Xarelto 15 mg film-coated tablets (100 tablets)

Patient Information Leaflet

Introduction

Package leaflet: Information for the user

Xarelto 15 mg film-coated tablets

Xarelto 20 mg film-coated tablets

rivaroxaban

Read the entire leaflet carefully before starting to take this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if the effects are not listed in this leaflet. See section 4.

Package leaflet

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

1. What Xarelto is and what it is 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 type of irregular heartbeat known as 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 recurring in the blood vessels of the legs 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 blood clots and prevent the recurrence of blood clots 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. It works by blocking a clotting factor (factor Xa), thereby reducing the tendency of the blood to form clots.

2. What you need to 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 are bleeding excessively
• if you have a disease or organ condition that increases the risk of severe bleeding (for example, stomach ulcer, brain injury or bleeding in the brain, or recent surgery on the brain or eyes)
• if you are taking medicines to prevent blood clots (e.g., warfarin, dabigatran, apixaban, or heparin), except when switching from one anticoagulant treatment to another or while heparin is being administered through a venous or arterial catheter to prevent blockage
• if you have a liver disease that increases the risk of bleeding
• if you are pregnant or breastfeeding.

Do not take Xarelto and inform your doctor if any of these situations apply to you.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Xarelto.

Exercise special caution with Xarelto

• if you have an increased risk of bleeding, as may occur in the following situations:
  • severe renal impairment in adults and moderate or severe renal impairment in children and adolescents, since kidney function may affect the amount of drug active in the body
  • if you are taking other medications to prevent blood clots (e.g., warfarin, dabigatran, apixaban, or heparin), when switching to another anticoagulant treatment, or while receiving heparin through a venous or arterial catheter to prevent it from becoming blocked (see section “Other medicines and Xarelto”)
  • hemorrhagic disorder
  • very high blood pressure not controlled by medical treatment
  • stomach or intestinal diseases that could cause bleeding, such as intestinal or gastric inflammation, esophageal inflammation (e.g., due to gastroesophageal reflux disease [a condition in which stomach acid flows back up into the esophagus]), or tumors located in the stomach, intestines, genital tract, or urinary tract
  • a problem in the blood vessels at 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 prosthesis
• if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor so they can decide whether treatment adjustment may be necessary
• if your doctor determines that your blood pressure is unstable or if you are scheduled to receive another treatment or undergo a surgical procedure to remove a blood clot from your lungs

Inform your doctor if you are in any of these situations before taking Xarelto. Your doctor will decide whether you should be treated with this medicine and whether you need to be more closely monitored.

If you need a surgical procedure

• It is very important to take Xarelto before and after surgery exactly at the times your doctor has instructed.
• If your operation requires the placement of a catheter or an injection into the spinal column (for example, 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 instructed.
  • Inform your doctor immediately if you experience numbness or weakness in the legs or problems with the bowel or bladder at the end of anesthesia, as urgent medical attention is required.

Children and adolescents

Xarelto tablets are not recommended in children with a body weight below 30 kg. There is insufficient information on the use of Xarelto in children and adolescents for the indications approved in adults.

Other medicines and Xarelto

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

• If you are taking
  • any medicine for a fungal infection (e.g., fluconazole, itraconazol, voriconazole, posaconazole), except if applied only to the skin
  • ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces excess 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 medicines and pain relievers (e.g., naproxen or acetylsalicylic acid)
  • dronedarone, a medicine used to treat irregular heartbeat
  • certain medicines used to treat depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs))

If any of the above situations apply to you, inform your doctor before taking Xarelto, as the effect of Xarelto could be increased. Your doctor will decide whether you should be treated with this medicine and whether you should be under closer monitoring.

If your doctor considers that you have an increased risk of developing a stomach or intestinal ulcer, they may recommend that you also receive preventive treatment.

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

If any of the above situations apply to you, inform your doctor before taking Xarelto, as the effect of Xarelto could be reduced. Your doctor will decide whether you should be treated with this medicine and whether you should be under closer monitoring.

Pregnancy and breastfeeding

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

Driving and operating machinery

Xarelto may cause dizziness (a common adverse effect) or fainting (an uncommon adverse effect) (see section 4 "Possible adverse effects"). You should not drive, ride a bicycle, or use tools or machinery if you are affected by these symptoms.

Xarelto contains lactose and sodium

If your doctor has informed you of an intolerance to certain sugars, consult with him before taking this medicine.

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

3. How to take Xarelto

Follow exactly the instructions given by your doctor for taking this medicine. If you are unsure, consult your doctor or pharmacist again.

You should take Xarelto with food.

Swallow the tablets, preferably with water.

If you have difficulty swallowing the tablet whole, consult your doctor about other ways of taking Xarelto. The tablet may be crushed and mixed with water or apple puree immediately before administration. 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 daily.

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

If you require a procedure to treat blocked blood vessels in your heart (called percutaneous coronary intervention - PCI with stent placement), there is limited evidence supporting reducing the dose to one Xarelto 15 mg tablet once daily (or one Xarelto 10 mg tablet once daily if your kidneys are not functioning properly), in addition to an antiplatelet medicine such as clopidogrel.

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

The recommended dose is one Xarelto 15 mg tablet twice daily for the first 3 weeks. For treatment beyond 3 weeks, the recommended dose is one Xarelto 20 mg 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 Xarelto 20 mg tablet once daily, your doctor may decide to reduce your treatment dose to one Xarelto 15 mg tablet once daily after 3 weeks, if your risk of bleeding is higher than your risk of developing another blood clot.

- Children and adolescents

The dose of Xarelto depends on body weight and will be calculated by the doctor.

• The recommended dose for children and adolescents with a body weight between 30 kg and less than 50 kg is one Xarelto 15 mg tablet once daily.
• The recommended dose for children and adolescents with a body weight of 50 kg or more is one Xarelto 20 mg 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 help you remember.
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 important to attend scheduled visits with the doctor, as the dose may need to be adjusted as body weight changes.

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

Do not split the tablet in an attempt to obtain a fraction of the tablet dose. If a lower dose is required, please use the alternative formulation of Xarelto granules for oral suspension.

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

If the oral suspension is not available, you may crush the Xarelto tablet and mix it with water or apple puree immediately before administration. Give some food after taking this mixture. If necessary, your doctor may also administer crushed Xarelto tablets 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 dose of Xarelto at the usual time.

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

When to take Xarelto

Take the tablets every day, as long as your doctor instructs you to do so.

Try to take the tablets at the same time each day to help you remember when to take them. Your doctor will decide how long you should continue the treatment.

To prevent the formation of blood clots in the brain (stroke) or in other blood vessels: If heart rhythm normalization is required through a procedure called cardioversion, take Xarelto at the times indicated by your doctor.

If you forget to take Xarelto

• Adults, children, and adolescents:

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

• Adults:

If you are taking a 15 mg tablet twice daily and you forget 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 may take two 15 mg tablets at once, to obtain a total of two tablets (30 mg) in one day. The following day, you should continue taking a 15 mg tablet twice daily.

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 interrupt treatment with Xarelto

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

If you have any further 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 everyone will experience them.

Like other similar medicines used to reduce blood clot formation, Xarelto can cause bleeding that may be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). In some cases, bleeding may not be obvious.

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, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness. This is a serious medical emergency. Seek immediate medical attention!)

• prolonged or excessive bleeding

• unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, difficulty breathing, chest pain, or angina, which may be signs of bleeding.

Your doctor may decide to monitor you more closely or change your treatment.

? Signs of serious skin reactions

• severe skin rashes that spread, blisters or mucosal lesions, e.g., in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
• drug reaction causing rash, fever, internal organ inflammation, blood abnormalities, and systemic illness (DRESS syndrome).

The frequency of these adverse effects is very rare (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 difficulty breathing; sudden drop in blood pressure.

The frequencies of serious 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 observed in adults, children and adolescents

Frequent (may affect up to 1 in 10 people)

• decrease in red blood cells that may cause paleness, weakness or difficulty breathing
• bleeding from 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 body tissue or cavity (hematoma, bruising)
• coughing up blood
• bleeding of the skin or under the skin
• bleeding after surgery
• discharge of blood or fluid from a surgical wound
• swelling of limbs
• limb pain
• impaired kidney function (may be seen in tests performed by the doctor)
• fever
• stomach pain, indigestion, dizziness or feeling lightheaded, constipation, diarrhea
• low blood pressure (symptoms may include feeling dizzy or faint upon standing)
• general decrease in strength and energy (weakness, fatigue), headache, dizziness
• rash, itching of the skin
• blood tests may show increased levels of certain liver enzymes

Uncommon (may affect up to 1 in 100 people)

• bleeding in the brain or within the skull (see above, signs of bleeding)
• bleeding into a joint, causing pain and swelling
• thrombocytopenia (low platelet count, cells that help blood clot)
• allergic reaction, including skin allergic reaction
• impaired liver function (may be seen in tests performed by the doctor)
• blood tests may show increased levels of bilirubin, certain pancreatic or liver enzymes, or increased 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
• cholestasis (reduced bile flow), hepatitis, including traumatic hepatocellular injury (liver inflammation or damage)
• yellowing of the skin and eyes (jaundice)
• localized swelling
• accumulation of blood (hematoma) in the groin following a complication from cardiac surgery 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 granulocytic white blood cells causing lung inflammation (eosinophilic pneumonia)

Frequency not known (frequency cannot be estimated from available data)

• kidney failure following severe bleeding
• bleeding in the kidney, sometimes with blood in the urine, leading to inability of the kidneys to function properly (anticoagulant-related nephropathy)
• increased pressure in the muscles of the legs or arms following bleeding, causing pain, swelling, altered sensation, numbness or paralysis (compartment syndrome following bleeding)

Adverse effects in children and adolescents

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

Adverse effects observed more frequently in children and adolescents:

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

• headache
• fever
• nosebleeds
• vomiting

Frequent (may affect up to 1 in 10 people)

• increased heart rate
• blood tests may show increased bilirubin (bile pigment)
• thrombocytopenia (low platelet count, cells that help blood clot)
• heavy menstrual bleeding

Uncommon (may affect up to 1 in 100 people)

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

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse reactions, you can help provide 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 expiry date stated on the packaging and on each blister or bottle after “CAD” or “EXP”.

The expiry date refers to the last day of the month indicated.

No special storage conditions are required.

Crushed tablets

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any unused medicine and its packaging. This will help protect the environment.

6. Contents of the container and other information

Composition of Xarelto

• The active substance is rivaroxaban. Each tablet contains 15 mg or 20 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".

Film coating: 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 film-coated tablets are round, red, biconvex tablets, with the BAYER cross engraved on one side and "15" and a triangle on the other.

They are packaged as follows:

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

Xarelto 20 mg film-coated tablets are round, reddish-brown, biconvex tablets, with the BAYER cross engraved on one side and "20" and a triangle on the other.

They are packaged as follows:

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

Only certain 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 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

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

Belgium / Belgique / Belgien Bayer SA-NV Tel/Tel: +32-(0)2-535 63 11	Lithuania UAB Bayer Tel: +370-5-233 68 68
Bulgaria Bayer Bulgaria EOOD Tel: +359-(0)2-424 72 80	Luxembourg / Luxemburg Bayer SA-NV Tel/Tel: +32-(0)2-535 63 11
Czech Republic Bayer s.r.o. Tel: +420-266 101 111	Hungary Bayer Hungária KFT Tel: +36-1-487 4100
Denmark Bayer A/S Tlf: +45-45 235 000	Malta Alfred Gera and Sons Ltd. Tel: +356-21 44 62 05
Germany Bayer Vital GmbH Tel: +49-(0)214-30 513 48	Netherlands Bayer B.V. Tel: +31–(0)297-28 06 66
Estonia Bayer OÜ Tel: +372-655 85 65	Norway Bayer AS Tlf: +47-23 13 05 00
Greece Bayer Ελλάς ΑΒΕΕ Tel: +30-210-618 75 00	Austria Bayer Austria Ges. m. b. H. Tel: +43-(0)1-711 460
Spain Bayer Hispania S.L. Tel: +34-93-495 65 00	Poland Bayer Sp. z o.o. Tel: +48-22-572 35 00
France Bayer HealthCare Tél (Free phone): +33-(0) 800 87 54 54	Portugal Bayer Portugal, Lda. Tel: +351-21-416 42 00
Croatia Bayer d.o.o. Tel: + 385-(0)1-6599 900	Romania SC Bayer SRL Tel: +40-(0)21-528 59 00
Ireland Bayer Limited Tel: +353 1 216 3300	Slovenia Bayer d. o. o. Tel: +386-(0)1-58 14 400
Iceland Icepharma hf. Tel: +354-540 80 00	Slovakia Bayer, spol. s r.o. Tel: +421-(0)2-59 21 31 11
Italy Bayer S.p.A. Tel: +39-02-3978 1	Finland Bayer Oy Puh/Tel: +358-(0)20-78521
Cyprus NOVAGEM Limited Tel: +357-22-48 38 58	Sweden Bayer AB Tel: +46-(0)8-580 223 00
Latvia SIA Bayer Tel: +371-67 84 55 63	United Kingdom Bayer plc Tel: +44-(0)118 206 3000

Date of the most recent review of this leaflet:

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