XARELTO GRANULES FOR ORAL SUSPENSION 1MG/ML [SIN16487P]

Product Info

XARELTO GRANULES FOR ORAL SUSPENSION 1MG/ML

[SIN16487P]

4.1 Therapeutic indications

Treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in term neonates, infants and toddlers, children, and adolescents aged less than 18 years after at least 5 days of initial parenteral anticoagulation treatment.

4.2 Posology and method of administration

Posology
The dose and frequency of administration are determined based on body weight (see Table 1).

The weight of the child should be monitored and the dose reviewed regularly, especially for children below 12 kg. This is to ensure that a therapeutic dose is maintained. Dose adjustments should be made based on changes in body weight only.

Frequency of dosing:

• For a once a day regimen
  The doses should be taken approximately 24 hours apart.

• For a two times a day regimen
  The doses should be taken approximately 12 hours apart.

• For a three times a day regimen
  The doses should be taken approximately 8 hours apart.

For patients with body weight of at least 2.6 kg to less than 30 kg only the oral suspension should be used. Do not split Xarelto tablets or use Xarelto tablets of lower strength in an attempt to provide doses for children with body weight below 30 kg.
For patients with body weight of at least 30 kg, Xarelto oral suspension or tablets of 15 mg or 20 mg strength can be administered once a day.

Xarelto oral suspension is provided with either 1 mL or 5 mL and 10 mL blue syringes (oral dosing syringe) with their adapter. To ensure accurate dosing it is recommended to use the blue syringes as follows (see Table 1):

• 1 mL blue syringe (with 0.1 mL graduations) must be used in patients weighing less than 4 kg

• 5 mL blue syringe (with 0.2 mL graduations) may be used in patients weighing 4 kg up to less than 30 kg

• 10 mL blue syringe (with 0.5 mL graduations) is only recommended for use in patients weighing 12 kg or more

For patients weighing 12 kg up to less than 30 kg, either 5 mL or 10 mL blue syringes can be used.
It is recommended that the healthcare professional advises the patient or caregiver which blue syringe to use to ensure that the correct volume is administered.
Instructions for Use booklet is provided with the medicinal product.

Initiation of treatment

• Paediatric patients from term neonates to less than 6 months
  Treatment for paediatric patients from term neonates to less than 6 months of age, who at birth had at least 37 weeks of gestation, weigh at least 2.6 kg, and have had at least 10 days of oral feeding should be initiated following at least 5 days of initial parenteral anticoagulation treatment (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Xarelto is dosed based on body weight using the oral suspension formulation (see Table 1).

• Paediatric patients from 6 months of age to less than 18 years
  Treatment for paediatric patients from 6 months to less than 18 years of age should be initiated following at least 5 days of initial parenteral anticoagulation treatment (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Xarelto is dosed based on body weight (see Table 1).

Duration of treatment

• All children, except those aged less than 2 years with catheter-related thrombosis
  Therapy should be continued for at least 3 months. Treatment can be extended up to 12 months when clinically necessary. There is no data available in children to support a dose reduction after 6 months treatment. The benefit-risk of continued therapy after 3 months should be assessed on an individual basis taking into account the risk for recurrent thrombosis versus the potential bleeding risk.

• Children aged less than 2 years with catheter-related thrombosis
  Therapy should be continued for at least 1 month. Treatment can be extended up to 3 months when clinically necessary. The benefit-risk of continued therapy after 1 month should be assessed on an individual basis taking into account the risk for recurrent thrombosis versus the potential bleeding risk.

Missed doses

• Once a day regimen
  If taken once a day, a missed dose should be taken as soon as possible after it is noticed, but only on the same day. If this is not possible, the patient should skip the dose and continue with the next dose as prescribed. The patient should not take two doses to make up for a missed dose.

• Two times a day regimen
  If taken twice a day, a missed morning dose should be taken immediately when it is noticed, and it may be taken together with the evening dose. A missed evening dose can only be taken during the same evening, the patient should not take two doses the next morning.

• Three times a day regimen
  If taken three times a day, the three times daily administration schedule with approximately 8-hour intervals should simply be resumed at the next scheduled dose without compensating for the missed dose.

On the following day, the child should continue with the regular once, twice or three times daily regimen.

Converting from parenteral anticoagulants to Xarelto
For patients currently receiving a parenteral anticoagulant, start Xarelto 0 to 2 hours before the time of the next scheduled administration of the parenteral medicinal product (e.g. LMWH) or at the time of discontinuation of a continuously administered parenteral medicinal product (e.g. intravenous unfractionated heparin).

Converting from Xarelto to parenteral anticoagulants
Discontinue Xarelto and give the first dose of parenteral anticoagulant at the time that the next Xarelto dose would be taken.

Converting from Vitamin K antagonists (VKA) to Xarelto
VKA treatment should be stopped and Xarelto therapy should be initiated once the International Normalised Ratio (INR) is ≤ 2.5.
When converting patients from VKAs to Xarelto, INR values will be falsely elevated after the intake of Xarelto. The INR is not valid to measure the anticoagulant activity of Xarelto, and therefore should not be used (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Converting from Xarelto to Vitamin K antagonists (VKA)
There is a potential for inadequate anticoagulation during the transition from Xarelto to VKA. Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that Xarelto can contribute to an elevated INR.
Children who convert from Xarelto to VKA need to continue Xarelto for 48 hours after the first dose of VKA. After 2 days of co-administration an INR should be obtained prior to the next scheduled dose of Xarelto. Co-administration of Xarelto and VKA is advised to continue until the INR is ≥ 2.0. Once Xarelto is discontinued INR testing may be done reliably 24 hours after the last dose (see above and section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Special populations
Renal impairment

• Children 1 year or older with mild renal impairment (glomerular filtration rate 50 – 80 mL/min/1.73 m²): no dose adjustment is required, based on data in adults and limited data in paediatric patients (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Children 1 year or older with moderate or severe renal impairment (glomerular filtration rate < 50 mL/min/1.73 m²): Xarelto is not recommended as no clinical data is available (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Children below 1 year: the renal function should only be determined using serum creatinine. Xarelto is not recommended in children younger than 1 year with serum creatinine results above 97.5th percentile (see Table 2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), as no data are available (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment
No clinical data is available in children with hepatic impairment.
Xarelto is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C (see section 4.3 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Body weight
For children the dose is determined based on body weight (see Posology above).

Gender
No dose adjustment (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Paediatric population
The safety and efficacy of Xarelto in children aged 0 to < 18 years have not been established in indications other than treatment of venous thromboembolism (VTE) and prevention of VTE recurrence. No data are available for other indications. Therefore, Xarelto is not recommended for use in children below 18 years of age in indications other than the treatment of VTE and prevention of VTE recurrence.

Method of administration
Xarelto is for oral use.
The oral suspension should be taken with feeding or with food (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

For details on preparation and administration of the oral suspension see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.
The oral suspension may be given through a nasogastric or gastric feeding tube (see sections 5.2 and 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Each dose should be immediately followed by the intake of one typical serving of liquid. This typical serving may include liquid volume used for feeding.
In case the patient immediately spits up the dose or vomits within 30 minutes after receiving the dose, a new dose should be given. However, if the patient vomits more than 30 minutes after the dose, the dose should not be re-administered and the next dose should be taken as scheduled.

If the oral suspension is not immediately available, when doses of 15 mg or 20 mg rivaroxaban are prescribed, these could be provided by crushing the 15 mg or 20 mg tablet and mixing it with water or apple puree immediately prior to use and administering it orally (see sections 5.2 and 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Active clinically significant bleeding.

Lesion or condition, if considered to be a significant risk for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.

Concomitant treatment with any other anticoagulants, e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, dabigatran etexilate, apixaban, etc.) except under specific circumstances of switching anticoagulant therapy (see section 4.2) or when UFH is given at doses necessary to maintain an open central venous or arterial catheter (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Pregnancy and breast-feeding (see section 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).