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HERKES GİDER MERSİNE SAĞLIK BAKANLIĞI GİDER....... FDA PFIZER'İN CHAMPIX İTİRAZINI REDDETTİ

CHAMPIX (sigara bıraktırma ilacı) kullanan veya Champix'i kestikten kısa süre sonra çok ciddi nöropsikiyatrik yan etkilere sebep olmakta. Champix kullanan hastalar ajitasyon, saldırganlık, depresyon, davranış değişikliği, intihar düşüncesi, intihar davranışı olan hastaların derhal doktora müracaatı istenmekte. Etkinliği tartışmalı olan bu ilaç için FDA danışma kurulu ilacın faydalı olup olmadığına karar vermek için yeni bir toplantı yapacak.
Türkiyede ise Sağlık Bakanlığı bizlerden toplanan vergilerle bu ilaçı sigara içenlere bedave verme kararı aldı!!!.. Ölen ölür ve sigaradn temelli kurtulur!

FDA Panel: Chantix Boxed Warning Should Stay
Published: Oct 16, 2014

An FDA advisory committee voted overwhelmingly that the stop-smoking drug should continue to carry a boxed warning about the risk of severe neuropsychiatric events, with several panel members suggesting it should be strengthened.

Of the 18 voting members, 11 indicated that it should be retained pending the outcome of a prospective trial now underway, results of which are expected next year, and six said the language should be modified -- with all six saying it should be strengthened. Only one panelist voted to remove the boxed warning.

Varenicline's manufacturer, Pfizer, has asked the FDA for permission to remove a boxed warning about suicidality, behavior changes, and other psychiatric risks from the label, citing research suggesting no or minimal psychiatric risk directly attributable to the drug.

Members of the FDA's Psychopharmacology Drugs Advisory Committee and its Drug Safety and Risk Management panel met jointly on Thursday to review the matter.

Going into the meeting, FDA staff had recommended that the agency keep the boxed warning for now. Instead, they said, the agency should delay action until the prospective trial, which is designed specifically to gauge varenicline's psychiatric risks, is completed next year. But, they said, Pfizer has pressed for an early decision and so they allowed the company to make its case to the panel.

Varenicline was initially approved in 2006. The following year, regulators began to see signals in adverse-event reporting systems of increased suicidality -- thoughts, attempts, and completed suicides -- associated with the drug. Within 18 months of approval, more than 260 such events were reported to the FDA. Hundreds more cases of changes in cognition, mood, and behavior, including hostile and violent actions toward others, were reported as well.

One very high-profile case was that of musician Carter Albrecht, who reportedly went on a violent rampage in September 2007 after taking a varenicline dose and was shot to death by a neighbor who felt threatened.

Regular warnings were quickly added to the drug's label, but as additional events accumulated, the FDA required the following boxed warning in 2009:

WARNING: SERIOUS NEUROPSYCHIATRIC EVENTS

See full prescribing information for complete boxed warning.

Serious neuropsychiatric events have been reported in patients taking CHANTIX.

Advise patients and caregivers that the patient should stop taking CHANTIX and contact a healthcare provider immediately if agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior while taking CHANTIX or shortly after discontinuing CHANTIX.

Weigh the risks of CHANTIX against benefits of its use. CHANTIX has been demonstrated to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo. The health benefits of quitting smoking are immediate and substantial.

Efficacy Unquestioned

As the warning indicates, varenicline's efficacy in helping smokers to quit is not in dispute, at least for purposes of the upcoming advisory committee meeting. The question is whether the neuropsychiatric risks are severe enough to warrant the FDA's strongest form of warning, short of restricting a drug's commercial availability.

Pfizer now asserts that the risks are not that severe, on the basis of five observational studies that reported neuropsychiatric medical encounters, completed suicides, nonfatal self-harming events, and/or initiation of antidepressant treatment -- the latter a surrogate measure of new-onset depression.

"Currently available evidence do not support the existence of a causal relationship" between varenicline and serious neuropsychiatric events, Pfizer executive Christopher Wohlberg, MD, PhD, told the committee.

In 11 different analyses conducted in the five studies, which had participant counts totaling more than 80,000 (of whom about 25,000 were non-using controls), no increase in adverse neuropsychiatric event risk was seen. Two of the analyses showed significantly decreased risk in varenicline users.

Two meta-analyses of clinical trial data -- one covering five trials, the other 18 -- proffered by Pfizer also showed no increase in risk associated with varenicline.

Pfizer said the drug's label should still include a warning about possible neuropsychiatric events in the main warnings-and-precautions section and even suggested that it be stated in boldface type. But it argued that the boxed warning on the label's first page is now overkill.

Wohlberg told the panel that studies had confirmed that varenicline is "the single most effective smoking cessation aid" now available, and that the warning was unnecessarily inhibiting patient access. He said research had shown that boxed warnings do have "a significant impact" on prescribing.

Observational Data

FDA staff disagreed with Pfizer on most of these points (except the effect of boxed warnings). Agency officials cited a host of limitations in the observational data and meta-analyses as well as in Pfizer's interpretation of the adverse event reports.

The FDA's Celia Winchell, MD, told the panel that many of the symptoms patients reported were not easily captured in standard coding symptoms used in the attempts to analyze the data systematically. One especially common symptom, she said, was "feeling like a zombie" -- which "is not a diagnosis," she observed.

She also noted that some patients complained that they couldn't get out of bed, and that this was sometimes coded as a problem with social function.

Although Pfizer has contended that many such symptoms are actually related to smoking cessation, Winchell said this hypothesis is undermined by the following observations:

Some patients with symptoms hadn't stopped smoking
Many said they had quit several times before trying varenicline previously and had not experienced such effects
Challenge studies supported a drug effect
Varenicline's mechanism of action, targeting nicotinic receptors, could provoke a withdrawal syndrome independent of smoking cessation
Also, FDA's presentations indicated, some of the studies cited by Pfizer used bupropion, another smoking-cessation drug that also has psychiatric side effects, as the control. And, the studies involved relatively small numbers of neuropsychiatric events that limited their statistical power.

In addition, the FDA reviewers suggested that patients at relatively high risk for adverse events had probably been "channeled away" from varenicline.

Studies used in the meta-analyses also were faulted for not having collected data on psychiatric adverse events prospectively, and probably missed some such events because of the symptom coding problems and other factors.

"The determination of whether to remove a boxed warning is a decision for which there is limited precedent," the reviewers wrote in briefing documents given to the panel.

Boxed In

Eric Brodsky, MD, of the FDA's labeling section, said the agency does not have specific regulations or guidance on when to remove a boxed warning. Its general approach is to do so when the criteria for requiring one -- an unusually serious risk or identification of a patient subgroup likely to experience serious risks, which are themselves flexible and open to interpretation -- are no longer met in light of new information.

That has not happened often, he said, but he offered a recent example of a drug with a boxed warning taken off. That is rosiglitazone (Avandia), which had a warning of myocardial infarction risk added in 2007 and then removed earlier this year. In that case, the readjudication of adverse event data in the RECORD trial, which established that the drug actually did not have a substantial risk of causing MI, prompted the action, Brodsky said.

They noted as well that Pfizer was told earlier -- at the point that the prospective postmarketing study was requested -- that "observation studies would not be adequate to address this safety question."

The reviewers suggested that the data collected by Pfizer "could be included in the varenicline labeling."

Speakers during the open public portion -- who included Joe and Terry Graedon, hosts of the "People's Pharmacy" radio program -- urged the FDA to keep the boxed warning or even strengthen it.

When it came time for committee members to speak, nearly all said they agreed with the FDA staff, that the data submitted by Pfizer were too limited to justify weakening the warning language.

Five of the six members who voted to modify the boxed warning voiced objections to the last paragraph, which highlights the drug's effectiveness. These panelists said the language was too promotional. Several also told the FDA that additional specific risks should be named in the boxed warning, such as sleep disorders.

The lone committee member who sided with Pfizer was Andrew Saxon, MD, of the University of Washington in Seattle. He said he found the new data persuasive that varenicline is no riskier than many other drugs with similar psychiatric effects and that don't have boxed warnings.

Saxon said that, in his experience, the boxed warning "does deter" patients from using the drug. He also noted that he works in the Veterans Affairs health system and the VA puts strict limits on how drugs with such warnings can be prescribed.

"We're talking about treating a life-threatening disorder," he said, and argued that putting up barriers to effective treatments was a mistake.