# Press coverage: New Data about Lotronex - April 18, 2001



## Jeffrey Roberts (Apr 15, 1987)

http://www.publiccitizen.org/Press/pr-sid45.htm April 18, 2001New Data Confirm Dangers of Controversial Drug LotronexFDA Should Not Put Drug Back on Market; Should Allow Use Only on Experimental, Restricted Basis, Public Citizen SaysWASHINGTON, D.C. ï¿½ New data obtained by Public Citizen confirm the dangers of the controversial drug Lotronex, indicating that the government would be reckless to consider remarketing the drug, Public Citizen said today in a letter to the U.S. Food and Drug Administration (FDA). Instead, if the government decides to allow patients to take the drug again, it should do so only on an experimental and highly restricted basis. The letter was sent to Bernard Schwetz, the FDAï¿½s acting principal deputy commissioner.Lotronex was used to treat irritable bowel syndrome (IBS) until it was withdrawn from the market last November because of dangerous adverse effects experienced by some patients taking it.The new data show that through the end of 2000, 63 patients taking Lotronex experienced ischemic colitis (an interruption of the blood supply to the large intestine, which results in severe damage to the intestine) ï¿½ up from 49 cases reported in mid-November. And 75 patients experienced severe constipation, up from 21 at that time. Most of the patients experiencing these problems required hospitalization. In all, the FDA has on record 141 cases of severe gastrointestinal complications in patients who took the drug ï¿½ twice as many as in early November, before the drug was withdrawn. (Although the drug was removed from the market, patients could have continued taking it until their supplies ran out or there may have been a delay in reporting the adverse effect.)Because of pressure from the drug industry and patient groups, the FDA apparently is considering putting Lotronex back on the market. But the drug poses too many dangers to be made widely available, Public Citizen said. Instead, the drug should be given to patients only under several conditions. First, the drug should be limited to patients who have previously used it and have not experienced adverse effects. Second, patients should be given an informed consent sheet explaining the potential dangers of the drug. Finally, a registry of all patients taking the drug and their physicians should be kept so the patients can be monitored."If anything other than this approach is used, the toll of needless deaths and serious injuries and the repeat ban that will inevitably occur will be on the hands of those FDA officials responsible for such a reckless remarketing," Public Citizenï¿½s letter said.


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## Jeffrey Roberts (Apr 15, 1987)

Patient Group Responds To Renewed Allegations That Lotronex Is Unsafe:April 18, 2001, Atlanta, GeorgiaResponding to comments by a consumer activist organization that the FDA would bereckless to consider renewed access of a treatment for irritable bowel syndrome(IBS), the Lotronex Action Group, a non-profit patient group seeking renewedaccess to Lotronex, today urged the FDA and GlaxoSmithKline not to lose sight ofthe patients.The medical community has been slow to recognize IBS as a legitimate diseasethat can have debilitating side affects. The Lotronex Action Group is veryconcerned that efforts for reintroduction of the only affective treatment forIBS patients, suffering from severe diarrhea and abdominal pain, will bederailed due to a lack of understanding of the severity of the symptioms IBS cancause.The Lotronex Action Group maintains the medicine is safe and that althoughclaims have been made that more cases of severe side affects have been linkedto Lotronex, it appears that less than a fraction of 1% of the 300,000 peopletaking the medicine were affected. Moreover, no data has been releasedproving those that suffered from side affects were properly diagnosed andshould have been taking the medicine to start with.Lotronex Action Group http://www.lotronexactiongroup.org <lotronexactiongroup###yahoo.com>Tom Bell, CoordinatorRichard Fireman, CoordinatorCorey Miller, CoordinatorJeffrey Roberts, IBSgroup.org


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## VernaEileenR (Feb 23, 2001)

Way to go Jeff, I knew we could count on you to be on top of this latest scurrilous piece of tripe.------------------Verna Eileen Radcliffe(without laughter there is no future)


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## Jeffrey Roberts (Apr 15, 1987)

http://dailynews.yahoo.com/h/nm/20010418/s...bowel_dc_1.html Wednesday April 18 5:45 PM ETBowel Drug Should Stay Off Market, Group Says By Lisa RichwineWASHINGTON (Reuters) - A U.S. consumer group on Wednesday urged regulators to resist pressure to put the irritable bowel treatment Lotronex back on the market, saying new data reinforced the drug's dangers.Public Citizen said reports to the Food and Drug Administration (news - web sites) showed 141 cases of severe intestinal problems in patients who took Lotronex.That figure is nearly twice the number of reports on hand in early November, shortly before the drug was withdrawn, the group said, adding that five deaths were ``related to adverse gastrointestinal reactions in people using Lotronex.''The FDA had asked for Lotronex's withdrawal, citing three deaths as possibly linked to the drug at the time.But the agency and drug maker GlaxoSmithKline Plc have been in talks since early this year about whether the drug could be made available again with restrictions to minimize side effects, said Dr. Victor Raczkowski, deputy director of the FDA division that reviewed Lotronex, said. Patient groups also are pressing for access to the drug.``We do have concerns about the safety of the drug, and we'd like to come up with conditions under which the drug could be used so that the benefit exceeds the risk,'' Raczkowski said.The FDA's database that tracks drug reactions included 61 possible cases of severe constipation and 66 possible cases of ischemic colitis, a condition that restricts blood flow to the colon and can cause serious damage, Raczkowski said. Four deaths were ``possibly associated with Lotronex,'' he said.GlaxoSmithKline spokeswoman Ramona DuBose said Public Citizen's data was ``incomplete and it's taken out of context,'' but she declined to discuss specific numbers.Irritable bowel syndrome afflicts millions of Americans, mostly women, and treatments offer limited relief. The disorder can cause disabling bouts of constipation, diarrhea, abdominal pain and bloating. Lotronex was approved for treating women whose main symptom was diarrhea.DuBose said thousands of patients had contacted the company and the FDA saying Lotronex was the only treatment that helped them. Both parties are working to devise ways for ``appropriate'' patients to have access to the drug, she said.Public Citizen pointed to an FDA memo from November in which agency reviewers concluded ``there are no known risk factors to predict'' when serious side effects might occur.Given that danger, the FDA should allow Lotronex only for experimental use in a closely-watched setting, if at all, the group said.``If anything other than this approach is used, the toll of needless deaths and serious injuries, and the repeat ban that will inevitably occur, will be on the hands of those FDA officials responsible,'' the group said in a letter to the FDA.The Lotronex Action Group, representing irritable bowel patients, said only 1 percent of the more than 300,000 people who took Lotronex had severe side effects.The group said it feared the drug's possible reintroduction ''will be derailed due to a lack of understanding of the severity of (IBS) symptoms.''


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## Jeffrey Roberts (Apr 15, 1987)

http://dailynews.yahoo.com/h/ap/20010418/p...wel_drug_1.html Wednesday April 18 6:23 PM ETFDA Caught in Bowel Drug Battle By PAUL RECER, AP Science Writer WASHINGTON (AP) - A group of patients is petitioning the government to allow distribution to resume of a drug that was withdrawn from the market last fall after it caused dozens of patients to be hospitalized, including some who died.The drug, marketed under the brand name Lotronex, is for treatment of irritable bowel syndrome, a disorder that causes millions of Americans, mostly women, to suffer abdominal pain, urgent bathroom needs, diarrhea or constipation, or both.When it was introduced last year, Lotronex was the first new drug for IBS in years, and some 150,000 patients began taking the medicine.After the drug was on the market for a few months, the Food and Drug Administration (news - web sites) received dozens of reports of side effects to Lotronex. The most severe were cases of ischemic colitis, where the blood supply is cut off to part of the bowel, a condition that can require surgery to repair. There was also severe and continuing constipation.After an FDA investigation, the agency said the drug could be sold only under tight restrictions. The drug manufacturer, Glaxo Wellcome, now GlaxoSmithKline, voluntarily pulled Lotronex from the market.Late last month, the Lotronex Action Group, a national organization of IBS sufferers, petitioned the FDA to allow Lotronex to be sold again.Some patients, the group said, ``have reported a complete cessation of their IBS symptoms while taking Lotronex.'' The organization acknowledged that some patients experienced serious side effects, but said Lotronex had ``benefits far outweighing the potential risk for adverse side effects.''The Public Citizen's Health Research Group, a drug watchdog organization, weighed in on Wednesday with a letter opposing returning Lotronex to the market.The group, led by Dr. Sidney M. Wolfe, said that new reports since last fall show that the number of patients suffering severe side effects from Lotronex has doubled and that there is no way to identify in advance the patients who will suffer such adverse reactions.``Until and unless there is a way to reliably predict who is at risk for ischemic colitis and severe constipation, there is no way to prescribe Lotronex safely for the population at large,'' the watchdog organization wrote to FDA officials.Dr. Victor F. C. Raczkowski of the FDA declined to discuss ongoing discussions with GlaxoSmithKline about the future of Lotronex, but noted that ``we have the same safety concerns that we had'' in November.Raczkowski said that in the past, the FDA has allowed some drugs to be sold to select and carefully monitored patients for whom the proven benefits exceeded possible side effects, but would not say if such limited and restricted distribution was under consideration for Lotronex.The FDA official said that since Feb. 28, there have been 127 reported severe adverse reactions to Lotronex. Sixty-six patients experienced ischemic colitis, with 40 requiring hospitalization. Another 61 had severe constipation, with 28 requiring hospital care. There have been at least four deaths among people taking the drug, said Raczkowski.-On the Net:Lotronex Action Group: http://www.lotronexactiongroup.org FDA: http://www.fda.gov/ Public Citizen's Health Research Group: http://www.citizen.org/


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## Jeffrey Roberts (Apr 15, 1987)

http://www.newsobserver.com/thursday/busin...7p-418561c.html GlaxoSmithKline seeks to again sell bowel drug By BILL KRUEGER, Staff Writer GlaxoSmithKline officials said Wednesday that they are negotiating with federal regulators to bring back to market a drug designed to relieve a condition known as irritable bowel syndrome. GSK pulled the drug, Lotronex, off the market late last year because of reports of severe health problems in people taking the drug.Ramona DuBose, a spokeswoman for GSK, said that both the company and the U.S. Food and Drug Administration have been deluged with pleas from doctors and people who had used Lotronex to make it available again."We were surprised with the numbers and the intensity of the patients' concerns over not having access to their drug," DuBose said.FDA officials could not be reached for comment late Wednesday.Lotronex, which first went on the market in March 2000, was the first drug to come along in decades to treat the diarrhea-predominant form of irritable bowel syndrome. Irritable bowel syndrome is a disabling and often embarrassing condition that afflicts as many as 52 million people in the United States. GSK pulled Lotronex off the market in November after meeting with FDA officials who were concerned about reports of five deaths and dozens of instances of severe health consequences in people taking Lotronex.Most troubling were reports of ischemic colitis -- a reduction in blood supply to the colon that can be life-threatening -- in some people who took Lotronex.DuBose would not describe in detail the nature of the talks between GSK and the FDA, which she said have been going on since January. She also declined to comment about the likelihood that Lotronex will be returned to the market.But Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, said that the discussion has accelerated in recent weeks.He said there is "a war going on" within the FDA over whether to allow Lotronex back on the market and, if so, under what conditions.Wolfe wrote to the FDA on Wednesday urging the agency not to allow Lotronex back on the market until there is a way to reliably predict who is at risk for ischemic colitis and severe constipation.Until then, he wrote, Lotronex should be used only in an investigational setting with strict limits. In an interview, Wolfe said that more people will be harmed by Lotronex if it is put back on the market without such knowledge."I have little doubt that if it goes on the market again, it will come off the market again," he said.DuBose of GSK said that appropriate safety precautions will be taken if Lotronex is brought back."If it comes back out," she said, "it will be in a way that both the company and the FDA believe will minimize risk and maximize benefit for patients." When GSK pulled Lotronex off the market, company officials said the FDA was seeking restrictions that GSK considered too severe. At the time, an FDA official said that the agency was open to restricting the use of the drug to the most severe cases of the syndrome. Staff writer Bill Krueger can be reached at 829-4522 or bkrueger###nando.com


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## Jeffrey Roberts (Apr 15, 1987)

http://www.njo.com/business/ledger/index.s...er/12fda0c.html Data on recalled bowel drug show more bad side effects 04/19/01BY ED SILVERMANSTAR-LEDGER STAFFLotronex, a treatment for irritable bowel syndrome that was withdrawn last year amid a health scare, caused nearly twice as many serious side effects as was known previously, according to newly disclosed data. The disclosure comes as regulators and GlaxoSmithKline Plc, which marketed the medicine to women, continue an unusual series of meetings begun in January to explore the possibility of returning Lotronex to pharmacy shelves this year. Those meetings came in response to complaints from patients who maintained they lacked an alternative treatment to a poorly understood disorder, which causes stomach cramps and either severe constipation or chronic diarrhea in nearly 15 percent of women. From the time it became available last March, Lotronex was controversial. Originally ballyhooed by Wall Street as a billion-dollar seller, Lotronex later was responsible for hospitalizations, surgeries and deaths. By January, the medication was responsible for 63 cases of ischemic colitis, which can cause severe damage to the intestine, and 75 cases of severe constipation, according to reports on side effects filed with the Food and Drug Administration. The recall became the latest in a string of newly approved medications that subsequently were withdrawn due to serious side effects. For that reason, the Lotronex recall refocused attention on FDA review procedures and policies. The side-effect data were disclosed yesterday by Public Citizen, a consumer watchdog group that criticized the FDA for approving Lotronex last year. The group recently urged the agency not to approve a similar drug developed by Novartis AG. In a letter to the FDA, Public Citizen yesterday urged the agency not to return Lotronex to the market without implementing severe restrictions, such as requiring patients to sign informed consent documents and creating a patient registry. In making its case, Public Citizen referred to a Nov. 16 memo, in which four FDA staffers disparaged plans to allow Lotronex to remain on the market, but only with unusually restrictive conditions designed to prevent further cases of serious side effects. Such an approach is known as risk management and is used only when the FDA believes no alternative exists to a troublesome drug. But the agency staffers concluded this was unlikely to eliminate the problem caused by Lotronex. "From our analysis, there are no known risk factors to predict either ischemic colitis or severe constipation, so any risk management strategy that focused on the patient's age or the management of constipation will fail to manage the risk in the majority of patients exposed to Lotronex," they wrote. Nonetheless, Victor Raczkowski, an FDA deputy director who oversees the gastrointestinal division, yesterday said the agency is looking for ways to balance the risks and the benefits to help patients who lack other effective treatments. "It becomes an access issue for patients without therapeutic alternatives as much as a concern for drug safety. There are two sides to these stories," Raczkowski said. "These are very complex issues, but just because it's complex doesn't mean it can't be done." Prior to last November's withdrawal, the FDA and Glaxo sparred over a host of issues. Among the issues under dispute were ways to monitor patients, physician prescribing practices and a so-called black box warning, which refers to serious side effects and necessary precautions for patients. A Glaxo spokeswoman, Ramona DuBois, yesterday said meetings with the FDA will continue. She was unable to say when a decision was expected. She confirmed that Glaxo would accept some restrictions on how Lotronex would be made available. Yesterday, Lotronex Action Group, which insisted it doesn't accept funding from Glaxo to promote awareness of irritable bowel syndrome, urged the FDA "not to lose sight of the patients." The group maintained the drug is safe. "No data has been released proving those that suffered from side effects were properly diagnosed and should have been taking the medicine to start with," Jeff Roberts, the group's president, said in a statement. Ed Silverman covers the drug industry and can be reached at (973) 392-1542 or esilverman###starledger.com. [This message has been edited by Jeffrey Roberts (edited 04-19-2001).]


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## Jeffrey Roberts (Apr 15, 1987)

http://www.usatoday.com/news/health/2001-0...-bowel-drug.htm 04/19/2001 - Updated 02:02 PM ET FDA, Glaxo reconsider pulled drug By Rita Rubin, USA TODAYBy the end of last year, the Food and Drug Administration had received reports of 141 cases of severe complications in patients who took a popular drug for irritable bowel syndrome that is no longer on the market, according to information obtained by a consumer advocacy group.That's twice as many as reported by early November, just a few weeks before manufacturer Glaxo Wellcome stopped selling Lotronex, Public Citizen's Health Research Group officials wrote Wednesday in a letter to Bernard Schwetz, acting principal deputy FDA commissioner.Glaxo, now GlaxoSmithKline, began selling Lotronex in March 2000 for the treatment of irritable bowel syndrome (IBS) in women with diarrhea. After the FDA began receiving reports of severe constipation and ischemic colitis ï¿½ an inflammation of the large bowel from a lack of blood flow ï¿½ Public Citizen petitioned the FDA in August to pull Lotronex from the market.Sidney Wolfe, director of the consumer advocacy group, says he is concerned that the FDA may bow to pressure from the manufacturer and patient groups and allow Glaxo to resume largely unrestricted marketing of Lotronex.Glaxo spokeswoman Ramona DuBose says the FDA and her company have heard from thousands of IBS patients who want the drug. In a statement Thursday, the Lotronex Action Group, an offshoot of the IBS Self-Help Group, urged the FDA and the company "not to lose sight of the patients.""The Lotronex Action Group maintains the medicine is safe," according to the statement issued by Jeffrey Roberts, president and founder of the self-help group. Roberts says the non-profit group receives no funding from Glaxo.In their letter to Schwetz, Wolfe and his colleagues argue that Glaxo should be allowed to make the drug available only in a closely monitored, experimental setting to previous Lotronex users who had not experienced adverse effects.FDA official Victor Raczkowski says that his agency has been working with Glaxo in trying to make Lotronex available to patients who might benefit from it. Raczkowski says he cannot comment on the specifics. DuBose would say only that "there has been no resolution up to this point."


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## Jeffrey Roberts (Apr 15, 1987)

http://interactive.wsj.com/fr/emailthis/re...32360688533.djm April 19, 2001 -------------------------------------------------------------------------------- HealthFDA Weighs Requests to ReturnLotronex to Consumer MarketBy CHRIS ADAMS Staff Reporter of THE WALL STREET JOURNALWASHINGTON -- Federal regulators are considering requests to make Lotronex available to consumers again, less than six months after the pill for irritable-bowel syndrome was pulled from the market because of safety concerns. Glaxo to Withdraw Disputed Drug After Losing Its Battle With FDA (Nov. 29, 2000) The drug's maker, GlaxoSmithKline PLC, is in discussions with the Food and Drug Administration over the drug's possible return, perhaps with some sort of "risk management" program to mitigate the drug's side effects.Lotronex was approved in February 2000 for the treatment of IBS in women. Sales totaled $55 million before the pill was pulled from the shelves, and analysts initially thought sales could top several hundred million dollars a year.Within months, however, several cases of ischemic colitis and severe constipation, requiring surgery or hospitalization, surfaced in people using Lotronex. The FDA also received reports of five deaths in patients taking the drug. The FDA asked Glaxo to voluntarily withdraw Lotronex.But the agency was soon inundated with requests from patients seeking continued access to the drug. Victor Raczkowski, an FDA drug official, said the phone calls, e-mails and letters ran "in the thousands."Regarding the most recent discussions, the FDA says they are "ongoing and serious," but wouldn't say what sort of status a renewed Lotronex would have -- whether, for example, Glaxo could market and distribute it freely, or whether it would be available only in tightly controlled circumstances."We had concerns back in November that the conditions under which the drug was being marketed were inadequate to address some of the serious safety issues with the drug," Dr. Raczkowski said. "The concerns we had at that time we still have."GlaxoSmithKline spokeswoman Ramona DuBose said the company recognizes "there will be restrictions on use of the drug, if it were to come back to market."The difficulty of fashioning a way to safely bring Lotronex back to the market was underscored by an internal FDA memo, obtained and released Wednesday by the consumer advocacy group Public Citizen. The November memo recounted the discussions between Glaxo and the FDA over the Lotronex safety data, and concluded that a "risk management program" that sought to allow the drug to stay on the market would be highly difficult.Write to Chris Adams at chris.adams###wsj.com


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## Jeffrey Roberts (Apr 15, 1987)

More complete stories over here: http://www.ibsgroup.org/ubb/Forum10/HTML/000333.html


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## IBS2 (Feb 7, 1999)

PC is not stupid. If you read their statement they leave just enough wiggle room to let them say they did include conditions that would allow patients to get Lotronex. Of course they know very well that those very same conditions would be unacceptable to the the drug company.I think it's time for a class action suit against PC. If they want to be a stong voice in matters of health care for the public then they should be responsible for their actions. Their actions have caused and continue to cause pain and suffering on the part of thousands of IBS suffers. Let them put their data to the test in the court of public opinion i.e. before a jury and see what happens.Tom


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## VernaEileenR (Feb 23, 2001)

Lead the way Tom...I'll follow.Verna Eileen Radcliffe


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## Jeffrey Roberts (Apr 15, 1987)

http://my.webmd.com/content/article/1728.77960 Patients Demand Return of Irritable Bowel DrugRemarketing Lotronex Would Be Unprecedented By Sean Martin WebMD Medical News April 20, 2001 (Washington) -- Patients who have benefited from the prescription drug Lotronex are asking the FDA to do something it has apparently never done before -- return a medication to market that was withdrawn because of deaths and other serious safety concerns. The Lotronex Action Group, a patient organization, formally petitioned the FDA last month to allow the drug back onto pharmacy shelves. The group, which says it takes no money from any drug companies, maintains that Lotronex is "safe, if dispensed properly" and that "the benefits far outweigh the potential risk for adverse side effects." Lotronex, a Glaxo SmithKline drug that first became available in February 2000, offered relief to many symptoms of irritable bowel syndrome (IBS) in women. It was the first drug approved for IBS in decades, and more than 450,000 prescriptions were filled before Glaxo announced in late November that it was withdrawing the medication at the FDA's request. IBS is not life-threatening, but it can cause abdominal pain, gas, diarrhea, and other bowel overactivity, symptoms that can bring about poor quality of life for those with the condition. Both the FDA and Glaxo have been in talks since January about how the drug might return to at least some use. "There are serious side effects associated with the use of the drug. On the other hand, there are patients who feel that they don't have therapeutic alternatives and who want access to it," Victor Raczkowski, MD, an FDA drug evaluation director, tells WebMD. "What we really are trying to work out with the company is some sort of conditions under which those two things can be balanced appropriately," he says, adding that the FDA has received "thousands" of emails, letters, and phone calls from patients asking that Lotronex be made available. "What we are trying to come up with is a plan that would help appropriate patients ... to have access to the drug in a way that would minimize the risk and maximize the benefits," Glaxo spokeswoman Ramona DuBose tells WebMD. "For a lot of reasons, not the least of which was the number of patient calls that we and the FDA had gotten, there was undeniably a major need to look for some sort of alternative." Neither side is saying how much longer the negotiations will take. "This is a complex and difficult issue," says Raczkowski. Indeed, the possible side effects of Lotronex are alarming. According to the FDA, through the end of February 2001, it had received reports of 66 cases of ischemic colitis, a potentially life-threatening inflammation of the large intestine. In addition, the FDA has reports of 61 cases of severe constipation that were possibly linked to the drug. Moreover, it says, four patient deaths are linked to Lotronex. But Dubose says, "All reports are not necessarily causally related to the drug. Everything that's reported gets counted, but it doesn't necessarily mean once you look at the data and you investigate the report, that you are going to find a link to the drug." It would be unprecedented if the withdrawn drug were to return to market availability for similar medical use. "This probably is a unique case. We've talked about this, and informally done polls, and no one can remember another circumstance where that has happened," Raczkowski says. The closest has been when a drug that is no longer being actively marketed is made available under strict investigational guidelines. For instance, the heartburn medication Propulsid, pulled from marketing last July, is still available now to study patients who meet certain conditions, Raczkowski notes. The consumer watchdog group Public Citizen, which urged last year that Lotronex be withdrawn, is of the opinion now that the drug should only be returned to use under very strict guidelines. Those guidelines, it says, should limit the drug to those who had already received it and should require special registration by every patient and physician who uses it. In a letter to the FDA this week, Public Citizen warns: "If anything other than this approach is used, the toll of needless deaths and serious injuries and the repeat ban that will inevitably occur will be on the hands of those FDA officials responsible for such a reckless remarketing." As the FDA andthe drugmaker ponder their options, the Lotronex patient group is goosing both sides to speed up their negotiations. "This has been five months of needless suffering," for people who have previously benefited from Lotronex, the organization said in a letter this month to Glaxo. "[T]he issue is simple. We had access to the only medicine that allowed us to live normal lives without pain and suffering from our illness and now we do not." Medically ReviewedBy Dr. Jacqueline Brooks, MBBCH, MRCPsych ï¿½ 2001 WebMD Corporation. All rights reserved.


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## Jeffrey Roberts (Apr 15, 1987)

http://www.dailyherald.com/health/health_s...sp?intID=370251 Big Brother in your medicine cabinetBy Lorilyn Rackl Daily Herald Health WriterPosted on May 14, 2001 Richard Fireman doesn't like to think about life without Lotronex. Until the tiny blue tablet came along last year, Fireman's irritable bowel syndrome was out of control. The 73-year-old Chicagoan had diarrhea three or four times a day. The disorder made him petrified to take the bus downtown for fear of being away from a bathroom for too long. He vividly recalls a few embarrassing instances when he ventured outside his Hyde Park home and couldn't make it to a bathroom fast enough. 'It's just dreadful, the things that can happen to you,' Fireman said. 'Lotronex made a total difference in my life. Now, it's like I'm normal, and it scares me to go back.'Before long, Fireman will have no choice but to go back. He has less than 25 Lotronex pills left. When Fireman's bottle is empty, he can't get a refill. That's because Lotronex's maker, pharmaceutical powerhouse GlaxoSmithKline, took its product off the market late last year, less than 10 months after the Food and Drug Administration approved it. More than 300,000 patients had taken Lotronex during its short life on the market. As of Feb. 28, there had been 127 reported severe adverse reactions to Lotronex, including at least four deaths thought to be linked to the drug. Sixty-six patients experienced ischemic colitis, a potentially fatal condition where the blood supply is cut off to part of the bowel. Another 61 had serious constipation, with nearly half requiring hospitalization.Safety concerns early on prompted Lotronex critics, most notably consumer watchdog group Public Citizen, to demand the drug's recall.Yet Lotronex also had helped thousands of patients suffering from a common disorder that's woefully lacking in effective medications. These people want their drug back. They recently filed a petition with the FDA asking for just that.The debacle illustrates an increasingly common quandary for the agency in charge of regulating our country's drugs: What do you do with medication that hurts some yet helps others, often many others? 'There are patients who feel they've benefited from the drug, and there are patients who've experienced serious side effects from the drug,' said Dr. Victor Raczkowski, deputy director of the the FDA office that evaluates gastrointestinal drugs. 'It's difficult trying to balance the benefits and the risks.'Lotronex is just one example of a high-profile drug pulled from pharmacy shelves last year. The heartburn drug Populsid was withdrawn after being linked to fatal heart rhythm disorders. Makers of the diabetes medicine Rezulin yanked it for being too toxic to the liver.To be sure, every drug has side effects. Even aspirin - a staple in most medicine cabinets - has killed people. But when does the bad overshadow the good? That's the question being asked by the FDA, GlaxoSmithKline, Public Citizen and former Lotronex users, and they all have a different answer. Lotronex's brief, troubled tenure began in February of last year, when the FDA approved the long-awaited treatment for IBS, sometimes called 'spastic colon.'The gastrointestinal disorder afflicts about 15 percent of the U.S. population. Its symptoms vary, both in scope and severity. Some people get cramping and diarrhea. Others suffer pain and constipation, or alternate between constipation and diarrhea. Lotronex was one of a new class of drugs being studied specifically for the treatment of IBS. The theory is that it blocked the body chemical serotonin in certain areas of the intestinal tract. Serotonin is thought by some scientists to cause abnormal sensitivity in the gut. Lotronex was aimed strictly at the diarrhea-predominant form of IBS. It also was approved only for women, who are nearly three times as likely as men to have the disorder. (Doctors were able to prescribe Lotronex 'off label' to men.) The FDA based its approval on the results of two, 12-week clinical trials involving 1,273 women. Patients on the drug had to go to the bathroom less and had firmer stools than those taking dummy pills. Some 41 percent of those on Lotronex had abdominal pain relief, compared to 26 to 29 percent taking placebos. Critics charged that Lotronex's benefits were modest at best; the FDA found them significant enough to warrant approval.When it came to safety, the studies raised some red flags but hardly set off major alarms. Four patients experienced ischemic colitis. The cases weren't deemed very serious and cleared up when patients stopped taking the drug. Constipation was another side effect, but it didn't prove dangerous enough to keep the FDA from giving Lotronex the OK.Not long after the much anticipated drug hit the market, reports of ischemic colitis and serious complications from constipation started filtering in. Experts say it's certainly not unusual for new or more severe side effects to surface once a drug moves out of the sheltered confines of clinical trials and into the mass market.'When you test a drug for effectiveness and safety, you can only study it in a certain number of patients,' said Jerry Bauman, professor of pharmacy at the University of Illinois at Chicago. 'When it opens up to a broad population, rare or unusual side effects may crop up.'This doesn't necessarily mean that something is wrong with the drug. It might mean something is wrong with the way the drug is being used, Bauman said. Patients may disregard the drug's instructions, mix it with other medications and cause dangerous interactions, or take it even though the drug isn't meant for them, which was the case in some instances with Lotronex. Doctors prescribed the drug for some IBS patients with constipation, despite warnings to the contrary.In August, Public Citizen's Health Research Group filed a petition with the FDA to immediately ban Lotronex after it had been associated with at least 26 cases of ischemic colitis. The consumer group argued that the drug didn't work well enough to justify these kinds of risks to treat a disorder that isn't life-threatening. This infuriated many Lotronex users who felt that Public Citizen was trivializing their IBS and threatening to take away the only treatment that worked for them.'You don't know what this is like until you have to live with it,' said Edna Wakeham, a 74-year-old widow from Crestwood. 'I would like to be able to live out the rest of my life without having to worry about 'losing it' while out in public.'Wakeham saved her last Lotronex pill for Christmas, so she could enjoy herself while eating dinner with her family. Now, she's back to the days when eating an apple is enough to spur an attack. Some days she spends hours on the couch clutching a heating pad, waiting for her cramps to die down. 'I've always said I would never wish this disease on anyone,' she said. 'I have to go back on my word, because I hope the people at PC (Public Citizen) experience it at some time in their lives.'Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, said he understands Lotronex users' fury; he just thinks it's misdirected.'They should be angry with the FDA and the company for approving the drug in the first place,' Wolfe said. 'It barely works better than a placebo. It doesn't make sense to have a drug that kills people and causes a very serious life-threatening form of colitis that would never occur from the disease it's being used to treat.'Wolfe is among the FDA's critics who say the agency's standards have slipped in recent years.The agency used to be lambasted for dragging its feet when it came to getting new drugs and medical devices on the market. Critics - including many members of Congress - complained that valuable, sometimes life-saving remedies were being held hostage by the FDA's too-rigorous approval process.A 1997 law designed to reform the agency created a fast-track program to speed up the review process for certain drugs. Under the law, average drug review times have plummeted from more than 30 months to about a year, FDA Senior Associate Commissioner Linda Suydam told a congressional panel earlier this month. Nearly 80 percent of new drugs now debut in the United States as opposed to other countries, up from 40 percent before the reforms, Suydam added.But the faster reviews have prompted questions about whether regulators are sacrificing safety for speed. The FDA notes that the percentage of recalled drugs has held steady for the last 20 years, averaging just under 3 percent of new drugs approved. Yet with record numbers of drugs being approved, safety-related recalls are on the rise.Wolfe argues that too many dangerous drugs are winding up on pharmacy shelves only to be pulled off a few months later when reports of dangerous side effects start stacking up. He points to Lotronex, which took only six months to get FDA approval, as the perfect example.Lotronex's mounting number of complications prompted the FDA in August to require a warning pamphlet be attached to every bottle, alerting patients about the risk of rare but serious side effects and telling them to act early to prevent harm. Then there were a few reports of deaths possibly linked to the drug. This spurred the FDA to meet with GlaxoSmithKline and take a hard look at the popular medicine.After a few months of negotiations, the FDA last fall said the drug could be sold only under tight restrictions. For one, the drug would be limited to patients with the most severe cases of IBS. And it would be available only to patients who fit the exact labeling specifications, meaning men were out of luck. GlaxoSmithKline said no, and voluntarily withdrew the drug from pharmacy shelves late last year.'We do not believe the FDA gave us any real options in November to keep the drug on the market,' said GlaxoSmithKline spokeswoman Ramona DuBose. The agency would have 'effectively required Glaxo to police physicians, and we don't believe that should be the role of any pharmaceutical company,' she added.Neither does Dr. Brian Fennerty, a professor of medicine and section chief of gastroenterology at Oregon Health Sciences University in Portland, Ore.Fennerty, who has been a paid clinical consultant for GlaxoSmithKline in the past, said he used Lotronex with much success in several of his patients. He thinks it's an extremely good drug when used the right way in the right people.'I see patients for a living. (Public Citizen's) Sidney Wolfe and the FDA do not. I think they made an extraordinarily callous, poor and short-sighted decision,' Fennerty said. He balks at the notion that GlaxoSmithKline's decision to pull the drug was 'voluntary.''If you handcuff the industry and they can't make money on a product, they sure as hell aren't going to keep it in the marketplace,' Fennerty said. 'They have stockholders they have to answer to.' And Fennerty has IBS patients to answer to, but he doesn't know what to tell them.'I had patients where nothing else worked,' he said. 'This puts me in an extremely difficult position.'Indeed, thousands of Lotronex users have found themselves in an extremely difficult position: they've found help, only to have it taken away from them.The IBS Self Help Group's Web site is littered with postings from people desperately searching for the drug. One posting asked how to get it on the black market. Another offered to pay any price for any amount.Rich of St. Charles considers himself lucky to still have a small stash of the pills. He's saving them for emergencies, such as airplane trips.Rich asked that his last name not be used because he doesn't want his co-workers to know about his condition, which has plagued him for more than a quarter century. 'There are times I can't even go out in the backyard and cut grass because I can't run to the bathroom fast enough,' he said. Rich said he's tried dozens of medications. He even had his gallbladder taken out, which didn't help at all. He keeps his briefcase and glove compartment stocked with Imodium AD to stave off diarrhea attacks, but he says that's no substitute for Lotronex.'Within four hours of taking my first Lotronex pill, my intestinal tract never felt so calm and settled,' Rich said. 'About two days later, everything was great. It was like going back 25 years.'Rich is one of the 1,105 people who signed the Lotronex Action Group's recent petition to the FDA, demanding their 'miracle drug' be put back on pharmacy shelves. The FDA has been inundated with letters, calls and e-mails from Lotronex fans outraged by the drug's disappearance. The FDA's Raczkowski said he's never seen such an outcry from the public.'I think one of the reasons for that is many of the patients don't feel they have satisfactory alternatives for their irritable bowel syndrome,' Raczkowski said. 'It was the first treatment shown to be truly effective for diarrhea-predominant IBS.'Even though Lotronex has been off the market for nearly six months, the issue is far from dead.The FDA and GlaxoSmithKline have been meeting behind closed doors since January, exploring different ways the drug might be made available again. Officials from both sides refused to speculate on the odds of Lotronex being resurrected, but they insisted that negotiations are ongoing. 'From the FDA's perspective, we're making progress,' Raczkowski said.Even Public Citizen admits that Lotronex might still have a place in treating some IBS patients, although only in an 'experimental and highly restricted basis.''If anything other than this approach is used, the toll of needless deaths and serious injuries and the repeat ban that will inevitably occur will be on the hands of those FDA officials responsible for such a reckless remarketing,' reads a Public Citizen letter sent last month to the FDA.While the drug's maker, FDA officials and Public Citizen try to come up with a solution, patients like Edna Wakeham wish they'd let her solve her own problem - with Lotronex.'I know the risks, and I would take it again, warts and all,' Wakeham said. 'I don't want Big Brother in my medicine cabinet.'Daily Herald wire services contributed to this report. -------------------------------------------------------------------------------- Copyright ï¿½ Daily Herald, Paddock Publications, Inc.


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## Guest (Jul 17, 2001)

Why is this group, Public Citizens, so against us having Lotronex? What about the deaths from Viagra? Why are they not attacking that as they are thisI am trying to recover from a bout of IBS that lasted five hours last night and leaves me so drained, weak and woosey I simply cannot bear to live like this much longer. It is even more difficult to know help is there and it is being kept from us as if we are little, naughty children they think they have to protect from ourselves! Please!I'm so upset about this!


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