Xarelto 1 mg/ml granules for oral suspension

Patient Information Leaflet

Introduction

Patient Information Leaflet

Xarelto 1mg/ml oral suspension granules

rivaroxaban

Read all of this leaflet carefully before you start taking this medicine because it contains important information. This leaflet has been written for the patient ("you") and for the parent or caregiver who will administer this medicine to the child.

• 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 or the child only. Do not give it 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 these are not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Xarelto is and what it is used for
2. What you need to know before taking or administering Xarelto
3. How to take or administer 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 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.

Xarelto is used in full-term newborns, infants, children, and adolescents under 18 years of age for:

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

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

2. What you need to know before taking or administering Xarelto

Do not take or administer Xarelto if you or the child

• are allergic to rivaroxaban or to any of the other ingredients of this medicine (listed in section 6)
• are bleeding excessively
• have a disease or organ problem in the body that increases the risk of serious bleeding (e.g., stomach ulcer, bleeding or injury in the brain, or recent surgery on the brain or eyes)
• are taking medicines to prevent blood clots (e.g., warfarin, dabigatran, apixaban, or heparin), except
  • when switching from one anticoagulant medicine to another, or
  • while heparin is being administered intravenously or via an arterial line to prevent blockage
• have liver disease associated with an increased risk of bleeding
• are pregnant or breastfeeding.

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

Warnings and precautions

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

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

• moderate or severe kidney impairment, as kidney function may affect the amount of medicine active in the body

• you or the child are taking other medicines to prevent blood clots (e.g., warfarin, dabigatran, apixaban, or heparin), if these are absolutely necessary (see section “Do not take or administer Xarelto”)

• bleeding disorders

• uncontrolled high blood pressure despite medical treatment

• stomach or intestinal diseases that may cause bleeding, such as intestinal or stomach inflammation, oesophagitis due to gastroesophageal reflux disease (acid from the stomach rising up into the oesophagus), or tumours in the stomach, intestines, genital or urinary tract

• a blood vessel problem at the back of the eyes (retinopathy)

• a lung disease in which the bronchi are widened and filled with pus (bronchiectasis), or previous lung bleeding

• you or the child have a heart valve prosthesis

• you or the child have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots)

• your or the child’s blood pressure is unstable

• you or the child are scheduled to receive another treatment or undergo a procedure to remove a blood clot from the lungs

Tell your doctor if you or the child have any of these conditions before taking or administering Xarelto. Your doctor will decide whether you or the child should be treated with this medicine and whether closer monitoring is needed.

Do not administer Xarelto to children under 6 months of age who

• were born before week 37 of gestation, or
• weigh less than 2.6 kg, or
• have been breastfed or formula-fed for less than 10 days

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

If you or the child need surgery

• It is very important to take or administer Xarelto before and after surgery exactly at the times your doctor has instructed.

• If the procedure requires placement of a catheter or injection into the spinal column (e.g., for epidural or spinal anaesthesia, or pain relief):

• it is very important to take or administer Xarelto before and after the injection or catheter removal exactly as directed by your doctor.

• inform your doctor immediately if you or the child experience numbness or weakness in the legs or problems with the bowel or bladder after the anaesthesia. In such cases, urgent medical attention is required.

Children and adolescents

Xarelto oral suspension should be used in patients under 18 years of age to treat blood clots and to prevent recurrence of blood clots in veins or blood vessels of the lungs. There is insufficient information on its use in children and adolescents for other indications.

Other medicines and Xarelto

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

• If you or the child are taking:

• a medicine for fungal infections (e.g., fluconazole, itraconazol, voriconazole, posaconazole), except when 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)

• a 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)

• medicines to relieve inflammation and pain (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 or the child, inform your doctor before taking or administering Xarelto, as the effect of Xarelto may be increased. Your doctor will decide whether you or the child should be treated with this medicine and whether closer monitoring is needed.

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

• If you or the child 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 or the child, inform your doctor before taking or administering Xarelto, as the effect of Xarelto may be reduced. Your doctor will decide whether you or the child should be treated with this medicine and whether closer monitoring is needed.

Pregnancy and breastfeeding

• If you or the adolescent is pregnant or breastfeeding, do not take or administer Xarelto.
• If there is any possibility that you or the adolescent could become pregnant, a reliable method of contraception should be used while taking Xarelto.
• If you or the adolescent become pregnant while taking this medicine, inform your doctor immediately. Your doctor will decide how treatment should continue.

Driving and using machines

Xarelto may cause dizziness or fainting. You or the child should not drive, ride a bicycle, or operate tools or machinery if affected by these symptoms.

Xarelto contains sodium benzoate and sodium

This medicine contains 1.8 mg of sodium benzoate (E 211) 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 4 weeks of age).

This medicine contains less than 1 mmol of sodium (23 mg) per millilitre; this is essentially “sodium-free”.

3. How to take or administer Xarelto

Follow exactly the dosing instructions for this medicine as provided by your doctor for you or the child. If you have any doubts, consult your doctor or pharmacist again.

Make sure that the correct information about how much and how often to take or administer Xarelto is written in the designated space on the carton. If not, ask your pharmacist or doctor to provide you with the relevant information.

Instructions for use

To learn how to prepare and take or administer Xarelto oral suspension:

• Refer to the Instructions for Use leaflet included in the carton, and
• Watch the educational video accessible via the QR code on the patient information card provided with this medicine.

How to take or administer

Take or administer Xarelto oral suspension with a feeding (breast milk or formula) or with a meal. Each dose of Xarelto should be swallowed with a normal amount of liquid (e.g., 20 ml in children aged 6 months up to 240 ml in adolescents). This normal amount may include the usual volume of drink used for feeding (e.g., breast milk, infant formula, nutritional drink).

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

What dose to take or administer

The dose of Xarelto depends on the patient's body weight. Your doctor will calculate it as an amount (volume) in millilitres (ml) of the oral suspension. This must be measured using the blue syringe (either the 1 ml, 5 ml, or 10 ml syringe—see Table 1) supplied with this medicine. Your doctor will prescribe the required volume and specify which syringe to use.

Your doctor will inform you of the amount of oral suspension you or the child should take.

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

All materials needed to prepare and administer the oral suspension are supplied with the medicine (except drinking water). Use only still water to avoid bubbles. Use only the syringe supplied to administer Xarelto to ensure accurate dosing. Do not use any other method to administer the solution, such as an alternative syringe, spoon, etc.

Because the dose of Xarelto is based on body weight, it is important to attend all scheduled medical appointments, as the dose may need to be adjusted as weight changes, especially in children weighing less than 12 kg. This ensures the child receives the correct dose of Xarelto.

Table 1: Recommended dose of Xarelto in children

Body weight [kg]	Individual dose*	Daily dosing frequency	Total daily dose*	Appropriate blue syringe
2.6 to less than 3	0.8 ml	3 times	2.4 ml	1 ml
3 to less than 4	0.9 ml	3 times	2.7 ml	1 ml
4 to less than 5	1.4 ml	3 times	4.2 ml	5 ml
5 to less than 7	1.6 ml	3 times	4.8 ml	5 ml
7 to less than 8	1.8 ml	3 times	5.4 ml	5 ml
8 to less than 9	2.4 ml	3 times	7.2 ml	5 ml
9 to less than 10	2.8 ml	3 times	8.4 ml	5 ml
10 to less than 12	3.0 ml	3 times	9.0 ml	5 ml
12 to less than 30	5.0 ml	2 times	10.0 ml	5 ml or 10 ml
30 to less than 50	15.0 ml	once	15.0 ml	10 ml
50 or more	20.0 ml	once	20.0 ml	10 ml
1 ml of oral suspension corresponds to 1 mg of rivaroxaban.

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

When to take or administer Xarelto

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

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

Please observe the child to ensure that the full dose is taken.

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

• once daily, take or administer it approximately 24 hours apart
• twice daily, take or administer it approximately 12 hours apart
• three times daily, take or administer it approximately 8 hours apart

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 30 minutes after taking Xarelto, take or administer a new dose
• more than 30 minutes after taking Xarelto, do not take or administer a new dose. Continue taking or administering the next scheduled dose of Xarelto at the usual time.

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

If you forget to take or administer Xarelto

• If you are taking or administering Xarelto once daily: Take or administer the missed dose as soon as you remember on the same day. If this is not possible, skip the missed dose. Then take or administer the next dose the following day. Do not take or administer more than one dose per day.

• If you are taking or administering Xarelto twice daily:

• Missed morning dose: Take or administer the missed dose as soon as you remember. You may take or administer it together with the evening dose.

• Missed evening dose: You may take or administer the missed dose only on the same evening. Do not take or administer two doses the following morning.

• If you are taking or administering Xarelto three times daily: Do not replace the missed dose. Continue with the next scheduled dose (to be administered every 8 hours).

The day after a missed dose, continue as prescribed by your doctor—once, twice, or three times daily.

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 or administering too much Xarelto increases the risk of bleeding.

If you stop 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, this medicine can cause adverse effects, although not everyone gets 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 or the child experience any of the following adverse effects:

• 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, shortness of breath, chest pain, or angina

Your doctor may decide to monitor you or the child more closely or change the 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), which causes 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 and in 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 hemorrhage (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 tissue or body cavity (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 the 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, itching of the skin
• blood tests may show an increase in certain liver enzymes

Uncommon (may affect up to 1 in 100 people)

• bleeding in the brain or inside the skull (see above, possible adverse effects that may be a sign of bleeding)
• bleeding into a joint, causing pain and swelling
• thrombocytopenia (low platelet count, the cells that help blood to clot)
• allergic reaction, including skin allergic reaction
• impaired liver function (may be seen in tests performed by the doctor)
• blood tests may show an increase in 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 hepatocellular liver injury (liver inflammation or damage), yellowing of the skin and eyes (jaundice)
• localized swelling
• accumulation of blood (hematoma) in the groin following a complication during heart surgery where a catheter is inserted into the leg artery (pseudoaneurysm)

Very rare (may affect up to 1 in 10,000 people)

• accumulation of eosinophils, a type of 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 the kidneys being unable to function properly (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)

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 seen in adults, and their severity was mainly mild to moderate.

Adverse effects observed more frequently in children and adolescents:

Very frequent (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 an increase in bilirubin (bile pigment)
• thrombocytopenia (low platelet count, the cells that help blood to clot)
• heavy menstrual bleeding

Uncommon (may affect up to 1 in 100 people)

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

Reporting of adverse effects

If you or the child 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 the bottle after “CAD” or “EXP”.

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

After preparation, the suspension is stable for 14 days at room temperature.

Do not store above 30°C.

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging 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. One glass bottle contains:

• 51.7 mg of rivaroxaban, for addition of 50 ml of water,

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

After preparation, each ml of 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), creamy sweet flavour (composed of flavouring substances, maltodextrin [corn], propylene glycol (E 1520), and acacia gum (E 414)).

Appearance of the product and contents of the pack

Xarelto oral suspension granules is a white granule contained in a glass bottle with a child-resistant screw cap.

Pack sizes

• For children weighing less than 4 kg:

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

• For children weighing 4 kg or more:

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

Only certain pack sizes may be marketed.

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

Carefully follow the Instructions for Use leaflet supplied with each pack.

Watch the educational video accessible via the QR code on the patient information card provided with the medicine.

Marketing Authorisation Holder and Manufacturer

Bayer AG
51368 Leverkusen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Belgium / Belgium / Belgium Bayer SA-NV Tel/Tel: +32-(0)2-535 63 11	Lithuania UAB Bayer Tel: +370-5-233 68 68
	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 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 (Toll-free): +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 last review of this leaflet:

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

Instructions for Use (IFU)

Instructions for Use

Xarelto 1mg/ml

100ml bottle with 2,625g of granules for oral suspension preparation

Active pharmaceutical ingredient: rivaroxaban

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

Glossary and symbols

• Granules: 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 Xarelto granules.
• Suspension: mixture of granules and water (for oral use).
• Blue syringe: syringe with a blue plunger used to withdraw and administer Xarelto orally.

Before you begin

• Read all sections of these Instructions for Use carefully before using Xarelto for the first time and before administering each dose.
• Watch the educational video accessible via the QR code included on the patient information card provided with the medicine.
• Make sure you understand the instructions before starting. If not, contact your doctor.
• For more information about Xarelto, refer to the package leaflet.

Pack contents

Each Xarelto pack contains the following components:

	1 bottle with a child-resistant screw cap containing Xarelto granules
	1 packaged 50 ml syringe of water (for single use)
	1 packaged bottle adapter
	2 packaged blue 1 ml syringes
	1 copy of the Instructions for Use (IFU) (this document)
	1 package leaflet Provides important information about Xarelto.
	1 patient information card Important information in case of emergency. The patient should carry it at all times and present it to every physician or dentist before treatment.

Warnings and precautions

• Use only still drinking water to prepare the suspension to avoid bubble formation. This means you may use
  • tap water from the mains supply or
  • non-carbonated (still) mineral water
• It is very important to add the exact amount of water to the granules in the bottle to ensure the correct concentration of Xarelto.
  • Use the water syringe to measure 50 ml of water; see below for further information.
  • Measure the amount of water to be added to the bottle very carefully.
• After preparation, the suspension can be used for 14 days if stored at room temperature. Be sure to write the expiry date of the suspension (date of preparation plus 14 days) in the designated space on the label of the bottle.
• Do not store the suspension at a temperature above 30 °C. Do not freeze. If the suspension has been stored in the refrigerator, allow the suspension to reach room temperature before withdrawing the prescribed dose.
• Shake the suspension for initial preparation for at least 60 seconds.
• Shake the suspension in the bottle for at least 10 seconds before each administration.
• It is very important that the prescribed dose volume of Xarelto is administered.
  • Make sure you know the prescribed dose and frequency of administration. Ask your doctor or pharmacist if you are unsure about the prescribed dose and frequency.
  • Carefully adjust the blue syringe to the prescribed volume.
  • Administer the prescribed dose using the blue syringe. Follow your doctor's instructions regarding how many times per day the prescribed dose should be administered.
  • Check that there are no air bubbles in the blue syringe before administering the oral suspension.
• If your child repeatedly fails to take the full required dose or spits out part of it, contact your child’s doctor to find out what to do.
• Between doses, keep the oral suspension out of sight and reach of children.
• Keep the Instructions for Use available for future reference during treatment with Xarelto.

Use of Xarelto

• Xarelto suspension is for oral use only.
• The volume and frequency of administration of Xarelto depend on your child’s weight and therefore may change over time if your child receives Xarelto for a prolonged period.
  • Your child’s doctor will inform you of the correct dose volume.
  • Do not change the dose on your own.
  • Always use the volume prescribed by your child’s doctor, and ensure the correct administration dose is written in the designated space on the outer carton.

If this information is not written in that space, ask your child’s doctor or pharmacist to provide it.

• Follow the detailed Instructions for Use provided in the following sections.

Take care to follow the instructions regarding administration (see package leaflet):

1. Preparation of the oral suspension

Step 1.1: Preparation – Getting ready

Suspension preparation is performed once per new container.

Before preparing the suspension:

	Wash hands thoroughly with soap and dry them afterwards.
	Check the expiration date on the label of the box. Do not use the medicine if it has expired.
	Gather the following additional items: Container with at least 150 ml of water: Tap water or non-carbonated (still) mineral water Water must be at room temperature
	Paper towel to absorb any excess water.

Step 1.2: Filling with the required volume of water

Each time you start a new package, use only the new materials included in the new package.

Unpack the water syringe Submerge the opening of the water syringe into the container with water. Draw a volume exceeding 50 ml. To do this, pull the plunger rod towards you and ensure that the opening of the water syringe remains below the water surface at all times. This will prevent air bubbles from entering the syringe. Remove the syringe from the water. Rotate the water syringe so that the opening points upward. Air bubbles will rise to the top when holding the syringe upright. Flick the syringe gently with your fingers to help the air bubbles move further upward. Push the plunger rod until the upper ring of the plunger reaches the 50 ml mark. When pressing the plunger, water may escape from the tip of the water syringe. This residual water can be absorbed using a paper tissue. Continue holding the water syringe with the opening facing upward and carefully inspect the water in the syringe: Regarding the correct volume, Regarding air bubbles. Small air bubbles are not critical, but large ones are. For further information on what to do, see below. If the syringe is not correctly filled or contains too much air: Empty the water syringe Repeat steps b. through h.

Step 1.3: Addition of water to the granulate

If the granules in the bottle appear clumped: Tap the bottle again in your hand. Be careful, as the bottle is made of glass. Unscrew the child-resistant closure cap from the bottle (press down and turn counterclockwise). Place the filled water syringe into the top edge of the bottle opening. Hold the bottle firmly. Slowly push the plunger of the syringe down. Dispose of the water syringe in household trash.

Step 1.4: Placing the adapter and mixing the oral suspension

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

	Unpack the adapter from the vial.
	Push the adapter completely into the neck of the vial.
	Close the vial securely with the screw cap.
	Gently shake the vial for at least 60 seconds. The purpose is to obtain a well-mixed suspension.
	Check that the suspension is well mixed: no lumps, no deposits.
	If lumps or sediment remain, repeat steps d to f. The suspension is ready for use when no lumps or deposits remain. Do not add more water to the vial. The suspension is stable for 14 days at room temperature.
	Write the expiration date of the freshly prepared suspension on the label of the vial. Date of preparation + 14 days The pictogram shown is for illustrative purposes only.

1. 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 enclosed blue syringe must be prepared according to the dose prescribed by your child's doctor. This information can be found in the section of the carton designated for this purpose. If no information has been entered here, consult the child's doctor or pharmacist.

After setting the dose, the same blue syringe can be used for all administrations from the suspension bottle prepared in step 1.

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

	The blue syringe has a scale (ml). The scale on the 1 ml blue syringe starts at 0.2 ml. The graduation marks are in increments of 0.1 ml. Note: Do not remove the peel-off label until instructed to do so in the Instructions for Use. The blue syringe has a red button to set the volume. This button is initially covered by a peelable label. The syringe volume is set by pressing the fixed red button, which can only be done once. Do not press the red button until instructed in the Instructions for Use. Once the red button has been pressed, the volume can no longer be adjusted.
	Check the dose indicated in the designated field on the outside of the carton.
	If this information is not available: Ask your pharmacist or doctor to provide it.
	Hold the blue syringe with the opening facing upward.
	Slowly pull the plunger rod until the upper edge reaches the mark corresponding to the volume to be administered. As you move the plunger rod, you will hear a "click" for each adjustable volume step. The pictogram shown is for illustrative purposes only. Your volume may differ. Be careful not to pull the plunger beyond the volume to be administered. Be careful not to press the label while pulling the plunger.
	Completely remove the label from the blue syringe. The red button for setting the volume is now visible. Double-check the position of the plunger. Ensure that the upper edge of the plunger is exactly aligned with the correct volume mark to be administered. If the position of the blue plunger does not match the required volume: Adjust it accordingly.
	If the position of the blue plunger matches the required volume, press the red button to lock in the setting. The required dose is now fixed. A clicking sound will occur when the red button is pressed. The clicking sound will no longer be audible afterward.
	Push the plunger fully upward in the blue syringe until it stops. The blue syringe is now ready for use.

1. Administration of the oral suspension

Follow the steps described below for each required administration.

Step 3.1: Mixing the oral suspension

	Gently shake the bottle for at least 10 seconds before each dose. The purpose is to obtain a well-mixed suspension.
	Check that the suspension is well mixed, i.e.: no lumps, no deposits. If there are lumps or deposits: Repeat steps a and b.
	Shaking may cause foam to form. Let the bottle stand until the foam has dissolved.
	Unscrew the closure cap from the bottle, but leave the adapter in place at the top of the bottle. Note: The larger opening visible on the adapter is used to attach the blue syringe. The surface of the bottle adapter must be free of liquid. If there is liquid on the adapter: Remove the liquid with a clean tissue paper.

Step 3.2: Extracting the required dose

Step 3.3: Administering the prescribed dose

	Place the blue syringe into the patient's mouth. Direct its tip toward the cheek to allow natural swallowing. Push the plunger rod down slowly until the plunger stops (the blue syringe is completely empty). Ensure the patient swallows the entire dose.
	Encourage the patient to drink a normal amount of fluid. For a 6-month-old baby, for example, this may be about 20 ml. It can also be breast milk.

1. Cleaning and storage

The blue syringe must be cleaned after each use.

Follow the steps below to clean the device. A total of three cleaning cycles are required to ensure proper cleaning.

Before beginning, you will need the following materials for step 4.1: Obtain two containers (such as a cup or bowl) one container filled with drinking water, the other container empty.

Step 4.1: Cleaning

	Immerse the tip of the blue syringe into the water container. Draw water up until the plunger stops moving.
	Empty the blue syringe into the prepared empty container.
	Repeat steps a. to c. two more times. After cleaning, push the plunger inward until it stops. Dry the outer surface of the syringe with a clean paper towel.

Step 4.2: Storage

Store the blue syringe in a clean and dry place until next use, e.g. keep it in the Xarelto box provided to you.

Keep away from sunlight.

Store the suspension below 30 °C.

1. Disposal

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.

1. Damage/Malfunction

Any serious incident occurring in relation to the product must be reported to the manufacturer and to the relevant authority in your country.

Instructions for Use (IFU)

Instructions for Use

Xarelto 1 mg/ml

250 ml bottle with 5.25 g granules for the preparation of an oral suspension

Active pharmaceutical ingredient: rivaroxaban

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

Glossary and symbols

• Granules: powder (supplied in the bottle) containing the active pharmaceutical ingredient.
• Water syringe: 100 ml syringe used to measure and add 100 ml of water to the bottle containing Xarelto granules.
• Suspension: mixture of granules and water (for oral use).
• Blue syringe: syringe with a blue plunger for withdrawing and orally administering Xarelto.

Before you start

• Read all sections of these Instructions for Use carefully before using Xarelto for the first time and before administering each dose.
• Watch the educational video accessible via the QRD code included on the patient information card provided with the medicine.
• Make sure you understand the instructions before starting. If not, contact your doctor.
• For more information about Xarelto, refer to the Package Leaflet.

Contents of the package

Each Xarelto box contains the following components:

	1 bottle with a child-resistant screw cap containing Xarelto granules
	1 packaged syringe of water (for single use)
	1 packaged bottle adapter
	2 packaged 5 ml blue syringes 2 packaged 10 ml blue syringes
	1 copy of the Instructions for Use (IFU) (this document)
	1 package insert Provides important information about Xarelto.
	1 patient information card Important information for emergency situations. The patient should carry it at all times and present it to every physician or dentist before treatment.

Warnings and precautions

• Use only still drinking water to prepare the suspension to avoid formation of bubbles. This means you may use
  • tap water or
  • non-carbonated (still) mineral water
• It is very important to add the exact amount of water to the granules in the bottle to ensure the correct concentration of Xarelto.
  • Use the water syringe to measure 100 ml of water; see below for further information.
  • Measure the amount of water to be added to the bottle very carefully.
• After preparation, the suspension can be used for 14 days if stored at room temperature. Be sure to write the expiry date of the suspension (date of preparation plus 14 days) in the designated space on the label of the bottle.
• Do not store the suspension at temperatures above 30°C. Do not freeze. If the suspension has been stored in the refrigerator, allow it to reach room temperature before withdrawing the dose.
• Shake the suspension for initial preparation for at least 60 seconds.
• Shake the suspension in the bottle for at least 10 seconds before each administration.
• It is very important that the prescribed dose volume of Xarelto is administered.
  • Make sure you know the prescribed dose and frequency of administration. Ask your doctor or pharmacist if you are unsure about the prescribed dose and how often it should be taken.
  • Carefully adjust the blue syringe to the prescribed volume.
  • Administer the prescribed dose using the blue syringe. Follow your doctor's instructions regarding how many times per day the prescribed dose should be administered.
  • Check that there are no air bubbles in the blue syringe before administering the oral suspension.
• If your child repeatedly fails to take the full required dose or spits out part of it, contact your child's doctor to find out what to do.
• Between doses, keep the oral suspension out of sight and reach of children.
• Keep the Instructions for Use available for reference during treatment with Xarelto.

Use of Xarelto

• Xarelto suspension is for oral use only.
• The volume and frequency of administration of Xarelto depend on your child's weight and will therefore change over time if your child receives Xarelto for a prolonged period.
  • Your child's doctor will inform you of the correct dose volume and frequency of administration.
  • Do not change the dose on your own.
  • Always use the volume prescribed by your child's doctor, and ensure the correct dose and frequency of administration are written in the designated space on the outer carton.

If this information is not written in that space, ask your child's doctor or pharmacist to provide it.

• Follow the detailed Instructions for Use provided in the following sections.
• Take care to follow the instructions regarding administration:

1. Preparation of the oral suspension

Step 1.1: Preparation – All ready

The preparation of the suspension is performed once for each new container.

Before preparing the suspension:

	Wash hands thoroughly with soap and dry them afterwards.
	Check the expiration date on the label of the box. Do not use the medicine if it has expired.
	Gather the following additional items: Container with at least 150 ml of water: Tap water or non-carbonated (still) mineral water Water must be at room temperature
	Paper tissue to absorb any excess water.

Step 1.2: Filling with the required volume of water

Each time you start a new package, use only the new materials included in the new package.

Unpack the water syringe. Immerse the opening of the water syringe into the container with water. Draw a volume exceeding 100 ml. To do this, pull the plunger towards you, ensuring that the opening of the water syringe remains below the water surface at all times. This will prevent air bubbles from entering the syringe. Remove the syringe from the water. Rotate the water syringe so that the opening points upward. Air bubbles will rise to the top when the syringe is held upright. Push the plunger until the upper ring of the plunger reaches the 100 ml mark. Pressing the plunger may cause water to escape from the tip of the water syringe. Any residual water can be absorbed with a paper towel. Continue holding the water syringe with the opening facing upward and carefully inspect the water inside the syringe: For correct volume, For presence of air bubbles. Small air bubbles are not critical, but large ones are. For further information on what to do, see below. If the syringe is not correctly filled or contains too much air: Empty the water syringe. Repeat steps b. through h.

Step 1.3: Addition of water to the granulate

	If the granules in the bottle appear clumpy: Gently tap the bottle in your hand. Be careful, as the bottle is made of glass.
	Unscrew the child-resistant closure cap from the bottle (press down and turn counterclockwise).
	Place the filled water syringe into the top opening of the bottle.
	Hold the bottle firmly. Slowly push the plunger down. All water volume must be transferred into the bottle. Dispose of the water syringe in household trash.

Step 1.4: Placing the adapter and mixing the oral suspension

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

	Unpack the adapter from the vial.
	Push the adapter completely into the neck of the vial.
	Close the vial securely with the screw cap.
	Gently shake the vial for at least 60 seconds. The purpose is to obtain a well-mixed suspension.
	Check that the suspension is well mixed: no lumps, no deposits.
	If lumps or sediments remain, repeat steps d. to f. The suspension is ready for use when no lumps or deposits remain. Do not add more water to the vial. The suspension is valid for 14 days at room temperature.
	Write the expiry date of the freshly prepared suspension on the vial label. Date of preparation + 14 days The pictogram shown is for illustrative purposes only.

1. 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 enclosed blue syringe must be prepared according to the dose prescribed by your child's doctor. This information can be found in the area of the carton designated for this purpose. If no information has been entered here, please consult your child's doctor or pharmacist.

After the dose has been set, the same blue syringe can be used for all subsequent administrations from the suspension bottle prepared in step 1.

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

Step 2.1: Selecting an appropriate blue syringe

This package contains dosing devices of different capacities:

	Blue 5 ml syringes for doses from 1 ml to 5 ml
	Blue 10 ml syringes for doses from 5 ml to 10 ml
	Select the appropriate blue syringe according to the dose prescribed by your child's doctor. Other blue syringes are not needed. Unpack the blue syringe. Note: Do not remove the peelable label until instructed in the Instructions for Use. The blue syringe has a red button to adjust the volume. This button is initially covered by a peelable label. The syringe volume is set by pressing the red button, which can only be done once. Do not press the red button until instructed in the Instructions for Use. Once the red button has been pressed, the volume can no longer be adjusted.
Step 2.2: Adjusting the required dose in the new blue syringe The blue syringe has a scale (ml). The scale on the 5 ml blue syringe starts at 1 ml. Graduation marks are in increments of 0.2 ml. The scale on the 10 ml blue syringe starts at 2 ml. Graduation marks are in increments of 0.5 ml.
	Check the dose indicated in the designated field on the outer box. Note: Use the 10 ml blue syringe for prescribed doses greater than 10 ml as follows: Dose of 15 ml: 2 x 7.5 ml from the blue syringe Dose of 20 ml: 2 x 10 ml from the blue syringe
	If the information is not available: Ask your pharmacist or doctor to provide it.
	Hold the blue syringe with the opening facing upwards.
	Slowly pull the plunger rod until the upper edge reaches the mark corresponding to the volume to be administered. As you move the plunger rod, you will hear a "click" for each adjustable volume step. The pictogram shown is for illustrative purposes only. Your volume may differ. Be careful not to pull the plunger beyond the volume to be administered. Be careful not to press the label while pulling the plunger.
	Completely remove the label from the blue syringe. You can now see the red button for adjusting the volume. Double-check the plunger position. Ensure that the upper edge of the plunger is exactly aligned with the correct volume mark to be administered. If the position of the blue plunger does not match the required volume: Adjust it accordingly.
	If the position of the blue plunger matches the required volume, press the red button to lock in the setting. The required dose is now set. Pressing the red button will produce an audible "click" sound. The "click" sound will no longer be heard afterwards.
	Push the plunger fully up into the blue syringe until it stops. The blue syringe is now ready for use.

1. Administration of the oral suspension

Follow the steps described below for each required administration.

Step 3.1: Mixing the oral suspension

	Gently shake the bottle for at least 10 seconds before each dose. The purpose is to obtain a well-mixed suspension.
	Check that the suspension is well mixed, i.e.: no lumps, no deposits. If there are lumps or deposits: Repeat steps a. and b.
	Shaking may cause foam to form. Let the bottle stand until the foam has dissolved.
	Unscrew the closure cap from the bottle, but keep the adapter in place on top of the bottle. Note: The larger opening visible on the adapter is used to connect the blue syringe. The surface of the bottle adapter must be free of liquid. If there is liquid on the adapter: Remove the liquid with a clean tissue paper.

Step 3.2: Extraction of the required dose

Keep the vial in an upright position. Insert the tip of the blue syringe completely into the large opening of the adapter. Invert the vial upside down. Pull the blue plunger rod slowly until it stops (i.e., until the set dose is reached). Carefully check for air in the blue syringe. Small air bubbles are not critical. If there are larger air bubbles: Return the suspension to the vial by pushing the plunger rod back into the blue syringe as much as possible. Repeat steps b. to e. Place the vial back in an upright position. Carefully remove the blue syringe from the adapter. Hold the blue syringe in an upright position and check: That the tip of the blue syringe is filled, Whether the correct dose has been drawn into the blue syringe, That there are no large air bubbles. If there are larger air bubbles or air in the tip: Reinsert the tip of the blue syringe completely into the large opening of the adapter. Return the suspension to the vial by pushing the plunger rod of the blue syringe fully in. Close the vial with the screw cap. Administer the suspension immediately after filling the blue syringe (step 3.3).

Step 3.3: Administration of the prescribed dose

	Place the blue syringe into the patient's mouth. Direct its tip toward the cheek to allow natural swallowing. Push the plunger down slowly until the plunger stops (the blue syringe is completely empty). Ensure the patient swallows the entire dose.
	Encourage the patient to drink a normal amount of liquid. For a 6-month-old infant, for example, this may be 20 ml. It may also be breast milk. For an adolescent, it may be a volume of 240 ml.

1. Cleaning and storage

The blue syringe must be cleaned after each administration.

Follow the steps below to clean the device. A total of three cleaning cycles are required to ensure proper cleaning.

Before beginning, you will need the following materials for step 4.1: Obtain two containers (such as a cup or bowl) one container filled with drinking water, the other container empty.

Step 4.1: Cleaning

	Submerge the tip of the blue syringe into the water container. Draw water in until the plunger stops.
	Empty the blue syringe into the prepared empty container.
	Repeat steps a. to c. two more times. After cleaning, push the plunger inward until it stops. Dry the outer surface of the syringe with a clean paper towel.

Step 4.2: Storage

Store the blue syringe in a clean and dry place until next use, e.g., keep it in the Xarelto box provided to you.

Keep away from sunlight.

Store the suspension below 30 °C.

1. Disposal

Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.