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Chantix: For people who are dying to quit smoking

Unnecessary public alarm



In July of 2011, the FDA issued a warning linking Chantix to an increase in the rate of heart attacks in patients with stable cardiovascular disease. That same month a meta-analysis published in the Canadian Medical Association Journal by Doctor Sonal Singh and his colleagues revealed that in smokers without a history of cardiovascular disease, Chantix was associated with a 72% increase in the relative risk of serious cardiovascular events, including ischemia, arrhythmia, congestive heart failure, sudden death, and cardiovascular-related death. Cardiovascular disease is an important cause of morbidity and mortality among smokers, and quitting smoking is widely supposed to reduce this risk, but in this case the data were going the other way. In fairness, it should be pointed out that the increase in risk was small -- on the order of one extra serious cardiovascular event per year for every 28 patients treated with Chantix -- but the benefits of Chantix also are small, and even those have been demonstrated only in highly artificial clinical situations unavailable to the average quitter.
Part 1: A fantastic individual Part 2: Quitting can be different this time Part 3: Is suicide an expected event? Part 4: Unnecessary public alarm Part 5: Rages that make no sense at all The following year, another meta-analysis published in BMJ, which looked at a greater number of clinical trials, also found that Chantix was associated with a small increase in the risk of serious cardiovascular events, although this time the difference was deemed not to be statistically significant. Doctor Judith Prochaska, the senior author of the study, is the recipient of an investigator-initiated research award from Pfizer, the manufacturer of Chantix. The authors of the BMJ paper concluded "The consequence of inflated risk estimates such as those from Singh and his colleagues inflated meta-analysis, can be unnecessary public alarm and real harm, since patients may discontinue their drug treatment out of fear of adverse effects." In a reply, Dr. Singh stated that the authors had excluded a number of incidences of serious cardiovascular events that had been reported from their analysis, and that none of the clinical trials included in the meta-analysis was sufficiently powered to detect differences in rare (but potentially lethal) events such as heart attack or stroke. He also noted that the FDA had requested a trial with sufficient power to detect these differences be performed, and that the results should be available in the year 2017 -- just in time for the patent on Chantix to expire. In a telephone interview, Dr. Singh indicated that he stood behind the conclusions of his paper. "Chantix increases the risk of cardiovascular events and these conclusions are reflected in the Chantix label as well. I shared these findings with the FDA and I think that's why there were warnings. Otherwise if we hadn't done the study there would have been no warnings." Dr. Singh indicated that he does prescribe Chantix to some of his patients who smoke, but he prefers to have them try non-drug methods first. His second choice is nicotine replacement therapy (NRT) or bupropion. Before he prescribes Chantix, he weighs the potential benefits against the risks. "What I do is, I look at: Do they have a psychiatric history? Do they they have a cardiovascular history? In those patients I kind of lean away from Chantix. On the other hand, if it's a young patient, no psychiatric history, no cardiovascular issues, then I'm less hesitant about prescribing."

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In February of 2013, Pfizer announced it was paying out $273 million to settle 80% of the 2,700 state and federal lawsuits filed on behalf of people purported to have been harmed by Chantix. In an SEC filing, company officials estimated that settling the remaining cases would cost another $15 million dollars. The following September Thomas Moore and his colleagues at the ISMP issued another report analyzing adverse event reports from 2007 through the third quarter of 2013. Chantix accounted for more cases of suicidal ideation, self-harm, and homicidal ideation than any other drug, by a more than three-fold margin. For cases of homicidal ideation, the difference was a whopping five-fold. In response to this avalanche of bad publicity, Pfizer and its allies went on the counterattack.

"Time to unring the alarm bell"

On October 16, 2014, the FDA convened a hearing to consider whether or not to drop the black-box warning from Pfizer's blockbuster stop-smoking drug Chantix. Doctor Christopher Wohlberg, Vice President and Safety Surveillance & Risk Management Group Head for Pfizer, presented the results of 18 randomized clinical trials (all funded by Pfizer) and four observational studies. "The current control data show no evidence of increased risk of serious neuropsychiatric events when compared to placebo, bupropion, or NRT," Dr. Wohlberg testified, and concluded that is was "time to unring the alarm bell" on Chantix. Dr. Wohlberg was followed by Thomas Moore of the Institute for Safe Medication Practices, who began by highlighting the human cost behind some relatively innocuous-sounding labels like "sleep disturbances, stating, "Some of them are the most horrifying dreams that people can actually not speak about." He then blasted the industry experts whose testimony preceded his. "Now I was here this morning and wondered -- I was listening to some of this -- to be frank, whether I was in Alice and Wonderland. So we have a manufacturer who, let's face the facts, paid 2,500 Chantix victims of neuropsychiatric side effects rather than try a single case in court. And now we hear a scientific presentation that ignores most of the evidence that says it doesn't cause psychiatric side effects." Moore went on to assert "Warnings have a real purpose in drug safety. They prevent harm. Symptoms often start early, often in many, many cases, long before reaching full titrated dose. And discontinuations really do stop a spiral that we've observed in case after case into really catastrophic adverse events." In regard to the hugely disproportionate number of violence case reports associated with Chantix, he stated "In 10 or 15 years of doing this kind of work, we just have not seen anything like this kind of drug."

"I am bound from saying anything"

Kim Witczak of Minneapolis, Minnesota became a patient advocate after her husband, Woody, hanged himself from the rafters of their garage. This was five weeks after he had been prescribed Pfizer's blockbuster antidepressant drug Zoloft for insomnia. Witczak testified at the 2004 FDA hearing that resulted in a black-box warning that Zoloft and other antidepressants increased the risk of suicidality in certain patient populations. She also testified at the Chantix hearings, noting that not one of the 2700 plaintiffs who had accepted Pfizer's settlement was there to testify, nor were their lawyers. She quoted from one plaintiff who settled: "I sincerely wish I could tell my story publicly, but like the other 2700 people who accepted Pfizer's settlement, I am bound from saying anything." Witczak went on to lament that the Chantix settlement meant that "22 million pages of documents and dozens of key dispositions may be forever lost without some sort of intervention." In the end, the FDA panel voted 11-7 to keep the black-box warning on Chantix, and last March the FDA issued another warning, stating that Chantix can decrease tolerance to alcohol, leading to increased drunkenness, unusual or aggressive behavior, and blackouts, and that rare cases of seizures had been recorded in users who either had no previous history of seizures, or whose seizures had been well-controlled. In a telephone interview, Ms. Witczak stated "This is part of my big message to attorneys: if you don't figure out a way to get the evidence released from under seal, it will forever stay under seal and all the public health knowledge is lost and the problem persists." Meanwhile, Pfizer and its allies continued their counteroffensive. Next: Part 5: "Rages that make no sense at all" List of Sources
  1. Sonal Singh, telephone interview, 17 November 2015.
  2. Thomas Moore, telephone interview 19 November 2015.
  3. Kim Witczak, telephone interview 20 November 2015.
  4. Singh, S. et al. 2011. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ 2011. doi:10.1503/cmaj.110218.
  5. Prochaska, J.J. and J.F. Hilton 2012. Risk of serious adverse cardiovascular events associated with varenicline use for tobacco cessation: a systematic review and meta-analysis. BMJ 2012;344:e2856.
  6. United States Securities and Exchange Commission 2013. Form 10-K/A Amendment No. 1.
  7. Staton, T. 2013. Pfizer settles 2,000-plus Chantix suits, takes $273M charge.
  8. Institute for Safe Medication Practices 2014. Quarter Watch: Monitoring FDA Medwatch reports. September 24, 2014 -- Date from Quarters 2 & 3.
  9. FDA 2014. Joint Meeting of the Psychopharmacologic Drugs and Drug Safety and Risk Management Advisory Committee.
  10. Burton, T.M. and J.D. Rockoff 2014. Chantix warnings to remain, panel votes. Wall Street Journal 17 October 2014.
  11. Witczak, K. 2014. Reflections on Fda Chantix Hearing.
  12. Cassels, A. 2014. Drug Bust.
  13. Brooks, M. 2014. Keep Chantix black box warning, FDA panel says.
  14. FDA 2015. FDA drug safety communication: FDA updates label for stop smoking drug Chantix (varenicline) to include potential alcohol interaction, rare risk of seizures, and studies of side effects on mood, behavior, or thinking.


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Patrick D Hahn -- Bio and Archives

Patrick D Hahn is the author of Prescription for Sorrow: Antidepressants, Suicide, and Violence (Samizdat Health Writer’s Cooperative) and Madness and Genetic Determinism: Is Mental Illness in Our Genes? (Palgrave MacMillan). Dr. Hahn is an Affiliate Professor of Biology at Loyola University Maryland.



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