Talk:Rivaroxaban

message: I just read this press release:
http://www.press.bayer.com/baynews/baynews.nsf/id/CEE29C7D543AB693C12574C5005133F1?Open&ccm=001
I am not a medical writer, but I think someone should update this page according to this release. E.g. This sentence: "If marketed, it will be a joint product by Bayer and Ortho-McNeil Pharmaceutical." now it is marketed.  —Preceding unsigned comment added by 78.49.187.116 (talk) 22:38, 16 September 2008 (UTC)
replies: text: Rhone-Poulenc () and Lilly () tried doing this, but it seems Bayer is winning. JFW | T@lk 00:07, 30 May 2006 (UTC)

text: Unless Boehringer-Ingelheim manage to market BIBR 1048 (dabigatran) first... JFW | T@lk 00:43, 30 May 2006 (UTC)

text: BI are also working on BIBT 986, a thrombin/factor X dual inhibitor. JFW | T@lk 09:37, 21 June 2006 (UTC)
thread_title:  Update required? 

message: I just read this press release:
http://www.press.bayer.com/baynews/baynews.nsf/id/CEE29C7D543AB693C12574C5005133F1?Open&ccm=001
I am not a medical writer, but I think someone should update this page according to this release. E.g. This sentence: "If marketed, it will be a joint product by Bayer and Ortho-McNeil Pharmaceutical." now it is marketed.  —Preceding unsigned comment added by 78.49.187.116 (talk) 22:38, 16 September 2008 (UTC)
replies: text: Rhone-Poulenc () and Lilly () tried doing this, but it seems Bayer is winning. JFW | T@lk 00:07, 30 May 2006 (UTC)

text: Unless Boehringer-Ingelheim manage to market BIBR 1048 (dabigatran) first... JFW | T@lk 00:43, 30 May 2006 (UTC)

text: BI are also working on BIBT 986, a thrombin/factor X dual inhibitor. JFW | T@lk 09:37, 21 June 2006 (UTC)
thread_title:  Update required? 

message: discusses all factor X inhibitors. JFW | T@lk 07:07, 6 September 2006 (UTC)
replies: text: does too. JFW | T@lk 20:41, 5 April 2007 (UTC)
thread_title:  Paper to read 

message: - body weight leads to minimal changes in plasma levels. JFW | T@lk 20:15, 20 May 2007 (UTC)
replies: text: - initial pharmacokinetics studies. JFW | T@lk 20:17, 20 May 2007 (UTC)
thread_title:  New papers 

message: New article from NEJM - http://www.nejm.org/doi/full/10.1056/NEJMoa1112277  Wawot1 (talk) 04:42, 6 January 2012 (UTC)
thread_title:  rivaroxaban in ACS  

message: According to some references, Xarelto is not absorbed as well when given to patients with G-tubes or other feeding tubes that extend into the intestines. The feeding tube must thus be retracted or adjusted so that the drug may be absorbed and this is an added consideration that can influence the decision on whether or not to use a subcutaneous LMWH instead in these kinds of patients. I think this should be added to the article 24.184.78.96 (talk) 09:41, 28 April 2012 (UTC)
replies: text: Interesting information. Can you name the references you mention? That would be a great help. Cheers, ἀνυπόδητος (talk) 09:56, 28 April 2012 (UTC)
thread_title:  Xarelto absorption and feeding tubes 

message: An ISTH subcommittee has issued recommendations on how the effect of rivaroxaban can be measured: doi:10.1111/j.1538-7836.2012.04784.x. JFW | T@lk 13:25, 22 May 2012 (UTC)
thread_title:  Measuring effect 

message: So there have been lots of changes to this page recently. I just reverted one that said "delete systematic review". I was just wondering, why remove this? Biosthmors (talk) 02:39, 8 September 2012 (UTC)
thread_title:  Lots of changes lately 

message: A debate: prothrombin time (doi:10.1111/jth.12166) vs anti-Xa assay (doi:10.1111/jth.12165) JFW | T@lk 21:35, 12 February 2013 (UTC)
thread_title:  How to measure 

message: Certainly, I recognize that the pharmacology of a drug like this is not simple and I don't suggest removal of anything which currently appears. What I do suggest is that someone who has the skills undertake to generally explain the findings of the various studies in relation to rivaroxaban. This is after all an encyclopedia not a medical textbook nor a professional practice guide. Thank you QuintBy (talk) 20:54, 29 October 2013 (UTC)
thread_title:  Jargon-dense medical articles which operate only at high levels of knowledge do not serve the general Wikipedia readership 

message: The secondary sources / content need to be merged into medical uses. We do not have this section per WP:MEDMOS.
===Pivotal trials for authorisation===
===Prevention of venous thromboembolism: perioperative===
Four clinical studies, the RECORD studies, with a total enrollment of over 12,000 patients have shown that oral rivaroxaban has non-inferior and possibly superior efficacy compared to 40 mg per day of the subcutaneous low molecular weight heparin (LMWH) enoxaparin in preventing venous thromboembolism in adult patients undergoing total hip or knee replacement surgery.  However, in RECORD 4 the risk of bleeding was higher in patients randomized to rivaroxaban (10 mg/day) rather than enoxaparin 30 mg twice daily.Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial Alexander GG Turpie, Michael R Lassen, Bruce L Davidson, Kenneth A Bauer, Michael Gent, Louis M Kwong, Fred D Cushner, Paul A Lotke, Scott D Berkowitz, Tiemo J Bandel, Alice Benson, Frank Misselwitz, William D Fisher, for the RECORD4 Investigatorsdoi:10.1016/S0140-6736(09)60734-0
===Treatment and long term prevention of venous thromboembolism and pulmonary embolism===
The EINSTEIN study for treatment and secondary prevention of venous thromboembolism shows that rivaroxaban can be a single-drug approach to the short-term and continued treatment of venous thrombosis and can also improve the benefit-to-risk profile of anticoagulation. The open-label (not blinded), randomized, noninferiority part of the study compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. 
Rivaroxaban had noninferior efficacy with respect to the primary outcome venous thrombolic events. The principal safety outcome, major bleedings, was not different. Overall, the INR was in the therapeutic range (2.0 to 3.0) for 57.7% of the time. So warfarin treatment was not optimal. 
In the EINSTEIN–Pulmonary Embolism Study, an open label (not blinded) trial rivaroxaban (after pretreatment of LWMH during 2 to 3 days) and usual care (LMWH and warfarin) had similar rates of recurrent venous thromboembolism and bleeding in symptomatic pulmonary embolism. The INR was in the therapeutic range 62.7% of the time.  There were more pulmonary embolisms leading to death. Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism  The EINSTEIN–PE Investigators  N Engl J Med 2012; 366:1287-1297DOI: 10.1056/NEJMoa1113572
===Prevention of stroke in non-valvular atrial fibrillation===
In the ROCKET-AF trial, a Bayer company based double blind trial, comparing a once-daily, fixed dose (20 mg daily or 15 mg daily in patients with a creatinine clearance of 30 to 49 ml per minute) of rivaroxaban with adjusted-dose warfarin in patients with nonvalvular atrial fibrillation who were at moderate-to-high risk for stroke, rivaroxaban was not inferior to warfarin in the prevention of subsequent stroke or systemic embolism. There were no significant differences in rates of major and clinically relevant nonmajor bleeding between the two study groups. Intracranial and fatal bleeding occurred less frequently in the rivaroxaban group, bleeding from gastrointestinal sites, including upper, lower, and rectal sites, occurred more frequently in the rivaroxaban group, as did bleeding that led to a drop in the hemoglobin level or bleeding that required transfusion.
 
Among patients in the warfarin group, the proportion of time in which the intensity of anticoagulation was in the therapeutic range TTR (mean, 55%), was lower than in previous studies of other new anticoagulants in patients with atrial fibrillation (range, 64 to 68%). Documents from the Food and Drug Administration (FDA) Advisory Committee meeting reported that when warfarin was administered skillfully within the trial, and the TTR was above approximately 68%, there was a relative increase in primary outcome events (stroke and systemic embolism) in the rivaroxaban group. It was noted that the hazard ratio increased sharply as the center TTR rose to above 65%, and at a TTR above 67%, the hazard ratio crossed 1.0. The FDA reviewer concluded: the poor warfarin control, as evidenced by the overall TTR in ROCKET of 55%, biased the study in favor of rivaroxaban. The study results do not convincingly demonstrate the non-inferiority, much less the superiority, of rivaroxaban to warfarin when the latter is used skillfully. TTR in ROCKET varied widely over regions and countries. In general, TTR was higher in Western Europe (especially in the UK and Scandinavia), North America (i.e., Canada and the US), and some areas in the Pacific basin (Australia, New Zealand, Singapore and Hong Kong), and tended to be low in Eastern Europe, South America, and the Asia-Pacific region. In AuriculA, the Swedish national quality registry for atrial fibrillation and anticoagulation the TTR for all patients was 76.2%.Wieloch M, Själander A, Frykman V, Rosenqvist M, Eriksson N, Svensson PJ: Anticoagulation control in Sweden: reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry AuriculA. Eur Heart J 2011, 32: 2282 – 2289 doi: 10.1093/eurheartj/ehr134. Epub 2011 May 26 
In the ROCKET AF study  23.7% of the patients in the rivaroxaban group and 36.2% in the warfarin group completed early study treatment and these patients were not recorded anywhere in the various analyses. The most frequent adverse reactions associated with permanent drug discontinuation were bleeding events, with incidence rates of 4.3% for rivaroxaban vs. 3.1% for warfarin. 
After termination of the trial all patients received warfarin treatment. 3 to 30 days after the end of the study, risk of stroke and systematic embolism, and bleeding risk was higher in the rivaroxaban group compared to the warfarin group. Potentially rivaroxaban discontinuation is associated with a prothrombotic rebound effect. Discontinuation of Rivaroxaban Filling in the Gaps Matthew R. Reynolds, MD, MSc J Am Coll Cardiol. 2013;61(6):659-660. doi:10.1016/j.jacc.2012.09.056 Another possible explication was poor INR controle.
===Negative trials===
===Prevention of venous thromboembolism: medically ill patients===
The MAGELLAN study was initiated for prevention of venous thrombosis in hospitalized medically ill patients. It shows that taking rivaroxaban 10 mg once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with enoxaparin by subcutaneous injection, in acutely ill hospitalized medical patients. However, bleeding rates were significantly increased with rivaroxaban. At day 10 there were 5 fatal bleedings against 1 for enoxaparin, after 35 days there were 7 fatal bleedings against 1 for enoxaparin.
Currently available evidence does not indicate that routine administration of post-discharge extended prophylaxis will be beneficial to the patients admitted for medical illness.
===Prevention of recurrent coronary events===
The ATLAS ACS 2 TIMI 51 trial for secondary prevention of major cardiovascular events in patients with acute coronary syndrome shows for the 2.5-mg twice-daily dose of rivaroxaban a reduction in overall (Absolute Risk Decrease 1,6%) and cardiovascular mortality vs placebo, despite an increased risk of TIMI (thrombolysis in myocardial infarction) major bleeding (Absolute Risk Increase 1,2%), bleeding requiring medical attention and intracranial haemorrhage (ARI 0,5%). There was no increased risk of fatal bleeding. For this low dose there was no effect on myocardial infarctions and stroke. In higher dose rivaroxaban (5 mg twice daily) the benefits on mortality were not observed, but bleeding effects were still higher. The studies were hindered by early patients withdrawals and incomplete follow up. FDA reviewer, Dr Thomas Marciniak, found the trial results were not interpretable because about 12% of the patients had incomplete follow-up, far higher than the 1% to 1.5% differences in the end-point rates between rivaroxaban and placebo. In May 2012 the missing data lead the FDA panel to vote against rivaroxaban for acute coronary syndrome.For the second time in april 2013 the FDA turned down the new drug application (NDA). In June 2013 the FDA rejected a new indication for rivaroxaban to prevent stent thrombosis in acute coronary syndrome patients.Forbes 6/28/2013 FDA Turns Back New Indication For Rivaroxaban To Prevent Stent Thrombosis In ACS Patientsfda-turns-back-new-indication-for-rivaroxaban-to-prevent-stent-thrombosis-in-acs-patients/ In January 2014 FDA advisors again voted against a treatment duration of 90 days. 
Secondary prevention of ACS with rivaroxaban 2.5 mg tablets in combination with antiplatelet therapy is contraindicated in people with a prior stroke or transient ischaemic attack; limited efficacy data available in this population indicate that they do not benefit from treatment.Secondary prevention in acute coronary syndrome: rivaroxaban Nicesecondary-prevention-in-acute-coronary-syndrome-rivaroxaban-
Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:05, 16 March 2014 (UTC)
thread_title: This content is overly details with to many primary sources

message: The ATLAS ACS 2 TIMI 51 trial for secondary prevention of major cardiovascular events in patients with acute coronary syndrome shows for the 2.5-mg twice-daily dose of rivaroxaban a reduction in overall (Absolute Risk Decrease 1,6%) and cardiovascular mortality vs placebo, despite an increased risk of TIMI (thrombolysis in myocardial infarction) major bleeding (Absolute Risk Increase 1,2%), bleeding requiring medical attention and intracranial haemorrhage (ARI 0,5%). There was no increased risk of fatal bleeding. For this low dose there was no effect on myocardial infarctions and stroke. In higher dose rivaroxaban (5 mg twice daily) the benefits on mortality were not observed, but bleeding effects were still higher. The studies were hindered by early patients withdrawals and incomplete follow up. FDA reviewer, Dr Thomas Marciniak, found the trial results were not interpretable because about 12% of the patients had incomplete follow-up, far higher than the 1% to 1.5% differences in the end-point rates between rivaroxaban and placebo. In May 2012 the missing data lead the FDA panel to vote against rivaroxaban for acute coronary syndrome.For the second time in april 2013 the FDA turned down the new drug application (NDA). In June 2013 the FDA rejected a new indication for rivaroxaban to prevent stent thrombosis in acute coronary syndrome patients.Forbes 6/28/2013 FDA Turns Back New Indication For Rivaroxaban To Prevent Stent Thrombosis In ACS Patientsfda-turns-back-new-indication-for-rivaroxaban-to-prevent-stent-thrombosis-in-acs-patients/ In January 2014 FDA advisors again voted against a treatment duration of 90 days. 
Secondary prevention of ACS with rivaroxaban 2.5 mg tablets in combination with antiplatelet therapy is contraindicated in people with a prior stroke or transient ischaemic attack; limited efficacy data available in this population indicate that they do not benefit from treatment.Secondary prevention in acute coronary syndrome: rivaroxaban Nicesecondary-prevention-in-acute-coronary-syndrome-rivaroxaban-
Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:05, 16 March 2014 (UTC)
thread_title: Prevention of recurrent coronary events

message: Under the chemistry section, it mentions that rivaroxaban is only approved for short term use, but the citation is outdated. The current document from the EMAhttp://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000944/WC500057108.pdf alludes to long term use throughout. Could someone with more knowledge on the approval status clarify this?
Thanks!
Bapride11 (talk) 20:30, 27 September 2014 (UTC)
replies: text: Thanks for the heads-up! I deleted the mention of short-term use. The approved uses are already mentioned above, and "stroke prophylaxis" implies long-term use. --ἀνυπόδητος (talk) 08:58, 29 September 2014 (UTC)
thread_title:  Long term vs. short term approval 

message: I think the SmPC referenced should rather be http://www.xareltohcp.com/about-xarelto/dosing-and-administration.html, which has a link to full PI PDF (and isn't indication-specific). Cloning jedi (talk) 08:43, 14 October 2014 (UTC)
thread_title: SmPC

message: Please review WP:MEDRS.  The sources that you have used here are not peer-reviewed and do not meet the requirements for medical content, to whit:
:"Ideal sources for biomedical content include: literature reviews – especially systematic reviews – published in reputable medical journals; academic and professional books written by experts in the field and from a respected publisher; and medical guidelines or position statements from nationally or internationally recognised expert bodies. Primary sources should generally not be used for biomedical content."
ISMP quarterly reports are primary research and are not peer reviewed.  The tort lawyer website is of course completely unacceptable.  2601:643:8100:8AF4:E913:D0DF:E7AB:D943 (talk) 18:23, 7 October 2015 (UTC)
replies: text: Agree Doc James (talk · contribs · email) 12:22, 11 October 2015 (UTC)
thread_title:  Citing tort lawyer websites as sources for  medical content 

message: The WHO has changed the ATC code for Rivaroxaban- it's now  B01AF01- sorry don't know how to edit it. 
https://www.whocc.no/atc_ddd_alterations__cumulative/atc_alterations/
Rexthewondersheep (talk) 13:18, 23 October 2017 (UTC)
thread_title:  Wrong ATC code  

message: I have removed the following content pending a WP:MEDRS-compatible source:
:There is a growing number of patient and physician reports submitted to pharmacovigilance databases like EudraVigilance that rivaroxaban may cause persistent erectile dysfunction and sexual dysfunction akin to post-SSRI sexual dysfunction (PSSD).
I note that this was added by  and that the blog cited was written by Spiros/Spyros Dolkas. JFW | T@lk 10:17, 27 May 2019 (UTC)
replies: text: As of May 2024 there is no mention of erectile dysfunction caused by rivaroxaban in the science journal literature database PubMed. David notMD (talk) 12:17, 12 May 2024 (UTC)
thread_title:  Sexual dysfunction