Xarelto 2.5 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Xarelto 2.5mg 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 effects, consult your doctor or pharmacist, even if they are adverse effects 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 adverse effects
5. How to store Xarelto
6. Contents of the pack and other information

1. What is Xarelto and what is it used for

You have been prescribed Xarelto because

• you have been diagnosed with acute coronary syndrome (a group of disorders that include myocardial infarction and unstable angina, a type of severe chest pain) and your blood tests have shown elevated results in certain cardiac markers.

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

Xarelto will be prescribed to you along with another medicine. Your doctor will also instruct you to take:

• acetylsalicylic acid, or
• acetylsalicylic acid plus clopidogrel or ticlopidine

or

• you have been diagnosed with a high risk of blood clot formation due to coronary artery disease or peripheral arterial disease causing symptoms. Xarelto reduces the risk of blood clots (atherothrombotic events) in adults.
  Xarelto will be prescribed to you along with another medicine. Your doctor will also instruct you to take acetylsalicylic acid.

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

Xarelto contains the active substance rivaroxaban, which 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 (for example, 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 blockage
• if you have acute coronary syndrome and have previously had a bleed or a blood clot in the brain (stroke)
• if you have coronary artery disease or peripheral artery disease and have previously had a brain bleed (stroke), a blockage in the small arteries supplying blood to deep brain tissues (lacunar stroke), or a blood clot in the brain (non-lacunar ischaemic stroke) within the past month
• if you have a liver disease that could increase 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

Talk to your doctor or pharmacist before starting Xarelto.

Xarelto must not be used in combination with other medicines that reduce blood clotting, other than acetylsalicylic acid or clopidogrel/ticlopidine, such as prasugrel or ticagrelor.

Take special care with Xarelto

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

• severe renal impairment, 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 may cause bleeding, such as inflammation of the stomach or intestine, inflammation of the oesophagus (throat), for example due to gastro-oesophageal reflux disease (a condition in which stomach acid rises up into the oesophagus), or tumours 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 widened and filled with pus (bronchiectasis), or if you have previously had a lung bleed

• if you are over 75 years old

• if you weigh less than 60 kg

• if you have coronary artery disease with severe symptomatic heart failure.

• 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.

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 instructs.

• If your surgery requires placement of a catheter or injection into your spine (e.g., for epidural or spinal anaesthesia, 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 your legs or problems with your bowel or bladder after the anaesthesia, as urgent medical attention is required.

Children and adolescents

Xarelto 2.5 mg tablets are not recommended for children and adolescents under 18 years of age. There is insufficient information on its use in children and adolescents.

Other medicines and Xarelto

Tell 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

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

• ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces excess 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, prasugrel and ticagrelor (see section “Warnings and precautions”))

• anti-inflammatory medicines and painkillers (e.g., naproxen or acetylsalicylic acid)

• dronedarone, a medicine used to treat irregular heartbeat

• certain antidepressants (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 may 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 may be reduced. Your doctor will decide whether you should be treated with Xarelto 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 Xarelto, inform your doctor immediately. Your doctor will decide how you should be treated.

Driving and using machines

Xarelto may cause dizziness (a common adverse effect) or fainting (an uncommon adverse effect) (see section 4, “Possible side effects”). You must 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; essentially “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.

What dose to take

The recommended dose is one 2.5 mg tablet taken twice daily. Take Xarelto at the same time each day (for example, one tablet in the morning and one in the evening). This medicine may be taken with or without food.

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.

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

You will be prescribed Xarelto together with another medication.

Your doctor will also instruct you to take acetylsalicylic acid.

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

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 to be taken in addition to acetylsalicylic acid for a short period of time.

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

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, at least 24 hours after hospital admission and at the time when parenteral anticoagulant treatment (by injection) would be discontinued.

Your doctor will advise 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 your usual time.

If you stop taking Xarelto

Take Xarelto regularly for the length of time prescribed by your doctor.

Do not stop taking Xarelto without first talking to your doctor. If you stop taking this medicine, your risk of having another heart attack, stroke, or dying from a heart or blood vessel-related disease may increase.

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

4. Possible adverse effects

Like all medicines, this medicine 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.

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, weakness on one side of the body, 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

Your doctor will decide whether to keep you under closer monitoring or change your treatment.

• Signs of serious skin reactions

• severe skin rash spreading rapidly, 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

Frequent (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 urine and heavy menstrual bleeding), nosebleeds, bleeding from gums
• bleeding in the eye (including bleeding in the white part of the eye)
• bleeding into tissue or body 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 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, the cells that help blood clot)
• allergic reaction, including skin allergic reaction
• 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 as a complication following cardiac surgery where a catheter was 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 cells causing inflammation in the lung (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 impaired kidney function (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 following bleeding)

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 detailed 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 vial after “CAD” or “EXP”. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

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 medicines and packaging that you no longer need. 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 2.5 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), yellow iron oxide (E 172).

Appearance of the product and contents of the pack

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

They are packaged:

• in blisters, in cartons containing 14, 20, 28, 30, 56, 60, 98, 168 or 196 film-coated tablets, or
• in unit dose blisters, in packs of 10 x 1 or 100 x 1, or
• in multiple packs containing 10 cartons, each containing 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 more information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

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.