Two lawsuits claim the plaintiffs tried to kill themselves as a result of using Chantix. The third is a wrongful death lawsuit filed on behalf of Indiana resident, claiming she committed suicide after using Chantix.

The lawsuits claim that each of the plaintiffs used the drug properly. They also claim that in each case the plaintiffs and their doctors were “not aware and through diligent efforts were not able to discover the risk of serious injury, and/or depressed mood and/or suicide associated with and/or caused by Chantix.”

On May 11, 2006, the FDA approved Chantix to assist people quit smoking. On November 20, 2007, the FDA began reviewing reports of suicidal behavior submitted to the administration by the drug maker, Pfizer, as well as instances of other side effects associated with Chantix.

The FDA is also requiring an additional study on Chantix and Zyban to determine the extent of the side effects. Pfizer Inc., the manufacturer of Chantix, had already updated its labeling following the beginning of an FDA investigation into the potential side effects in 2007 after receiving several reports of psychiatric problems in patients.

Despite the new, stricter warnings, the FDA said consumers and doctors still have to weigh the benefit versus the risks when taking the drug.

“The risk of serious adverse events while taking these products must be weighed against the significant health benefits of quitting smoking,” said Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research.

“Smoking is the leading cause of preventable disease, disability, and death in the United States and we know these products are effective aids in helping people quit.”

Last fall, the FDA also began looking into scores of patient reports about blackouts and injuries while taking Chantix.

The Federal Aviation Administration later banned use of Chantix by pilots and air traffic controllers. The drug’s label also warns that patients may be too impaired to drive or operate heavy machinery.

Chantix was approved in 2006, and reached sales of $846 million in 2008.

“The labeling update underscores the important role of health care providers in treating smokers attempting to quit and provides specific information about Chantix and instructions that physicians and patients should follow closely,” said Dr. Briggs W. Morrison, senior vice president of the primary care development group at Pfizer.

Pfizer said it made the revised label warnings in agreement with the FDA and is immediately making the information available to health care providers and patients.

Chantix was among the 20 medications under investigation for potential safety issues, according to an updated list from the FDA. The FDA is investigating reports of injury, visual impairment and other problems connected with Chantix, which is designed to help smokers quit.

Pfizer said it’s continuing to track side effects with the medication. “As with all our medicines, we work with the FDA to ensure our labeling reflects the latest safety information,” Sally Beatty, a spokeswoman for the New York-based company, said in a statement.

Regulators initially began investigating Chantix in 2007 after receiving numerous reports of psychiatric problems, including suicidal thoughts. That prompted Pfizer to update the drug’s labeling that patients should be monitored for unusual behavior.

The FDA last fall began looking into scores of patient reports about blackouts and injuries while taking Chantix. A nonprofit group highlighted 1,001 reports to the FDA of serious injuries linked to the drug over a three-month period, more than for the 10 best-selling brand name drugs combined. Pfizer said at the time that the high number of reports might be linked to greater publicity about the side effects.

The Federal Aviation Administration (FAA) later banned use of Chantix by pilots and air traffic controllers.

Current warnings on the drug say patients may be too impaired to drive or operate heavy machinery, but such language is standard for many medications.

The FDA began publishing quarterly lists of drugs under investigation last year to give consumers and doctors early notice about emerging safety issues. Drugs on the list have a “potential safety issue,” but have not necessarily been directly linked to a problem.

First approved in May 2006, Chantix quickly became one of the fastest growing products for Pfizer, with sales $846 million in 2008.

The medication acts on sites in the brain affected by nicotine. It helps ease withdrawal symptoms and blocks the effects of nicotine if a user resumes smoking. The drug has been sold in Canada since April 2007. From January to November 2008, nearly 1.1 million Champix prescriptions were dispensed from Canadian retail pharmacies, according to IMS Health Canada, which tracks the pharmaceutical industry.

Each prescription comes with a long list of potential side-effects, from depression to aggression to suicidal thoughts. One person who reported a complaint to Health Canada, said she was on Champix for a couple of months to try to quit smoking when she noticed dramatic changes in her personality she had become intolerant, argumentative, emotional, and then one day, suicidal.

“As I’m driving along the [Hamilton] mountain brow, I just thought that driving off would have been the easy way out at that point and would solve all my problems,” the individual said.

In the United States, the drug is called Chantix. Last year, the U.S. FDA used a video to warn doctors about the drug. The manufacturer, Pfizer Inc., warned the public in a commercial, telling people who develop suicidal thoughts or actions to stop taking the drug and to call their doctor right away.

New advice coming

But Health Canada has been slower to act, posting a warning on its website months after the FDA issued its warnings. In January, the department promised to add an even stronger warning on the label.

In an email to CBC News, Health Canada said that “new advice for health professionals and Canadians will come in the near future.”

Pfizer Canada said that “based on the totality of data, Pfizer stands by the efficacy and safety profile of Champix when used as directed.”

Furthermore a widow whose ex-husband took the medication and killed himself in early January would like to see further testing done on Champix. “I think the safer thing would be to take it off the shelf,” she said. “If there are people that are having serious side-effects you don’t want anyone to have to go through what we’re going through.”

Recently, Chantix has been associated with depression, suicidal thoughts, blackouts and serious injuries.

Heiligenstein put in 14 days for Pfizer and was paid $10,000 to $20,000. Heiligenstein also gave paid talks for Pfizer in 2006.

For two consecutive quarters, Chantix was connected with more serious injuries than any other prescription drug, according to an October report by the Institute for Safe Medication Practices.

Since its approval in 2006, Chantix has been associated with 3,325 serious injuries and 112 deaths in the United States.

Heiligenstein, clinical director of psychiatry for University Health Services, said he does not have second thoughts about his Chantix talks. He noted that another smoking-cessation drug, bupropion, also is associated with serious risks. And smoking itself is a risk factor for serious injury, he said.

“This is not to diminish the risk associated with Chantix,” he said. When prescribing Chantix, he has to weigh risk vs. benefit for each patient, he said. “I suspect we have underestimated the morbidity and mortality associated with all smoking-cessations treatments,” he said.

A spokesman for Pfizer declined to discuss Heiligenstein’s consulting work, citing privacy.
In a statement, the company said it stands by the safety and efficacy of Chantix.

It said the institute’s report provides no evidence that smokers not taking Chantix have fewer accidents or injuries than those who take the drug.

In December 2007, Heiligenstein also began working as the medical director of a state-funded program to develop a plan to integrate nicotine-dependence treatments into the services provided to people with mental health and substance abuse problems.

Chantix is one of the drugs that may be used once the program starts, said Randy Glysch, a research scientist with the state’s tobacco prevention program.

Heiligenstein is continuing to work as medical director for the state program in 2009.

Health Canada has received a few hundred reports of psychiatric problems among those taking the drug, including suicidal behavior, hostility, abnormal dreams or thinking, aggression and depression. Health Canada first issued a warning about the product last June to make the public and health professionals aware of the potential health risks.

Although the department said it is still unclear whether Champix caused the psychiatric problems, new reports of “serious psychiatric adverse events” linked to the drug in Canada and around the world prompted health officials to issue the additional caution. Now, health officials are working with Pfizer to create a stronger warning label for the product, which is expected to be made public in the near future.

In addition to the new reports of side effects, Health Canada said, it issued the warning after Pfizer submitted new information about the drug.

A Pfizer spokesman declined to provide details of any new information pertaining to the drug.

While the drug may pose health problems for some, Health Canada said, the benefits of Champix to the public still outweigh the risks.

“A close monitoring of patients taking Champix by family, caregivers and the patients themselves for adverse events; such as unusual thoughts, feelings or behaviors, especially those related to depression, aggression or self-harm and immediate discontinuation of the drug should any of these signs be present or worsen while taking the drug is considered a reasonable risk-mitigation approach,” spokesman Paul Duchesne wrote in an e-mail.

One drug-safety expert said the warning probably reflects serious concern among health officials.

If the concerns are borne out, they may eventually lead to the drug’s removal from the market, said Alan Cassels, a drug policy researcher at the University of Victoria.

“This is what they do before they pull the drug off the market or require the manufacturer to pull the drug off the market. We’ve seen lots of cases like this,” Mr. Cassels said.

A company may be inclined to pull a drug off the market if it starts seeing numerous lawsuits, Mr. Cassels said. Pfizer is involved in several lawsuits in the U.S., where the drug is marketed as Chantix.

Health Canada said it will continue monitoring the drug and will update the public if any further action is necessary.

Part of the reason for the new warning is to increase awareness of the potential risks. Even though Health Canada aired concerns about Champix last year, the drug seemed to rise in popularity.

From April to the end of December, 2007, its first year on the market, just fewer than 259,000 Champix prescriptions were dispensed from Canadian retail pharmacies, according to IMS Health Canada, which tracks the pharmaceutical industry. That number jumped to nearly 1.1 million from January to November last year.

The prescriptions are worth an estimated total of more than $99-million, IMS Health Canada said.

Pfizer Canada’s manager of corporate communications said the new warning is intended to remind Canadians who may be at risk about side effects, and to reiterate that the drug is still considered safe and effective.

“Champix is absolutely a safe product. It’s the most efficacious product out there,” said Christian Marcoux, adding that people who want to quit smoking should work with a health-care professional.

Mr. Marcoux said it’s common for Health Canada to update the safety information of a particular drug, and that the company has confidence in Champix.

Documents posted by the Medicines and Healthcare products Regulatory Agency gives the following advice: “Patients who are taking [Chantix] who develop suicidal thoughts or who develop agitation, depressed mood, or changes in behavior that are of concern for the doctor patient, family, or caregiver should stop their treatment and contact their doctor immediately.”

MHRA has said that 10 people have taken their own lives after using Chantix (sold as Champix over there), according to the Daily Mail, a paper that’s not on our usual reading list. Another 213 people said they’d had suicidal thoughts and 407 said they were suffering from depression, the newspaper reported. Through June, about 450,000 people had used the drug in the U.K., the MHRA said.

Still, the MHRA has also said the reactions aren’t necessarily caused by the drug and may relate to other factors, such as nicotine withdrawal or other medications patients take. But the agency also pointed out that suicide-related events have been reported by Chantix patients who had no known pre-existing psychiatric conditions and in some who continued to smoke.

A spokesman for the MHRA told the Daily Mail that while reports of side effects may have increased, so may have the number of people taking the drug.

More than 1,000 health problems and injuries were reported in the first quarter of 2008 in patients taking the drug, including 50 deaths, researchers at the nonprofit Institute for Safe Medication Practices and Wake Forest University found.

The scientists analyzed post-marketing data submitted to the FDA on people who took the drug, which was approved in 2006.

In a statement, Pfizer said it was aware of the types of reported events the researchers analyzed but that such reports are inconclusive. Chantix is safe and effective when used as directed, the company added.

The FDA has said it is reviewing all the reports. Agency representatives could not be immediately reached for comment on the researchers’ latest findings.

Chantix already carries a warning for depression, suicidal behavior, agitation and other unusual activity.

In May, the researchers first reported the rise of serious accidents, vision problems and heart trouble in patients taking Chantix. At that time they cited 173 reports of accidents and injuries.

In their latest findings, they said there were 1,001 new reported complications and deaths that included 15 traffic accidents and 52 incidents of loss of consciousness.

The reports of problems with Chantix were greater than for any other prescription drug for the second quarter in a row, the researchers added.

Despite the stinging report, the agency has decided to proceed with the experiment, including allowing participants to take a drug that carries risks of suicide and other psychotic behavior, officials said.

The investigation, prompted by a series of stories earlier this summer in The Washington Times as part of a joint investigation with ABC News, said that the smoking cessation study “did not adequately fulfill VA’s singular responsibility to maximize safeguards for veterans who volunteer to participate in research.”

The review by the VA’s Office of Research Oversight (ORO) also found “unacceptable failures to maximize safeguards for the veterans who had volunteered to participate” in the study, including the lack of a system in place to alert researchers and participants when drug safety warnings are issued.

Researchers responsible for the smoking cessation study first failed to notify internal review boards that oversaw the experiment at 10 locations when the FDA first publicized concerns in November that the drug varenicline, commercially known as Chantix, may induce suicidal thoughts or actual suicides.

When a second warning was issued in February it took anywhere from 16 to 134 days to alert veterans, and the review expressed doubts as to whether all veterans in the study received the warnings.

Despite a multitude of discrepancies and failures identified by the review, the study made no recommendation either in favor of terminating or of continuing the study, which involves more than 900 veterans.

VA spokeswoman Alison Aikele told The Washington Times on September 19, 2008,  that the experiment will continue, and that Chantix, prescribed to 240 veterans in the study by their own doctors, will continue to be made available to the participants.

“It is an FDA-approved medication, and guidelines have been distributed to providers and information to patients,” Miss Aikele said.

The smoking cessation study came under fire in June after a Washington Times/ABC News joint investigation reported that the VA had taken at least three months before it began to alert the veterans taking Chantix about the possible new side effects.

The notice came nearly one month late for Iraqi war veteran James Elliott, who suffered a mental breakdown while taking the drug. In what he later described as an attempt at “suicide by cop,” Mr. Elliott was shocked with a Tazer during a stand-off with police in Silver Spring.

The report urged VA officials to conduct an investigation to “hold appropriate individuals accountable for any research protection failures in [the study], specifically including responsibility for factors contributing to undue delays in notifying participants about the risks associated with varenicline.”

Rep. Bob Filner, California Democrat and chairman of the House Veterans Affairs Committee, held a July 9 hearing in response to the Times/ABC News investigation where Dr. Tom Puglisi, chief officer of the ORO and author of the review, said he feared that similar notification problems exist throughout the agency’s human-subject testing programs, particularly those that target veterans with PTSD.

Dr. Puglisi’s testimony then said he was “very concerned” about the study, but he did not explicitly back either canceling or continuing it. Mr. Filner and other lawmakers have demanded that the VA end the study.

The review recommended that the VA establish a reliable system to notify the researchers and study participants about new or emerging medication safety information, and the VA says it has developed an action plan to implement this and all the recommendations contained in the report.

The spots run 90 seconds, which is 30 seconds more than the ones Pfizer ran for just four months last year and hew to the same narrative as the old one, using a race between a tortoise and a Belgian hare to dramatize the fact that quitting smoking that favors the slow and steady and that Chantix can help.

Side effect information takes up 41 seconds of the advertisement, with about 20 seconds devoted to a warning that patients taking Chantix should stop taking it if they experience agitation, suicidal thoughts or suicidal behavior. Pfizer says the role of Chantix in those symptoms is “not known.”

“Some people think the drug has been withdrawn from the market,” says Veronique Cardon, team leader of U.S. marketing for Chantix. “More importantly, a lot of people haven’t heard of Chantix yet.”

Safety controversies only make that tougher. When ads are pulled because of new and serious side effects, some reappear in a longer form with more detail about the new risks, says Ruth Day, director of the Medical Cognition Laboratory at Duke University. This also happened with ads for Celebrex (also a Pfizer drug) after it was linked to an elevated risk of heart disease.

Day would not comment on the ad without seeing it. “It is good news if the serious risks are now present physically, but are they there functionally in a way that people will understand and remember them?” she asks.

Chantix, launched in May 2006, is the only drug designed specifically to combat nicotine addiction ever sold in the U.S. Previous stop-smoking aids either contain nicotine, like gums and patches, or are re-purposed antidepressants. Chantix is more effective than Zyban, an antidepressant, but the large majority of patients still don’t succeed in stopping smoking. Doctors say there is a huge need for new options. In 2007, Pfizer booked Chantix sales of $883 million.

That early success came without the support of any direct-to-consumer advertising. Drug industry critics had suggested drugs be marketed for a year before advertising began, and Pfizer did exactly that, running the first of its tortoise and hare ads for Chantix in September 2007.

But as soon as the ads started, so did the controversy did. An up-and-coming musician who was taking Chantix was shot on Sept. 3, 2007 after a night of strange behavior; he had also been drinking. The case drew national attention.

Last November, the FDA issued an alert saying it was looking into neurological and psychological side effects for Chantix. In January, Pfizer and the FDA added concerns about those side effects to the drug’s label, which serves as a guide for doctors and the basis for claims in advertising. At that point, Pfizer stopped airing ads that advertised Chantix by name.

Then in May, the Institute for Safe Medicine Practices issued a report linking Chantix to more side effects, including traffic accidents. Federal regulators warned first pilots, then truckers, not to take the drug.

Psychiatric side effects are a particular concern for an anti-smoking drug because the mentally ill are more likely to smoke than other people. The vast majority of schizophrenics use tobacco and 40% of cigarettes are sold to people suffering from mental illness.

But some doctors defend Chantix.

“It would be a major public disservice if the few people with negative experiences get in the way of the smokers who are dying early from their inability to quit,” says Carlos Roberto Jaén, head of family and community medicine at the University of Texas Health Science Center at San Antonio. He has no financial ties to Pfizer.

Pfizer says that some cases where there were neurological and psychiatric symptoms associated with Chantix may have been complicated by nicotine withdrawal. An analysis of neurological and psychiatric effects in placebo-controlled Chantix studies of 5,000 patients will be presented at a medical meeting in Rome later this month.

Sales of Chantix last quarter were down 35% in the U.S., although that decline was offset by international sales. Pfizer says Chantix has had a strong uptake in the U.K., France, Belgium and Japan. But analysts at Natixis still expect sales to come in $50 million short of last year’s total.