Download Rivaroxaban for stroke prevention in atrial fibrillation

Clinical Guideline
Rivaroxaban (Xarelto®) for stroke prevention in atrial fibrillation
NICE TA256 published in May 2012. Rivaroxaban is recommended as an option
for the prevention of stroke and systemic embolism within its licensed indication,
that is, in people with nonvalvular atrial fibrillation with one or more risk factors
such as:

congestive heart failure

hypertension

age 75 years or older

diabetes mellitus,

prior stroke or transient ischaemic attack.
1. Baseline assessment prior to initiation of rivaroxaban
1.1 Baseline Activated Partial Prothrombin Time (aPTT), International Normalised Ratio
(INR), haemoglobin, urea & electrolytes and liver function tests
1.2 Weigh patient
1.3 Calculate baseline creatinine clearance (CrCL)
1.4 Establish bleeding risk for individual patient – (See table 1)
1.5 Complete initiation checklist for rivaroxaban and file in patient records.
1.6 Informed discussion with patient regarding risks and benefits of rivaroxaban
This MUST include that there is currently no available antidote for reversing rivaroxaban
in the event of a major bleed
1.7 Confirm if patient already taking other anticoagulants and switch according to Section 3
1.8 ALL patients MUST be given the rivaroxaban alert card.
2. Dose of rivaroxaban (Xarelto®)
20mg daily once daily. Therapy should be continued long term. Some patients require a lower
dosage of rivaroxaban (See table 1)
Rivaroxaban for stroke prevention in atrial fibrillation – clinical guideline, v1
Approved by Wirral Drug & Therapeutic Panel: May 2013
Principal author: Alice Foster
Review by: May 2016
Page 1 of 6
Clinical Guideline
Table 1. Bleeding risks and recommended dosage adjustments
Patient Factors
Dose of rivaroxaban
If your patient has any of these MAJOR risk factors:
 Hypersensitivity to the active substance or to any of the
excipients
 Severe renal impairment (CrCL < 15 ml/min)
 Active clinically significant bleeding or organic lesion at risk of
bleeding
 High risk of falls that are likely to cause injury and
contraindicate the use of anticoagulation
 Hepatic disease associated with coagulopathy and clinically
relevant bleeding risk including cirrhotic patients with Childs
Pugh B & C.
 Prosthetic heart valve
 Concomitant treatment with systemic ketoconazole,
voriconazole and itraconazole. HIV protease inhibitors e.g.
ritonavir and dronedarone.
 Concomitant treatment with any other anticoagulant. Except
under the circumstances of switching therapy from
rivaroxaban. Or when unfractionated heparin is given at doses
necessary to maintain a central venous or arterial catheter.
 Breastfeeding and pregnancy
 Diseases/procedures with special haemorrhagic risks

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
If your patient has impaired renal function (AMBER):
CrCL 15-49 mls/min
If both RED and AMBER factors are excluded
Rivaroxaban for stroke prevention in atrial fibrillation – clinical guideline, v1
Approved by Wirral Drug & Therapeutic Panel: May 2013
Avoid as contraindicated
Initiate reduced
dose of
15mg once daily
Initiate standard
dose of
20mg once daily
Principal author: Alice Foster
Review by: May 2016
Page 2 of 6
Clinical Guideline
3. Switching anticoagulants
Rivaroxaban treatment to parenteral anticoagulant. Give the first dose of parenteral
anticoagulant at the time the next rivaroxaban dose would be taken.
Parenteral anticoagulants to rivaroxaban - Rivaroxaban should be started 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).
Rivaroxaban treatment to Vitamin K antagonists (VKA) e.g. warfarin, There is a
potential for inadequate anticoagulation during the transition from rivaroxaban to VKA.
Continuous adequate anticoagulation should be ensured during any transition to an
alternate anticoagulant. It should be noted that rivaroxaban can contribute to an elevated
INR.
In patients converting from rivaroxaban 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 guided by INR testing. While patients are on both
rivaroxaban and VKA the INR should not be tested earlier than 24 hours after the previous
dose but prior to the next dose of rivaroxaban. Once rivaroxaban is discontinued INR testing
may be done reliably at least 24 hours after the last dose.
Vitamin K antagonists to rivaroxaban
VKA treatment should be stopped and rivaroxaban therapy should be initiated when the INR
is ≤ 3.0.
4. Monitoring
There is no routine anticoagulant blood monitoring for dabigatran.
The activated partial thromboplastin time (aPTT) and HepTest are also prolonged dosedependently; however, they are not recommended to assess the pharmacodynamic effect of
rivaroxaban. There is no need for monitoring of coagulation parameters during treatment with
rivaroxaban in clinical routine.
Rivaroxaban is a black triangle drug. ANY adverse effects must be reported to the
Committee on Safety of Medicines (CSM). http://yellowcard.mhra.gov.uk/
4.1. Renal Function
Assess renal function at baseline and every six months thereafter.
Close clinical supervision is required in patients with stage 3 chronic kidney disease (CKD)
CrCL 30-60ml/min, e.g. monitor renal function every three months or more frequently if
clinically appropriate.
While on treatment, renal function should be assessed in certain clinical situations when it is
suspected that renal function could decline or deteriorate (such as hypovolemia, dehydration,
Rivaroxaban for stroke prevention in atrial fibrillation – clinical guideline, v1
Approved by Wirral Drug & Therapeutic Panel: May 2013
Principal author: Alice Foster
Review by: May 2016
Page 3 of 6
Clinical Guideline
and with certain co-medications e.g. high dose diuretics). The dose of rivaroxaban should be
reviewed in these circumstances.
4.2. Bleeding risk
As with all anticoagulants, rivaroxaban should be used with caution in conditions with an
increased risk of bleeding. Bleeding may occur at any site during therapy with rivaroxaban.
An unexplained fall in haemoglobin and/or haematocrit or blood pressure should lead to an
investigation to identify a bleeding site. Close clinical surveillance is recommended
throughout the treatment period, especially if risk factors are combined.
5. Problem Solving
5.1 Drug Interactions
Table 2. Selected interactions and recommended dosage adjustments:
(Refer to BNF/SPC for a full up-to-date list of interactions)
Drug Interactions with rivaroxaban
Dronedarone , HIV Protease Inhibitors e.g. ritonavir
and systemic azole antifungals. e.g. ketoconazole,
itraconazole and voriconazole
Avoid co-prescribing.
Phenytoin, rifampicin, carbamazepine,
Phenobarbital, St Johns Wort
Co-administer with caution. May lead to a
reduction in rivaroxaban concentrations.
Antiplatelets, NSAIDs, SSRIs and SNRIs.
Increased risk of GI bleeding. Use
combination with extreme caution – consider
GI protection.
UFH, LMWH, heparin derivatives (fondaparinux),
thrombolytic agents, GPIIb/IIIa receptor
antagonists, dextran, sulphinpyrazone, dabigatran,
apixaban and vitamin K antagonists
Increased risk of bleeding. Avoid coprescribing.
Amiodarone, diltiazem, quinidine, verapamil
Clarithromycin
No recommendation regarding concomitant
use.
Concomitant use will increase rivaroxaban
levels. This is not clinically significant in normal
renal function, but may be significant in
patients with CKD stage 3. Consider
alternative antibiotic therapy.
Digoxin
No interactions reported to date
Beta - blockers
No interactions reported to date
5.2. Acute Bleeding
See Bleeding — Management in patients taking oral anticoagulants.
Rivaroxaban for stroke prevention in atrial fibrillation – clinical guideline, v1
Approved by Wirral Drug & Therapeutic Panel: May 2013
Principal author: Alice Foster
Review by: May 2016
Page 4 of 6
Clinical Guideline
5.3. Surgery
If an invasive procedure or surgical intervention is required, rivaroxaban should be stopped
at least 24 hours before the intervention, if possible and based on the clinical judgement of
the physician.
If the procedure cannot be delayed the increased risk of bleeding should be assessed
against the urgency of the intervention.
Rivaroxaban should be restarted after the invasive procedure or surgical intervention as
soon as possible provided the clinical situation allows and adequate haemostasis has been
established.
5.4. Acutely unwell patients
While on treatment with rivaroxaban renal function should be assessed in clinical situations
where it is suspected that renal function could decline or deteriorate.
Consider temporarily substituting rivaroxaban with prophylactic low molecular weight
heparin in patients who are admitted to hospital with sepsis, acute kidney injury,
hypovolaemia, dehydration or who are started on high dose diuretics. It is recommended to
wait until the next dose of rivaroxaban is due before starting parenteral anticoagulation.
5.5. Compliance Aids – If a patient has been assessed as being appropriate for a multicompartment compliance aid (MCA), often known as a dosette box, consideration can be
given to including rivaroxaban tablets as they do not have any special storage
requirements.
Patients should be able to identify the rivaroxaban tablet in the compliance aid so that it can
be omitted if bleeding occurs.
5.6. Swallowing difficulties
Rivaroxaban tablets may be crushed and either mixed with apple sauce or suspended in
water and administered via a nasogastric tube.
5.7. Overdose with rivaroxaban
Overdose exposes the patient to an increased risk of bleeding. Refer to Bleeding —
Management in patients taking oral anticoagulants if patient is bleeding acutely.
Rare cases of overdose up to 600 mg have been reported without bleeding complications or
other adverse reactions. Due to limited absorption a ceiling effect with no further increase in
average plasma exposure is expected at supratherapeutic doses of 50 mg rivaroxaban or
above.
A specific antidote antagonising the pharmacodynamic effect of rivaroxaban is not available.
The use of activated charcoal to reduce absorption in case of rivaroxaban overdose may be
considered.
Rivaroxaban for stroke prevention in atrial fibrillation – clinical guideline, v1
Approved by Wirral Drug & Therapeutic Panel: May 2013
Principal author: Alice Foster
Review by: May 2016
Page 5 of 6
Clinical Guideline
6. Patient information





All patients should be given the rivaroxaban alert card and counselled on the details
Patient understands the potential bleeding risks with rivaroxaban and is aware that there
is currently no readily available antidote for its effects and the potential ramifications of
this.
All patients should be advised on what action to take if they miss a dose of rivaroxaban
Rivaroxaban should be taken with food
All patients should be counselled to inform their dentist or any other healthcare
professional performing invasive treatments or surgery that they are taking rivaroxaban.
Patients should be able to identify the rivaroxaban tablet in the compliance aid so that it can
be omitted if bleeding occurs.
7. References



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Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation.
NICE TA 256 (May 2012). Available from http://publications.nice.org.uk/rivaroxaban-for-theprevention-of-stroke-and-systemic-embolism-in-people-with-atrial-fibrillation-ta256
Summary of product characteristics for Xarelto Accessed available online at
www.medicines.org.uk
British National Formulary, March 2013
Rivaroxaban patient alert card available at: http://www.xarelto-info.co.uk/hcp.htm
Rivaroxaban for stroke prevention in atrial fibrillation – clinical guideline, v1
Approved by Wirral Drug & Therapeutic Panel: May 2013
Principal author: Alice Foster
Review by: May 2016
Page 6 of 6