Publications

Spotlight on rivaroxaban (Xarelto)

Prescriber Update 40(1): 8–10
March 2019

Key Messages

Rivaroxaban (Xarelto) is a direct-acting oral anticoagulant recently funded by PHARMAC.
The dose of rivaroxaban differs depending on the indication. Patients with reduced renal function may need a dose reduction, depending on the indication.
Monitoring of anticoagulant effect is not required except in special clinical situations such as overdose.
There is no anticoagulant reversal agent for rivaroxaban.
Rivaroxaban is metabolised by both CYP 3A4 and P-gp and is therefore contraindicated in patients taking medicines that strongly inhibit both CYP 3A4 and P-gp (eg, ritonavir).
Care needs to be taken when switching patients to and from rivaroxaban due to the increased risk of bleeding.

Rivaroxaban (Xarelto) was first approved for use in August 2009. It was added to the Pharmaceutical Schedule in August 2018 and is now fully subsidised.

Please refer to the medicine data sheet for full prescribing information (www.medsafe.govt.nz/profs/Datasheet/x/Xareltotab.pdf).

What is rivaroxaban and what is it used for?

Rivaroxaban is a direct-acting oral anticoagulant (DOAC), like dabigatran. It acts by inhibiting factor Xa in the coagulation cascade, thereby preventing the conversion of prothrombin to thrombin, and ultimately slowing clot formation^1–3.

In New Zealand, rivaroxaban is indicated for²:

prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery
prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors
prevention and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).

The dose and duration of rivaroxaban treatment differs depending on the indication and the patient’s renal function; full instructions are provided in the data sheet.

Rivaroxaban is contraindicated in patients with creatinine clearance <15 mL/min and in patients with significant hepatic disease². The full list of contraindications is provided in the data sheet.

Take care when switching patients to and from rivaroxaban, due to the increased risk of bleeding^1,2.

In case of haemorrhage

Currently, there is no specific antidote for rivaroxaban^2,4.

Rivaroxaban is not expected to be dialysable as it is highly bound (92–95%) to plasma protein².

More information is available in the data sheet. See also the ‘Guidelines for management of bleeding with dabigatran or rivaroxaban’ available for download from the bpac website (https://bpac.org.nz/2018/docs/dabigatran-rivaroxaban-bleeding-management.pdf).

Drug interactions

Table 1: Examples of drugs that interact with rivaroxaban

Example	Effect on rivaroxaban	Comment
Strong CYP 3A4 and P-gp inhibitors: eg, voriconazole, ritonavir	Large increase in plasma concentration	Contraindicated
Strong CYP 3A4 and moderate P-gp inhibitors: eg, fluconazole	Small increase in plasma concentration	No need to change dose – not clinically relevant
Strong 3A4 and P-gp inducers: eg, rifampicin, phenytoin	Reduces plasma concentration by 50%	No need to change dose – not clinically relevant
Anticoagulants: eg, warfarin	Pharmacodynamic interaction	Avoid. See data sheet for switching instructions
NSAIDs	Pharmacodynamic interaction	Caution
Platelet aggregation inhibitors: eg, clopidogrel	Pharmacodynamic interaction	Caution
SSRIs, SNRIs	Pharmacodynamic interaction	Caution

Source: Bayer New Zealand Limited. 2017. Xarelto 10 mg, 15 mg and 20 mg film-coated tablets New Zealand Data Sheet 11 December 2017. URL: www.medsafe.govt.nz/profs/datasheet/x/Xareltotab.pdf (accessed 22 January 2019).

Adverse drug reaction (ADR) reporting in New Zealand

Between 1 January 2014 and 31 December 2018 the Centre for Adverse Reactions Monitoring (CARM) received 49 reports where rivaroxaban was considered to be the suspect medicine.

Of these reports, 19 described events indicative of bleeding. There were also three reports of stroke (CARM ID: 109955, 118725, 130307) and three reports were coded as medicine ineffective (113627, 115065, 130043).

References

Best Practice Advocacy Centre NZ. 2018. Rivaroxaban: a fully-subsidised oral anticoagulant. 27 July 2018. URL: https://bpac.org.nz/2018/rivaroxaban.aspx (accessed 22 January 2019).
Bayer New Zealand Limited. 2017. Xarelto 10 mg, 15 mg and 20 mg film-coated tablets New Zealand Data Sheet 11 December 2017. URL: www.medsafe.govt.nz/profs/datasheet/x/Xareltotab.pdf (accessed 22 January 2019).
New Zealand Formulary. 2019. New Zealand Formulary v79: Rivaroxaban 1 January 2019. URL: https://nzf.org.nz/nzf_1508 (accessed 22 January 2019).
Waitemata District Health Board. 2017. Safe Rx: Rivaroxaban – Safe Prescribing – Be Bleeding Careful. June 2017. URL: www.saferx.co.nz/assets/Documents/full/edffead37d/rivaroxaban.pdf (accessed 22 January 2019).