XARELTO 15 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Xarelto 15mg film-coated tablets

Xarelto 20mg 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

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. Storing Xarelto
6. 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) or in other blood vessels of the body if you have a form of irregular heart rhythm 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 these blood clots from happening again in the veins and/or lungs.

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

• treat and prevent blood clots in the veins or in the blood vessels of the lungs after at least 5 days of initial treatment with injectable medicines used to treat blood clots.

Xarelto belongs to a group of medicines called antithrombotic agents. It works by blocking a factor in the blood that is involved in blood clotting (factor Xa), and thus reduces the tendency of the 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 serious bleeding (e.g. stomach ulcer, recent bleeding or lesions in the brain or recent brain or eye surgery)
• if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when switching from one anticoagulant to another or when heparin is given through a catheter to keep it from getting blocked
• if you have a liver disease that increases the risk of bleeding
• if you are pregnant or breast-feeding.

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

Warnings and precautions

Talk to your doctor or pharmacist before taking Xarelto.

Be careful with Xarelto

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

• severe kidney problems in adults and moderate or severe kidney problems in children and adolescents, as kidney function may affect the amount of medicine that works in the body
• if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), when switching from one anticoagulant to another or when receiving heparin through a catheter to keep it from getting blocked (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 inflammation of the intestines or stomach, inflammation of the esophagus (throat), e.g. due to gastroesophageal reflux disease (a disease in which stomach acid rises up into the esophagus), or tumors located in the stomach, intestines, genital or urinary tract
• a problem in the blood vessels of the back of your eyes (retinopathy)
• a lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous lung bleeding

• if you have a heart valve replacement
• if you know you have a disease called antiphospholipid syndrome (a disorder of the immune system that increases the risk of blood clots), inform your doctor to decide if it may be necessary to modify the treatment.
• if your doctor determines that your blood pressure is unstable or if you are scheduled to receive another treatment or undergo surgery to remove a blood clot from your lungs.

Tell your doctorif 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 surgery, exactly at the times your doctor tells you.
• If your operation requires the placement 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 your doctor has indicated.
• 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 tablets are not recommended in children with a body weight below 30kg.

There is not enough information about the use of Xarelto in children and adolescents for the indications in adults.

Other medicines and Xarelto

Tell your doctor or pharmacist if you are taking, have recently taken or might take 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)
• anti-inflammatory and pain-relieving medicines (e.g. naproxen or acetylsalicylic acid)
• 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 the above applies 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 recommend that you also take 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 the above applies 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 this medicine and if you should be kept under closer observation.

Pregnancy and breast-feeding

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

Driving and using machines

Xarelto may cause dizziness (common side effect) or fainting (uncommon side effect) (see section 4 "Possible side effects"). You should not drive, ride a bicycle or use 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

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

You must take Xarelto with food.

Swallow the tablets, preferably with water.

If you have difficulty swallowing the tablet whole, ask your doctor about other ways to take Xarelto. The tablet can be crushed and mixed with water or apple puree, immediately before taking it. Then take 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 placement), 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 work properly) in addition to an antiplatelet medicine such as clopidogrel.

• to treat blood clots in the veins of the legs and in the blood vessels of the lungs, and to prevent these blood clots from happening again.

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 treatment for blood clots, your doctor may decide to continue treatment with one Xarelto 10 mg tablet once a day or one Xarelto 20 mg tablet once a day.

If you have kidney problems and are taking one Xarelto 20 mg tablet once a day, your doctor may decide to reduce the treatment dose to one Xarelto 15 mg tablet once a day after 3 weeks if the risk of bleeding is higher than the risk of having 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 30kg to less than 50kgis one Xarelto 15mgtablet once a day.
• The recommended dose for children and adolescents with a body weight of 50kgor more is one Xarelto 20mgtablet 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: watch the child to make sure they take the entire dose.

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

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

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

In children and adolescents who cannot swallow whole tablets, please use Xarelto granules for oral suspension.

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

If you spit up the dose or vomit

• less than 30 minutes after taking Xarelto, take a new dose.
• more than 30 minutes after taking Xarelto, do nottake a new dose. In this case, take the next dose of Xarelto at the usual time.

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

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 how long you should continue taking the treatment.

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

If it is necessary to normalize your heartbeat through a procedure called cardioversion, take Xarelto at the times your doctor has indicated.

If you forget to take Xarelto

• Adults, children and adolescents:

If you are taking one 20 mg or one 15 mg tablet oncea day, and you forget a dose, take it as soon as you remember. Do not take more than one tablet in one day to make up for a forgotten dose. Take the next tablet the next day and then continue taking one tablet every day.

• Adults:

If you are taking one 15 mg tablet twicea day, and you forget a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in one day. If you forget a dose, you can take two 15 mg tablets at the same time, for a total of two tablets (30 mg) in one day. The next day, you should continue taking one 15 mg tablet twice a day.

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 stop taking Xarelto

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

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

4. Possible Adverse Effects

Like all medicines, Xarelto can cause adverse effects, although not all people suffer from them.

Like other similar medicines to reduce blood clot formation, Xarelto can 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, the bleeding may not be evident.

Inform 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, unilateral weakness, 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, which can be signs of bleeding.

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

• Signs of severe skin reactions

• intense skin rashes that spread, 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 adverse 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 uncommon (angioedema and allergic edema; may affect up to 1 in 100 people).

General list of possible adverse effects found in adults, children, and adolescents

Frequent(may affect up to 1 in 10 people)

• decrease in red blood cells that can cause paleness and weakness or difficulty breathing
• stomach or intestinal bleeding, urogenital hemorrhage (including blood in the urine and heavy menstrual bleeding), nasal bleeding, gum bleeding
• 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 include 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

Uncommon(may affect up to 1 in 100 people)

• bleeding in the brain or inside the skull (see above, signs of bleeding)
• bleeding into a joint, causing pain and swelling
• thrombocytopenia (low platelet count, cells that help blood clotting)
• 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 into 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
• accumulation of blood (hematoma) in the groin after a complication in heart surgery where 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 white blood cell granulocytes that cause inflammation in the lung (eosinophilic pneumonia).

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

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

Adverse Effects in Children and Adolescents

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

Adverse effects that were more frequently observed 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)

• accelerated heart rate
• blood tests may show an increase in bilirubin (bile pigment)
• thrombocytopenia (low platelet count, cells that help blood clotting)
• heavy menstrual bleeding

Uncommon(may affect up to 1 in 100 people)

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

Reporting of 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 leaflet. You can also report them 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 medicine.

5. Storage of Xarelto

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

Do not use this medicine after the expiration date that appears on the packaging and on each blister or bottle after "EXP" or "CAD".

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 puree for up to 4 hours.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the 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 15 mg or 20 mg of rivaroxaban.
• The other ingredients 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), red iron oxide (E 172).

Product Appearance and Package Contents

The Xarelto 15 mg film-coated tablets are round, red, biconvex, and bear the Bayer cross on one side, and "15" and a triangle on the other.

They are packaged

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

The Xarelto 20 mg film-coated tablets are round, brown-red, biconvex, and bear the Bayer cross on one side, and "20" and a triangle on the other.

They are packaged

• in blisters, in packs of 10, 14, 28, or 98 film-coated tablets, or
• in unit-dose blisters, in packs of 10 x 1 or 100 x 1, or
• in multiple packs containing 10 packs of 10 x 1 film-coated tablets, or
• in bottles containing 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 pack 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 medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

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