This effect is minimised by ingestion of the anticoagulant drug at least 2 hours before ingestion of the other medications.
Rivaroxaban and apixaban should not be co-administered with azone antifungals or HIV protease inhibitors. In the atrial fibrillation studies, gastrointestinal bleeding was encountered more frequently with dabigatran and rivaroxaban than with warfarin; this was not the case for apixaban.
If a patient has a predisposition to this condition untreated ulcer symptoms, previous gastrointestinal bleeding with non-remediated cause , apixaban or warfarin may be more prudent options. Patients with atrial fibrillation and haemodynamically significant valvular heart disease were excluded from the trials evaluating the NOACs. Warfarin remains the standard of care for these patients and, until further studies are performed, NOACs are not recommended for patients with atrial fibrillation and valvular heart disease.
Patients with prosthetic valves represent a particularly high-risk group for whom warfarin has been the mainstay of therapy. To date, only dabigatran has been evaluated in this population. However, the study was terminated prematurely because of an increased rate of thromboembolism and bleeding in patients receiving dabigatran.
Although NOACs do not require routine monitoring, laboratory testing is informative in the context of bleeding, urgent surgery or recurrent thromboembolism. Standard coagulation assays are variably affected by NOACs but cannot provide drug quantification and results are not equivalent to INR testing for warfarin.
The cause of bleeding should be evaluated and the presence of residual or excessive anticoagulant effect assessed. Minor bleeding may be managed with local measures and temporary drug cessation. Patients with clinically significant bleeding may be managed with charcoal, standard resuscitation measures and surgical, radiological or endoscopic intervention. Prohaemostatic agents may be used but have no proven efficacy. Dabigatran may be removed with dialysis but factor Xa inhibitors are too highly protein-bound.
Reversal agents have now been developed for NOACs but they are just entering clinical trial evaluation. Management of bleeding often requires expert haematological advice and GPs should ensure they have ready access to these services when commencing patients on a NOAC. The more selective mechanisms of action of the NOACs and the fact that they do not require routine laboratory monitoring make them viable alternatives to warfarin for many, but not all, conditions requiring anticoagulant therapy.
The NOACs are contraindicated in patients with end-stage renal failure and should be used carefully in patients with renal impairment. Given that experience with these agents is limited, prescribers need to be vigilant for adverse events and report these to the TGA. If required in cases of urgent surgery or bleeding, laboratory monitoring can be performed in specialised laboratories in most teaching hospitals.
For currently approved indications, bleeding risk with NOACs is not increased when compared with warfarin. When clinically significant bleeding does occur, it should be managed in conjunction with specialist haematology advice. Currently, no antidotes are available; however, reversal agents for each drug have been developed and are undergoing evaluation in clinical trials.
She received support from BI, Bayer and Pfizer to attend conferences. Provenance and peer review: Commissioned, externally peer reviewed.
Australian Family Physician. Search for: Search AFP. Filter Relevance Date. Issues by year. Volume 43, Issue 5, May The TGA approved dabigatran for the prevention of venous thromboembolic events in adult patients who have undergone major orthopaedic surgery of the lower limb elective total hip or knee replacement in November In April , the approved indications for dabigatran were extended to include the prevention of stroke and systemic embolism in patients with non-valvular AF and at least one risk factor for stroke.
An increase in adverse event reports occurred after this extension of indication was approved. On this page: Bleeding results from clinical trials Adverse event reports. In the RE-LY trial, the risk of bleeding major or minor was less with dabigatran than with warfarin when the trial was considered as a whole. In clinical trials, the risk of bleeding per year of treatment with dabigatran was The risks of major bleeding events from the RE-LY trial are shown in the table below.
Prescribers should refer to the PI for further information. In addition to the initial RE-LY trial data analysis, a post-hoc analysis of the data showed that the risk of major bleeding is similar between dabigatran and warfarin when the patient is well controlled on warfarin. In patients well controlled on warfarin there was a higher risk of gastrointestinal bleeding associated with dabigatran.
Any interested person can search the DAEN for publically available reports, which include reports received between and 3 months prior to the date of access. Clinical Trials The submission presented one randomised trial comparing dabigatran mg twice daily bd and mg bd with adjusted-dose warfarin in patients with NVAF the RE-LY trial.
New England Journal of Medicine ; 12 Connolly S et al Newly Identified Events in the RE-LY Trial New England Journal of Medicine ; 19 Wallentin L et al Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial Lancet ; ; Indirect comparison: adjusted-dose warfarin as common reference Adjusted-dose warfarin vs aspirin AFASAK I Petersen P et al Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation.
Lancet ; Petersen P et al Prevention of stroke in atrial fibrillation. Archives of Internal Medicine Lancet Chinese ATAFS Hu D et al The randomized study of efficiency and safety of antithrombotic therapy in nonvalvular atrial fibrillation: warfarin compared with aspirin. Age and Ageing Non-inferiority of both dabigatran doses mg bd and mg bd compared to adjusted-dose warfarin was demonstrated in the RE-LY trial for the primary efficacy outcome, based on non-inferiority thresholds of 1.
Clinical Claim The submission described dabigatran as superior in terms of comparative effectiveness and superior in terms of comparative safety over adjusted-dose warfarin. Economic Analysis The submission presented a modelled economic evaluation. Recommendation and Reasons The PBAC recommended the listing of dabigatran mg and an extension to the listing of dabigatran mg for the prevention of stroke or systemic embolism in moderate-to-high risk patients with non-valvular atrial fibrillation on the basis of acceptable cost effectiveness.
NOTE No applications for increased maximum quantities will be authorised. Shared Care Model For prescribing by nurse practitioners where care of a patient is shared between a nurse practitioner and medical practitioner in a formalised arrangement with an agreed management plan. Max qty: 60 Repeats: 5 Summary of Submission and Findings: The submission presented additional sensitivity analyses in the modelled economic evaluation regarding the efficacy of dabigatran versus optimal warfarin therapy.
Optimal Warfarin Control The submission presented an additional reference Connolly et al which considered the benefits of dose adjusted warfarin versus clopidogrel plus aspirin. Economic Analysis The submission presented the same model from the March submission, but included additional components to simulate optimal warfarin treatments for a sensitivity analysis. Three modelling approaches were used in the sensitivity analysis: 1. Using published estimates from Jones et al to adjust the efficacy of warfarin for a given level of TTR, and 3.
Time horizon Life time was presented. The PBAC noted a preference for 20 years. Results reported over a lifetime and over 20 years. Structure Based on the model by Sorensen et al These reductions represent important reductions in morbidity, and can be expected to result in mortality reductions. Based on the high incidence of atrial fibrillation which increases with increasing age and the financial estimates in the submission over the first four years of listing, the Committee noted that the opportunity cost to the Commonwealth of listing dabigatran would be significant.
The PBAC noted that dabigatran derives its advantage over warfarin when warfarin is used suboptimally and also noted that improving the use of warfarin, by means of an education campaign aimed at prescribers, pharmacists and patients would be less costly.
A number of patients who are currently reluctant to take warfarin because of the stringent monitoring requirements and interactions with other drugs and foods, but who should be taking oral anticoagulation based on available evidence, would now be treated with dabigatran and this would likely lead to additional benefits and costs not measured in the trial.
The listing of dabigatran may result in patients at low risk currently managed on aspirin being unnecessarily transferred to dabigatran at a much higher cost, although the submission proposed a risk share arrangement to address this possibility. Although dabigatran was superior to warfarin in the RE-LY ITT population, this benefit may or may not be reflected wholly in the Australian population. The effectiveness of dabigatran in patients who are not fully compliant with the twice daily dosing regimen is unknown, but given its pharmacology it is likely to be reduced in poorly compliant patients.
Overall, with better control of warfarin and less compliance with dabigatran, the modelled gain in benefit with dabigatran would be reduced. In the event of PBS listing, the National Prescribing Service should carry out an education campaign on the prescribing of oral anticoagulation therapy.
Alternative similar treatments are expected to come to the market shortly. These include apixaban, rivaroxaban, edoxaban and darexaban. The PBAC was concerned about the combined effect of the following inputs on the base-case cost-effectiveness ratio previously calculated for dabigatran in March and more recently, in , for the other two drugs: type of clinical event for which an advantage should be modelled — the consensus was that only intracranial bleeding and haemorrhagic stroke as the most consistent benefit seen in all NOAC trials , should be valued in this regard.
In addition for dabigatran, the split between mg and mg dosing — PBAC noted more use of the mg dose in clinical practice than initially assumed and this should be reflected in modelling The PBAC requested that multivariate analyses be provided by all three sponsors, using the revised parameters outlined above together with costs offsets in relation to monitoring international normalised ratio INR added to the cost of warfarin.
PBAC consideration of the evidence All sponsors provided submissions, which were evaluated. Economic Analysis The PBAC noted the challenges of making comparisons across the multivariate sensitivity analyses of the three submissions, given that each submission adopted a distinct economic modelling approach. Recommendation and Reasons Since the March advice to the Minister recommending the PBS listing of dabigatran, the following new information has emerged: The Final Report of the Review of Anticoagulation Therapies in Atrial Fibrillation The RELY-ABLE data New experience of use of dabigatran in clinical practice which had accumulated beyond what was originally presented in the trials, including new safety analyses conducted by regulatory agencies New multivariate sensitivity analyses presented in the dabigatran minor submission New multivariate sensitivity analyses conducted during the evaluation of the dabigatran minor submission The availability for the consideration of the PBAC at its March meeting of an alternative therapy with a lower incremental cost-effectiveness ratio versus warfarin, namely rivaroxaban.
As a consequence, the PBAC made a new recommendation for dabigatran which varies its initial recommendation of March as follows: The PBAC recommended the listing of dabigatran on the PBS on a cost-minimisation basis to rivaroxaban for the prevention of stroke in patients with non-valvular atrial fibrillation, with the equi-effective dose based on average doses in the trials, and subject to the same risk-sharing arrangement and PBS restriction.
Qty No. Prescriber Instructions Risk factors for developing stroke or systemic ischaemic embolism are: i. Prior stroke ischaemic or unknown type , transient ischaemic attack or non-central nervous system CNS systemic embolism; ii.
Administrative Advice No increase in the maximum quantity or number of units may be authorised. No increase in the maximum number of repeats may be authorised. The privately-owned German firm has also been fighting new allegations, first made in July by The BMJ, that information about the benefits of monitoring blood levels of Pradaxa — and how this would reduce the risk of major bleeding in patients taking the drug — was not shared with regulators. The condition affects around , Britons and more than three million Americans, and raises the risk of stroke by up to five times.
Skip to Navigation Skip to content. Search this site:.
0コメント