin, some pancreatic or liver enzymes, or platelet count
• Fainting
• Unpleasant feeling
• Increased heart rate
• Dry mouth
• Hives

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

• Bleeding into a muscle
• Bile duct obstruction, hepatitis, which includes traumatic liver cell injury (inflammation or liver damage)
• Yellow discoloration of the skin and eyes (jaundice)
• Localized swelling
• Accumulation of blood (hematoma) in the groin as a complication after cardiac 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 unknown(frequency cannot be estimated from available data)

• Renal insufficiency after severe bleeding
• Bleeding in the kidney, sometimes with blood in the urine, which causes the kidneys to function improperly (anticoagulant-related nephropathy)
• Increased pressure in the muscles of the legs or arms after bleeding, which causes pain, swelling, altered sensitivity, numbness, or paralysis (compartment syndrome after bleeding)

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational reporting systemincluded in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the 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 disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Xarelto

-The active ingredient is rivaroxaban. Each tablet contains 2.5 mg of rivaroxaban.

-The other components are:

Core tablet: microcrystalline cellulose, sodium croscarmellose, lactose monohydrate, hypromellose (2910), sodium lauryl sulfate, magnesium stearate. See section 2 “Xarelto contains lactose and sodium”.
Coating of the tablet: macrogol (3350), hypromellose (2910), titanium dioxide (E 171), iron oxide yellow (E 172).

Appearance of the product and contents of the pack

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

They are presented in:

-blister packs, in packs of 14, 20, 28, 30, 56, 60, 98, 168 or 196 film-coated tablets, or

-single-dose blister packs, in packs of 10 x 1 or 100 x 1, or

-multi-pack containers containing 10 blister packs, each containing 10 x 1 film-coated tablets, or

-100 film-coated tablets in a container.

Only some pack sizes may be marketed.

Marketing Authorisation Holder

Bayer AG

51368 Leverkusen

Germany

Responsible Person

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

•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

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorisation holder:

Last update of this leaflet:

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