# Cilansetron



## Jeffrey Roberts (Apr 15, 1987)

Drugs Today (Barc). 2005 Oct;41(10):661-6. Cilansetron.Olden KW, Crowell MD.Division of Gastroenterology, University of South Alabama, Mobile, Alabama, USA. kolden###usouthal.edu.Irritable bowel syndrome is an extremely common disorder affecting approximately 10-20% of the population of North America and Europe. This disorder is characterized by abdominal pain and altered bowel habit. The altered bowel habit can take a number of forms. These include a predominant diarrhea form, a form with constipation and one in which patients alternate between diarrhea and constipated forms of the disorder. Irritable bowel syndrome to date has not been associated with any excess mortality. However, the morbidity associated with irritable bowel syndrome is quite high. This mainly takes on the form of impairment in health-related quality of life, interference with activities of daily living and a considerable degree of human suffering. Likewise, the economic impact of irritable bowel syndrome is not trivial and has been estimated to be between US$20 to 30 billion in the United States alone. In an effort to address this common disabling disorder, a number of new drugs have been developed. One of the latest is cilansetron, which is a competitive type 3 serotonin (5-HT(3)) receptor antagonist. In phase III trials, cilansetron has been shown to be efficacious for the relief of a wide spectrum of symptoms related to irritable bowel syndrome with diarrhea both in male and female patients. By and large, cilansetron is extremely well tolerated and highly efficacious. The most common side effect of cilansetron is constipation, which is seen in 3-12% of subjects at 6 months. Ischemic colitis, a side effect associated with previous drugs of this class, has been seen in eight subjects (six women and two men) to date. All of these ischemic colitis events have been self-limited and did not require surgery. Because of its high degree of efficacy, the fact that it is well tolerated by the overwhelming majority of patients and that it shows efficacy in both genders, cilansetron represents a major advance in the treatment of irritable bowel syndrome with diarrhea predominance. © 2005 Prous Science. All rights reserved.PMID: 16389408 [PubMed - in process]http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_DocSum


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## 14397 (Mar 28, 2005)

Jeffrey,Great news about Cilansetron! Why hasn't it been approved yet by the FDA and what is the update on the drug? I suffer from IBS-D and just got prescribed Lomotil and haven't started it yet but would love to try Cilansetron. Any news would be great


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## Jeffrey Roberts (Apr 15, 1987)

Solvay Pharma pulled their appplication for Cilansetron in the US in the Fall 2005. They are continuing to work with the Europe to have the drug approved there.Jeff


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## 14397 (Mar 28, 2005)

Jeffrey, why was it pulled in the USA if it was so successful, that makes no sense to me? Is there any chance this drug will ever get approved?


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## Jeffrey Roberts (Apr 15, 1987)

No, there is no logic here.All appearances indicate that it was a political decision by the FDA to force Solvay Pharma to conduct further clinical studies. The FDA has always made it difficult for these classification of drugs to be approved. Solvay made the decision to focus on the additional clinical data that Europe is looking for rather then to spend more effort in the US.I don't have any information as to whether Solvay will attempt to seek approval again in the US. I suppose it likely depends on what happens in Europe.Jeff


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## jjohnson (Apr 29, 2004)

My understanding was that Solvay has only appealed the European rejection but has not committed to any further studies anywhere. And given the fact that in December, European authorities refused once again to approve Zelnorm (a safe drug by any standard of measure) I would think the prospects for cilansetron look very bleak indeed. The only chance I see for cilansetron is if Glaxo makes some major headway in figuring out why IC is occurring with Lotronex. A report from the Phase IV studies is due to the FDA by mid-year, last I heard, but there is no guarantee of success, of course. But even if a discovery were made on this front big enough to rekindle Solvay's interest in cilansetron, it would still be a long time before we might actually ever see the drug. I think Astellas' ramosetron looks like a much better bet. We should see the phase II results from Europe in the next few months I would think, and hopefully the already very encouraging data on efficacy AND safety will continue with this drug.Sage,Have you thought about giving Procter & Gamble's probiotic Align a try? It did beat the placebo in a high-quality trial and is available now, so it may be something to consider. There is quite a long thread on this in Products & Services.


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## 14397 (Mar 28, 2005)

Jeffrey what is the deal with Ramosetron, how does is work and when is it going to be approved? I suffer from IBS-D and am just waiting for that miracle drug to come out and help my stomach! Thanks for all your help and info


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## 15031 (Aug 31, 2006)

Anything new going on with Cilansetron? We haven't heard much from Solvay. Is it considered dead in the US and Europe?Thanks


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## jjohnson (Apr 29, 2004)

This article came out a few months ago. Not very encouraging, I'd say."Solvay says cilansetron no longer a priority."http://pharmamarketing.pl/PharmaNews2.asp?Id=9526


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## cat crazy (Jan 28, 2002)

jjohnson Since reintroduction of Lotronex have there been any more cases of ic? Dear God, I hope not!


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## jjohnson (Apr 29, 2004)

Hanna,Sorry to see you're still here. Yes, there have been some cases of IC since the reintroduction (at about the same rates as the clinical studies,) but as far as I know no one has been seriously injured by (much less died from) taking it. So hopefully people know to look for the warning signs and stop taking it before things get too serious.The FDA website should have a transcript from the 2004 advisory committee meeting. There is also a fairly recent article by Lin Chang about Lotronex and adverse events but it is not available for free. I would imagine Lotronex will be reviewed at some time in the future by an FDA advisory committee since they seem to have finished the phase IV studies, though God knows when. It would be nice if they would finally figure out how to minimize the risk of IC already, so that more people could get access to this medication.


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## jjohnson (Apr 29, 2004)

This 10/3 report from Solvay lists cilansetron as "available for licensing." I find it hard to believe that any other company would be interested in this drug, so "available for licensing" is probably just a euphemism for "dead," and is probably just Solvay's way of trying to save face about the whole thing. This may well be the last time we'll ever hear about cilansetron.http://www.solvaypress.com/pressreleases/0,,46528-2-0,00.htmPS I've included this link just as a reference. Don't bother reading the report since it says absolutely nothing else besides "cilansetron - available for licensing."


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## 13594 (May 14, 2006)

I think cilansetron has died an early death. Despite the fact that the risk of IC is lower than Alosetron (Lotronex) and that Alosetron has had no further fatalities under the new programme; the regulators have developed a sour taste for all 5HT-3 antagonists.Despite the extensive evidence from solvay's tests, that cilansetron is safe enough to be used under higher observation perscribing in the UK and EU: I can't see the MHRA granting a license at gunpoint.I agree that Ramosetron is the best option to hope for now. Athlough to get it licensed in Europe extensive tests will have to be repeated here. I can easily see it being licensed the other side of 2010 if at all. The best hope in the short term is for everyone who can to try and get Ondansetron (Zofran.) There are UK studies that prove it works (see earlier post.)The more gastro docs that can be convinced that its an option for severe IBS-D where conventional drugs don't work; the more likely there is a chance someone will apply for a license change to include IBS-D.Until that happens (if it does) its gonig to be up to the personal determination of people to convince their docs that its worth Px'ing it off-label. The main problem is the cost, which hopefully will drop like a stone when it goes completly generic here in the uk.Good luck to everyone,Oliver.


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## jjohnson (Apr 29, 2004)

It's probably pointless to mention this now, but I do believe that the deaths associated with alosetron were caused by severe complications of constipation (which cilansetron did not cause) and mesenteric ischemia (an extremely rare event never conclusively attributed to alosetron) and not by ischemic colitis.I think at the FDA there are some people who were somewhat sympathetic to IBS sufferers (e.g. Janet Woodcock), but they weren't about to put their careers on the line for cilansetron, especially with the Vioxx scandal reaching a fever pitch. Former FDA Commissioner Lester Crawford was probably too involved in his affair with his secretary (for which he was later fired) to even give a passing thought to IBS sufferers. Europe is another story altogether. That they rejected Zelnorm shows just how contemptuous they are of IBS as a condition even though far more "subjective" conditions like clinical depression are universally regarded as "real."Anway, sorry about the rant. I went through the process of anger, denial, etc., etc. over cilansetron a long time ago, but it still kind of ticks me off on the rare occasions that I still think about it. We will just have to wait and see with ramosetron. I think if future studies confirm the findings of previous studies, it will be approved.


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## 13594 (May 14, 2006)

Does anyone know what exactly Japan's health system is like; I'm just wondering how much it would cost and if doctors will perscribe through the post. This is of course after receiving written diagonsis and treatment records. I'm just wondering if Japan is a good bet for getting it imported. Uk law means the drug doesn't have to be licensed here: As long as its perscribed by a doctor, not a controlled substance, for personal use and no more than a 90-day supply, its fine to import.But would Japan be fairly affordable to import from. How much is Ramosetron likely going to cost when it gets licensed there?mr_colt


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