In PIONEER AF-PCI, Xarelto significantly reduced clinically significant bleeding in NVAF patients undergoing PCI with stenting vs standard therapy with VKA plus DAPT.1 The Xarelto 15 mg OD dose in addition to a P2Y12 inhibitor for a maximum of 12 months post PCI with stent placement has already been adopted in clinical practice.

Xarelto is the only NOAC that is recommended specifically in the focused update of the 2017 ESC Guidelines for DAPT in patients with an indication for an OAC with a IIb/B recommendation based on the PIONEER AF-PCI results.,

In a retrospective analysis of 14,865 patients from a US administrative database, Yao et al concluded that NOAC underdosing is associated with a higher risk of stroke without any advantages for patients.

The study found that, among the 13,392 patients with no renal indication for dose reduction, 13.3% were potentially underdosed.

Suboptimal stroke protection from inappropriate NOAC dosing has no advantages for patient’s safety. There was no statistically significant relationship between dose reduction and risk of stroke or bleeding in patients who received Xarelto.

Ideally, adult PE/DVT patients should be assessed for individual risk at month 6 and children after 3 months of Xarelto treatment.

After 6 months, you have the option to reduce the dose of Xarelto to 10 mg once daily. In patients in whom the risk of recurrent VTE is considered high, like those patients with complicated comorbidities or who have developed recurrent VTE, (while on 10 mg OD) a dose of Xarelto 20 mg once daily should be considered. This dosing choice is unique to Xarelto.

In children with VTE, dosing is based on their individual body weight, and should be adjusted if the child is on Xarelto for an extended period of time.4 The weight of the child should be monitored and the dose reviewed regularly. Please see the Xarelto dosing guide for more information. There is no data available in children to support a dose reduction after 6 months treatment.

From month 6 onwards, the dosage of Xarelto should be increased back to 20 mg OD in adults patients if they experienced recurrent VTE while on Xarelto 10 mg OD.

The dosing of Xarelto in children aged <18 years old is based on their weight, which should be regularly monitored and reviewed, particularly for children below 12 kg. Dose adjustments should be made based on changes in body weight only. The full details of body weight-adjusted dosing can be found in the dosing guide. Children weighing ≥30 kg can also take a 15 mg or 20 mg once-daily tablet depending on the child's weight, which can be crushed and mixed with water or apple puree. Prior to initiation with Xarelto, paediatric patients should receive at least 5 days of parenteral anticoagulation, such as with heparin.

To prepare the oral suspension, add 50 ml of drinking water using the provided syringe to the Xarelto granules and shake well for at least 60 seconds until no clumps or deposit remain. The suspension can be used for 14 days after preparation if stored at room temperature. Using the blue syringe, the correct dose can be selected according to volume and emptied directly into the child’s cheek. For full information on preparing the oral suspension, please refer to the Instructions for Use Booklet.

Xarelto is eliminated via both the faecal and the renal pathway, with two thirds metabolised by the liver and one third of active drug eliminated unchanged via the kidneys. Xarelto does not require any dose adjustments in patients with mild renal impairment (CrCl 50–80 ml/min). Xarelto should be used with caution in patients with severe renal impairment (CrCl 15–29 ml/min), and renal impairment concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations. Xarelto has not been studied in the patient population with a creatinine clearance <15 ml/min and its use is not recommended in this patient population.

There is limited data in children with VTE with renal impairment. No dose adjustment is required for children 1 year or older with mild renal impairment [glomerular filtration rate 50–80 mL/min/1.73 m²]. As no clinical data is available, Xarelto is not recommended in children 1 year or older with moderate or severe renal impairment [glomerular filtration rate < 50 mL/min/1.73 m²]. Xarelto is not recommended in children younger than 1 year with serum creatinine results above 97.5th percentile.

Rivaroxaban clearance is decreased with increasing renal impairment. Consequently, and based on the Phase 3 study (ROCKET AF), a dose reduction is recommended for SPAF (20 mg OD to 15 mg OD) in patients with moderate renal impairment [CrCl 30–49 ml/min] and severe renal impairment [CrCl 15–29 ml/min]. For VTE patients with moderate [CrCl 30–49 ml/min] or severe renal impairment [CrCl15–29 ml/min] a dose reduction (20 mg OD to 15 mg OD) can be considered if the bleeding risk outweighs the thrombotic risk. No dose adjustment is necessary in patients taking Xarelto 10 mg OD or 2.5 mg BID.

Rivaroxaban shows consistent, dose dependent plasma levels across a range of patient populations. With a fixed dose, a wide therapeutic window, few drug interactions, and predictable pharmacodynamics, no routine monitoring of coagulation parameters is required.^[],^[]

Factor Xa activity closely correlates with the plasma concentration. The prothrombin time (PT) varies in a linear dose-dependent fashion with plasma levels of Xarelto.^[]

The Anti-Factor Xa Chromogenic Assay and the Prothrombin Time11 (PT), using Neoplastin Plus as reagent, have been identified as suitable coagulation tests for rivaroxaban using validated rivaroxaban calibrators and controls.

The PK profile of rivaroxaban including timing of last drug intake, C_max and C_trough has to be taken into account when interpreting results of these tests.,

The Anti-Factor Xa Chromogenic Assay accurately estimates rivaroxaban plasma concentration. The PT is prolonged