Package Insert: Information for the User

Xarelto 15Film-Coated Tablets

Xarelto 20Film-Coated Tablets

rivaroxaban

Read this package insert carefully before starting to take this medication, as it contains important information for you.

-Keep this package insert, as you may need to refer to it again.

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

-This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor or pharmacist even if they are not listed in this package insert. See section4.

1.What is Xarelto and how is it used

2.What you need to know before starting to take Xarelto

3.How to take Xarelto

4.Possible adverse effects

5.Storage of Xarelto

6.Contents of the package and additional information

Xarelto contains the active ingredient rivaroxaban.

Xarelto is used in adults for:

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

Xarelto is used in children and adolescents under 18years and with a body weight of 30kg or more for:

-treat blood clots and prevent the recurrence of these blood clots in the veins or in the blood vessels of the lungs, after an initial treatment of at least 5days with injectable medications used to treat blood clots.

Xarelto belongs to a group of medications called antithrombotic agents. 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 condition in an organ that increases the risk of severe bleeding (e.g., stomach ulcer, brain injury or hemorrhage, or recent surgery in the brain or eyes)
• if you are taking medications to prevent blood clotting (e.g., warfarin, dabigatran, apixaban, or heparin), except when switching from one anticoagulant to another or while receiving heparin through a central venous or arterial catheter to prevent blockage
• if you have liver disease that increases 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.

Be extra careful with Xarelto

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

• severe kidney disease in adults and moderate to severe kidney disease in children and adolescents, as kidney function may affect the amount of medication that acts in the body
• if you are taking other medications to prevent blood clotting (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 inflammatory bowel disease or stomach inflammation, esophageal inflammation (e.g., due to gastroesophageal reflux disease), or localized tumors in the stomach, intestines, genital tract, or urinary tract
• problem with blood vessels in the back of the eyes (retinopathy)
• lung disease with dilated and filled bronchi (bronchiectasis) or previous lung hemorrhage

• 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 clotting), inform your doctor to decide if treatment modification is necessary
• if your doctor determines that your blood pressure is unstable or you are planning to receive another treatment or undergo a surgical procedure to remove a blood clot from your lungs.

Inform your doctorif 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 surgery, 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 catheter removal, exactly at the hours indicated by your doctor.
• Inform 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 required.

Children and adolescents

Xarelto tabletsare not recommended for children with a body weight of less than 30kg.

There is not enough information available on the use of Xarelto in children and adolescents for adult indications.

Other medications and Xarelto

Inform your doctor or pharmacist if you are using, have used recently, or may need to use 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)
• any antiviral medication for HIV/AIDS (e.g., ritonavir)
• other medications to prevent blood clotting (e.g., enoxaparin, clopidogrel, or vitamin K antagonists, such as warfarin or acenocoumarol)
• anti-inflammatory and pain-relieving medications (e.g., naproxen or acetylsalicylic acid)
• dronedarone, a medication for treating irregular heartbeats
• some medications for treating 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

• any medication for treating epilepsy (phenytoin, carbamazepine, phenobarbital)
• St. John's Wort (Hypericum perforatum),a medicinal plant for treating depression
• rifampicin,an antibiotic.

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

Pregnancy and breastfeeding

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

Driving and operating machinery

Xarelto may cause dizziness (frequent adverse effect) or fainting (infrequent adverse effect) (see section4 “Possible adverse effects”). You should 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 1 mmol 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.

You should take Xarelto with food.

Swallow the tablets, preferably with water.

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. Then, take some food.

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

What dose to take

• Adults

• To prevent the formation of blood clots in the brain (stroke) or in other blood vessels of the body

The recommended dose is one Xarelto 20 mg tablet once a day.

If you have kidney problems, the dose may be reduced to one Xarelto 15 mg tablet once a day.

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

• To treat blood clots in the veins of the legs and in the blood vessels of the lungs, and to prevent new blood clots from forming

The recommended dose is one Xarelto 15 mg tablet twice a day for the first 3 weeks. For treatment after 3 weeks, the recommended dose is one Xarelto 20 mg tablet once a day.

After at least 6 months of blood clot treatment, your doctor may decide to continue treatment with one 10 mg tablet once a day or one 20 mg tablet once a day.

If you have kidney problems and take one Xarelto 20 mg tablet once a day, your doctor may decide to reduce the dose to one Xarelto 15 mg tablet once a day after 3 weeks if the risk of bleeding is greater than the risk of another 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 of between 30 kg and less than 50 kg is one Xarelto 15 mg tablet once a day.
• The recommended dose for children and adolescents with a body weight of 50 kg or more is one Xarelto 20 mg tablet once a day.

Take each dose of Xarelto with a drink (e.g. water or juice) during a meal. Take the tablets every day at approximately the same time. Consider setting an alarm to remind you.

For parents or caregivers: observe the child to ensure they take the entire dose.

Since the dose of Xarelto is based on body weight, it is essential to attend scheduled visits with your doctor, as the dose may need to be adjusted as body weight changes.

Never adjust the dose of Xarelto on your own. Your doctor will adjust the dose if necessary.

Do not divide the tablet to try to obtain a fraction of the dose of the tablet. If a smaller dose is required, please use the alternative Xarelto granule presentation for oral suspension.

In children and adolescents who cannot swallow the entire tablets, please use Xarelto granule for oral suspension.

If oral suspension is not available, you can crush the Xarelto tablet and mix it with water or apple sauce immediately before taking it. Take some food after taking this mixture. If necessary, your doctor may also administer the crushed Xarelto tablet through a tube inserted into the stomach.

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 the next Xarelto dose at the usual time.

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

When to take Xarelto

Take the tablets every day until your doctor tells you to stop.

Try to take the tablets at the same time every day to remember when to take them.

Your doctor will decide for how long you should continue treatment.

To prevent blood clots in the brain (stroke) or in other blood vessels:

If necessary, normalize heart rhythm by a procedure called cardioversion, take Xarelto at the hours your doctor has indicated.

If you forgot to take Xarelto

• Adults, children, and adolescents:

If you are taking one 20 mg or one 15 mg tablet once a day, and you forgot to take a dose, take it as soon as you remember. Do not take more than one tablet in a single day to compensate for a missed dose. Take the next tablet the next day and then continue to take one tablet every day.

• Adults:

If you are taking two 15 mg tablets a day, and you forgot to take a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in a single day. If you forgot to take a dose, you can take two 15 mg tablets at once to get a total of two tablets (30 mg) in a day. The next day you should continue to take one 15 mg tablet twice a day.

If you take too much Xarelto

Call your doctor immediately if you have taken too many Xarelto tablets. Taking too much Xarelto increases the risk of bleeding.

If you interrupt Xarelto treatment

Do not stop Xarelto treatment without consulting your doctor first, as Xarelto treats and prevents serious conditions.

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

Like all medications, Xarelto may cause side effects, although not everyone will experience them.

Like other medications 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 apparent.

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

• Bleeding signs

• Brain or intracranial bleeding (symptoms may include headache, unilateral weakness, 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 pectoris,which may be signs of bleeding.

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

• Bleeding signs

• 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 found in adults, children, and adolescents

Frequent(may affect up to 1 in 10 people)

• Decreased red blood cells that may cause pallor and weakness or difficulty breathing
• Gastrointestinal bleeding 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
• Renal function alteration (may be seen in tests performed by the doctor)
• Fever
• Abdominal pain, indigestion, dizziness, or feeling dizzy, constipation, diarrhea
• Low blood pressure (symptoms may include dizziness or fainting when standing up)
• General weakness and fatigue (weakness, fatigue), headache, dizziness,
• Rash, itching skin
• 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 reaction
• Liver function alteration (may be seen in tests performed by the doctor)
• Tests may show an increase in bilirubin, some pancreatic or liver enzymes, or platelet count
• Fainting
• Feeling unwell
• Increased heart rate
• Dry mouth
• Hives

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

• Bleeding into a muscle
• Bile duct obstruction (decreased bile flow), hepatitis, which includes liver cell injury (inflammation or liver damage)
• Yellowing of the skin and eyes (jaundice)
• Localized swelling
• Blood accumulation (hematoma) in the groin after a complication in a heart surgery where a catheter is inserted into the leg artery (pseudoaneurysm)

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

• Eosinophil accumulation, a type of granulocytic white blood cell that causes inflammation in the lungs (eosinophilic pneumonia).

Unknown frequency(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)

Side effects in children and adolescents

In general, the side effects observed in children and adolescents treated with Xarelto were similar to those observed in adults, and their severity was mainly mild to moderate.

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

Very frequent(may affect more than 1 in 10 people)

• Headache
• Fever
• Nasal bleeding
• Vomiting

Frequent(may affect up to 1 in 10 people)

• Increased heart rate
• Tests may show an increase in bilirubin (bile pigment)
• Thrombocytopenia (low platelet count, cells that help blood clotting)
• Heavy menstrual bleeding

Infrequent(may affect up to 1 in 100 people)

• Tests may show an increase in a subcategory of bilirubin (direct bilirubin, bile pigment)

Reporting side effects

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

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.

No special storage conditions are required.

Crushed tablets

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Composition of Xarelto

- The active ingredient is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban.

- The other components are:

Nucleus of the 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 red (E 172).

Appearance of the product and contents of the package

Xarelto 15 mg tablets are round, red, biconvex, and have the Bayer cross engraved on one side and “15” and a triangle on the other.

They are packaged in:

• blister packs, in cartons of 10, 14, 28, 42 or 98 tablets, or
• single-dose blister packs, in packs of 10 x 1 or 100 x 1, or
• multi-pack containers containing 10 cartons of 10 x 1 tablets, or
• 100-tablet containers.

Xarelto 20 mg tablets are round, reddish-brown, biconvex, and have the Bayer cross engraved on one side and “20” and a triangle on the other.

They are packaged in:

• blister packs, in cartons of 10, 14, 28, or 98 tablets, or
• single-dose blister packs, in packs of 10 x 1 or 100 x 1, or
• multi-pack containers containing 10 cartons of 10 x 1 tablets, or
• 100-tablet containers.

Only some package 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 carton 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

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

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