News reports this morning that the smoking cessation drug Chantix (varenicline) has been linked to an increasing number and variety of side-effects was disturbing.
The announcement that the Federal Aviation Administration has decided to ban the use of Chantix by pilots and air-traffic controllers certainly doesn't give one a sense of comfort.
The report was released by The Institute for Safe Medication Practices.
For those of you, like me, who have never heard of this institute, you may be interested to know the following, as listed on Healthfinder.gov, a website of the Department of Health and Human Services:
“The purpose of the Institute for Safe Medication Practices (ISMP) is to educate healthcare practitioners and institutions, regulatory agencies, professional organizations and the pharmaceutical industry about adverse drug events and their prevention. The Institute provides an independent review of medication errors submitted by practitioners to a national Medication Errors Reporting Program (MERP) operated by the United States Pharmacopeia. ISMP is an FDA MEDWATCH partner and regularly communicates with the FDA to help to prevent medication errors.”
Their credentials look good to me.
The report released today is pretty blunt in its comments:
“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 US 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 report goes on to point out that there has been a steady increase in the number of adverse drug events reported to the FDA over time. The number of reports in the 4th quarter of 2007 was 988 serious injuries for varenicline, compared to a median of 5 reports of serious injury for 769 different drugs in the same 4th quarter.
The authors also note that just because a report is filed does not mean that there is a link to the drug. However, these reports are generated and filed according to a standard format that is designed to try to improve the chances that the statistics are valid.
The recommendations in the report are very direct:
“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….We promptly notified the FDA of our findings.”
We have previously reported on Chantix in this blog, both when it was first approved by the FDA as a smoking cessation aid in May 2006 and more recently this past February when concerns were raised about possible psychiatric side effects and increased suicide ideation related to Chantix use.
As I pointed out in my first blog on Chantix in 2006, there are always new or more frequent side effects found with almost every prescription medication once it is released for widespread use by physicians and their patients. My second blog this past February discussed the psychiatric risks, but also pointed out that this drug was tested in perhaps the healthiest group of smokers the researchers could find.
So, it’s no surprise that when you study a drug on relatively healthy people, and that drug impacts the central nervous system directly as its mode of action, that you might expect to find some additional side effects when it gets out into the real world.
After all, the smokers that I used to see in clinical practice had chronic lung disease (emphysema), heart disease, high blood pressure, diabetes, depression and many other medical conditions.
Here is a list of drugs and diseases that would have excluded you from the clinical trials of Chantix, as described in their research report in the Journal of the American Medical Association in July 2006:
· Any serious or unstable disease within six months
· Seizure risk
· Diabetes mellitus requiring insulin or oral hypoglycemic medications
· Hepatic (liver) or renal (kidney) impairment
· Significant cardiovascular disease within 6 months
· Uncontrolled hypertension (my comment: most patients in this country with increased blood pressure are not adequately controlled)
· Severe chronic obstructive pulmonary disease
· History of cancer (except treated basal or squamous cell skin cancers)
· History of clinically significant allergic reactions
· Major depressive disorder within the past year requiring treatment
· History of panic disorder, psychosis, bipolar disorder or eating disorders
· Alcohol or drug abuse/dependency within the past year
· Use of tobacco products other than cigarettes
· Use of nicotine replacement therapy, clonidine, or nortiptyline within the month prior to enrollment
· BMI less than 15 or greater than 38
There are certainly reasons to be a bit skeptical about reports of this type. After all, according to the Wall Street Journal, an estimated 5.5 million people have taken Chantix since it was released two years ago. There are inevitably going to be things happening to some of those people, including falls, heart attacks, seizures, etc. It would be impossible to link these few hundred problems to Chantix, considering the large number of people taking the drugs.
But when you read the full report from The Institute for Safe Medication Practices, you find they employed an analytical process designed to separate background noise from potentially serious problems.
In this research, they looked at a trend of adverse drug reports for a number of drugs over time, and found that beginning in late 2006 through late 2007, varenicline continued to move up the ladder (so to speak) to the point where—for some of the specific types of side effects—it was number one on the list.
And, then in the 4th quarter of 2007, “varenicline accounted for more reports of serious drug adverse events in the United States than any other drug.”
What the news reports don’t tell you is that there were more cases of side effects (998) reported for varenicline than drugs such as interferon (640), etanercept (555), infliximib (554), fentanyl (404) and oxycodone (372).
My friends, all of those drugs listed above are far from “routine” medications. They are used in the treatment of cancer and other diseases, have a high incidence of side effects that are known, and the last two are narcotics.
What the newspapers also haven’t told you is that 2817 out of 3063—or 92%--of the reports on this drug came from the drug company itself.
The report says, “A large share of these reports were investigated and submitted by the drug manufacturer, presumably with consistent procedures, and potential events were selected using criteria that had been previously undergone (sic) validation testing. In addition, there events occurred under real world conditions and not the narrowly selected patient population in the clinical trials.”
To be sure, many of these patients who had these adverse events were taking other medications. After all, they are smokers and smokers get sick more often than many of us. But 1/3 of the patients were on no other medicines, and 14% were taking only one medicine in addition to varenicline. The most common “other medicines?” Aspirin and multivitamins. #3? Xanax.
“However, since the clinical trials of varenicline prohibited taking an overwhelming majority of drugs active in the nervous system, we cannot exclude the possibility of a potent interaction with one of more other drugs, especially psychiatric drugs.
I agree with that statement now, and agreed with it two years ago.
So what do you do?
As you probably know, I cannot offer specific medical advice in this blog. I can’t tell you to stop your medicine, or not to start it.
There are benefits and risks involved in any medication, and by any measure we have seen, Chantix is effective in helping people quit smoking (although we await data from “the real world” on how effective Chantix is in typical smokers leading their typical lives).
From the beginning, there was awareness that additional side effect reports would be inevitable. They always are with prescription medicines. No medication is free of risk. That is specifically why I put the link to the FDA’s MedWatch in the original Chantix blog.
Smoking tobacco is bad for your health. Quitting smoking is good for your health. Chantix can help you quit smoking.
So, when these types of reports about adverse drug effects—which many doctors consider preliminary--come to light, I have always recommended that you talk to your doctor or other health care professional and figure out what is best for you. She/he knows you best, and is your best advisor as to what you should do right now if you are taking Chantix, or contemplating starting the medication.
These data do raise some serious concerns. No, they are not peer reviewed, and no they haven’t appeared in a major medical journal.
I’ll leave it to the experts to determine whether the approach used by these researchers is valid, and I am sure there will be comments by many who know more about this research than I do. There is a lot at stake here, not just for the drug company that manufactures and sells Chantix, but for those who want to stop smoking and for the tobacco control community around the world.
It would seem to me that the FDA should now expedite its review of Chantix, which up until this moment has focused on the psychiatric questions that have been raised recently.
There is too much at stake for too many people for the FDA to ignore.
As I write this, I don’t know these serious side effects are a blip on the horizon, or a more serious situation such as what we have seen over this past year with ESAs.
I don’t know, you don’t know, and we need to know.
FDA, please help!!!!
For information on smoking cessation, call the American Cancer Society at 1-800-ACS-2345 any time, day or night. Or go to our website www.cancer.org and check out our "Guide to Quitting Smoking."