Posology : מינונים

4.2 Posology and method of administration

Posology
Prevention of VTE in adult patients undergoing elective hip or knee replacement surgery The recommended dose is 10 mg rivaroxaban taken orally once daily. The initial dose should be taken 6 to 10 hours after surgery, provided that haemostasis has been established.

The duration of treatment depends on the individual risk of the patient for venous thromboembolism which is determined by the type of orthopaedic surgery.
•    For patients undergoing major hip surgery, a treatment duration of 5 weeks is recommended.
•    For patients undergoing major knee surgery, a treatment duration of 2 weeks is recommended.

Prevention of recurrent DVT and PE
When extended prevention of recurrent DVT and PE is indicated (following completion of at least 6 months therapy for DVT or PE), the recommended dose is 10 mg once daily.
The safety and efficacy of treatment duration beyond 12 months has not been established. It should be considered whether to continue treatment beyond 12 months.

Time Period              Dosing schedule        Total daily dose
Treatment and          Day 1-21                 15 mg twice daily      30 mg prevention of recurrent DVT and      Day 22 onwards           20 mg once daily       20 mg PE


Prevention of           Following completion     10 mg once daily         10 mg recurrent DVT and       of at least 6 months
PE                      therapy for DVT or
PE

If a dose is missed during the 15 mg twice daily treatment phase (day 1 - 21), the patient should take Xarelto immediately to ensure intake of 30 mg Xarelto per day. In this case two 15 mg tablets may be taken at once. The patient should continue with the regular 15 mg twice daily intake as recommended on the following day.

If a dose is missed during the once daily treatment phase, the patient should take Xarelto immediately, and continue on the following day with the once daily intake as recommended.
The dose should not be doubled within the same day to make up for a missed dose.

Converting from Vitamin K Antagonists (VKA) to Xarelto
For patients treated for DVT, PE and prevention of recurrence, VKA treatment should be stopped and Xarelto therapy should be initiated once the INR is ≤ 2.5.

When converting patients from VKAs to Xarelto, International Normalised Ratio ( 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).

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.
In patients converting from Xarelto to VKA, VKA should be given concurrently until the INR is ≥ 2.0. For the first two days of the conversion period, standard initial dosing of VKA should be used followed by VKA dosing, as guided by INR testing. While patients are on both Xarelto and VKA the INR should not be tested earlier than 24 hours after the previous dose but prior to the next dose of Xarelto. Once Xarelto is discontinued INR testing may be done reliably at least 24 hours after the last dose (see sections 4.5 and 5.2).

Converting from parenteral anticoagulants to Xarelto
For patients currently receiving a parenteral anticoagulant, discontinue the parenteral anticoagulant and start Xarelto 0 to 2 hours before the time that the next scheduled administration of the parenteral medicinal product (e.g. low molecular weight heparins) would be due or at the time of discontinuation of a continuously administered parenteral medicinal product (e.g. intravenous unfractionated heparin).

Converting from Xarelto to parenteral anticoagulants
Give the first dose of parenteral anticoagulant at the time the next Xarelto dose would be taken.

Special populations
Renal impairment
Limited clinical data for patients with severe renal impairment (creatinine clearance 15 - 29 ml/min) indicate that rivaroxaban plasma concentrations are significantly increased.
Therefore, Xarelto is to be used with caution in these patients. Use is not recommended in patients with creatinine clearance < 15 ml/min (see sections 4.4 and 5.2).
No dose adjustment is necessary in patients with mild renal impairment (creatinine clearance 50 - 80 ml/min) or moderate renal impairment (creatinine clearance 30- 49 ml/min) (see section 5.2).

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 sections 4.3 and 5.2).


Elderly population
No dose adjustment (see section 5.2).
Body weight
No dose adjustment (see section 5.2).

Gender
No dose adjustment (see section 5.2).

Paediatric population
The safety and efficacy of Xarelto 10 mg tablets in children aged 0 to 18 years have not been established. No data are available. Therefore, Xarelto 10 mg tablets are not recommended for use in children below 18 years of age.

Method of administration
Xarelto is for oral use.
The tablets can be taken with or without food (see sections 4.5 and 5.2).

Crushing of tablets
For patients who are unable to swallow whole tablets, Xarelto tablet may be crushed and mixed with water or apple puree immediately prior to use and administered orally.
The crushed Xarelto tablet may also be given through gastric tubes after confirmation of the correct gastric placement of the tube. The crushed tablet should be administered in a small amount of water via a gastric tube after which it should be flushed with water (see section 5.2 and 6.6).
There is no data regarding chewing or halving the tablets.