Label: information for the user

Xarelto 1mg/ml powder for oral suspension

rivaroxaban

Read this label carefully before starting to take this medication, as it contains important information. This label has been written for the patient (“you”) and for the parent or caregiver who will administer this medication to the child.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you or the child, and should not be given to other people even if they have the same symptoms, as it may harm them.
• If you or the child experience any adverse effects, consult your doctor or pharmacist even if they are not listed in this label. See section4.

1.What is Xarelto and how is it used

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

3.How to take or administer Xarelto

4.Possible adverse effects

5.Storage of Xarelto

6.Contents of the package and additional information

Xarelto contains the active ingredient rivaroxaban.

Xarelto belongs to a group of medications called antithrombotic agents. It acts by blocking a coagulation factor (factor Xa) and thereby reducing the tendency of blood to form clots.

Xarelto is used in term newborns, infants, children, and adolescents under 18 years old for:

• treating blood clots and preventing the recurrence of blood clots in veins or pulmonary vessels, after an initial treatment of at least 5 days with injectable medications used to treat blood clots.

Read and follow the Instructions for use provided with this medication, as they will show you how to prepare and take or administer Xarelto oral suspension.

Do not take or administer Xareltoif you or the childis allergic to rivaroxaban or any of the other components of this medication (listed in section6)

• excessively bleeds
• has a disease or problem in an organ of the body that increases the risk of severe bleeding (e.g., stomach ulcer, brain injury or hemorrhage, or recent surgery in the brain or eyes)
• is taking medications to prevent blood clot formation (e.g., warfarin, dabigatran, apixaban, or heparin), except
• • when switching to a medication to prevent blood clots or
  • while receiving heparin through a vein or artery to prevent blockage
• has liver disease associated with an increased risk of bleeding
• is pregnant or breastfeeding.

Do not take or administer Xarelto and inform your doctorif any of these circumstances apply to your case or the child.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Xarelto if:

• you or the child has an increased risk of bleeding. This may occur in the following situations:

• moderate or severe renal insufficiency, as kidney function may affect the amount of medication that acts in the body
• if you or the child is taking other medications to prevent blood clot formation (e.g., warfarin, dabigatran, apixaban, or heparin), if these are absolutely necessary (see section “Do not take or administer Xarelto”)
• bleeding disorder
• uncontrolled high blood pressure
• gastrointestinal or intestinal diseases that may cause bleeding, such as inflammatory bowel disease or stomach inflammation, esophageal inflammation due to a condition in which stomach acid rises into the esophagus, 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 in which the bronchi are dilated and filled with pus (bronchiectasis) or previous lung hemorrhage

• you or the child has a heart valve prosthesis
• you or the child has a condition called antiphospholipid syndrome (a disorder of the immune system that increases the risk of blood clots)
• your blood pressure or the child's blood pressure is unstable
• you or the child is scheduled to receive another treatment or undergo a surgical procedure to remove a blood clot from the lungs

Inform your doctorif you or the child presents any of these situationsbefore taking or administering Xarelto.The doctor will decide if you or the child should be treated with this medication and be under closer observation.

Do not administerXarelto to children under 6months of age who

-have been born before 37 weeks of gestation, or

-weigh less than 2.6kg, or

-have taken breast milk or received formula feed for less than 10days

In these cases, the Xarelto dosage cannot be determined reliably and has not been studied in these children.

If you or the child needs a surgical intervention

• It is very important to take or administer Xarelto before and after surgery, exactly at the hours indicated by your doctor.
• If the 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 or administer Xarelto, before and after the injection or catheter removal, exactly at the hours indicated by your doctor.
• Inform your doctor immediately if you or the child presents numbness or weakness in the legs or problems with the intestines or bladder after anesthesia. In this case, urgent attention is required.

Children and adolescents

Xarelto oral suspension should be used in patientsunder 18yearsto treat blood clots and prevent the recurrence of blood clots in the veins or pulmonary blood vessels. There is not enough information available on its use in children and adolescents for other indications.

Other medications and Xarelto

Inform your doctor or pharmacist if you or the child is taking, has taken recently, or may need to take any other medication, including those purchased without a prescription.

• If you or the child are taking:

• any medication for a fungal infection (e.g., fluconazole, itraconazole, voriconazole, posaconazole), except if only 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 medication for HIV/AIDS (e.g., ritonavir)
• other medications to reduce blood clotting (e.g., enoxaparin, clopidogrel, or vitamin K antagonists, such as warfarin or acenocoumarol)
• medications to relieve inflammation and pain (e.g., naproxen or acetylsalicylic acid)
• dronedarone, a medication for the treatment of irregular heartbeat
• somemedicationsfor treating depression(selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs))

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

If the doctor considers that you or the child has a higher risk of developing a stomach or intestinal ulcer, a preventive treatment may be necessary.

• If you or the child are taking:

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

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

Pregnancy and breastfeeding

• If you or the adolescent is pregnant or breastfeeding,do not take or administer Xarelto.
• If there is anypossibilityof you or the adolescent becoming pregnant,use a reliable contraceptivewhile taking Xarelto.
• If you or the adolescent becomes pregnant while taking this medication, inform your doctor immediately, who will decide how to continue treatment.

Driving and using machines

Xarelto may cause dizziness or fainting. Neither you nor the child should drive, ride a bike, or use tools or machines if affected by these symptoms.

Xarelto contains sodium benzoate and sodium

This medication contains 1.8mg of sodium benzoate (E211) per ml of oral suspension. Sodium benzoate (E 211) may increase the risk of jaundice (yellowing of the skin and eyes) in newborns (up to 4weeks of age).

This medication contains less than 1 mmol of sodium (23mg) per milliliter; it is essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor for you or the child. In case of doubt, consult your doctor or pharmacist again.

Ensure that the correct information about how much and how often to take or administer Xarelto is written in the designated area of the box. If not, ask your pharmacist or doctor to provide the relevant information.

Instructions for use

To know how to prepare and take or administer the oral suspension of Xarelto:

• Consult the Instructions for use leaflet included in the box and
• Watch the educational video that you can access through the QR code that appears on the patient information card provided with this medication.

How to take or administer

Take or administer Xarelto oral suspension with food (breast milk or formula) or with a meal. Each dose of Xarelto must be swallowed with a normal amount of liquid (for example, 20ml in children from 6months to 240ml in adolescents). This normal amount may include a usual amount of feeding liquid (for example, breast milk, infant formula, nutritional drink).

Your doctor may also administer the oral suspension through a tube inserted into the stomach.

How much to take or administer

The dose of Xarelto depends on the patient's body weight. The doctor will calculate it as an amount (volume) in milliliters (ml) of the oral suspension. This must be measured using the blue syringe (either the 1ml or 5ml or 10ml syringe, see table1) provided with this medication. Your doctor will prescribe the necessary volume including the specific syringe to use.

Your doctor will tell you how much of the oral suspension to take or administer.

Below is the table that your doctor will use.Do not adjust the dose on your own.

All materials for preparing and administering the oral suspension are provided with the medication (except for tap water). Use only still water to avoid bubbles.Use only the syringe providedto administer Xarelto to ensure exact dosing. Do not use any other method to administer the solution, such as an alternative syringe, spoon, etc.

Since the dose of Xarelto is based on body weight, it is essential to attend scheduled visits with the doctor, as the dose may need to be adjusted as the weight changes, especially in children under 12kg. This ensures that the child receives the correct dose of Xarelto.

Table1: Recommended dose of Xarelto in children

Your doctor may also prescribe tablets if you or the child are able to swallow the tablet and weigh at least 30kg.

When to take or administer Xarelto

Take or administer the oral suspension as instructed every day until your doctor tells you to stop.

Take or administer the oral suspension at the same time every day to help you remember. Consider setting an alarm to remind you.

Please observe the child to ensure they take the entire dose.

If your doctor has instructed you to take or administer the Xarelto dose:

-once a day, take it with approximately 24hours of difference

-twice a day, take it with approximately 12hours of difference

-three times a day, take it with approximately 8hours of difference

Your doctor will decide how long you or the child should continue treatment.

If you or the child spits out the dose or vomits

• less than 30minutes after taking Xarelto, take a new dose.
• more than 30minutes after taking Xarelto,do nottake a new dose. Continue taking the next scheduled dose of Xarelto.

Call your doctor if you or the child repeatedly spits out the dose or vomits after taking Xarelto.

If you forgot to take or administer Xarelto

• If you are taking Xarelto once a day, take the missed dose of Xarelto as soon as you remember on the same day. If this is not possible, skip that dose. Then take the next scheduled dose of Xarelto the next day. Do not take more than one dose per day.
• If you are taking Xarelto twice a day:

• morning dose forgotten: take the missed dose as soon as you remember. You can take it with the evening dose.
• evening dose forgotten: you can take the missed dose only in the same evening. Do not take two doses the next morning.

• If you are taking Xarelto three times a day, do not replace the missed dose. Continue with the next scheduled dose (administered every 8hours).

The next day after the missed dose, continue as prescribed by your doctor, one, two, or three times a day.

If you take or administer more Xarelto than you should

Call your doctor immediately if you have taken or administered too much Xarelto oral suspension. 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 using this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Like other medicines 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 immediatelyif you or the child experiences any of the following side effects:

• Bleeding signs

• Brain or intracranial bleeding (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 medical attention immediately.)
• Prolonged or excessive bleeding
• Exceptional weakness, fatigue, pallor, dizziness, headache, unexplained swelling, difficulty breathing, chest pain, or angina

Your doctor may decide to keep you or the child under closer observation or change the 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 causing 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 uncommon (angioedema and allergic edema; may affect up to 1 in 100 people).

General list of possible side effects found in adults and children and adolescents:

Frequent(may affect up to 1 in 10 people)

• Decreased red blood cells that can cause pallor and weakness or difficulty breathing
• Stomach 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
• Alteration of kidney function (may be seen in tests performed by the doctor)
• Fever
• Stomach 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

Uncommon(may affect up to 1 in 100 people)

• Brain or intracranial bleeding (see above, possible side effects that may be a sign of bleeding)
• Bleeding into a joint, which causes pain and swelling.
• Thrombocytopenia (low platelet count, cells that help blood clotting)
• Allergic reaction, including skin rash
• Alteration of liver function (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, hepatitis, including liver cell injury (inflammation or liver damage)yellow discoloration 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)

Frequency unknown(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 incorrectly (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

Uncommon(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 or the child experiences any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. 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 medicine.

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 in the bottle after “CAD” or “EXP”.

The expiration date is the last day of the month indicated.

After preparation, the shelf life of the suspension is 14days at room temperature.

Do not store at a temperature above 30°C.

Do not freeze. Store the prepared suspension in an upright position.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. By doing so, you will help protect the environment.

Composition of Xarelto

• The active ingredient is rivaroxaban. A glass bottle contains

• 51.7 mg of rivaroxaban, for the addition of 50 ml of water,
• or 103.4 mg of rivaroxaban, for the addition of 100 ml of water.

After preparation, each ml of the oral suspension contains 1 mg of rivaroxaban.

• The other components are:

• Citric acid, anhydrous (E 330), hypromellose (2910), mannitol (E 421), microcrystalline cellulose, sodium carboxymethylcellulose, sodium benzoate (E 211) (see section 2 “Xarelto contains sodium benzoate and sodium”), sucralose (E 955), xanthan gum (E 415), sweet and creamy flavor (constituted by fragrances, maltodextrin [wheat], propylene glycol [E 1520] and gum arabic [E 414]).

Appearance of the product and contents of the package

Xarelto granulated for oral suspension is a white granulated in a glass bottle with a child-resistant screw cap.

Package sizes

• For children weighingless than 4 kgkg:

Foldable box with a brown glass bottle containing 2.625 g of granulate (equivalent to 51.7 mg of rivaroxaban), two blue syringes of 1 ml, a 50 ml water syringe and an adapter.

• For children weighing4 kg or more:

Foldable box with a brown glass bottle containing 5.25 g of granulate (equivalent to 103.4 mg of rivaroxaban), two blue syringes of 5 ml and two blue syringes of 10 ml, a 100 ml water syringe and an adapter.

Only some package sizes may be marketed.

The adjusted dose volume and frequency according to individual weight must be specified by the prescribing physician. They must be written on the outer box when provided to parents, caregivers or patients.

Follow the Instructions for Use leaflet supplied with each package.

Watch the educational video that can be accessed through the QR code on the patient information leaflet provided with the medication.

Holder of the marketing authorization and responsible for manufacturing

Bayer AG

51368 Leverkusen

Germany

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu.

Instructions for Use (IU)

Instructions for Use

Xarelto 1 mg/ml

Package of 100 ml with 2.625 g of granulate for the preparation of an oral suspension

Active pharmaceutical ingredient: rivaroxaban

Preparation and administration of the oral suspension (granulate and water mixture)

Glossary and symbols

• Granulate: powder (supplied in the bottle) containing the active pharmaceutical ingredient.
• Water syringe: 50 ml syringe used to measure and add 50 ml of water to the bottle containing the Xarelto granulate.
• Suspension:granulate and water mixture (for oral use).
• Blue syringe: syringe with a blue plunger for extracting and orally administering Xarelto.

Before starting

• Read carefully all sections of these Instructions for Use before using Xarelto for the first time and before administering each dose.
• Watch the educational video that can be accessed through the QR code included in the patient information leaflet provided with the medication.
• Make sure you understand the instructions before starting. If not, call your doctor.
• For more information about Xarelto, consult the leaflet.

Contents of the package

Each package of Xarelto contains the following components:

Warnings and precautions

• Useonlypotable water without gas to prepare the suspension to avoid bubble formation. This means you can use
• • tap water or
  • mineral water without gas
• It is very important to add the exact amount of water to the granulate in the bottle to ensure the correct concentration of Xarelto.
• • Use the water syringe to measure 50 ml of water, see below for more information.
  • Measure carefully the amount of water to be provided to the bottle.
• After preparation, the suspension can be used for 14 days if stored at room temperature.
  Make sure to write the expiration date of the suspension (preparation date + 14 days) on the label of the bottle.
• Do notstore the suspension at a temperature above 30°C.Do notfreeze.
  If the suspension has been stored in the refrigerator, let the suspension reach room temperature before extracting the corresponding dose.
• Shake the suspension for the initial preparationfor at least 60 seconds.
• Shake the suspension in the bottlefor at least 10 secondsbefore each administration.
• It is very important to administer the prescribed volume of Xarelto.
• • Make sure you know the prescribed dose and administration frequency. Ask your doctor or pharmacist if you do not know the prescribed dose and frequency.
  • Adjust the blue syringe carefully according to the prescribed volume.
  • Administer the prescribed dose using the blue syringe. Follow your doctor's instructions on the daily frequency with which to administer the prescribed dose.
  • Check that there are no large bubbles in the blue syringe before administering the oral suspension.
• If your child does not take the required dose repeatedly or spits out part of it, call your child's doctor to know what to do.
• Between doses, keep the oral suspension out of sight and reach of children.
• Keep the Instructions for Use for future reference during the use of Xarelto.

Use of Xarelto

• The Xarelto suspension is only for oral use.
• The volume and frequency of Xarelto administration depend on the child's weight, so they will change over time if the child receives Xarelto for a prolonged period.
• • Your child's doctor will indicate the correct dose volume.
  • Do notchange the dose on your own.
  • Always use the prescribed volume by your child's doctor and have the correct dose and administration frequency written on the designated field on the outside of the package.

If not written on the designated field, ask your child's doctor or pharmacist to provide the relevant information.

• Follow the detailed Instructions for Use listed below.

Be careful to comply with the instructions related to administration:

1. Preparation of the oral suspension

Paso1.1: Preparation – Ready to go

The suspension preparation is done once with each new package.

Before preparing the suspension:

Paso1.2: Filling the required water volume

Each time a new package is started, only the new materials included in the new package should be used.

Paso1.3: Adding water to the granulate

Paso1.4: Placing the adapter and mixing the oral suspension

The adapter is used to fill the blue syringe with the suspension.

2. Adjusting the prescribed dose with each new blue syringe

To avoid overdosing or underdosing, an exact dose of suspension is required.

Before taking the first dose from the bottle, the blue syringe provided must be prepared according to the prescribed dose by your child's doctor. This information can be found in the designated area of the package. If no information has been entered here, consult with your child's doctor or pharmacist.

After setting the dose, the same blue syringe can be used for all administrations to be made from the prepared suspension bottle in step1.

Once the dose has been set in the blue syringe, it cannot be changed.

Paso2.1: Selecting a suitable blue syringe

In this package, devices of different capacities are included:

1. Administration of the oral suspension

Follow the steps described below for each necessary administration.

Paso3.1: Mixing the oral suspension

Paso3.2: Extracting the required dose