Talk:Rivaroxaban

True cost comparison?
Re: [Using rivaroxaban rather than warfarin costs 70 times more]

But warfarin users must have weekly blood tests - rivaroxaban users do not.

For a economic value comparison the whole treatment cost should be considered...

Update required?
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)

Although this drug is still under development, it may well become what ximelagatran could not: a safe oral anticoagulant that does not require monitoring. Comments invited. JFW | T@lk  09:02, 21 December 2005 (UTC)

If that is your opinion, you should not mention Ximelagatran as related drug. Otherwise readers could get the intention that both medications have similar mode of actions. German Wiki-User, 7 December 2007. —Preceding unsigned comment added by 212.64.224.241 (talk) 10:23, 7 December 2007 (UTC)


 * Rhone-Poulenc and Lilly  tried doing this, but it seems Bayer is winning. JFW |  T@lk  00:07, 30 May 2006 (UTC)


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


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

Update required?
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)

Although this drug is still under development, it may well become what ximelagatran could not: a safe oral anticoagulant that does not require monitoring. Comments invited. JFW | T@lk  09:02, 21 December 2005 (UTC)

If that is your opinion, you should not mention Ximelagatran as related drug. Otherwise readers could get the intention that both medications have similar mode of actions. German Wiki-User, 7 December 2007. —Preceding unsigned comment added by 212.64.224.241 (talk) 10:23, 7 December 2007 (UTC)


 * Rhone-Poulenc and Lilly  tried doing this, but it seems Bayer is winning. JFW |  T@lk  00:07, 30 May 2006 (UTC)


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


 * BI are also working on BIBT 986, a thrombin/factor X dual inhibitor. JFW | T@lk  09:37, 21 June 2006 (UTC)  — Preceding unsigned comment added by BWernham (talk • contribs)

Paper to read
discusses all factor X inhibitors. JFW | T@lk  07:07, 6 September 2006 (UTC)


 * does too. JFW | T@lk  20:41, 5 April 2007 (UTC)

New papers
- body weight leads to minimal changes in plasma levels. JFW | T@lk  20:15, 20 May 2007 (UTC)


 * - initial pharmacokinetics studies. JFW | T@lk  20:17, 20 May 2007 (UTC)

Pubmed search
All results of rivaroxaban (to update rapidly). JFW | T@lk  15:38, 21 September 2007 (UTC)


 * NEJM this week:
 * Hip study
 * Knee study
 * Both need citing. JFW | T@lk  05:50, 26 June 2008 (UTC)

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

Xarelto absorption and feeding tubes
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)
 * Interesting information. Can you name the references you mention? That would be a great help. Cheers, ἀνυπόδητος (talk) 09:56, 28 April 2012 (UTC)

"When rivaroxaban granulate is released in the proximal small intestine, there was a 29% and 56% decrease in AUC and Cmax, and an even greater reduction was reported when drug was released in the distal small intestine or ascending colon. In other words, NG and G-tube administration of rivaroxaban is acceptable once proper tube placement has been confirmed, but J-tube administration should be avoided." 18.2, p13 — Preceding unsigned comment added by 143.104.48.134 (talk) 23:27, 8 December 2012 (UTC)

"Ensure gastric placement of feeding tube if rivaroxaban tablets are crushed and administered via this route; absorption is impaired if administered directly into the small intestine." 

"Bioavailability is decreased by 26% in the proximal small intestine..."  143.104.48.134 (talk) 22:49, 8 December 2012 (UTC)

Measuring effect
An ISTH subcommittee has issued recommendations on how the effect of rivaroxaban can be measured: 10.1111/j.1538-7836.2012.04784.x. JFW &#124; T@lk  13:25, 22 May 2012 (UTC)

Lots of changes lately
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)

I removed this systematic review and placed it further on in the discussion of the Einstein trials. The review concerned treatment and prevention of vte in non orthopedic situations.Janbaekelandt (talk) 10:24, 8 September 2012 (UTC)

How to measure
A debate: prothrombin time (10.1111/jth.12166) vs anti-Xa assay (10.1111/jth.12165) JFW &#124; T@lk  21:35, 12 February 2013 (UTC)

Jargon-dense medical articles which operate only at high levels of knowledge do not serve the general Wikipedia readership
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)

Accuracy concerning Stroke Prevention in Atrial Fibrillation?
This Sept 2013 article says (my emphasis): Key Points for Decision Makers Yet the Wikipedia article currently says: "As for all new oral anticoagulants treatment benefits compared with warfarin are small and vary depending on the control achieved by warfarin treatment." The publication seems more positive than Wikipedia. Should Wikipedia be updated or is there any reason to doubt the reliability of the article? pgr94 (talk) 13:37, 31 January 2014 (UTC)
 * A large proportion of patients with atrial fibrillation (AF) and moderate to high risk of stroke do not receive thromboprophylaxis or are not optimally controlled with vitamin K antagonists (VKAs).
 * Rivaroxaban (Xarelto), a once-daily agent, is one of the novel oral anticoagulants that are now recommended by recent international guidelines as broadly preferable to VKAs for patients with non-valvular AF.
 * The present analysis suggests that rivaroxaban is a cost-effective alternative to warfarin therapy for the prevention of stroke in patients with AF in the Belgian healthcare setting.
 * "Treatment benefits" refers to reduction of strokes, and it is true that rivaroxaban is comparable to warfarin in its stroke prevention / bleeding ratio, i.e. you can only prevent significantly more strokes if you use a dosing scheme associated with a higher bleeding rate. The advantages of rivaroxaban vs. warfarin are others: no need of frequent INR measuring, simpler dosing scheme, much fewer interactions etc.
 * However, the Systematic reviews section also sounds to me as if rivaroxaban had no advantages at all, which simply is not true. Not sure how to fix this, though. --ἀνυπόδητος (talk) 09:54, 1 February 2014 (UTC)

This content is overly details with to many primary sources
The secondary sources / content need to be merged into medical uses. We do not have this section per WP:MEDMOS.

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.

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.

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%.

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. Another possible explication was poor INR controle.

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. 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. Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:05, 16 March 2014 (UTC)

Long term vs. short term approval
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 EMA 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)


 * 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)

SmPC
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)

Citing tort lawyer websites as sources for medical content
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)
 * Agree Doc James  (talk · contribs · email) 12:22, 11 October 2015 (UTC)

Wrong ATC code
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)

Summary
User:JRSpriggs Per "will begin to lose patent protection in 2020 (depending on its application)" last bit not really needed.

Ref says "Patent expiration dates: December 11, 2020 ✓ Drug substance" Sounds like the substance to me. Doc James (talk · contribs · email) 11:43, 10 March 2019 (UTC)


 * The source used for that sentence in the article is this. When I first read the sentence, I was confused because I thought that the substance was what was patented. If it were just the substance, then either the patent would be in effect or it would not be in effect. So " begin to lose patent protection" would make no sense.
 * Under "patent expiration dates", the source says
 * February 17, 2034 ✓ Patent use: REDUCE THE RISK OF STROKE IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION WITH ONCE DAILY, RAPID-RELEASE TABLET ADMINISTERED FOR AT LEAST FIVE CONSECUTIVE DAYS
 * This is the part that is relevant to my case. So prescription of a generic version of Xarelto for me would be illegal until 2034 (not 2020). JRSpriggs (talk) 12:17, 10 March 2019 (UTC)
 * User:JRSpriggs Not really. Physicians prescribe generics off patent all the time. It is just about a question of marketing not about use. Doc James  (talk · contribs · email) 04:11, 11 March 2019 (UTC)


 * If we want to avoid confusing the reader, the sentence should read either:
 * (a) "... and will begin to lose patent protection in 2020 (depending on its application)." or
 * (b) "... and will lose patent protection in 2020.".
 * Pick one! JRSpriggs (talk) 04:48, 11 March 2019 (UTC)
 * Okay gone with the second. Doc James  (talk · contribs · email) 11:42, 23 March 2019 (UTC)
 * Okay. JRSpriggs (talk) 01:00, 24 March 2019 (UTC)

Sexual dysfunction
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 &#124; T@lk  10:17, 27 May 2019 (UTC)
 * 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)