Chantix: 36,342 adverse events, 595 suicide attempts

JohnPolito
Joined: 11 Nov 2008, 19:22

16 Dec 2010, 15:41 #11

Anti-Smoking Drug Chantix Tops List of Drugs Linked to Violence in New Study By Lilly Fowler on December 16, 2010

A new study says a smoking cessation drug manufactured by the pharmaceutical giant Pfizer Inc. is the prescription medication most often linked in the U.S. to violent acts or violent thoughts toward others.

The study, published Wednesday in the journal PLoS ONE , reviewed drugs most often linked to violent thoughts or actual violent acts, such as physical assaults, in reports received by the Food and Drug Administration. It covered a five-year period ending in 2009.

The Pfizer medication Chantix, generically known as varenicline, led the way with 408 reports related to violence.

As FairWarning has reported, Chantix has been associated with serious adverse events, including suicides and attempted suicides and is the subject of about 1,000 lawsuits. But Thomas J. Moore, lead author of the study and a scientist with the the nonprofit Institute for Safe Medication Practices in Horsham, Pa., argues that more attention needs to be paid to the drug’s potential to induce violence.


Second on the list, after Chantix, was the antidepressant Paroxetine, also known as Aropax, Paxil and Seroxat. It drew 177 reports of violent thoughts or actions.

Among smoking cessation aids, Zyban, also known as bupropion, followed Pfizer, with 35 incidents.


Michael Cummings, a smoking cessation expert at the Roswell Park Cancer Institute in Buffalo, N.Y., who was not involved in the study, questioned the validity of the results. He said the reports reviewed by the researchers are “probably not good enough” by themselves to draw a strong conclusion.

Pfizer, for its part, said “there is no reliable scientific evidence that Chantix causes violent thoughts or actions.”
Among the other drugs associated with violence were medications for attention deficit disorder and sedatives. Moore was joined in the study by researchers from the Harvard University and Wake Forest University medical schools.

Story Source Link 
Copyright:  http://www.fairwaring.org/ 2010

A free full-text copy of this study Chantix violence adverse events paper is available at: http://www.plosone.org/article/info%3Ad ... ne.0015337

In the above article it should be noted that Michael Cummings is paid by Pfizer, Chantix's maker, as a member of Pfizer's Speakers Bureau.  If he wants to keep his job what would we expect him to say?

So what's going on here with 9 times as many FDA violence reports for Chantix than NRT?  We can only speculate.  We know that anger is a normal phase associated with an significant emotional loss, including smoking cessation.  We also know that an angry quitter always retains the ability to quickly suppress escalating anger via relapse.  Or do they?  What happens when Chantix (varenicline) with its 24 hour chemical half-life has bonded with all brain a4b2 type nicotinic receptors, effectively blocking nicotine from attaching and causing significantly greater dopmaine pathway stimulation than afforded by the partial agonist varenicline?   For some, can anger escalate into rage?   We don't know.  It's likely vastly more complex (genetics, mental illness, and including other brain neuro pathways besides dopamine).

What we do know is that cold turkey is free, chemical free and safe!

Breathe deep, hug hard, live long,

John (Gold x11) 

Last edited by JohnPolito on 16 Dec 2010, 15:45, edited 2 times in total.
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JohnPolito
Joined: 11 Nov 2008, 19:22

30 Mar 2011, 16:30 #12

The below new Chantix/Champix study review proclaims that the difference in success rates between the NRT and Chantix/Champix at six months is "not statistically significant."  If true, with so much concern about serious varenicline adverse events, why isn't this rather important decision making info being widely shared with smokers?   I submit that it's the exact same reason that pharm industry financial influence worked so hard in 1999/2000 to get cold turkey (abrupt nicotine cessation) declared non-science-based and black-listed as a government approved quitting method: money/profits. 

There is nothing wrong with making money.  What's wrong is leading smokers to believe that these products are vastly more effective than they really are.  What's wrong is marketing that suggests that few succeed at quitting cold turkey, when each year it generates more successful long-term quitters than all other quitting methods combined, or that these products prevailed over cold turkey quitters when no such trials have ever been conducted, when the industry is afraid to do so, when it knows that doing so would expose and kill its golden "placebo" goose. 

Although an extremely limited view that only shows us quitting rates at week 4, the best on-going real-world varenicline data we have to look at comes from the UK  NHS Stop Smoking Services, possibly the best/most intense government quitting programs of any nation (except for heavy reliance upon approved quitting products).   When reflecting upon the below figures, keep in mind the following factors:  (1) that these are 4 week figures, not 6 month rates as discussed in the below study review; and (2) that at 4 weeks, non-medication quitters have already ended dopamine pathway stimulation, re-sensitized receptors and down-regulated the number of receptors to levels seen in non-smokers, while those using "medication" still have 4 to 8 weeks of "treatment" before attempting to adjust to and get comfortable with natural stimulation. 

So why does UK NHS limit the data it presents to 4 weeks?  We don't know.  What we know is that these products were evaluated and approved using 8 to 12 week treatment plans.  We also know that the pharmaceutical industry's ties to UK government health officials is likely as great or greater than here in the U.S.  Anyway,
Stop Smoking Services 4 week quitting method quit rates between 2007 and 2010 were as follows:

UK NHS Week 4 Quitting Rates
2007-08  -   Non-medication quitters 55%  |  NRT 49% |  Varenicline 63%
       (Source: 1st XLS doc - .74MB - see Table 4.5)
2008-09  -   Non-medication quitters 48%  |  NRT 48% |  Varenicline 61%
       (Source: 1st XLS doc - 1.06MB - see Table 4.5)
2009-10   -  Non-medication quitters 49%  |  NRT 47% |   Varenicline 60%
      (Source: 1st XLS doc - 1.16MB - see Table 4.4)


Link to entire NHS Stop Smoking Services data collection


ImageSo what do long-term (6 months to 1 year)  UK NHS Stop Smoking Services quitting rates look like?  Well, so far there has only been one study which looked at long-term rates (1 year), the sampling was rather small, and was conducted prior to Chantix /  Champix coming on the market.  Still, it's the only long-term UK data we have.  I prepared the chart to the right from it (link to full text copy of the study - see bottom of Table 6) . 

Now, in your mind try to guess where varenicline will fall at 1 year, once users attempt to adjust to its absence and natural stimulation of brain dopamine pathways.  Putting it all together, I suspect that varenicline would fall slightly higher than NRT but substantially lower than no medication.

I've shared this info to try and help those just starting out feel a tad more comfortable about your quitting method decision, to help you understand that those claiming that these products double your chances are not being truthful.   Yes, inside randomized clinical trials  they consistently defeat placebo but placebo isn't a real quitting method.  So why do they work inside clinical trials and yet fall flat on their face in real-world use?  

The quick answer is that clinical trials were not blind as claimed, that you cannot hide full blown withdrawal from an experienced quitter who is an expert at knowing exactly how it feels.  Participants joined the trial seeking 8 to 12 weeks worth of free quitting products that they hoped with diminish withdrawal's intensity.  They grew frustrated upon realizing that they had been given an inert placebo instead.  We know from the few blinding integrity assessments that have been published that 3 to 4 times as many placebo group members correctly identify their assignment to placebo as guess wrong.  If you'd made the same realization, would you have stuck around and allowed researchers to toy with you for weeks or months?  Many of them didn't either.

So, if just starting out and worrying that maybe you've taken the less successful road, rest assured that you've made an excellent selection!   In fact, cold turkey provides 100% odds of success so long as all nicotine remains on the outside.   Yes, there was always only one rule ... no nicotine today!

Breathe deep, hug hard, live long,

John (Gold x11)
















Varenicline Increases Smoking Abstinence at 6 Months to a Year Compared With Placebo or Bupropion; Nausea Is the Most Commonly Reported Adverse Effect

 
Evidence-Based Medicine. 10.1136/ebm1200 [doi]. March 9, 2011, [Epub ahead of print].
 
Sofuoglu, M.; Duffey, D.; Mooney, M.E.
Commentary on:

Cahill K, Stead LF, Lancaster T.  Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2010; 12 - CD006103.
Context Cigarette smoking is the leading cause of preventable premature death in the world, with an estimated 5 million smoking-related deaths worldwide. Quitting substantially reduces the health risk associated with smoking. Treatments available for smoking cessation include nicotine replacement therapies (NRTs), bupropion and the most recently marketed, varenicline. Varenicline, an analogue of cytisine, is a partial agonist for the α4β2 subtype of nicotinic cholinergic receptors, which are associated with the addictive effects of nicotine. Varenicline may help smokers quit smoking by reducing the rewarding effects of nicotine as well as attenuating the withdrawal symptoms.1 This meta-analysis evaluated the efficacy and safety of partial nicotine agonists, varenicline or cytisine, compared with placebo or other treatments in clinical trials conducted worldwide.


Methods Cahill and colleagues conducted a Cochrane review evaluating the efficacy of partial nicotine agonists, varenicline or cytisine, for smoking cessation. Randomised controlled trials comparing active drug with placebo were included in the analyses. The review also included studies comparing the efficacy of varenicline with bupropion or NRT. Studies were excluded if they did not have a minimum of 6-month follow-up data from the beginning of treatment. Literature searches were conducted using the Cochrane trial register and other databases including MEDLINE, up to September 2010. The main outcome was the smoking abstinence rate at 6 months or more. Biochemical measures of smoking abstinence were the preferred outcome. One author extracted the data, and another author checked them. The authors used a meta-analysis to produce a RR, using the Mantel–Haenszel fixed-effect model. The heterogeneity of the studies and publication bias were also assessed.


Findings A total of 16 studies were included in the analyses, 15 for varenicline and 1 for cytisine. Twenty-one studies were excluded. The main finding of the review was that the usual recommended dose of varenicline, 1 mg twice daily, was more effective than placebo for continuous abstinence at 6 months or longer (RR 2.31, 95% CI 2.01 to 2.66). Lower or variable doses of varenicline were also more effective than placebo (RR 2.09, 95% CI 1.56 to 2.78). Results also indicated that varenicline was more effective than bupropion at 1 year after the initiation of treatment (RR 1.52, 95% CI 1.22 to 1.88). Similarly, varenicline was more effective than NRT at 24 weeks, although this effect was not statistically significant (RR 1.13, 95% CI 0.94 to 1.35). Overall, varenicline was well tolerated even beyond the 12-week recommended treatment period. Nausea was the most common side effect, with a dose-dependent effect. The results did not show the behavioural adverse events reported in the postmarketing stage including depressed mood, agitation and suicidal behaviour or ideation. The single trial of cytisine was inconclusive.


Commentary The results demonstrate the efficacy of varenicline, relative to placebo, as a pharmacological treatment for smoking cessation in the usual recommended dose as well as at lower or flexible-dosing schedules. The results also suggest that varenicline may be more effective than bupropion. However, this comparison of efficacy was based on only a few studies. Future studies specifically designed to compare the efficacy of NRTs, bupropion and varenicline are needed.

What remains to be determined is whether varenicline will have similar efficacy in samples representative of all smokers. The clinical trials included in the meta-analyses excluded smokers with medical or psychiatric comorbidity or with other addictions. It has been estimated that at least one-third of smokers in the USA have a psychiatric disorder or another addiction.2 Thus, it will be important to conduct studies including these subject populations as well. Indeed, the authors identified numerous ongoing trials in these areas. In addition, clinical trials generally provide more psychosocial treatment than those provided in clinical settings. It will also be important to show the efficacy of varenicline in real-world settings.

This meta-analysis supports the safety of varenicline up to 1-year duration. These findings do not support the postmarketing reports of depressed mood, agitation and suicidal behaviour or ideation associated with varenicline treatment. However, due to the selection biases of the included studies, the absence of these putative severe adverse events in this review is by no means dispositive. The causal relationship of these side effects to varenicline treatment or smoking cessation effect remains to be determined.


Footnotes Competing interests MEM has received unrestricted research grants, including salary support, from Pfizer. MS and DD have no conflicting interests.

References
  1. Sofuoglu M, Herman AI, Mooney M, et al. Varenicline attenuates some of the subjective and physiological effects of intravenous nicotine in humans. Psychopharmacology (Berl) 2009; Volume 207: Pages 153 to 162.
  2. Grant BF, Hasin DS, Chou SP, et al. Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 2004; Volume 61, Pages 1107- 1115.

[/b]     
Copyright © 2011 the BMJ Publishing Group Ltd. All rights reserved
Last edited by JohnPolito on 30 Mar 2011, 16:59, edited 4 times in total.
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JohnPolito
Joined: 11 Nov 2008, 19:22

19 May 2011, 15:29 #13



Varenicline (CHANTIX) Risks Underestimated

[Below is the Chantix portion of a May 19, 2011 report by the Institute
of Safe Medicine Practices
entitled QuarterWatch 2010:  Quarter 3] 
While reported serious psychiatric side effects of varenicline prompted the FDA to require a boxed warning and mandatory Medication Guide for patients in 2009, we discovered the FDA had been unaware of hundreds of serious psychiatric adverse event reports that were originated by Pfizer and dated back as far as 2006. These reports had not been promptly submitted into the agency's AERS safety database as the FDA had expected. Thus, FDA analysts could not evaluate 150 completed suicides reported to the company, along with hundreds of other cases indicating psychosis, depression, or attempted suicide. We explain this significant breakdown in safety surveillance below, and recommend the FDA investigate why Pfizer was reporting suicide deaths as "expected adverse events."

Varenicline, an aid to smoking cessation, was approved in 2006, and by 2008 was being taken by hundreds of thousands of smokers who wanted to quit. But as patient exposure increased, the FDA adverse event reporting system received hundreds of reports of psychiatric side effects and other potential safety problems. When we first examined quarterly data for varenicline in May 2008, adverse event reports for the drug outnumbered those for other prescription drugs on the U.S. market including inherently toxic cancer chemotherapy agents, high-alert drugs that suppress the immune system, and extremely potent synthetic opioids. [21] Pfizer told the FDA that it thought stronger warnings were not necessary, and said “it was not unexpected” to see psychiatric side effects among smokers, and in particular those who might be experiencing nicotine withdrawal. [22] The FDA disagreed after completing its own analysis of the adverse event data [23] [24] and in July 2009 required strong warnings for both doctors and patients. [25] Even these warnings, we have now learned, were based on significantly incomplete data about psychiatric side effects.

Results for Third Quarter 2010

We began a new investigation into a signal for varenicline after observing the drug was again setting records. After peaking in 2008, both dispensed prescriptions and reports of serious injury then declined modestly. With a new spike totaling 1055 serious adverse drug events meeting QuarterWatch criteria for the third quarter of 2010, it again surpassed all other drugs we regularly monitor (Excludes 226 cases linked to legal claims. See Table 4.) It also ranked first in reported deaths, more than twice as many as any other drug we regularly monitor. Varenicline cases also outnumbered all regularly monitored drugs for specific conditions as measured by Standardized MedDRA Queries (SMQs). It accounted for more possible cases than any other drug for suicidal/self-injurious behavior, depression, psychosis, hostility/aggression, and convulsions.

Further analysis uncovered the reason for the sudden spike in varenicline reports. The third quarter totals for 2010 had been boosted by 589 reports about serious and fatal adverse events that had occurred in prior years but were not entered into the FDA AERS monitoring system until July 2010. We found 12 newly entered cases with manufacturer dates from 2006, the year varenicline was first approved, 119 from 2007, and 176 additional cases from 2008. The rest of the 589 cases were for 2009 and early 2010, but also not entered into the reporting system until July 2010 or later.

150 Completed Suicides

Prominent among these newly available cases were 150 completed suicides identifying varenicline as the primary suspect drug. These additional cases more than doubled the total suicides that were in the AERS system and available to the FDA and others for safety analysis. Here is our breakdown:
  • Prior to July 2010 the AERS system had 37 completed suicide cases submitted by the manufacturer identifying varenicline as primary suspect drug.
  • Another 85 suicides associated with varenicline were reported directly to the FDA by health professionals or consumers, and entered into the system without manufacturer involvement.
  • In July 2010, these additional 150 suicide cases from the manufacturer first become available.
The newly available completed suicides were not the only reporting and coding problems we detected. These suicides numbered among the 589 cases that met the regular QuarterWatch criteria. This group also included 102 possible cases of hostility/aggression, 156 cases of depression, and 56 cases of possible psychosis. (A case could be classified into more than one of these categories.) In addition, the manufacturer submitted in July 2010 more than 26,000 additional varenicline adverse event cases that did not meet the standing QuarterWatch criteria for serious, domestic adverse events. While we have not fully analyzed this larger group of 26,000 cases, a preliminary survey indicates this group includes numerous additional cases of psychiatric side effects that affect the safety profile of varenicline. Having discovered this large body of significant new safety information submitted in July 2010, we sought to learn how this had occurred.

Comments Sought

We communicated our preliminary findings to the manufacturer, Pfizer, and sought an explanation of these delayed case reports. As has been the case since 2008, Pfizer declined to respond to our questions about varenicline or any other of its products. In a minor policy change, Pfizer said that this time, it could not respond because QuarterWatch data or one of the QuarterWatch project team members might be involved in the future in legal cases involving the safety of varenicline. Previously Pfizer had not indicated why it chose not to respond to ISMP's offer to discuss its findings in advance.

In addition, we communicated our preliminary findings to the FDA. The agency provided a useful and detailed response that resolved some of our questions, but left others unanswered. Based on the information available, a review of the FDA's adverse event reporting regulation and other industry guidance, here is our understanding of what went wrong.

What Went Wrong

Since 1998 the FDA's primary tool for postmarket safety surveillance has been its computer database called the Adverse Event Reporting System (AERS) into which hundreds of thousands of case reports flow each year. Safety analysts at the FDA search this data base routinely to identify reports that might signal a safety issue for additional study. For new, serious adverse events (called expedited reports) the manufacturer is required to report within 15 days, and today most submissions are electronic and flow automatically into the agency safety database. For the less important non-serious events and a few serious adverse effects that are well-characterized, the updates take place on a quarterly basis and are called Periodic Reports. However, the 26,000 cases described above had not been previously submitted to this key safety data system as the FDA expected.

In addition, the FDA requires manufacturers to submit a text report and analysis on a quarterly basis for the less important periodic cases. Listings of the 26,000 case reports were included in these quarterly text documents, the FDA said. Until 2010, the FDA said, it had not been fully aware that some manufacturers were not submitting the case reports into both systems. The agency also said the problem was not limited to varenicline or to Pfizer alone.

Unanswered Questions

We still do not understand why Pfizer grouped hundreds of cases of suicide, suicide attempt, and psychosis among more than 26,000 mostly non-serious adverse events submitted in an inaccessible text report format—especially prior to July 2009 while these safety issues were being actively evaluated by the FDA. To classify a suicide or suicide attempt as an “expected adverse event” rather than submitting it promptly as a 15-day report where it would have been immediately available is troubling in our view. Additional questions arise about how Pfizer coded hundreds of reports of depression and suicidal ideation. When the FDA surveillance system did not include more than half the reported suicide deaths in which varenicline was primary suspect drug, it is a safety lapse that warrants careful investigation.

FDA Warning Letter Sent

In addition, the agency has raised other concerns found in an inspection of Pfizer’s adverse event reporting program. The FDA’s Inspections, Compliance, Enforcement and Criminal Investigations unit sent Pfizer a six-page warning letter on May 26, 2010 indicating the agency had found deficiencies in the company’s adverse event reporting program dating back to 2004. [26] Among the violations the FDA alleged had occurred were failure to submit serious adverse event reports for cases already in company files until identified by an inspector, misclassifying and downgrading events without reasonable justification, and failing to submit expedited reports within 15 days as required. The agency also alleged Pfizer had failed to keep prior commitments to improve training and performance for adverse event reporting. The specific cases cited as examples in the letter did not include varenicline but applied broadly to Pfizer’s safety surveillance program.


Link to free full-text copy of Institute for Safe Medicine Practices May 19, 2011 report

© 2011 Institute for Safe Medication Practices. All rights reserved
Last edited by JohnPolito on 19 May 2011, 15:39, edited 1 time in total.
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JohnPolito
Joined: 11 Nov 2008, 19:22

19 May 2011, 16:14 #14

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JohnPolito
Joined: 11 Nov 2008, 19:22

27 May 2011, 23:52 #15

Smoking-pill suicides
overlooked in missing reports
Drugmaker sent data to FDA through 'improper channels'
By JoNel AlecciaHealth writer - MSNBC.com  -  updated 5/27/2011 8:34:38 AM ET
Hundreds of reports of suicides, psychotic reactions and other serious problems tied to the popular stop-smoking drug Chantix were left out of a crucial government safety review because Pfizer Inc., the drug's manufacturer, submitted years of data through "improper channels."

Some 150 suicides — more than doubling those previously known — were among 589
delayed reports of severe issues turned up in a new analysis by the non-profit Institute for Safe Medication Practices.

"We've had a major breakdown in safety surveillance," said Thomas J. Moore, the ISMP senior scientist who analyzed the data. The serious problems — including reports of completed suicides, suicide attempts, aggression and hostility and depression — had been mixed among some 26,000 records of non-serious side effects such as nausea and rashes, with some dating back to 2006, the year Chantix, or varenicline, was approved.

They echo previous claims that the drug can induce extreme reactions in people trying to quit cigarettes, including vivid nightmares, crippling depression and sudden, violent outbursts.

"It's really chilling," said Moore, who analyzed 26 Chantix reactions in a paper published in the September 2010 issue of the Journal of Pharmacotherapy. "This seems to unleash something in people. It can be violence to anything around."

Moore's case studies describe "inexplicable and unprovoked" reactions in Chantix patients with no previous history of violence or mental illness, including:

A 24-year-old woman who started beating her boyfriend in bed because "he
looked so peaceful" and later attempted suicide;

A 42-year-old man who punched a stranger at a bowling alley;

A 47-year-old woman who died after she came out of a room, yelled at her
daughters and then shot herself.

Federal Food and Drug Administration officials acknowledged that they asked Pfizer to resubmit thousands of records after realizing that the company was sending required reports in an inappropriate format that could not be added to the agency's Adverse Events Reporting System, or AERS.

"Last year, FDA became aware that a few manufacturers were submitting adverse
events reports to FDA through improper channels," the agency said in a statement.

Pfizer officials said they were submitting reports as required and that when the FDA asked them to change, they did so immediately. They said there's no proof that Chantix causes suicide or other serious side effects.

Moore, who has served as an expert witness in court regarding Chantix, said it's the riskiest drug among those analyzed from the FDA's adverse event reports. In the third quarter of 2010, it ranked first in reported deaths, with twice as many fatalities logged as any other drug, he said.

New reports don't change FDA's position.

FDA officials said the new reports did not change the agency's position on the risks and benefits of the controversial drug, which received a black box warning that included suicide — the strongest caution possible — in 2009, according to agency officials who would not speak on the record.

"At this point, based on the data, FDA does not have any new safety concerns with Chantix, though those that have been established remain under active review,” the agency said in a statement posted in response to the ISMP report.

Agency officials said they're continuing to review Chantix in clinical trials and two large observational studies with the Veterans Administration and the Department of Defense.

But Moore said the new data should raise immediate alarms about the drug that was prescribed 3.2 million times last year to people trying to stop smoking — and 1.1 million times already this year, according to data from the firm Wolters Kluwer Pharma Solutions.

"To us, it raises questions about whether this drug is safe for widespread clinical use," Moore said. "Does this tip the balance?"

That's a view echoed by families of people who allegedly became suddenly and inexplicably violent after taking Chantix. Sean M. Wain, 34, of Beaver County, Pa., shot himself and his wife, Natalie, 33, in May 2009 in what a lawyer
for their families claims was a Chantix-fueled rage.

If the FDA had more information about suicides and other side effects tied to Chantix, the agency might have taken stronger action sooner, said Victor H. Prebanic, who represents Robert Erdelen and George Wain, fathers of the slain couple.

"If Pfizer had been more forthcoming, the black box warning might have emerged
earlier," Prebanic said. "For all we know, the drug would not have been available."

The lawsuit, filed this month, is the latest among hundreds of claims filed against Pfizer regarding Chantix. At least 1,545 injury claims that cite Chantix are pending in federal court.

Pfizer officials, however, said that the firm was following the FDA's rules and changed their reporting process once the agency asked for clarification.

"All post-marketing reports of adverse events are reviewed by Pfizer and reported to regulators, including FDA, in accordance with regulatory guidelines," the company said in a statement. "Pfizer takes patient safety and
regulatory reporting obligations very seriously."

Suicide is an 'expected' event?

The problem appears to have been caused in
part by federal Food and Drug Administration rules that don’t require firms to submit new reports of death or serious harm in the agency's system for urgent review when such risks are already known.

FDA requires drugmakers to submit adverse events in two ways: There's an "expedited" system that requires companies to report serious and unexpected adverse events into the AERS system within 15 days.

Companies are also required to submit less-serious and expected adverse events quarterly in so-called "periodic reports." In those cases, problems previously included on drug labels — including suicide and suicide attempts — are considered to be expected events.

In Pfizer's case, the firm was submitting the periodic reports as required, but combining summaries and individual case reports in a single text file, the FDA said.

That meant that the individual reports of injury were not logged in the FDA's AERS system, drastically reducing known reports of suicides and other psychiatric problems tied to Chantix, Moore said.

"It's very clear the suicide risk of this drug was higher than we knew," he said.

Overall, there were 1,055 reports of serious problems with Chantix reported in the third quarter of 2010, more than any other prescription medication regularly monitored  by the drug safety agency, Moore said.

Before last July, the FDA had logged 122 reports of suicides linked to Chantix, including 37 reported by Pfizer and 85 reported by health professionals or consumers, Moore reported. After the 150 new Pfizer reports were added, the total jumped to 272.

In addition, the 589 new reports of severe problems included 102 cases of possible hostility and aggression, 156 cases of depression and 56 cases of possible psychosis. Those were mixed among the 26,000 reports of less-serious problems.

Moore has asked the FDA to investigate the 150 new suicide reports, particularly if the events occurred before the 2009 black box warning listed suicide as a possible side effect.

For their part, FDA officials said they are considering changing regulations to allow expedited reports of suicides and other serious problems, even if they've previously been identified as expected. First proposed in 2003, that change is still pending.
Copyright © 2011 msnbc.com

Online MSN story source link
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JohnPolito
Joined: 11 Nov 2008, 19:22

07 Jul 2011, 16:03 #16

Varenicline Cardiovascular Risk?
Thanks to all who wrote making me aware of the Canadian Medical Association Journal (CMAJ) study suggesting existence of varenicline (Champix / Chantix) cardiovascular risks, especially Kathleen Craig. A free full-text PDF copy of the study entitled "Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis" by Sonal Singh and others can be found at this CMAJ link.  But before spending time reading it you need to be aware tht the magnitude of any cardiovascular risks associated with varenicline use is being challenged via CMAJ online "Responses" suggesting that the authors have significantly overestimated risk of serious cardiovascular events if they used the figures presented in their paper.

Regardless of the outcome of the debate over the actual odds of cardiovascular risk, I submitted my own CMAJ response (below), pointing out how, to this day, physicians are unable to engage in meaningful varenicline risk benefit analysis or adequately advise patients, because as of yet there have been no studies evaluating varenciline's worth as a stand-alone aid, unaccompanied by counseling or support, the manner used by most quitters.  

In my mind, it makes no sense to toy with risk of serious injury or death without any idea as to the likelihood of long-term success after doing so.

In looking at my below comments please, be sure to note my Conflict of Interest disclosure statement at the bottom.   Still just one guiding principle making sure that quitting method concerns never again need be our concern ....  no nicotine just one day at a time,  Never Take Another Puff, Dip or Chew!

Breathe deep, hug hard, live long,

John - Gold x12   

  




Varenicline's missing risk-benefit analysis   While Singh and colleagues add risk of serious adverse cardiovascular events to an already frightening drug risk profile, how can physicians engage in meaningful risk-benefit analysis when varenicline has yet to be studied as a stand-alone quitting aid, unaccompanied by formal counseling and support? According to the June 2000 U.S. Clinical Practice Guideline, the number of clinical trial counseling/support contacts and total contact time could account for nearly all successful cessation


While Singh and colleagues add risk of serious adverse cardiovascular events to an already frightening drug risk profile, how can physicians engage in meaningful risk-benefit analysis when varenicline has yet to be studied as a stand-alone quitting aid, unaccompanied by formal counseling and support? According to the June 2000 U.S. Clinical Practice Guideline, the number of clinical trial counseling/support contacts and total contact time could account for nearly all successful cessation among varenicline users in all trials to date.[1]

The just released Hughes varenicline study is the closest yet to replicating real-world conditions.[2] There, success rates declined to just 14 percent at 24 weeks among a population of moderately motivated smokers who wanted to quit, but when asked, had no plans within the next 30 days. That's roughly a 200 percent decline over six-month varenicline rates seen in Pfizer's phase III FDA drug approval studies.[3]

Those 2006 studies provided participants up to nineteen counseling/support sessions by week 24.[3] In contrast, the Hughes et al study provided only eight: four counseling sessions and four follow-up data seeking telephone calls.[2] But still, varenicline is vastly superior to products already on the market, correct?
The Aubin 2008 Thorax study found that when analyzed using 7-day point prevalence rates, varenicline failed to show statistically significant benefit over nicotine patch, reporting "no significant differences at week 24 ... or at week 52," despite varenicline having been used two weeks longer than the patch.[4]

Here in the U.S., according to the latest report of Food & Drug Administration (FDA) adverse event watchdog Institute for Safe Medication Practices (ISMP), varenicline ranks first in reported deaths, more than twice as many as any other drug regularly monitored.[5] According to the report, there were "1055 serious adverse drug events meeting QuarterWatch criteria for the third quarter of 2010," and varenicline accounted for "more possible cases than any other drug for suicidal/self-injurious behavior, depression, psychosis, hostility/aggression, and convulsions."[5]

An email yesterday from ISMP's senior scientist states that the total number of U.S. varenicline adverse event cases reported to the FDA through the 3rd quarter of 2010 stands at 36,342, including "272 cases of completed suicide, 323 cases of suicide attempt and 63 cases described as suicidal behavior."[6]

What percentage of Canadian varenicline users use it in a stand-alone manner? I submit that far more are doing so than not. If so, prior to a decision accepting varenicline's risks, should patients be told varenicline's long-term cessation rate when unaccompanied by counseling or support? In that varenicline's stand-alone worth is still unknown, how can patient informed consent, as yet, be meaningful?

John R. Polito
Nicotine Cessation Educator

[1] USDHHS, Clinical Practice Guideline, Treating Tobacco Use and Dependence, June 2000, Tables 13 and 14 - Link to Full-Text PDF.

[2] Hughes JR, Rennard SI, Fingar JR, Talbot SK, Callas PW, Fagerstrom KO, Efficacy of Varenicline to Prompt Quit Attempts in Smokers Not Currently Trying to Quit: A Randomized Placebo-Controlled Trial, Nicotine Tob Res. 2011 Jun 7 [Epub ahead of print] - PubMed Abstract.

[3] Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR, Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial, JAMA. 2006 Jul 5;296(1):47-55, PubMedAbstract JAMA Free Full-Text; Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR, Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial, JAMA. 2006 Jul 5;296(1):56-63. Erratum in: JAMA. 2006 Sep 20;296(11):1355, PubMed Abstract, JAMA Free Full-Text.

[4] Aubin HJ, Bobak A, Britton JR, Oncken C, Billing CB Jr, Gong J, Williams KE, Reeves KR, Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial, Thorax. 2008 Aug;63(8):717-24. Epub 2008 Feb 8 - rel="nofollow" target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed/18263663">PubMed Abstract, PubMed Central Free Full-Text.

[5] Institute for Safe Medication Practices, New Signals for Liraglutide, Quetiapine and Varenicline, QuarterWatch 2010, Quarter 3, Monitoring MedWatch Reports, May 19, 2011, www.ismp.org/quarterwatch/2010Q3.pdf

[6] Thomas J. Moore, a July 6, 2011 email from [url=mailto:tmoore@ismp.org]tmoore@ismp.org[/url]  signed by Thomas J. Moore, Senior Scientist, Institute for Safe Medication Practices to John R. Polito sharing varenicline data from the QuarterWatch data base, a master file of all cases reported to the U.S. Food and Drug Administration, July 06, 2011.

Conflict of Interest: I am an advocate of abrupt nicotine cessation (cold turkey), the method that each year produces more successful Canadian ex-smokers than all other methods combined.






Copyright 1995-2011, Canadian Medical Association. All rights reserved

Online Source Link:  Beneath "Responses to this article" at the bottom of page:

http://www.cmaj.ca/content/early/2011/0 ... 8.abstract
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JohnPolito
Joined: 11 Nov 2008, 19:22

16 Aug 2011, 14:58 #17

Hospital Patient Smoking Cessation
24 week results - Placebo 31%, Chantix 23%
So why does varenicline (Chantix / Champix) routinely prevail over placebo inside clinical trials in which smokers seek out study participation,  yet below fail to prevail over placebo among a somewhat captive population of  hospitalized smokers/quitters?  Could it be that particpant medication expectations are significantly diminished when hospitalized?  Hopefully this study has researchers reflecting upon natural study biases introduced through study marketing and disclosures during informed consent.  With researchers needing to disclose so many Chantix/Champix potential adverse event risks, just maybe after hearing them the hospitalized particpant was just as happy to be assigned to receive an inert sugar placabo pill instead.  Image 

Still just one rule for each of us ... no nicotine today!

Breathe deep, hug hard, live long,

John - Gold x12



  Tobacco dependence treatment for hospitalized smokers: A randomized, controlled, pilot trial using varenicline.

Addictive Behaviors
2011 Jul 23. [Epub ahead of print]

Steinberg MB, Randall J, Greenhaus S, Schmelzer AC, Richardson DL, Carson JL.

Abstract OBJECTIVE: The hospital can be an important opportunity for smoking cessation interventions. This is the first randomized, double-blinded, placebo-controlled pilot trial utilizing varenicline and post-discharge, in-person behavioral treatment for hospitalized smokers.

METHOD: Seventy-nine smokers admitted to a university-based hospital with various diagnoses were enrolled from 2007 to 2009. The primary outcome was biochemically confirmed abstinence at 24weeks following discharge. Secondary outcomes included withdrawal symptoms, motivation, utilization of treatment, and medical events.

RESULTS: Overall abstinence at 24weeks was 27% with no difference between varenicline and placebo treatment groups (23% vs. 31%). There were no significant differences in motivation to stop smoking or withdrawal symptoms. Over 40% of all subjects utilized post-discharge behavioral treatment with significantly higher abstinence rates compared with those who did not (53.1% vs. 8.5%, p<0.01). Overall adverse events were similar in both treatment groups with the only significant difference being more nausea in the varenicline group (25% vs. 5%; p<0.01). Twenty-three subjects were re-hospitalized with no significant differences between treatment groups (13 varenicline vs. 10 placebo).

CONCLUSION: This pilot trial of varenicline in hospitalized smokers demonstrated feasibility of implementation, produced some hypothesis-generating findings, and suggested the potential benefit of face-to-face treatment following discharge.

Copyright © 2011 Elsevier Ltd. All rights reserved.


PMID:  21835552     [PubMed - as supplied by publisher]

PubMed Link:  http://www.ncbi.nlm.nih.gov/pubmed/21835552
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JohnPolito
Joined: 11 Nov 2008, 19:22

28 Nov 2011, 14:02 #18

The Wrong Way to Quit Smoking By Neil Wagner
A new study published in PLoS One found that 90 percent of the reported suicides of people taking anti-smoking drugs over the past 13 years involved the drug Chantix (varenicline)



It's not easy to quit smoking, and many who try turn to anti-smoking drugs for help. But some medications can do more harm than good.

Consider the drug Chantix (varenicline), marketed by Pfizer. Of the reported suicides of people taking anti-smoking drugs from 1998 through September 2010, more than 90 percent were taking varenicline. And the drug was on the market for only four of those years. Add in other safety concerns about varenicline, and you're left with an extremely poor choice for people who want to quit smoking.

That's the conclusion of a recently published study that looked at reports of adverse events since 1998 for the three major types of smoking cessation drugs: varenicline, the antidepressant bupropion, and nicotine replacement products such as gum and patches.

Varenicline and bupropion already carry a black box warning to doctors about possible suicide and depression. But there's been little information about how often each drug causes these side effects or comparisons between them of how frequently they do so. This study found that varenicline did so much more frequently than bupropion.

Varenicline has also been linked to aggression and violence in three studies and carries a warning about this. Its effects on vision, cognition, and motor control have led to its being banned for airline pilots, air traffic controllers, military pilots, and missile crews, and restricted for truck drivers.

Quitting smoking brings undeniable health benefits, but the risks associated with this drug suggest that other methods should be tried first. In the study authors' own words, Chantix or varenicline is "unsuitable for first-line use in smoking cessation."

Often, serious side effects of a drug don't become apparent until years after the drug is first marketed. The place they tend to show up first is the FDA's Adverse Event Reporting System (AERS).

In the current study, the researchers found 3,249 AERS reports of serious injurious behavior or depression from people taking the three types of smoking cessation drugs from 1998-2010. Fully 2,925 of these came from people taking varenicline (90 percent), compared to 229 for bupropion (seven percent) and 95 for nicotine replacement products (three percent). There were 295 successful suicides; 272 of these were in varenicline users (92 percent), 19 in bupoprion users (six percent) and four in nicotine replacement drug users (one percent). Results were similar for attempted suicide.

Using a statistical method called disproportionality analysis, the researchers calculated that varenicline was 8.4 times as likely as nicotine replacement products and 2.9 times as likely as bupropion to lead to suicidal behavior or depression.

Disproportionality analysis isn't powerful enough to give a reliable estimate of how frequently a drug causes a particular side effect like suicidal behavior or depression from this small number of cases. But it is an accepted way of measuring whether a drug is causing a higher than normal amount of a particular side effect and of comparing the ability of two different drugs to cause a side effect. Here, it's showing that varenicline seems by far to be the most dangerous of the three anti-smoking treatments.

The researchers speculate that the actual incidence of depression or suicidal behavior from varenicline could be anywhere from around a tenth of a percent to over one percent. It would take information from a much larger number of users to fine tune this estimate.

The study seems to contradict a recent review by the FDA that found no difference in psychiatric hospitalizations between varenicline and nicotine replacement patches. But the study authors explain that this is probably because suicide, depression, and other serious psychiatric side effects often don't result in hospitalization.

For people who are taking varenicline, some signs that it's affecting your behavior are thoughts about suicide or dying, new or worse depression, anxiety, panic attacks, feeling very agitated or restless, acting aggressively, or being angry or violent. A more complete list can be found in the Chantix Medication Guide.

"Suicidal Behavior and Depression in Smoking Cessation Treatments" was published by PLoS One on November 2, 2011, and is freely available.

Image: zuender/Shutterstock.

This article originally appeared on TheDoctorWillSeeYouNow.com, an Atlantic partner site.

This article available online at:

http://www.theatlantic.com/life/archive ... ng/248916/



Copyright © 2011 by The Atlantic Monthly Group. All Rights Reserved.
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JohnPolito
Joined: 11 Nov 2008, 19:22

27 Jun 2012, 02:06 #19

We now have two clinical trial efficacy findings and the following population level effectiveness finding documenting that varenicline is no more effective than NRT, when all population level findings since 2000 indicate that long-term NRT use is no more effective than quitting without it.   So the question becomes, why is this important decision making information not being shared with smokers when varenicline use risk concerns are so great?
Effectiveness of varenicline for smoking cessation at 2 urban academic health centers.

European Journal of Internal Medicine, July 2012, Volume 23(5), Pages 461-464. Epub 2012 May 3.

Dhelaria RK, Friderici J, Wu K, Gupta E, Khan C, Rothberg MB.

Source:  Division of General Medicine, Baystate Medical Center, Springfield, MA, United States; Tufts University School of Medicine, Boston, MA, United States.

Abstract

BACKGROUND:

Smoking is a major cause of morbidity in lower socioeconomic groups. In randomized trials, varenicline improves long term quit rates, but effectiveness in a clinic setting is unknown.

METHODS:

We conducted a retrospective cohort study of adults who received a prescription for varenicline or nicotine replacement therapy (NRT) at two inner city health centers in 2008-9. Primary outcome was smoking status at 52weeks. Secondary outcomes included follow up visits, behavioral counseling, and side effects. Multivariable Poisson regression was used to compare quit rates with varenicline and NRT adjusted for covariates.

KEY RESULTS:

A total of 371 patients received a prescription for varenicline (46%) or NRT (54%). The mean age was 43years, 58% were female, 44% white, 29% African American and 12% Hispanic. Mental illness, alcohol and drug abuse were common. Within one year, 247 (67%) had follow-up, and 26 (10.5%) maintained abstinence through week 52, 10.2% with varenicline and 10.8% with NRT (p=1.0). Loss to follow-up was 37% for varenicline, 31% for NRT (p=0.20). Including lost patients as smokers, the adjusted quit rates for varenicline and NRT were similar (6.5% vs. 7.6%, p=0.69). Only 69/371 (19%) received behavioral counseling. Counseled patients were more likely to maintain abstinence (13% vs. 7.8%, p=0.04). Side effects were more common with varenicline than NRT (6.5% vs. 2.5%, p=0.07).

CONCLUSION:

In an inner city clinic, abstinence rates were lower than those in clinical trials and did not differ between varenicline and NRT.

Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

PMID: 22726377 [PubMed - in process]

PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/22726377
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