Chantix: 3,063 serious injuries, 78 deaths?

John (Gold)
John (Gold)

May 22nd, 2008, 9:08 am #1

Strong Safety Signal Seen
for New Varenicline Risks
May 21, 2008
EXECUTIVE SUMMARY

A strong signal of multiple safety problems with Chantix (varenicline), a drug to help people stop smoking, has been seen in a pilot program to identify new drug risks in adverse drug events reported to the U.S. Food and Drug Administration.
Varenicline is suspected in various adverse drug event reports of causing a wide spectrum of injuries, including serious accidents and falls, potentially lethal cardiac rhythm disturbances, severe skin reactions, acute myocardial infarction, seizures, diabetes, psychosis, aggression and suicide. The cases were analyzed and classified using computerized excerpts of adverse event reports which the FDA publishes for research use.

The FDA approved varenicline in May 2006 after granting it a priority review. Varenicline is a partial agonist of one of the nicotinic acetylcholine receptors in the brain and nervous system,1 and currently the only marketed and approved drug with this mechanism of action.

In the 4th quarter of 2007 varenicline accounted for 988 serious injuries in the U.S. reported to the FDA, more than any other individual drug in this time period. By comparison the FDA received a median of 5 reports of serious injury for 769 different drugs in the 4th quarter. Only 35 drugs accounted for 100 or more reports. This large volume of reports prompted us to conduct an analysis of all adverse events for varenicline since marketing approval in 2006.

The FDA has recently issued a Public Health Advisory about one of the most marked adverse effects of varenicline, psychiatric symptoms that included "changes in behavior, agitation, suicidal ideation, attempted and completed suicide." 2 However, the FDA alert provided no information about the numbers of reported neuropsychiatric events among treated smokers.

From May 2006 through December 2007, the FDA had received 227 domestic reports of suicidal acts, thoughts or behaviors, 397 cases of possible psychosis and 525 reports of hostility or aggression. These totals included 28 cases of suicide and 41 mentions of homicidal ideation, 60 cases of paranoia and 55 cases of hallucination. The categories were not mutually exclusive.

However, the adverse drug event reports for varenicline describe other kinds of serious harm for which no warnings now exist, either from the FDA or from the manufacturer, Pfizer Inc. The cases (including those with psychiatric effects) were classified using standardized medical queries developed by the pharmaceutical industry to identify potential adverse events in clinical studies and postmarket surveillance. Adverse event reports in themselves do not establish a causal link to the drug, only that an observer suspected a relationship. Depending on the features of the specific event, it could be counted in multiple categories, and classifications are not definitive. Among the most prominent were:
  • Accidents and injuries. A total of 173 serious events described accidental injury, including 28 road traffic accidents and 77 falls, some leading to fractures of rib, facial bones, hand, ankle, spine, and lower limbs. In these cases a variety of potential causes were identified, including loss of consciousness, mental confusion, dizziness and muscle spasms.
  • Vision disturbance. At least 148 reports contained medical terms indicating vision disturbances, including 68 cases described as blurred vision and 26 terms indicating transient or other forms of blindness. This reported effect could also describe a mechanism that could or did contribute to accidents and injuries.
  • Heart rhythm disturbances. The FDA received 224 domestic reports classified as potential cardiac rhythm disturbances. This category, however, was dominated by reports of sudden loss of consciousness, an event that could also have non-cardiac causes. However, this category also included smaller numbers of cardiac arrests and identifiable abnormal cardiac rhythms
  • Seizures and abnormal muscle spasms or movements. Serious reported events included 86 cases of convulsions (seizures), 372 reports of a wide variety of movement disorders, including tremors, muscle spasms, twitching, tics, drooling, and motor hyperactivity. The extent to which these problems resolved with a reduced dose or by halting treatment could not be determined from these data.
  • Moderate and severe skin reactions. Reported serious events included 338 cases of hives or swelling of the tongue, face, eyes, lips or other areas. In addition, 65 cases were classified as severe and included blisters, exfoliation of the skin and lips, and Stevens-Johnson Syndrome.
  • Diabetes. The FDA has received 544 reports suggesting varenicline may be related to a loss of glycemic control. This category included many cases of weight loss or gain that could have alternative causes, but also identified numerous cases of symptoms and laboratory tests consistent with new onset diabetes.
Recommendations

We have immediate safety concerns about the use of varenicline among persons operating aircraft, trains, buses and other vehicles, or in other settings where a lapse in alertness or motor control could lead to massive, serious injury. Other examples include persons operating nuclear power reactors, high-rise construction cranes or life-sustaining medical devices. Based on reports of sudden loss of consciousness, seizures, muscle spasms, vision disturbances, hallucinations, paranoia and psychosis, we believe varenicline may not be safe to use in these settings. The extent to which varenicline has already contributed to accidental death and injury has not yet been investigated because these adverse effects had not been previously reported. The Federal Aviation Administration approved varenicline for use by airline pilots3 before most of these reports were available.

In addition, we recommend that patients and doctors exercise caution in the use of varenicline and consider the use of alternative approaches to smoking cessation.
Finally, we urge the FDA and the manufacturer to provide warnings to doctors and patients for those adverse effects that can be adequately documented through existing data, and to undertake on a priority basis epidemiological studies or other research to assess other potential risks. We promptly notified the FDA of our findings.

This report was written by:

Thomas J. Moore, Senior Scientist, Drug Safety and Policy, ISMP
Michael R. Cohen RPh, MS, ScD, President, ISMP
Curt D. Furberg, MD, PhD, Professor of Public Health Sciences, Wake Forest University School of Medicine.

Institute for Safe Medication Practices
200 Lakeside Drive, Suite 200
Horsham, PA 19044
215-947-7797
www.ismp.org

Corresponding Author
Thomas J. Moore
[url=mailto:tmoore@ismp.org]tmoore@ismp.org[/url]


Full report available at the above link
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John (Gold)
John (Gold)

May 22nd, 2008, 9:09 am #2

Chantix blamed for 3,063
serious injuries and 78 deaths
May 21, 2008[/size]
A study released today examined 6,363 U.S. Food and Drug Administration (FDA) adverse drug reaction reports implicating Pfizer's quit smoking pill Chantix (varenicline) and found that 3,063 involved serious injuries. Its recommendation? "We recommend that patients and doctors exercise caution in the use of varenicline and consider the use of alternative approaches to smoking cessation."

Authored by The Institute for Safe Medication Practices (ISMP), a non-profit medication watchdog, ISMP looks for safety flags while monitoring all adverse events reported to the FDA for all medications.

ISMP monitoring noted that "by the 3rd quarter of 2007 varenicline produced a signal not previously seen for any other drug. It produced more serious reports than any other drug for multiple types of events: more potential cases of angioedema, cardiac arrhythmia, diabetes and severe cutaneous injury. By the 4th quarter of 2007 varenicline accounted for more reports of serious drug adverse events in the United States than any other drug."

During the 4th quarter of 2007 the FDA received 998 reports of serious varenicline adverse events compared to only 372 for the addictive troublemaker oxycodone, a potent medication for relief of moderate to severe pain. While ISMP estimates that a total of 3.5 million Chantix (varenicline) prescriptions were written in the U.S. since FDA approval in May 2006, government estimates place annual oxycodone prescriptions written at more than 7 million.

The study found that while the FDA has issued warnings regarding Chantix's link to suicidal acts, thoughts or behaviors, psychosis, hostility and aggression, it has ignored "other kinds of serious harm for which no warnings now exist, either from the FDA or from the manufacturer, Pfizer Inc."

While the FDA received 78 death reports in which "varenicline was the principal suspect drug," only 28 resulted from suicide. There were "numerous reports suggesting cardiac causes, both thromboembolic and arrhythmic," writes ISMP.

Among reports of serious events were 173 accidents and injuries, 338 angioedemas, 224 cardiac arrhythmias, 86 convulsions, 139 embolic and thrombotic events, 372 extrapyramidal syndromes, 544 cases of hyperglycemia/new onset diabetes mellitus, 525 reports of hostility/aggression, 397 psychosis and psychotic disorders, 227 reports of suicide/self-injury, 65 severe cutaneous adverse reactions, and 148 vision disturbances.

Could there possibly be a common thread among such a diverse group of disorders? Yes, says the ISMP study. A subtype of acetylcholine receptor known as alpha 4 beta 2 plays "numerous roles in the brain and body and is central to muscle contractions -- both voluntary movement and heart muscle contractions, as well as the tone of the smooth muscles that line the blood vessels."

According to the study, Pfizer researchers found that varenicline was most active against alpha 4 beta 2 type acetylcholine receptors. They focused on the fact that it caused the release of dopamine within the brain while blocking nicotine from occupying alpha 4 beta 2 receptors. It notes that "many antipsychotic drugs block dopamine receptors, but they also cause movement disorders. The loss of muscle control seen in Parkinson's disease is the result of the destruction of dopamine-producing cells in the brain."

The gravity and number of serious injuries attributed to Chantix caused the report to lightly touch on an equally pressing risk analysis concern, the value of Chantix in helping smokers quit. While noting that counseling rich varenicline clinical trials produced 52-week quit rates of approximately 22 percent, it cites two early nicotine gum studies while noting that they achieved comparable rates.

In fact, a 1976 nicotine gum study headed by Russell found that 23% of nicotine gum users were still not smoking at 1 year. The 1980 nicotine gum study by Raw produced a whopping 38% rate, in 1982 Jarvis found a 31% rate, in 1983 Schneider 30%, in 1984 Hialmarson 29%, in 1986 Daughton 31%, in 1987 Kornitzer 32%, and in 1989 Tonnesen boasted a 44% one year quit smoking rate.

What wasn't mentioned in the ISMP study was that in real-world competition, outside of clinical trials that were rich in support and counseling, nearly all quitting method surveys to date show that, long-term, cold turkey quitters actually perform better than users of nicotine gum, patch, lozenge and Zyban.

A 2006 National Cancer Institute quitting method survey of 8,200 smokers found that at 9 months 16% of "on your own" quitters were still not smoking compared to just 14% among quitters relying upon the nicotine patch, gum, lozenge or Zyban.

While ISMP faults the FDA for neglect in warning Chantix users about risks other than mental and emotional, just as culpable is its approval of Pfizer's clinical trial design when: (1) they involved a record number of provider counseling/support contacts (twenty-five), contacts the FDA knows could account for nearly all effectiveness seen; (2) no assessments to test study blinding was requested or conducted, when the FDA knows that it is probably impossible to blind drug addiction studies, as smokers with any quitting history recognize the onset of full-blown nicotine withdrawal; (3) excluded 28% of study applicants, including nearly all having any significant medical condition, and then permitted Pfizer to market Chantix to groups intentionally excluded; and (4) allowed NRT use between the end of treatment and week 52, and then certified ongoing NRT users as having been successful Chantix quitters.

If Pfizer knows, via real-world quitting data gathered through its www.GetQuit.com website, that Chantix's real-world effectiveness is substantially less than shown in clinical trials, with Chantix injuries so numerous and serious, does Pfizer have both legal and ethical duties to immediately share that data with both the FDA and smokers considering using Chantix?

If Chantix isn't living up to Pfizer marketing hype, do reports like this ISMP study obligate Pfizer to be more forthright, honest and clear about both varenicline's safety and effectiveness?

"These data provide a strong signal that the risks of varenicline treatment have been underestimated, and show that a wide spectrum of serious injuries are being reported in large numbers," ISMP warns.

"Table 1 shows that in the 4th quarter of 2007, the other highest ranked drugs (e.g. fentanyl, interferon beta, etanercept) are all high alert drugs with black box warnings, are intended for serious illness in patients and have benefits that are accompanied by substantial risks. In comparison, varenicline is intended for use in healthy people to help stop smoking."

Does it make sense, if inside a very slow burning building, to pay money for the right to use the most dangerous exist path out?

Never in the history of smoking cessation has any quitting product harmed so many. It makes one wonder whether instead of helping smokers the FDA and Pfizer have declared war upon them.
XXX
No Copyright - This Article is Public Domain
John R. Polito is solely responsible for the content of this article.
Any factual error will be immediately corrected upon receipt of credible authority
in support of the writer's contention. E-mail comments to [url=mailto:john@whyquit.com]john@whyquit.com[/url]
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John (Gold)
John (Gold)

May 22nd, 2008, 9:15 am #3

Pfizer's Chantix Going Up In Smoke

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Gump19690
Gump19690

May 22nd, 2008, 9:17 am #4

I for one don't want my pilot on chantix. Just too much at stake. Think about it.
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suechef2
suechef2

May 22nd, 2008, 11:38 am #5

Holy moly. My husband gets a big hug when he gets back - I was very close to calling my doctor about getting on this stuff since we had met some people who were happy with their experience. I decided not to because I noted that it could cause some psychological issues (and I have history there), plus my sweetie really laid it out for me - "You just have to quit everything". He was so right.

(and yeah, now I wonder about double-checking with the pilot!).
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John (Gold)
John (Gold)

May 22nd, 2008, 6:50 pm #6

May 22, 2008 - New York Times
F.A.A. Bans Antismoking Drug, Citing Side Effects By STEPHANIE SAUL
The Federal Aviation Administration said Wednesday it would no longer permit pilots or air traffic controllers to use the smoking cessation drug Chantix, citing potential side effects that could pose a threat to the safe operation of aircraft.

The Food and Drug Administration issued a public health advisory in February, saying that some Chantix users had developed a variety of serious psychiatric symptoms, and that some had committed suicide.

An F.A.A. spokeswoman, Laura Brown, said the agency had approved the use of Chantix for airline pilots and flight controllers last year, but was notifying 150 pilots and 30 air traffic controllers known to be using it that the drug was no longer acceptable and should be discontinued.

Ms. Brown said the decision was based on emerging data on the drug, including a report from a watchdog group, the Institute for Safe Medication Practices, linking Chantix to a wide array of health and safety problems. They include accidents and falls, potentially lethal heart rhythm disturbances, heart attacks, seizures, diabetes and various psychiatric disturbances.

The institute's findings, which were based on an analysis of adverse events reported to the F.D.A., said that from May 2006 through December 2007, there were 227 reports of suicide attempts or suicides, 397 cases of possible psychosis and 525 reports of hostility or aggression. Those reports included 28 suicides and 41 mentions of homicidal thoughts, 60 cases of paranoia and 55 cases of hallucinations.

The data, the report said, "provide a strong signal" that the risks of treatment with varenicline, the active chemical in Chantix, have been underestimated. This year, Public Citizen's Health Research Group, another consumer watchdog organization, had called for a black-box warning - F.D.A.'s strongest drug alert - on Chantix.

Chantix, made by Pfizer, was approved in 2006 for sale in this country and the European Union. Worldwide sales of the drug were $883 million last year, and an estimated 6.5 million people have used it.

Pfizer issued a statement Wednesday saying that the current labeling for Chantix reflected the product's safety profile, including warnings that it had the potential to cause psychiatric problems and might impair driving.

"There are few things that provide greater health benefits than quitting smoking," said the Pfizer statement, issued by a company spokesman, Francisco Gebauer. "When considering the use of Chantix for their patients, health care providers should discuss the risks of smoking, the health benefits of quitting smoking, and the product's efficacy and safety profile."

In after-hours trading Wednesday, Pfizer's shares fell 22 cents, to $19.79, a 1.1 percent decline.

Dr. Timothy Anderson, a pharmaceutical analyst for Sanford C. Bernstein & Company, responded to Wednesday's report by downgrading estimates for Chantix sales in 2012, to $700 million, from $1.6 billion.

Chantix, taken in pill form, partly blocks and partly stimulates a nicotine receptor in the brain and in clinical studies was shown to help smokers quit. Potential problems associated with Chantix were first publicized last September when a Dallas musician, Jeffrey Carter Albrecht, was shot to death after he began behaving bizarrely while taking Chantix.

The Institute for Safe Medication Practices study noted that some of the reports of adverse events it analyzed could have been spurred by that publicity and by a November 2007 early warning about the drug from the F.D.A.

An F.D.A. spokeswoman, Susan Cruzan, said the agency was also conducting a special safety review of Chantix and was requiring pharmacists to distribute a medication guide to patients, warning of the potential side effects.

The F.A.A. was also planning to notify associations representing both commercial and private pilots that Chantix was no longer permitted, Ms. Brown said.

Online story source link
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VICKIGOLD2006
VICKIGOLD2006

May 23rd, 2008, 1:52 am #7

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Rochelle2422
Rochelle2422

May 23rd, 2008, 4:08 am #8

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Ilona
Ilona

May 23rd, 2008, 8:18 pm #9

Thanks for the update, John

Good for the FAA! They are protecting their employees, even if they are probably just trying to avoid a law suit due to the possibility of planes crashing when managed by people on Chantix...

This whole Chantix affair is scandalous. Even if the FDA will now distribute a "medication guide" that warns patients of the side effects of Chantix, the prescription itslef is construed by patients as a medical endorsement of the product...

Shame on the pharmacological industry.

ILona
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WavyDavy7
WavyDavy7

September 28th, 2008, 1:56 am #10

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John (Gold)
John (Gold)

September 28th, 2008, 9:49 pm #11

Freedom's No Debate Policy
We ask members to remain mindful that here inside Freedom our mission truly is single minded: nicotine cessation. Whether your family is into tobacco farming or you are an executive at a tobacco company or work for Pfizer or are a health care provider who has recommended Chantix or Champix, you are as welcome here as any. This forum cannot permit posts that attack or vilify any profession or occupation or that have potential to promote debate that could divide or weaken the forum's support efforts and damage its mission.

Chantix is once again being actively marketed by Pfizer here in the U.S. and it won't be long before it's back in the headlines. So far, 5 of 6 varenicline sales worldwide have been in the United States. I'm told that reports of serious adverse reactions continue to pour into the FDA. Product liability lawsuits are now being filed across the nation on behalf of hundreds of users who have committed or attempted suicide, or sustained other serious injury or death.

Over the next two years Pfizer will be compelled to produce risk-benefit documentation showing what it knew both in regard to risks and effectiveness and when it knew it. This is the first time ever that nationwide civil litigation has focused upon a cessation product. We can expect lots of finger-pointing and headlines.

We will continue to share risk and effectiveness news here at Freedom for the the benefit of visitors looking in who may be considering varenicline. We may even share judicial findings. What we will not do is share allegations and arguments that will be traded during litigation, or permit attack upon any lawful occupation. There are plenty of forums that invite such discussions. If our objective is operation of a forum where all who are dependent upon nicotine are made to feel comfortable being here then this cannot be one of them.

Our sincere thanks to all members for helping keep Freedom united, strong and focused upon the forum's mission, staying nicotine-free today.

Breathe deep, hug hard, live long,

John (Gold x9)
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John (Gold)
John (Gold)

September 28th, 2008, 9:52 pm #12

Freedom's No Debate Policy
We ask members to remain mindful that here inside Freedom our mission truly is single minded: nicotine cessation. Whether your family is into tobacco farming or you are an executive at a tobacco company or work for Pfizer or are a health care provider who has recommended Chantix or Champix, you are as welcome here as any. This forum cannot permit posts that attack or vilify any profession or occupation or that have potential to promote debate that could divide or weaken the forum's support efforts and damage its mission.

Chantix is once again being actively marketed by Pfizer here in the U.S. and it won't be long before it's back in the headlines. So far, 5 of 6 varenicline sales worldwide have been in the United States. I'm told that reports of serious adverse reactions continue to pour into the FDA. Product liability lawsuits are now being filed across the nation on behalf of hundreds of users who have committed or attempted suicide, or sustained other serious injury or death.

Over the next two years Pfizer will be compelled to produce risk-benefit documentation showing what it knew both in regard to risks and effectiveness and when it knew it. This is the first time ever that nationwide civil litigation has focused upon a cessation product. We can expect lots of finger-pointing and headlines.

We will continue to share risk and effectiveness news here at Freedom for the the benefit of visitors looking in who may be considering varenicline. We may even share judicial findings. What we will not do is share allegations and arguments that will be traded during litigation, or permit attack upon any lawful occupation. There are plenty of forums that invite such discussions. If our objective is operation of a forum where all who are dependent upon nicotine are made to feel comfortable being here then this cannot be one of them.

Our sincere thanks to all members for helping keep Freedom united, strong and focused upon the forum's mission, staying nicotine-free today.

Breathe deep, hug hard, live long,

John (Gold x9)


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John (Gold)
John (Gold)

October 23rd, 2008, 4:16 am #13

Pfizer's Chantix
Continues Killing Quitters
October 22, 2008[/size]
Marketed in the U.S. as Chantix and other nations as Champix, another bomb just fell on Pfizer's quit smoking pill varenicline. According to a just released report by The Institute for Safe Medication Practices (ISMP), a non-profit medication watchdog, "In the first quarter of 2008, varenicline accounted for more reports of serious injury than the 10 best selling brand name prescription drugs combined."

The report indicates that the U.S. Food and Drug Administration (FDA) received serious adverse event reports on 773 different drugs during the 1st quarter of 2008. Chantix topped the list. During that period there were 1,001 new reports of serious injuries among varenicline users, including 50 additional deaths. By comparison, varenicline users accounted for 998 serious injury reports and 78 deaths during the 4th quarter of 2007.

The ISMP report notes that there were only 17 reports of serious injury among all forms of nicotine replacement therapy combined (the nicotine patch, gum, lozenge, spray, and inhaler). This quitting method risk data, when combined with results from the only head-to-head study pitting varenicline against NRT, should allow FDA officials to engaged in informed risk-benefit analysis.

A Pfizer smoking cessation study published in February 2008 compared 10 weeks of nicotine patch use to 12 weeks of varenicline use. Even after Pfizer gifted varenicline a two-week treatment advantage, varenicline failed to prove superior in 7-day point prevalence findings. Participants were asked at both 6 months and 1 year whether or not they had smoked a cigarette in the past 7 days. Pfizer's researchers, which included four Pfizer employees, were forced to report that there "were no significant differences" between nicotine patch and Chantix smoking abstinence rates at either 6 months or a year.

According to the ISMP report, varenicline again recorded the highest number of suicide/self-harm events of any medication with 226. The combined total for the next two closest drugs reporting suicide attempts was 22% less (oxycodone with 89 reports and acetaminophen with 87).

The ISMP report asserts that broader warnings are needed. It encourages the FDA and Pfizer to add a prominent warning about accident risks to both the patient Medication Guide and prescribing information sheet for doctors, a warning similar to the new warnings about psychiatric side effects.

The ISMP report also flags additional kinds of side effects, including serious accidental injuries. It highlights traffic accidents and concerns that varenicline induced seizures, disturbances in vision, panic attacks or impaired judgment may be playing a role.

It encourages further investigation of possible varenicline links to diabetes, potentially life-threatening interruption of the heart rhythm, heart attacks, strokes, and moderate to severe allergic reactions.

The ISMP's May 2008 report raised concerns about potential alertness and motor control related accidents among transportation industry workers using varenicline. In response, the Federal Aviation Administration banned the use of Chantix by airline pilots, the Department of Transportation limited its use among truck drivers, and the Department of Defense prohibited its use by aircraft and missile crews.

This time the bomb dropped on varenicline may prove fatal. If varenicline is not more effective than NRT, while causing nearly 5,800% greater harm than NRT, then why is it sill on the market? If the FDA has difficulty answering this question, it may well be that our nation's medication system has far greater concerns than just varenicline.
XXX
No Copyright - This Article is Public Domain
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