Xarelto 20 mg film-coated tablets (28 tablets)

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Xarelto 15mg film-coated tablets

Xarelto 20mg film-coated tablets

rivaroxaban

Read the entire 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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 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 known as 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 for preventing 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 for:

• treating blood clots and preventing the recurrence of these blood clots in the veins or in the blood vessels of the lungs, after 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 condition affecting an organ in your body that increases the risk of serious bleeding (e.g., stomach ulcer, 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 receiving heparin through a venous or arterial catheter to prevent it from becoming blocked
• 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 circumstances apply to you.

Warnings and precautions

Talk to your doctor or pharmacist before you start taking Xarelto.

Take special care with Xarelto

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

• severe renal impairment in adults and moderate to severe renal impairment in children and adolescents, as kidney function may affect the amount of medicine active 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 venous or arterial catheter 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 could cause bleeding, such as intestinal or stomach inflammation, esophageal inflammation (e.g., due to gastroesophageal reflux disease (a condition in which stomach acid flows back up into the esophagus), or tumors in the stomach, intestines, genital tract, or urinary tract

• a problem with blood vessels at the back of your eyes (retinopathy)

• a lung disease in which the bronchi are widened 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 your treatment needs to be adjusted.

• 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 any of these situations apply to you before taking Xarelto. Your doctor will decide whether you should be treated with this medicine and whether you need closer monitoring.

If you need surgery

• It is very important to take Xarelto before and after surgery exactly at the times your doctor tells you.

• If your surgery requires placement of a catheter or injection into your spine (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 times your doctor has instructed.

• Inform your doctor immediately if you experience numbness or weakness in your legs or problems with your bowel or bladder after anesthesia, as urgent medical attention is required.

Children and adolescents

Xarelto tablets are not recommended for children weighing less than 30 kg.

There is insufficient information on the use of Xarelto in children and adolescents for adult indications.

Other medicines and Xarelto

Tell your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines, including those not prescribed.

• If you are taking

• a medicine for fungal infection (e.g., fluconazole, itraconazole, voriconazole, posaconazole), unless applied only to the skin

• ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol)

• a medicine for bacterial infections (e.g., clarithromycin, erythromycin)

• an 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 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 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 need closer monitoring.

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

• If you are taking

• a 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 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 need closer monitoring.

Pregnancy and breastfeeding

Do not take Xarelto if you are pregnant or breastfeeding. If there is any possibility you could 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 on appropriate treatment.

Driving and use of machines

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

Xarelto contains lactose and sodium

If your doctor has informed you that you have an intolerance to certain sugars, consult them before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which is essentially “sodium-free.”

3. How to take Xarelto

Follow exactly the instructions for using this medicine as given by your doctor. 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 to take 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 crushed Xarelto tablets through a gastric tube.

What dose to take

• Adults

• To prevent 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 need 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 in the 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 after 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 the risk of having 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 every day at approximately the same time. Consider setting an alarm to help you remember.

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

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

For 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 taking it. After taking this mixture, eat some food. 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

• within 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 your next dose of Xarelto at the usual time.

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

When to take Xarelto

Take the tablets every day, until your doctor tells you otherwise.

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 treatment.

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

If a procedure called cardioversion is needed to normalize your heart rhythm, take Xarelto at the times your doctor has instructed.

If you forget to take Xarelto

• Adults, children and adolescents:

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

• Adults:

If you are taking one 15 mg tablet twice daily and you miss a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in a single day. If you missed 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, resume taking one 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 stop taking 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 using this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, Xarelto can cause adverse effects, although not everyone experiences them.

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

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, 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, shortness of breath, 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 with eosinophilia and systemic symptoms (DRESS syndrome), characterized by rash, fever, internal organ inflammation, blood abnormalities, and systemic illness.

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; 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

Common (may affect up to 1 in 10 people)

• decrease in red blood cells that may cause paleness, weakness or difficulty breathing
• stomach or intestinal bleeding, urogenital hemorrhage (including blood in the 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 tissue or body cavities (hematoma, bruising)
• coughing up blood
• bleeding from or under the skin
• bleeding after surgery
• discharge of blood or fluid from a surgical wound
• swelling of the limbs
• limb pain
• impaired kidney function (may be seen in tests performed by your doctor)
• fever
• stomach pain, indigestion, dizziness or feeling dizzy, 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, skin itching
• blood tests may show increased levels of certain 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 reactions
• impaired liver function (may be seen in tests performed by your doctor)
• blood tests may show increased levels of bilirubin, certain 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
• 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 inflammation in the lung (eosinophilic pneumonia).

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

• renal failure following severe bleeding.
• bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (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, adverse effects observed in children and adolescents treated with Xarelto were similar in type to those seen in adults, and their severity was mostly 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

Common (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 clotting)
• 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 effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, 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 properly dispose of any unused medicine and its packaging. This will help protect the environment.

6. Contents of the pack 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, croscarmellose sodium, 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 pack

Xarelto 15 mg film-coated 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 blisters, in cartons of 10, 14, 28, 42 or 98 film-coated tablets, or
• in single-dose blisters, in packs 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 and have the BAYER cross engraved on one side and “20” and a triangle on the other.

They are packaged:

• in blisters, in cartons of 10, 14, 28, or 98 film-coated tablets, or
• in single-dose blisters, in packs 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 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 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 on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Belgium / Belgium / Belgium 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 / Luxembourg Bayer SA-NV Tél/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 Hellas S.A. 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 summary:

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