Smokers trying to quit find drug brings suicide risk, other dangers.

Barely two years after the FDA first approved the prescription smoking-cessation drug Chantix for use in the United States, Pfizer, its manufacturer, faces lawsuits by plaintiffs claiming that the drug has caused users to commit suicide, experience manic and aggressive behavior, and suffer injuries after losing consciousness during a seizure.

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"The magnitude of the safety signal associated with using Chantix is alarming both in terms of severity of injury and the number of different serious, life-threatening adverse events associated with this dangerous drug," said Kristian Rasmussen of Birmingham, Alabama, the chair of AAJ's new Chantix litigation group. Rasmussen's firm has been investigating claims involving Chantix for about a year, and he represents the plaintiffs in the recently filed lawsuits.

"My opinion is similar to that of many leading independent experts: Chantix is dangerous, and Pfizer either knew or should have known the risks for a long time," he said.

Chantix is Pfizer's brand name for varenicline. The drug reportedly acts both as an agonist and an antagonist--partially stimulating a nicotinic acetylcholine receptor in the brain while simultaneously blocking the ability of nicotine to stimulate the receptor. This dual mechanism is thought to block or reduce the ability of nicotine to stimulate the central nervous system's dopamine system and produce the pleasure associated with smoking.

Varenicline is partially derived from cytosine, a smoking-cessation drug that has been used in Europe for decades. The FDA approved Chantix for use in the United States in May 2006, after an accelerated review process.

Pfizer markets Chantix as a breakthrough medicine to help smokers quit. In Pfizer's clinical trials, at the end of 12 weeks of using Chantix and undergoing counseling, 44 percent of patients quit smoking, versus 18 percent for those given a placebo and counseling.

More than 70 other countries also have approved Chantix, and Pfizer estimates that it has been used by more than 6.5 million people worldwide, with 5.5 million of them in the United States.

The patient medication guide for Chantix tells users that the drug's side effects may include nausea, constipation, gas, vomiting, and sleep problems--either trouble sleeping or having vivid, unusual, or strange dreams.

Many of the first users of Chantix have written or blogged about their "Chantix dreams" as being "crazy," "amazing," "weird," and "funny and bizarre," and have commented that they would miss the dreams when they stopped taking the drug. But there are reports of disturbing experiences, too. One user wrote that, while taking Chantix, every time he'd drift off to sleep, "I'd dream that an invisible, malevolent entity was emanating from my air conditioner ... that something increasingly ominous--carbon monoxide? vampires?--was sucking vital essence out of me." (Derek de Koff, This Is My Brain on Chantix, N.Y. Mag. (Feb. 10, 2008).)

But vivid dreams aren't the only side effects that Chantix users have experienced. Baltimore attorney Ronald Miller, who is evaluating injury claims related to the drug, said, "[There are] so many different kinds of problems with Chantix. It's unbelievable how many adverse-effect reports there are."

In fact, reports of serious neuropsychiatric side effects, such as changes in behavior, agitation, depressed mood, suicidal ideation, and suicidal behavior, soon arose, especially after the widely publicized death last year of Carter Albrecht, a popular Texas musician. A neighbor shot and killed Albrecht as he banged on the man's back door in the middle of the night, ranting and yelling. Albrecht's family and fiancee blamed his outburst on hallucinations caused by Chantix, which he had been taking for about a week before his death.

Soon after Albrecht's death last September, the FDA released the first of several warnings about suicidal thoughts and aggressive and erratic behavior in Chantix patients, which had been documented in Pfizer's own postmarketing case reports. The FDA cautioned health care professionals and patients about behavior and mood changes and recommended that patients "use caution when driving or operating machinery until they know how quitting smoking with Chantix may affect them."

Then, on February 1, the FDA issued an alert regarding Chantix use and serious neuropsychiatric symptoms, listing reports of changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide. In May, the FDA followed up with a public health advisory about many of the same symptoms. Pfizer updated the warnings on the drug's label in November of last year and in January and May of this year.

Failure-to-warn lawsuits

Linda Collins is the widow of David Collins, who died of a self-inflicted gunshot wound on January 3, just a few weeks after he began using Chantix to stop smoking. In July, she brought a lawsuit against Pfizer, claiming that the company intentionally proceeded with the manufacturing, marketing, and sale of Chantix "knowing that persons would be exposed to serious injury and death." It charges Pfizer with misleading users about the product and failing to adequately warn about its risks. (Collins v. Pfizer, Inc., No. l:08-cv-0888-DFH-JMS (S.D. Ind. filed July 8, 2008).)

Rasmussen, who represents Collins, said that "Pfizer either knew or should have known that Chantix posed a significant risk for causing suicide" before the drug was launched onto the open market. He noted that its active ingredient has been used for decades as a smoking-cessation drug in eastern European countries and had been linked as early as 1972 to cases of suicide and attempted suicide.

And, said Rasmussen, the Collins case is not unique.

"We have received many compelling calls from family members on behalf of Chantix victims who committed suicide. The reports vary, and all are truly horrific events. For example, we represent the estate of a mother who used a handgun to commit suicide in front of her two young children. Another man came home to discover his wife dead after committing suicide with a shotgun. A grandmother who wanted to prolong her life ended it with carbon monoxide poisoning. The common fact in each case is Chantix," he said.

Another recent lawsuit alleges that Chantix use brought on psychotic behavior. The plaintiff, Brian Kline, was hospitalized in August 2007 for manic, aggressive, and violent behavior and a psychotic disorder a month after he was prescribed Chantix. Kline's lawsuit charges that Pfizer negligently or intentionally failed to thoroughly study the drug's mechanism of action and its effects and intentionally excluded certain patients--those with any mental or psychological problems--from its clinical trials. (Kline v. Pfizer, Inc., No. 08-3238 (E.D. Pa. filed July 10, 2008).)

Monitoring adverse events

Meanwhile, the Institute for Safe Medication Practices (ISMP), a nonprofit organization in Horsham, Pennsylvania, created a data-monitoring program that it hoped would identify emerging drug risks that were not detected in clinical trials. In ISMP's analysis of the FDA's adverse-event reports, Chantix stood out.

The institute noted that Chantix first appeared in the adverse-event reports in the fourth quarter of 2006, when it was one of a small group of drugs that had 100 or more reports of serious injury in the time period. By the fourth quarter of 2007, Chantix accounted for 988 serious drug adverse events reported in the United States--more than any other individual drug in the time period. This prompted ISMP to look closely at all the Chantix-related adverse-event reports the FDA received since the drug's approval in 2006.

ISMP's report detailed multiple safety problems. Most significant for the researchers were the reports of other kinds of serious harm that were not covered either by the FDA's public health advisory or Pfizer's prescribing information, including serious accidents and falls, potentially lethal cardiac rhythm disturbances, severe skin reactions, heart attacks, seizures, and diabetes.

ISMP found 173 serious events describing accidental injuries, including 77 cases of falls and 28 traffic accidents, and identified the potential causes of these events, such as dizziness or loss of consciousness. It issued a strong warning to health care providers and the public: "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. 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."

In the days following the release of the ISMP report, the Federal Aviation Administration banned pilots and air traffic controllers from using Chantix. Similarly, the Federal Motor Carrier Safety Administration, which regulates the medical qualification of interstate truck and bus drivers, said that "medical examiners should not certify a driver taking Chantix because the medication may adversely affect the driver's ability to safely operate a commercial motor vehicle."

And the Washington, D.C.-based consumer advocacy organization Public Citizen called for the FDA to require Pfizer to add a "black-box" warning to Chantix highlighting the risk of suicidal thoughts, depression, agitation, and serious adverse skin reactions, in addition to a warning that users should not drive or operate machinery until they know whether Chantix will impair them.

As of press time, only two lawsuits that involve claims of injuries caused by a Chantix-related loss of consciousness had been brought, both arising from the same incident. Daniel Williams and Melinda Lofton were hurt when Williams had a seizure while driving and lost consciousness; their car veered off a country road in Louisiana and into a bayou. According to Rasmussen, who represents the couple in separate lawsuits, Williams had no history of seizures and had started taking Chantix just three days before the crash. (Williams v. Pfizer, Inc., No. 40528 (La., Richland Parish Dist. filed July 11, 2008); Lofton v. Pfizer, Inc., No. 40529 (La., Richland Parish Dist. filed July 11, 2008).)

In the aftermath of the ISMP report, U.S. sales of Chantix have dropped by one-third, and Pfizer launched a media campaign to calm concerns about the drug. It published full-page ads in the five largest U.S. newspapers, featuring a letter from its chief medical officer on the dangers of smoking and the benefits of Chantix, and it sent letters to 300,000 health care professionals, advising them of the latest label change.

As for the recently filed Chantix lawsuits, a Pfizer spokeswoman stated that "Pfizer will vigorously fight these suits, which attack a medicine that is an important option in the battle against smoking. At all times, Pfizer has acted responsibly, appropriately, and in the best interests of patient safety."