Posology : מינונים

4.2   Posology and method of administration

Posology
The recommended dose is 2.5 mg twice daily.

•     ACS
Patients taking Xarelto 2.5 mg twice daily should also take a daily dose of 75 - 100 mg ASA or a daily dose of 75 - 100 mg ASA in addition to either a daily dose of 75 mg clopidogrel.

Treatment should be regularly evaluated in the individual patient weighing the risk for ischaemic events against the bleeding risks. Extension of treatment beyond 12 months should be done on an individual patient basis as experience up to 24 months is limited (see section 5.1).

Treatment with Xarelto should be started as soon as possible after stabilisation of the ACS event (including revascularisation procedures); at the earliest 24 hours after admission to hospital and at the time when parenteral anticoagulation therapy would normally be discontinued.

•     CAD/PAD
Patients taking Xarelto 2.5 mg twice daily should also take a daily dose of 75 - 100 mg ASA.

Duration of treatment should be determined for each individual patient based on regular evaluations and should consider the risk for thrombotic events versus the bleeding risks.

In patients with an acute thrombotic event or vascular procedure and a need for dual antiplatelet therapy, the continuation of Xarelto 2.5 mg twice daily should be evaluated depending on the type of event or procedure and antiplatelet regimen.

Safety and efficacy of Xarelto 2.5 mg twice daily in combination with ASA plus clopidogrel has only been studied in patients with recent ACS (see section 4.1). Dual antiplatelet therapy has not been 
studied in combination with Xarelto 2.5 mg twice daily in patients with CAD/PAD (see sections 4.4 and 5.1).

If a dose is missed the patient should continue with the regular dose as recommended at the next scheduled time. The dose should not be doubled to make up for a missed dose.

Converting from Vitamin K Antagonists (VKA) to Xarelto
When converting patients from VKAs to Xarelto, International Normalised Ratio (INR) values could 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 sections 4.4 and 5.2).
The risk of bleeding increases with increasing age (see section 4.4).

Body weight
No dose adjustment (see sections 4.4 and 5.2).
Gender
No dose adjustment (see section 5.2).

Paediatric population
The safety and efficacy of Xarelto 2.5 mg tablets in children aged 0 to 18 years have not been established. No data are available. Therefore, Xarelto 2.5 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 (see sections 5.2 and 6.6).
There is no data regarding chewing or halving the tablets.