Xarelto product review supplement

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Carlos cropped

Experience with pre-labelled initiation packs of Xarelto® (rivaroxaban) in the acute treatment of DVT and PE in Ipswich Hospital

Carlos Gonzalez, Clinical Pharmacist at The Ipswich Hospital, Pharmacy and Medicines Optimisation Department

Introduction

At The Ipswich Hospital we keep all of the direct oral anticoagulants (DOACs; apixaban, dabigatran, edoxaban, and rivaroxaban) in our joint formulary with the CCG for the acute treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Xarelto (rivaroxaban) is one of our preferred choices in the acute treatment of this condition.

Rivaroxaban is a NICE recommended option for the treatment of acute DVT and PE, and for the prevention of recurrent DVT and PE (venous thromboembolism, VTE).1,2

Initiating treatment with rivaroxaban

For the initial treatment of acute DVT, PE, and prevention of recurrent VTE, the recommended dosage of rivaroxaban is 15 mg twice daily for the first 21 days followed by 20 mg once daily for continued treatment and prevention of recurrence. For patients with moderate or severe renal impairment, a reduced dose of following the first 21 days of treatment should be considered if the patient’s assessed risk for bleeding outweighs the risk for recurrent DVT and PE (see summary of product characteristics for further details).3 The duration of treatment will depend on the bleeding risk of the patient as well as other clinical criteria. A short period of treatment (at least 3 months) is recommended for patients with DVT or PE provoked by events such as recent surgery and trauma. A longer duration of therapy should be considered in patients with DVT or PE not related to major transient risk factors, unprovoked DVT or PE, or a history of recurrent DVT or PE.3

Once the DVT or PE has been diagnosed by one of our clinicians in the Emergency Assessment Unit, if a patient meets the criteria for treatment with a DOAC (such as rivaroxaban) they will be prescribed the drug by a qualified prescriber in the unit and dispensed a supply of this drug by the pharmacy team.

Before November 2017, it was normal practice to supply a box containing 42 of the 15 mg rivaroxaban tablets, which covered the first 3 weeks of treatment. The patient would then be referred to their GP, who would start the 20 mg once-daily treatment of rivaroxaban. This practice would normally be efficient and trouble free. Nevertheless, a few minor incidents occurred, due mainly to poor communication; for example, a patient getting a supply of both 15 mg and 20 mg tablets and starting to take both doses at the same time. No major incidents occurred as these issues were picked up very quickly and no side-effects or bleeding events were reported.

The Xarelto initiation pack

A Xarelto treatment initiation pack has now been launched, which is for the treatment of acute PE and DVT and prevention of recurrence. The pack contains a 3-week supply of the 15 mg tablets and one further week’s supply of the 20 mg tablets, contained in calendar packs.3 This starter pack helps to avoid the potential confusion between the different doses of rivaroxaban mentioned in the previous paragraph. On top of this, dispensing these packs resulted in a considerable saving to the Trust. Since November 2017, we have included this initiation pack in our formulary and started to use it for our patients with acute DVT or PE.

Pre-labelling drugs to facilitate patient discharge

We have taken a step further in our Trust and included the Xarelto initiation packs as part of our list of pre-labelled ‘to take away’ (TTA) packs. In Ipswich Hospital the drugs most often dispensed for patient discharge, which includes items such as aspirin, common painkillers, certain laxatives, and antihypertensive drugs, are available as TTA pre-labelled packs. We pre-dispense these packs with a label that includes dosage instructions, hospital contact details, and enough space for the hospital staff to write the name of the patient and the dispensing date on discharge. These packs can be given directly to patients while still following hospital procedures (such as appropriate training of colleagues and keeping a log of all dispensed packs) and therefore facilitate and speed the discharge process.

The TTA Xarelto treatment initiation packs are specifically labelled ‘for the treatment of Pulmonary Embolism / Deep vein Thrombosis ONLY,’ followed by patient instructions: ‘Take ONE 15 mg tablet TWICE a day with food for 21 days and then take ONE 20 mg tablet DAILY with food to continue. Please obtain further supplies from your GP (It is ESSENTIAL there is no break in treatment)’. 

As pre-labelled TTA Xarelto treatment initiation packs are now available on our Emergency Admission Unit, they can be dispensed by authorised and properly trained members of staff to patients admitted with acute DVT and PE on discharge. They should be dispensed with the corresponding manufacturer leaflet for rivaroxaban.4

Conclusion

In conclusion, the advantages of using these TTA pre-labelled Xarelto treatment initiation packs include:

  • a simple dose transition after 21 days when prescribing Xarelto in the treatment of acute DVT and PE
  • an improved discharge process from the Emergency Admission Unit in our Trust
  • savings due to the Xarelto initiation pack price
  • savings due to not requiring an on-call pharmacist to be on site to dispense the drug out of hours.

Conflicts of interest

Carlos Gonzalez has received an honorarium from Bayer plc for his work on this article.

Key points

  • NICE recommends rivaroxaban as an option for the the treatment of acute DVT and PE, and for the prevention of recurrent DVT and PE1,2
  • For the initial treatment of acute DVT, PE, and prevention of recurrent VTE, the recommended dosage of rivaroxaban is 15 mg twice daily for the first 21 days followed by 20 mg once daily for continued treatment and prevention of recurrence3
  • The Xarelto treatment initiation pack helps to avoid potential confusion between the different doses of rivaroxaban
  • Pre-labelled TTA Xarelto initiation packs facilitate and speed the discharge process.

DVT=deep vein thrombosis; PE=pulmonary embolism; VTE=venous thromboembolism; TTA=to take away

References

  1. NICE. Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism. Technology Appraisal 261. NICE, 2012. Available at: www.nice.org.uk/guidance/ta261
  2. NICE. Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism. Technology Appraisal 287. NICE, 2013. Available at: www.nice.org.uk/guidance/ta287
  3. Bayer plc. Xarelto 15-20mg Film-Coated Tablets Treatment Initiation Pack—summary of product characteristics. August 2018. Available at: www.medicines.org.uk/emc/product/8419
  4. Bayer plc. Xarelto 15-20mg Film-Coated Tablets Treatment Initiation Pack—patient leaflet. August 2018. Available at: www.medicines.org.uk/emc/product/8419

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Jecko cropped

Using Xarelto® (rivaroxaban) for the initial and extended treatment of venous thromboembolism

Jecko Thachil, Consultant, Department of Haematology, Central Manchester University Hospitals NHS Foundation Trust

Introduction

Venous thromboembolism (VTE) management has become an important topic in the current era with increasing awareness of this dangerous condition among healthcare professionals and the public alike. We discuss the acute management of VTE as well as extended anticoagulation therapy with the help of a case study.

A 40-year-old man was diagnosed with an iliofemoral thrombosis after he presented to the accident and emergency department with discomfort in his thigh. The patient was otherwise fit and well with no family history of thrombosis. Two months prior to the presentation he had been on a flight to Hong Kong. This is the most recent of several long-haul flights he has been on. He was started on the direct oral anticoagulant (DOAC), Xarelto (rivaroxaban) 15 mg twice daily for 3 weeks and then 20 mg daily to be taken with the main meal of the day. He was sent back to his GP for continuation of anticoagulation.

Here, we discuss three scenarios—how to start rivaroxaban, how long to continue treatment for, and how often should the patient should be reviewed by the GP.

How to start rivaroxaban

A patient with a confirmed deep vein thrombosis (DVT) or pulmonary embolism (PE) can be started on a DOAC like apixaban or rivaroxaban for the acute treatment. Other currently licensed DOACs, such as dabigatran or edoxaban, cannot be given without at least a 5-day lead-in treatment with low molecular weight heparin.1 Prior to starting the patient on rivaroxaban it is ideal to check:2

  • full blood count
    • a low haemoglobin level can indicate bleeding and a cause for this should be considered
    • a low platelet count/thrombocytopenia may be a contraindication for anticoagulation
  • renal profile (patients with moderate or severe renal impairment require dose adjustments, refer to the summary of product characteristics)3
  • liver profile (rivaroxaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk)3
  • clotting screen if there is a personal or family history of bleeding.

Rivaroxaban requires dose reduction after 3 weeks of the acute treatment from 15 mg twice daily to 20 mg once daily.3 A practical consideration when prescribing rivaroxaban is to ask  patients to take the once daily dose with their main meal and possibly at night. The peak action and therefore highest bleeding risk with any DOAC is in the first 12 hours, so taking them at night would be beneficial for patients who do not work night shifts.4 This is not possible with DOACs that are taken twice daily. 

How long to continue rivaroxaban

The decision on how long to continue anticoagulation is one that requires discussion. The NICE guideline on Venous thromboembolic diseases makes the following recommendations for anticoagulation with vitamin K antagonists (VKA): ‘Offer VKA beyond 3 months to patients with an unprovoked PE’ and ‘Consider extending the VKA beyond 3 months for patients with unprovoked proximal DVT if their risk of recurrence is high and there is no additional risk of major bleeding.’5 In other words, if the VTE episode was not precipitated by a risk factor then an extended period of anticoagulation is beneficial as long as the patient does not have bleeding risks; this advice can also be applied to DOACs. The recurrence risk is higher if the patient is male.5 Women who have received hormonal treatment in the previous 1–2 years also have an increased risk of VTE.6

Historically, extending anticoagulant treatment with VKA was inconvenient due monitoring requirements, drug interactions, and a long half-life making interuptions for procedures difficult.2,4 Extended anticoagulation is simpler with DOACs, such as rivaroxaban, since there is no routine monitoring required, minimal drug interactions, and a shorter half-life.2,4 One of the key benefits with rivaroxaban in this regard is the ability to decrease the dose and still obtain good efficacy without a significant increase in bleeding risk.3,7,8

The EINSTEIN CHOICE trial found that rivaroxaban, at either 20 mg or a reduced dose of 10 mg, was more effective than aspirin for the prevention of recurrent VTE among patients who were in equipoise for continued anticoagulation.8 The added attraction with rivaroxaban was a similar rate of bleeding to that with aspirin.8

If we consider the patient described above, he developed thrombosis after a long-haul flight, which could be considered as provoked. However, there are factors that would make you consider extended treatment in this circumstance. The the large clot developed 2 months after the flight despite him having taken long flights in the past. It is also likely that he may want to continue to fly as part of his work or lifestyle, which in the absence of anticoagulation can be risky and may raise concerns for him. This patient is, in other words, in equipoise for continued anticoagulation. A reduced dose of rivaroxaban, 10 mg once daily, would be ideal for him to mitigate any further risks of thrombosis with minimal bleeding risks. When extended treatment is indicated (following at least 6 months of therapy for DVT or PE), the recommended dose of rivaroxaban is 10 mg once daily.7

Follow-up visits for patients on rivaroxaban

Since DOACs do not require monitoring, follow-up visits are only required for comprehensive patient care. It would be ideal to review the patient at the following points:4

Review 3–4 weeks after initiating rivaroxaban

This review is to ensure the patient has reduced the dose to 20 mg daily and to check if there are any issues with the medication and reassess bleeding risk. It would be useful at this visit to enquire about any symptoms suggestive of a malignancy. NICE guidelines recommend in addition to physical examination, to ‘consider further investigations for cancer … in all patients aged over 40 years with a first unprovoked DVT or PE who do not have signs or symptoms of cancer based on initial investigation.’5

Review 3 and 6 months after commencing treatment

Patients should be reviewed after 3 months. After 6 months of treatment discuss continuation of anticoagulation after assessing bleeding risks and patient preference. Consider reducing the dose of rivaroxaban to 10 mg in selected individuals who are in equipoise for extended anticoagulation.

Annual review

Patients should be reviewed annually to reassess the need for continued anticoagulation, check for any new bleeding risks, and discuss patient preference. It may be considered good practice to check full blood count and renal function every 12 months. If renal function is abnormal, it may need more frequent monitoring and consideration of dose reduction.

Referral and procedures

The patient should be referred to secondary care if they develop a thrombosis or bleeding complication while on a DOAC or if renal function deteriorates dramatically. 

Primary care is often asked to provide advice on how to interrupt rivaroxaban for procedures. The current guidelines recommend that:9

  • if the creatinine clearance is ≥30, interrupt for 24 hours for procedures with low risk of bleeding and 48 hours for procedures with high risk of bleeding
  • if the creatinine clearance is <30, interrupt for 48 hours for procedures with low risk of bleeding and 72 hours for procedures with high risk of bleeding.

Summary

DOACs are a convenient option for treatment and prevention of VTE as they do not require specific monitoring. A reduced dose of rivaroxaban is an option for patients in equipoise for extended anticoagulation, and is more effective than aspirin in the prevention of recurrent VTE in these patients.8

Conflicts of interest

Jecko Thachil has received honoraria from Bayer plc, Bristol-Myers Squibb, Pfizer Ltd, Boehringer Ingelheim Ltd, and Daichii Sankyo UK Ltd.

References

  1. Howard L, Barden S, Condliffe R et al. British Thoracic Society Guideline for the initial outpatient management of pulmonary embolism (PE). Thorax 2018; 73 (Suppl 2): ii1–ii29.
  2. Heidbuchel H, Verhamme P, Alings M et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; 17 (10): 1467–1507.
  3. Bayer plc. Xarelto 15-20mg Film-Coated Tablets Treatment Initiation Pack—summary of product characteristics. August 2018. Available at: www.medicines.org.uk/emc/product/8419
  4. Steffel J, Verhamme P, Potpara T et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39 (16): 1330–1393.
  5. NICE. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. NICE Clinical Guideline 144. NICE, 2012. Available at: www.nice.org.uk/guidance/cg144
  6. Beyer-Westendorf J, Bauersachs R, Wunderle V et al. Sex hormones and venous thromboembolism – from contraception to hormone replacement therapy. Vasa 2018; 47 (6): 441–450.
  7. Bayer plc. Xarelto 10 mg film-coated tablets—summary of product characteristics. August 2018. Available at: www.medicines.org.uk/emc/product/6402
  8. Weitz J, Lensing A, Prins M et al. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. N Eng J Med 2017; 376 (13): 1211–1222.
  9. Keeling D, Campbell Tait R and Watson H. Peri-operative management of anticoagulation and antiplatelet therapy. Br J Haematol 2016; 175 (4): 602–613.

 

This supplement has been developed in partnership with Bayer plc. Bayer plc suggested the topic, funded production of the supplement, and suggested the authors; the content has also been checked for factual accuracy, to ensure it is fair and balanced, and to ensure its compliance with appropriate regulations. The sponsorship fee included the honorarium for the authors.

The views and opinions expressed are not necessarily those of  Bayer plc or of Guidelines in Practice, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher. 

No part of this publication may be reproduced in any form without the permission of the publisher.

PP-XAR-GB-0123

Date of preparation: April 2019