UNBLOCK VENOUS THROMBOEMBOLISM IN ASSOCIATION WITH HOW TO TREAT DVT IN THE COMMUNITY

Transcription

1 VENOUS THROMBOEMBOLISM IN ASSOCIATION WITH AN HSJ SUPPLEMENT/5 SEPTEMBER 2014 UNBLOCK THE SYSTEM HOW TO TREAT DVT IN THE COMMUNITY Bayer HealthCare sponsored this report. The company has reviewed the data solely to ensure factual accuracy in relation to Bayer products and compliance with industry guidelines. The views expressed in these articles are not necessarily those of the sponsoring company. Rivaroxaban prescribing information available on page 8

2 CONTENTS IN ASSOCIATION WITH Job code: L.GB b Date of preparation: August 2014 SERVICE REDESIGN In much of the country, venous thromboembolism is still seen as being secondary care s business. But new treatments and pioneering trusts are showing how VTE can be managed very differently. Page 2 SERVICE REDESIGN A RICH VEIN OF REFORM Trusts urged to consider new drugs and pathways for venous thromboembolism and potentially cut a yearly NHS treatment bill that runs into hundreds of millions CASE STUDIES How one Bradford GP s light bulb moment led to radical change in his local health economy, prompting the treatment of DVT to shift out of hospital. Page 2 CASE STUDIES Bristol GPs frustration with a secondary care system that made DVT patients wait days to start treatment has prompted the creation of a new community-based pathway that is producing huge savings for the NHS. Page 5 FRONT COVER: ALAMY Full references to all the sources used in this special report can be found on page 6 In England in any given year, it s likely that one in a thousand will be affected by deep vein thrombosis (DVT) or pulmonary embolism (1,2,3). Venous thromboembolism (VTE), the umbrella group for the two conditions, costs the NHS hundreds of millions of pounds a year, leads to tens of thousands of hospital admissions, and rates are only likely to increase as the population continues to age (4). In most parts of the country, VTE is still seen as secondary care s business, with patients being seen largely in acute settings, with associated costs, both financial and human. Increasingly, however, pioneering commissioners such as those in Bradford and Bristol are developing new pathways. These see DVT treated in the community, saving the NHS time and money, and providing a better experience for patients (see case studies). A DVT is a blood clot that occurs in the deep veins of extremities, usually the leg. This can block the flow of blood, which causes the symptoms of DVT and can also have unpleasant longer term consequences, such as leg ulcers; if untreated, DVT can be fatal. If the clot travels and lodges in the lung, the serious and potentially fatal condition of pulmonary embolism (PE) can develop. Dr Mike Dixon, chair of the 2 Health Service Journal supplement 5 September 2014 NHS Alliance, says: When I started practice as a GP 30 years ago, patients with DVT would spend up to 10 days in hospital; now it s something that can be treated easily in general practice. New methods of investigation, and alternative treatment options, especially the novel oral anticoagulants (NOACs) mean that treatment can be started earlier, and in general practice where it should be. Pathways like that in Bradford are trailblazers that should be replicated across the country. It s hard to find up-to-date figures for the costs of VTE to the health economy. But the House of Commons health committee estimated in 2005 that managing VTE cost the UK approximately 640m a year, with a further annual cost of 400m for treating venous leg ulcers (4). In most areas, a DVT will still mean a spell in A&E and at least an overnight hospital stay, followed by treatment with traditional agents, for example treatment with heparin for at least five days and warfarin for three months or more (5). While effective, these methods have known drawbacks. Low molecular weight heparin is often given subcutaneously, causing distress to those with a phobia and necessitating a longer hospital stay (6). The common use of ultrasound and isotope or CTPA (computed tomographic pulmonary angiography) scans means a

3 number of departments are called upon. But the approval of novel treatments for VTE has made it much easier to create new pathways for treating this relatively common and costly condition. Two years ago, the National Institute for Health and Care Excellence (NICE) approved the NOAC rivaroxaban for the treatment of DVT and PE, and prevention of recurrent DVT and PE (see product information on the outside back cover). NICE noted the disadvantages of current favoured treatments, including warfarin, which requires constant monitoring, frequent blood tests and visits to anticoagulation clinics (6). It also said that these drugs, also known as Xabans / DTI (Factor Xa Inhibitors / Direct Thrombin Inhibitors), relieve the concerns that people may have about maintaining the correct warfarin dose. NICE has said patients should have access to the novel treatments, and there is evidence that prescribers want to offer them. But uptake has been slow, with many patients still going through the traditional secondary-care-based pathway despite the national advice to the contrary. This is an issue that has been raised by Lifeblood: The Thrombosis Charity. It carried out a survey last year which found that almost two thirds of GPs had faced problems in trying to get access to the latest treatments, largely because commissioners had concerns about costs (7). So what is the situation, and how much of an issue is it for the NHS, and for patients? In some ways, the situation around VTE has transformed over the past 20 years. But according to campaigners, the full potential has not yet been realised, despite action at a national level from both government and from bodies such as NICE. In Bradford, the vast majority of people with DVT are now diagnosed and treated in primary care, saving money for the local health economy, and providing a better experience for patients. Hospital admissions have been radically reduced, waiting times for scans to confirm diagnosis have been cut, and feedback from patients has been consistently good. Previously, the majority of people in Bradford with suspected DVT would be referred to A&E then admitted to hospital for diagnosis and for treatment. This meant at least one overnight stay while the scan and other tests were arranged and carried out. For most patients (apart from those at highest risk), this was simply unnecessary, says Greg Fell, consultant in public health with Bradford Council. In the old world, the patient would see the GP, and be sent to A&E for a risk assessment, blood test and ultrasound scan. A&Es are busy places and would be unable to organise a scan within four hours, so patients would be admitted to the MAU [medical assessment unit]. In practice, almost everyone was admitted around 1,000 people per year. A local GP, Dr Matthew Fay, who is based in Shipley, was instrumental in developing a different pathway which, for most patients, cut A&E and the MAU out entirely. Under the new system, patients are risk assessed and have blood taken for tests in general practice, and are then referred directly for an ultrasound scan. The GP will also start them on treatment, which will be continued if the DVT is confirmed. Patients will then be seen at the thrombosis clinic within three weeks, where a decision will be made on future treatment. The pathway is easier for patients, who can avoid a hospital stay, and who, in line with NICE guidance, are offered 5 September 2014 Health Service Journal supplement 3 ALAMY Pathways like that in Bradford are trailblazers that should be replicated across the country

4 It was a genuine light bulb moment. I read the paper on a train journey and drew up the pathway on the way home Primary purpose: Bradford, where most DVT patients are now treated in primary care the novel oral anticoagulation drug, rivaroxaban, rather than warfarin (8). In its first month alone, around 80 patients avoided admission, saving the local healthcare economy 26,000, and it s estimated that the pathway will deliver annual savings of more than 500,000. It was an easy decision to include rivaroxaban in the pathway, says Mr Fell. The EINSTEIN trial had recently been published and the evidence was stacking up behind it (9). Patients like it too, because it doesn t involve injections, is much simpler than warfarin, and doesn t involve frequent INR checks (to make sure patients are in the right therapeutic range so that they are not at risk of bleeding or clotting). This agent makes it cleaner and easier for the GP and the patient, and we know that it s cost effective for short term anticoagulation, he says. Yes, you pay more for the medicine but less for INR monitoring. Drawing up the initial pathway was relatively straightforward and took around three months, he says. We then took it to a broader body of GPs and their input was really valuable they came up with things we hadn t thought about, so we developed a list of FAQs, which really helped the process. When implementing the pathway, there were important matters to be considered, such as the potential impact on secondary care services: yes, they would save resources (in terms of A&E and MAU), but they would also lose income. To make sure that services were not destabilised, the commissioners involved secondary care clinicians and managers at an early stage. For example, it was important to ensure that radiology services could respond to increased demand for scans from GPs, and that haematology which reviews patients was ready for additional activity. For patients, it cuts delays and makes the system much more streamlined, adds Mr Fell. The GP orders the blood test and the ultrasound scan but puts the patient on rivaroxaban straight away, he explains. The patient is asked if their record can be shared with the haematologist, and we take it from there. It is anticipated that the cost savings will be significant. Moving anticoagulation out of secondary care for most patients is expected to save around 140,000 per year while 600,000 will be saved on MAU admissions. His advice for anyone considering doing something similar is to get the commissioning business managers involved from the start, as they understand contracting and how to ensure that new processes are implemented properly. Also, don t underestimate the value of consulting a broader body of clinicians, he adds. Their input was a really important part of making this a success. THE EINSTEIN STUDY AND A NEW PATHWAY FOR DVT When Dr Matthew Fay read the results of the EINSTEIN clinical trial into treatment for venous thromboembolism he realised it was exactly what he was looking for. The GP from West Yorkshire had been struggling to draw up a suitable pathway to improve the way that patients in the Bradford area with DVT, or suspected DVT, were treated and this appeared to provide the answer. It was a genuine light bulb moment, he says. I read the paper on a train journey and drew up the pathway on the way home. The EINSTEIN DVT clinical trial programme compared the safety and efficacy of a novel anticoagulant drug, rivaroxaban, with standard treatment in patients with DVT ( ly/1qgptdy). It concluded that rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. Dr Fay quickly realised that this had the potential to revolutionise treatment for his patients, and for those in the rest of Bradford. The pathway we had previously wasn t very well understood and was very fragmented, he says. Different people were trying to do different bits of the pathway in different ways. There was no standard way of diagnosing DVT, or of treating and monitoring it, and there were differences in approach between primary and secondary care. When I read the EINSTEIN study I thought wow. It meant that rather than needing to go to hospital, or be seen by the community intervention team, the patient could be started on a simple intervention there and then. For me, as a GP, that was a real benefit. Patients who had been treated previously have noticed a real difference... and say they much prefer the new pathway. Initially patients who had previously had a DVT were not included in the new pathway, but GPs rebelled; having seen the benefits of the regimen for new patients, they wanted all their patients to have the option. It s working well and saving money in Bradford but Dr Fay regrets that other parts of the country are not as well served. When I read the study I thought wow. It meant the patient could be started on a simple intervention there and then As last year s commissioning support document from NICE remarks, practice and services currently vary in quality and effectiveness across the country. The novel anticoagulants are not uniformly given in this country, he says. I ve particularly noticed that in my real passion, which is atrial fibrillation although NICE has said very clearly that this is a cost effective medicine but I m hearing it about DVT as well. Most areas are still insisting on a trial of warfarin first [before they will allow GPs to prescribe novel anticoagulants]. He believes that clinical commissioning groups are being influenced by the cost of the drug, but also by the prescribing score card, which identifies variation and adoption of NICE technology appraisals (www. england.nhs.uk/ourwork/ innovation/innovationscorecard/). He wholeheartedly believes, however, that primary care is the best place to manage patients with DVT and suspected DVT. For every ten patients who come in with a swollen leg, only one has DVT, he says. The vast majority will not need major follow-up, but it s a common presentation. Pulmonary embolism, as a more serious condition, presents different challenges, he says. Again, however, he believes there is potential to treat it in the community. It s an area that s being considered at the moment, but it might need more specialist input, he adds. Nevertheless it s clear his light bulb moment is benefiting patients, clinicians, and commissioners, in Bradford and potentially beyond. l 4 Health Service Journal supplement 5 September 2014

5 SERVICE REDESIGN: CASE STUDY THIS COULD SAVE 50M NATIONALLY Community based services mean many Bristol DVT patients avoid hospital and can get modern treatments as well as producing some impressive savings for the NHS Ask patients in the Bristol area what they think about the community DVT pathway and the responses are overwhelmingly positive. For one 52-year-old woman, being treated in primary care, and with a novel, convenient anticoagulant, came as a particularly welcome surprise because of her previous experiences. Many years ago I had to undergo warfarin treatment, and my memories of having to wait hours in a corridor for a blood test, twice weekly, still give me the heebie jeebies, she said. The service now offered is truly excellent and I can t praise it enough; thank you. This anonymous woman was responding to a survey of patients who had experienced the Community DVT Service run by GP Care, a federation of 100 GP practices across Bristol and the surrounding area. The organisation has been contracted to run community- based DVT services since 2008, meaning that some 97 per cent of patients with DVT or suspected DVT now avoid hospital admission. That service was well received, but last year it took a step further. Since April 2013, GP Care has been operating a pathway whereby patients are offered the novel oral anticoagulant drug, rivaroxaban, which they can choose to take instead of warfarin. The new pathway is already receiving recognition: for example, in March, it took third prize in the Thrombus Innovation Awards designed to reward projects that demonstrate real innovation and excellence in the field of thrombosis care for the second year running. The community based pathway was designed to address GPs concern that the old, secondary care based system meant patients could often wait days to start treatment. GPs 5 September 2014 Health Service Journal supplement 5 ALAMY Staying out: DVT patients served by Bristol s GP Care are largely treated in the community

6 Commissioners should note their obligations in meeting the recommendations made in the NICE technology appraisals REFERENCES 1 Martinez C, Rietbrock S, Bamber L, Cohen AT. Incidence of venous thromboembolism (VTE) in the general population VTE Epidemiology Group study. XXIII Conference of The International Society on Thrombosis and Haematosis (ISTH); 11 Jul; Office for National Statistics. National Population Projections: England, Wales, Scotland and Northern Ireland. Single year of age, 2012-based ons/rel/npp/national-populationprojections/2012-based-projections/ stb-2012-based-npp-principal-andkey-variants.html (last accessed: August 2014) 3 Bayer HealthCare. Data on file: Incidence of VTE from database linkage study Health Select Committee, The prevention of venous thromboembolism in hospitalised patients, February BMJ, Best practice: Deep Vein Thombosis treatment step-by-step, 25 April 2014, bmj.com/best-practice/ monograph/70/treatment/step-bystep.html 6 NICE, Venous thromboembolism - reducing the risk (CG92), January 2010, 7 Lifeblood, Over 80,000 patients at risk of missing out on clot-busting drugs, 22 May www. thrombosis-charity.org.uk/news/ post.php?s= over patients-at-risk-of-missingout-on-clot-busting-drugs 8 NICE, Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism (TA261), July 2012, www. nice.org.uk/guidance/ta261 9 The EINSTEIN Investigators, The New England Journal of Medicine, 2010; 363: were frustrated by how long it took to organise a scan [for suspected DVT], says Lina Middleton, DVT service lead with GP Care. They asked for this service to be set up. GP Care is contracted by clinical commissioning groups to run the service and also works for some GP practices directly. But, she says, the real customer is the patient. That s who we see as our most important customer, she says. That s who is always in our minds. The community based service was already proving a financial boon to the NHS, she explains, and the move to novel anticoagulation saves even more. In the areas that we operate in, we save more than 60 per cent of tariff prices for patients who are treated for a confirmed DVT. This equates to over 500,000 per annum, she says. If applied nationally, this would mean more than 50m in savings. GP Care decided to offer rivaroxaban after a thorough examination of the evidence led them to believe it was the only way to go. Our medicines management board investigated the issue we felt it was either a case of get on board with it, or be left behind, she says. The benefits to patients include greater treatment choice, and much less impact on daily life, she adds. With warfarin, patients are coming in every other day for INR testing; with rivaroxaban we have decided to see people weekly [though this is not required, as patients do not need monitoring], there are no injections, it s an oral drug taken with food. The feedback from patients is that they find it much easier. Since April 2013, the overwhelming majority of patients on the GP pathway have chosen to be treated with rivaroxaban even those who had expected to be treated with warfarin. One 82-year-old patient responded to the GP Care telephone survey saying it had been the right choice for her. The DVT came as a great surprise to me, she said. I was given reading material but only knew of warfarin through other people being on it, but I wasn t sure I wanted all the to-ing and fro-ing to appointments, so chose rivaroxaban. It was, she said, very, very good. GP Care worked closely with secondary care colleagues to develop the pathway, which involves near-patient blood tests at the patient s own practice, same or next-day ultrasound scans from community-based locations, and community-based anticoagulation. Patients are followed up and supported regardless of their treatment choice. Previously people could wait for days, but the service is much more instant now, says Ms Middleton. It s a much more positive experience. SUPPORT FOR COMMISSIONERS Just over a year ago (May 2013), the National Institute for Health and Care Excellence updated its support on commissioning anticoagulation therapy. The aim was to help commissioners work with clinicians and managers to commission high-quality, evidence-based anticoagulation therapy for adults with conditions including venous thromboembolism and atrial fibrillation. In particular, the advice says that commissioners should ensure they are in line with recommendations from NICE technology appraisals on the novel oral anticoagulants rivaroxaban, dabigatran and apixaban for people with AF and rivaroxaban for those with VTE. It also supports the commissioning of anticoagulant therapy for people with deep vein thrombosis and pulmonary embolism in line with the NICE quality standard for diagnosis and management of VTE. Importantly, NICE is encouraging commissioners to review current anticoagulation services with a view to rationalising services for monitoring people on traditional anticoagulation drugs such as warfarin, as more people move to the novel anticoagulation medication. The support package includes a budgeting and commissioning tool to help model current and future requirements in terms of capacity and likely demand. This reduces costs by saving capacity in traditional monitoring services of vitamin K antagonist (such as warfarin) patients as more people are prescribed the novel drugs in a primary care setting. Extending anticoagulation to people who don t currently receive treatment but should, and changing the drug used also result in savings. Launching the advice last year, Professor Gillian Leng, NICE deputy chief executive and director of health and social care, called for effective commissioning of services to improve outcomes. Anticoagulation therapy is a rapidly changing area of practice, driven in large part by the availability of novel anticoagulants, she said. Given the pace of change in this area it is not surprising that there is evidence that practice and services currently vary in quality and effectiveness across the country. She added: The fundamental premise of this support for commissioning package is that effective commissioning for anticoagulation therapy in line with NICE guidance will improve outcomes for patients by increasing the number of people receiving safe and effective anticoagulation therapy. The support package also points out that the novel oral anticoagulants can be readily prescribed in primary care by GPs and that a dedicated monitoring service is not needed. It says that some commissioners have not taken on board the recommendations in the NICE technology appraisals to prescribe the new drugs. In some areas there are local policies that restrict the prescribing of the novel oral anticoagulants, the support document says. Commissioners should note their obligations in meeting the recommendations made in the relevant NICE technology appraisals. l FIND OUT MORE support-for-commissioninganticoagulation-therapy-cmg49 Commissioning support package CG144 Clinical guideline on venous thromboembolic diseases Prescribing information is provided on page 8 nhspatients/deep_vein_thrombosis/ More about GP Care s anticoagulation services, or call , or info@gpcare.org.uk 6 Health Service Journal supplement 5 September 2014

7 PATIENT EXPERIENCE THE NEXT LEASE OF LIFE In just over a decade, the thrombosis charity Lifeblood has achieved huge breakthroughs in how the condition is managed and perceived, but the charity s director Robin Offord says there is much to do to improve access to treatment In 2002, Lifeblood was founded to raise awareness of thrombosis and to promote research in this areas something the charity s director, clinical pharmacist Robin Offord, says was imperative because of the risks of patients developing VTE in a healthcare setting at that time. In its relatively short life, the small charity has made big achievements, and has been instrumental in a step-change in the way VTE is managed and thought about in the health service and beyond. The Lifeblood Stop the Clots campaign, launched in 2005, helped precipitate a parliamentary select committee investigation, resulting in recommendations to the Department of Health (4). In 2010, NICE published a guideline ( CG92) focusing on cutting VTE risk in people admitted to hospital and recommending that all patients should be riskassessed, and then given preventative treatment to suit their individual needs. Importantly, the NICE guideline has been underlined by the inclusion of the risk assessment for VTE in CQUIN targets meaning that trusts lose money if 95 per cent of adults admitted don t receive appropriate blood clot prevention. The result is significant, says Mr Offord. Today if you ask any junior doctor or nurse, they know the key facts about the risks of VTE; it s part and parcel of their work. That certainly wasn t the case 20 years ago. Mr Offord, who is also director of clinical pharmacy with University College London Hospitals Foundation Trust, says that development of novel anticoagulant medicines has also There has been a change in how VTE is thought about in healthcare settings been an important factor in transforming the VTE landscape. Go back 25 years and all we had was warfarin and heparin, he says. Now we have other oral agents. We d been waiting for these for decades warfarin was first used as a medicine in the 1950s and nothing had come through to better it. Now we ve got two different classes of oral drugs, which is very good news. Access to the drugs is an issue, he acknowledges. Lifeblood research published last May, found that 64 per cent of GPs had encountered barriers to prescribing NOAC drugs, with almost all (98 per cent) citing cost restrictions imposed by local commissioners and their own practice managers as the main obstacle to patient access (7). The charity also found out that although 97 per cent of hospitals had a protocol in place for the management of VTE, 61 per cent had not updated it to include the new treatments, nor had they issued any prescribing advice for the new treatments (7). NICE has approved these drugs and wants them to be used, says Mr Offord, adding that NICE considered them to be value for money, although they cost more than warfarin. I think there s been a bit of protectionism from old anticoagulant clinics, but this is misplaced because there will still be some patients on warfarin. He is generally supportive of moving services for DVT into the community, provided it is done in a properly planned way. What needs to happen is that commissioners should step back and rethink their model, he says. And they probably will have to do some restructuring of their pathway. Clinical commissioning groups have been slow to embrace the drugs, with most choosing to make them available only for those for whom warfarin isn t suitable, rather than as a first line drug, he says. That s a shame, because the benefits are now well evidenced, not least the difference that they make to the patient experience. On the traditional pathway, patients will be started on low molecular weight heparin, which has to be injected, followed by warfarin, both of which need to be adjusted for patient weight. Warfarin is a challenge for patients and for health services because it requires regular attendance at a clinic for checks to ensure the dose does not need to be adjusted. Other organisations, including the former National Patient Safety Agency, have reported potential harm from inappropriate warfarin dosing, and there is a body of evidence that suggests the drug is associated with adverse drug events and prescribing errors. Rivaroxaban is the only NOAC to have NICE guidelines for the treatment of VTE. They say it has benefits in in comparison to warfarin, which conclusively makes it cost effective for short term use. This includes removing the need for constant monitoring, frequent blood tests and visits to an anticoagulation clinic. The treatments benefit people who are needlephobic, or who want to get back to a normal pattern of life without having to attend clinics frequently, and addresses concerns that people may have about not being on the correct warfarin dose to remain in the right therapeutic range. The move also reduces the need for support services, and provides cost savings in the short term, and remains cost effective in the longer term, according to NICE. As the NOACs have been shown to be cost effective overall and offer some patients an enhanced quality of care (6), commissioning services to include correct use of NOACs or Xabans also meets the NHS QIPP challenge launched in 2010 aimed at improving quality while delivering efficiency savings. The charity Anticoagulation Europe also calls for greater access. Patients have told them that they have been refused novel treatments, or have not had their options fully explained. For Mr Offord and colleagues at Lifeblood it s quite frustrating. We have been, and are, quite excited; we ve seen real breakthroughs, he says. But the disappointing thing is that it s not happening everywhere yet. I do feel positive, but there s a long way to go. l ALAMY 5 September 2014 Health Service Journal supplement 7

8 This medicinal product is subject to additional monitoring Xarelto 10, 15 and 20 mg film-coated tablets (rivaroxaban) Prescribing Information (Refer to full Summary of Product Characteristics (SmPC) before prescribing) Presentation: 10mg/15mg/20mg rivaroxaban tablet Indication(s): 10mg - Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery. 15mg/20mg - 1. Prevention of stroke & systemic embolism in adult patients with nonvalvular atrial fibrillation with one or more risk factors such as congestive heart failure, hypertension, age 75, diabetes mellitus, prior stroke or transient ischaemic attack (SPAF). 2. Treatment of deep vein thrombosis (DVT) & pulmonary embolism (PE), & prevention of recurrent DVT & PE in adults (see W&P for haemodynamically unstable PE patients). Posology & method of administration: 10mg - Dosage 10 mg rivaroxaban orally once daily; initial dose should be taken 6 to 10 hours after surgery provided haemostasis established. Recommended treatment duration: Dependent on individual risk of patient for VTE determined by type of orthopaedic surgery: for major hip surgery 5 weeks; for major knee surgery 2 weeks. 15mg/20mg - SPAF: 20 mg orally o.d. with food. DVT & PE: 15 mg b.i.d. for 3 weeks followed by 20 mg o.d. for continued treatment & prevention of recurrent DVT & PE; take with food. 10mg/15mg/20mg - Refer to SmPC for full information on duration of therapy & converting to/from Vitamin K antagonists (VKA) or parenteral anticoagulants. For patients who are unable to swallow whole tablets, refer to SmPC for alternative methods of oral administration. Renal impairment: mild (creatinine clearance ml/min) - no dose adjustment; 10mg - moderate (creatinine clearance ml/min) no dose adjustment. Severe (creatinine clearance ml/ min) - limited data indicate rivaroxaban concentrations are significantly increased, use with caution. 15mg/20mg - moderate & severe renal impairement - limited data indicates rivaroxaban plasma concentrations are significantly increased, use with caution SPAF: reduce dose to 15mg o.d., DVT & PE: 15mg b.i.d. for 3 weeks, thereafter 20mg o.d. Consider reduction from 20mg to 15mg o.d. if patient s bleeding risk outweighs risk for recurrent DVT & PE; 10mg/15mg/20mg - Creatinine clearance <15 ml/ min - not recommended. Hepatic impairment: Do not use in patients with coagulopathy & clinically relevant bleeding risk including cirrhotic patients with Child Pugh B & C patients. Paediatrics: Not recommended. Contra-indications: Hypersensitivity to active substance or any excipient; active clinically significant bleeding; lesion or condition considered to confer a significant risk for major bleeding (refer to SmPC); concomitant treatment with any other anticoagulants except when switching therapy to or from rivaroxaban or when unfractionated heparin is given at doses necessary to maintain an open central venous or arterial catheter; hepatic disease associated with coagulopathy & clinically relevant bleeding risk including cirrhotic patients with Child Pugh B & C; pregnancy & breast feeding. Warnings & precautions: 10mg - Not recommended in patients: undergoing hip fracture surgery; receiving concomitant systemic treatment with strong CYP3A4 and P-gp inhibitors, i.e. azole-antimycotics or HIV protease inhibitors; with creatinine clearance <15 ml/min. Please note - Increased risk of bleeding, therefore careful monitoring for signs/ symptoms of bleeding complications & anaemia required after treatment initiation in patients: with severe renal impairment, with moderate renal impairment concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations; treated concomitantly with medicinal products affecting haemostasis; with congenital or acquired bleeding disorders, uncontrolled severe arterial hypertension, active ulcerative gastrointestinal disease (consider appropriate prophylactic treatment for at risk patients), vascular retinopathy, bronchiectasis or history of pulmonary bleeding. Take special care when neuraxial anaesthesia or spinal/epidural puncture is employed due to risk of epidural or spinal haematoma with potential neurologic complications. 15mg/20mg - Clinical surveillance in line with anticoagulant practice is recommended throughout the treatment period. Discontinue if severe haemorrhage occurs. In studies mucosal bleedings & anaemia were seen more frequently during long term rivaroxaban treatment compared with VKA treatment haemoglobin/haematocrit testing may be of value to detect occult bleeding. The following sub-groups of patients are at increased risk of bleeding & should be carefully monitored after treatment initiation so use with caution: in patients with severe renal impairment or with renal impairment concomitantly receiving medicinal products which increase rivaroxaban plasma concentrations; in patients treated concomitantly with medicines affecting haemostasis. Not recommended in patients: with creatinine clearance <15 ml/min; with an increased bleeding risk (refer to SmPC); receiving concomitant systemic treatment with azole-antimycotics or HIV protease inhibitors; with prosthetic heart valves; with PE who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy. If invasive procedures or surgical intervention are required stop Xarelto use at least 24 hours beforehand. Restart use as soon as possible provided adequate haemostasis has been established. See SmPC for full details. 10mg/15mg/20mg - There is no need for monitoring of coagulation parameters during treatment with rivaroxaban in clinical routine, if clinically indicated rivaroxaban levels can be measured by calibrated quantitative anti-factor Xa tests. Elderly population Increasing age may increase haemorrhagic risk. Xarelto contains lactose. Interactions: Concomitant use with strong inhibitors of both CYP3A4 & P-gp not recommended as clinically relevant increased rivaroxaban plasma concentrations are observed. Avoid coadministration with dronedarone. Use with caution in patients concomitantly receiving NSAIDs, acetylsalicylic acid (ASA) or platelet aggregation inhibitors due to the increased bleeding risk. Concomitant use of strong CYP3A4 inducers should be avoided unless patient is closely observed for signs and symptoms of thrombosis. Pregnancy & breast feeding: Contra-indicated. Effects on ability to drive and use machines: syncope (uncommon) & dizziness (common) were reported. Patients experiencing these effects should not drive or use machines. Undesirable effects: Common: anaemia, dizziness, headache, eye haemorrhage, hypotension, haematoma, epistaxis, haemoptysis, gingival bleeding, GI tract haemorrhage, GI & abdominal pains, dyspepsia, nausea, constipation, diarrhoea, vomiting, pruritus, rash, ecchymosis, cutaneous & subcutaneous haemorrhage, pain in extremity, urogenital tract haemorrhage, renal impairment, fever, peripheral oedema, decreased general strength & energy, increase in transaminases, post-procedural haemorrhage, contusion, wound secretion. Serious: cf. CI/Warnings and Precautions in addition: thrombocythemia, angioedema and allergic oedema, occult bleeding/haemorrhage from any tissue (e.g. cerebral & intracranial, haemarthrosis, muscle) which may lead to complications (incl. compartment syndrome, renal failure, fatal outcome), syncope, tachycardia, abnormal hepatic function, hyperbilirubinaemia, jaundice, vascular pseudoaneurysm following percutaneous vascular intervention. Prescribers should consult SmPC in relation to full side effect information. Overdose: No specific antidote is available. Legal Category: POM. Package Quantities and Basic NHS Costs: 10mg - 10 tablets: 21.00, 30 tablets: and 100 tablets: mg 14 tablets: 29.40, 28 tablets: 58.80, 42 tablets: 88.20, 100 tablets: ; 20mg 28 tablets: 58.80, 100 tablets MA Number(s): 10mg - EU/1/08/472/001-10, 15mg/20mg - EU/1/08/472/ Further information available from: Bayer plc, Bayer House, Strawberry Hill, Newbury, Berkshire RG14 1JA, U.K. Telephone: Date of preparation: January Xarelto is a trademark of the Bayer Group. Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported to Bayer plc. Tel.: , Fax.: , phdsguk@bayer.co.uk