Smoking Cessation Drugs
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
The U.S. Food and Drug Administration (FDA) is warning that the prescription smoking cessation medicine Chantix (varenicline) can change the way people react to alcohol. In addition, rare accounts of seizures in patients treated with Chantix have been reported. We have approved changes to the Chantix label to warn about these risks. Until patients know how Chantix affects their ability to tolerate alcohol, they should decrease the amount of alcohol they drink. Patients who have a seizure while taking Chantix should stop the medicine and seek medical attention immediately.
Millions of Americans have serious health problems caused by smoking, which can be reduced by quitting. Chantix is a prescription medicine that is FDA-approved to help adults quit smoking. In clinical trials, Chantix increased the likelihood of quitting smoking and “staying quit” for as long as 1 year compared to treatment with a placebo, an inactive treatment.
We reviewed the case series submitted by Pfizer, the manufacturer of Chantix, as well as the cases in the FDA Adverse Event Reporting System (FAERS) database describing patients who drank alcohol during treatment with Chantix and experienced adverse reactions. Some patients experienced decreased tolerance to alcohol, including increased drunkenness, unusual or aggressive behavior, or they had no memory of things that happened (see Data Summary).
We also reviewed FAERS and the medical literature1 for cases of seizures with Chantix and identified cases in which the patients who had seizures while taking Chantix either had no history of seizures or had a seizure disorder that had been well-controlled. In most of these cases, the seizures occurred within the first month of starting Chantix. Information about these risks has been added to the Warnings and Precautionssection of the drug label and to the patient Medication Guide.
We also updated the Warnings and Precautions section of the label to include information about several studies that investigated the risk of neuropsychiatric side effects on mood, behavior, or thinking occurring with Chantix. These included observational studies,2-5 as well as analyses that Pfizer conducted of randomized controlled clinical trial data.6 These studies did not show an increased risk of neuropsychiatric side effects with Chantix; however, they did not examine all types of neuropsychiatric side effects, and they had limitations that prevented us from drawing reliable conclusions.
We previously communicated about possible serious neuropsychiatric side effects with Chantix in 2009 and2011, and these recent studies were discussed at an FDA Advisory Committee meeting in October 2014. Pfizer is conducting a large clinical safety trial of Chantix to investigate this risk and results from this study are expected in late 2015. We will update the public as appropriate when this new information becomes available.
Source : FDA (April 2015)
FDA risk finding adds fuel to fire around Pfizer's Chantix
The FDA says Pfizer's ($PFE) smoking-cessation drug Chantix is probably the cause of higher risk for heart attacks among those who use it, but it can't be sure. It says it's certain that smoking can kill you and Chantix can help some people stop.
The agency statement says a meta-analysis of clinical trials for the controversial drug charted a higher rate of heart attacks or strokes in patients using the treatment than in those who took placebos. The results were not statistically significant, the FDA said, but it appears "more likely that it is related to the drug and not purely a chance finding," the agency said.
Chantix has been tied to heart risks and to risk of suicide, which its label warns against. As Bloomberg points out, the FDA last year asked Pfizer to further study the risks with the extended analysis. The agency's announcement Wednesday followed that analysis.
Pfizer has been battling a number of lawsuits related to health concerns. The company recently settled some by families who say members killed themselves after taking Chantix. The lawyers for one claimant recently got a court to agree that they could put Pfizer CEO Ian Read on the stand to testify about Chantix.
The FDA was adamant in reminding people that there are huge heart risks tied to smoking and that the benefits of stopping the habit are "immediate and substantial." It suggests doctors and patients take all of that into consideration when deciding if they should use Chantix.
Source : FiercePharma
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FDA Drug Safety Communication: Safety review update of Chantix (varenicline) and risk of neuropsychiatric adverse events
The U.S. Food and Drug Administration (FDA) has reviewed the results from two FDA-sponsored epidemiological studies that evaluated the risk of neuropsychiatric adverse events associated with the smoking cessation drug Chantix (varenicline).
Neither study found a difference in risk of neuropsychiatric hospitalizations between Chantix and nicotine replacement therapy (NRT; e.g., NicoDerm patches). However, both studies had a number of study design limitations, including only assessing neuropsychiatric events that resulted in hospitalization, and not having a large enough sample size to detect rare adverse events (see Data Summary below for more information). Although these two studies did not suggest an increased risk of neuropsychiatric events that result in hospitalization, they do not rule out an increased risk of other neuropsychiatric events with Chantix.
Healthcare professionals and patients should continue to follow the recommendations in the physician label and the patient Medication Guide, and to monitor for neuropsychiatric symptoms when prescribing or using Chantix. Based on FDA’s assessment of currently available data, the Agency continues to believe that the drug’s benefits outweigh the risks and the current warnings in the Chantix drug label are appropriate.
The risk of serious neuropsychiatric events with Chantix is currently highlighted in the Boxed Warning and Warnings and Precautions section of the physician label and in the patient Medication Guide. Such events can include changes in behavior, hostility, agitation, depressed mood, and suicidal thoughts or actions. These warnings were based on postmarketing reports describing changes in mood and behavior during and after Chantix use (see 2008 Public Health Advisory and 2009 Public Health Advisory).
FDA is continuing to evaluate the risk of neuropsychiatric events with Chantix. The drug manufacturer is conducting a large safety clinical trial of Chantix to assess neuropsychiatric adverse events, and results from this study are expected in 2017.
Additional Information for Patients
- Some patients have experienced changes in behavior, hostility, agitation, depressed mood, and suicidal thoughts or actions while using Chantix to help them quit smoking. Some patients had these symptoms soon after they began taking Chantix, and others developed them after several weeks of treatment, or after stopping Chantix.
- Before taking Chantix, patients should inform their healthcare professional if they have ever had depression or other mental health problems.
- If a patient develops agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for them, or if a patient develops suicidal ideation or behavior, they should immediately discontinue Chantix and report these symptoms to their healthcare professional.
- Patients should read the Medication Guide that they get along with their Chantix prescription. It explains the risks associated with the use of Chantix.
- Patients should report serious side effects from the use of Chantix to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of this page.
- Healthcare professionals should continue to follow the recommendations in the drug label when prescribing Chantix.
- Serious neuropsychiatric adverse events, including, but not limited to, depression, suicidal ideation, suicide attempt, and completed suicide, have been reported in patients taking Chantix.
- Healthcare professionals should ask patients about any history of psychiatric illness, especially depression, prior to initiating treatment with Chantix.
- Healthcare professionals should advise patients and caregivers that the patient should immediately stop taking Chantix and contact a healthcare professional 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 or shortly after discontinuing Chantix.
- Healthcare professionals should encourage patients to read the Medication Guide they receive along with their Chantix prescription.
- Healthcare professionals should report adverse events involving Chantix to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of this page
FDA sponsored two observational studies of neuropsychiatric adverse events with Chantix. One was conducted by the Department of Veterans Affairs’ (VA) Center for Medication Safety (VAMedSAFE), and the other by the Department of Defense’s (DoD) U.S. Army Medical Command’s Pharmacovigilance Center (PVC; hereafter referred to as the “DoD study”).
The VA study was a retrospective cohort study to evaluate the incidence of mental health hospitalizations among veterans using Chantix or nicotine replacement therapy (NRT). Patients starting Chantix or NRT between May 1, 2006 and September 30, 2007, but with no Chantix or NRT use in the previous year, were selected and matched in a 1:1 ratio by use of propensity scores (reflecting demographic characteristics, comorbidities, and psychiatric history). Propensity score matching is a method of balancing patient characteristics between the treatment groups being compared. The study’s main outcome was psychiatric hospitalization, with a coded primary discharge diagnosis for one of a number of psychiatric conditions, including drug-induced mental disorders, schizophrenic disorders, other psychotic disorders, depression, suicide attempts, and other mood disorders. Because the spontaneous adverse event reports for Chantix suggested a relatively short time to onset for psychiatric reactions, psychiatric hospitalizations for selected psychiatric diagnoses were assessed for 30 days after a prescription fill for Chantix or NRT.
The VA study population included 14,131 Chantix users and an equal number of NRT users. Among these patients, there were 16 psychiatric hospitalizations in Chantix-treated patients, and 21 in NRT patients. A Cox proportional hazards analysis showed no statistically significant difference in the risk of psychiatric hospitalization for Chantix users compared to NRT users (hazard ratio [HR] for Chantix/NRT = 0.76; 95% confidence interval [CI] 0.40-1.46). A complementary analysis in a prevalent user cohort of patients who had used NRT in the past before initiating Chantix or refilling an NRT prescription also showed no statistically significant difference in psychiatric hospitalizations between the two treatment groups. Also, the results using time periods longer than 30 days after a prescription fill were similar.
The DoD study was also a retrospective cohort study comparing the acute (30-day) rates of hospitalizations for neuropsychiatric adverse events among new users of Chantix (n=19,933) and NRT patch (n=15,867) who started therapy from August 1, 2006 to August 31, 2007 in the Military Health System. Patients were drawn from active duty military personnel, military retirees, and the dependents of either. Chantix users were matched using propensity scores to NRT users, with subgrouping by concomitant use of the prescription smoking cessation drug bupropion. After propensity score matching, there were 11,978 Chantix users and an equal number of NRT users in the study sample. The main outcome was a primary hospital discharge diagnosis for a neuropsychiatric condition. The following neuropsychiatric diagnoses were identified using ICD-9 codes: drug-induced mental disorders, transient mental disorders, schizophrenia, episodic and mood disorders, delusional disorders, other nonorganic psychoses, anxiety disorders, personality disorders, posttraumatic stress disorder (PTSD), depressive disorders, and suicide attempt.
In the DoD study’s propensity score matched samples, there were 18 psychiatric hospitalizations among Chantix users and 16 among NRT users. A Cox proportional hazard analysis did not show a statistically significant difference (HR for Chantix/NRT = 1.13; 95% CI 0.57-2.21). There was also no significant difference in psychiatric hospitalizations for Chantix users compared to NRT users when patients with concomitant bupropion use were excluded (HR = 0.91; 95% CI 0.39-2.14). Most (43) of the 55 neuropsychiatric hospitalizations (18 of the 23 Chantix events and 25 of the 32 NRT events) occurred in patients with a neuropsychiatric diagnosis in the year preceding the Chantix/NRT prescription fill, although such patients were a minority of the cohorts. Among patients with a neuropsychiatric diagnosis in the preceding year, 0.7% of Chantix users and 1.4% of NRT users were hospitalized for psychiatric care.
A strength of both studies was the inclusion of patients with pre-existing psychiatric disorders, since these patients were typically excluded from the clinical trials conducted with Chantix before it was approved (i.e., in premarketing trials).
Although neither study found a measurable increase in psychiatric hospitalizations with Chantix versus NRT, these results should be interpreted with the limitations of both studies in mind. The sample sizes in both studies were too small to assess rare, idiosyncratic events. Focusing on psychiatric hospitalizations is a useful approach for assessing the risk of serious neuropsychiatric adverse events, but it does not allow an assessment of less severe neuropsychiatric events that did not result in a psychiatric hospitalization (in the periods studied). Although the studies did not find a difference in psychiatric hospitalization risk between Chantix and NRT, they do not exclude the possibility that both treatments carry a similar risk. In addition, the VA study did not include PTSD as a reason for psychiatric hospitalization; one published report suggested that patients with PTSD may be more susceptible to the neuropsychiatric adverse effects of Chantix.3 Also, the DoD study only assessed a 30-day risk period following the fill date of the first qualifying prescription for Chantix or NRT and did not evaluate the rate of neuropsychiatric hospitalizations occurring over a longer duration following a Chantix prescription fill.
Overall, FDA has determined that the current warnings in the Chantix drug label, based on postmarketing surveillance reports, remain appropriate.
FDA is continuing to evaluate the risk of neuropsychiatric adverse events with Chantix. The manufacturer of Chantix, Pfizer, is conducting a large safety clinical trial of Chantix to assess neuropsychiatric adverse events as outcomes. Results from this trial are expected in 2017.
- MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US). Drug & Supplements Monograph: Varenicline. Available from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a606024.html. Accessed September 6, 2011.
- SDI, Vector One®: National (VONA) and Total Patient Tracker (TPT). May 2006-July 2011. Data extracted September 2011.
- Campbell AR, Anderson KD. Mental health stability in veterans with posttraumatic stress disorder receiving varenicline. Am J Health Syst Pharm. 2010;67:1832-7.
Facts about Chantix (varenicline)
- A prescription medicine used to help adults quit smoking
- Increases the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo.
- Works by blocking the effects of nicotine (from smoking) on the brain.1
- From approval in May 2006 through July 2011, approximately 21.8 million Chantix prescriptions were dispensed and approximately 8.9 million patients received Chantix prescriptions from U.S. outpatient retail pharmacies.2
Source : FDA
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Pfizer Did Not Report Chantix Side Effects Correctly?
Adverse event data from the third quarter of 2010 show the risks of serious psychiatric side effects of Chantix, the smoking-cessation drug, were previously underestimated because Pfizer apparently failed to correctly submit hundreds of these episodes to the FDA, according to an analysis by the Institute for Safe
Medicine Practices, a non-profit that regulary reviews the FDA adverse event database.
Notably, the ISMP found 150 cases of completed suicides, some of which dated back to 2007, that were not reported promptly as suicides within 15 days as required. Instead, the drugmaker apparently coded the suicides as “expected adverse events” among 26,000 such events, and added these to a quarterly
periodic report, which is how less important, non-serious side effects are sent to the FDA.
What ISMP calls a “breakdown in safety surveillance” meant that, until July 2010, FDA analysts were not aware of more than half of the reported suicide cases in which Chantix was the primary suspect. And the agency also did not have available hundreds of other reported cases of serious psychiatric side effects,
including psychosis, depression, or attempted suicide.
Consequently, the non-profit says the FDA should investigate why Pfizer was reporting suicide deaths as “expected adverse events,” especially prior to 2009, when safety concerns were being reviewed by the FDA. ISMP adds that this is not the first time issues have been raised with Pfizer’s adverse event reporting.
The agency last year sent Pfizer a warning letter for failing to meet regulatory deadlines for reporting serious side effects with many of its drugs, although Chantix was not among those listed (the report is available here).
This is only the latest difficulty for Pfizer and its Chantix pill. For the past four years, the drug has caused a stir after being associated with suicidal behavior and vivid dreams (see here and here). Consequently, the government banned the Pfizer drug for pilots and licenses wouldn’t be issued to truck drivers taking the med
(see this). The FDA subsequently imposed a risk management program and Pfizer added warnings.
A Pfizer spokesman sends us this to explain why there was a sudden spike in reports in the third quarter of 2010: “Pfizer has complied fully with FDA requirements regarding adverse events reports it has received related to the use of Chantix. The company has reviewed and analyzed these reports, shared them
with the FDA, and communicated with the FDA with respect to them. All post-marketing reports of adverse events are reviewed by Pfizer, and reported to regulators, including the FDA.
“During discussions with the FDA in December 2009 and January 2010 regarding voluntary implementation of periodic Individual Case Safety Report submissions in electronic format, the FDA requested that Pfizer use this new format to resubmit the ICSRs for our products, including Chantix. This new format was to
facilitate entry of reports into the AERS database. As a result of this request, Chantix reports previously submitted from 2006-2009 were resubmitted in third quarter 2010, with the majority of these reports being resubmitted in July.”
ISMP, for its part, had begun examining Chantix adverse event reports in May 2008, after noticing these outnumbered reports for other meds, including opioids and chemotherapy agents, which are known to be toxic (read this). At the time, you may recall Pfizer explained that stronger warnings were not necessary, and
it was not surprising to see psychiatric side effects among smokers, especially those who might be experiencing nicotine withdrawal.
More recently, though, a pair of studies have linked to Chantix to disturbing behavior. One study in PLoS One found an association with serious acts of violence, such as physical abuse, physical assault and homicide (read here). Another that was published in the Annals of Pharmacotherapy cited links to violent and aggressive thoughts and acts, and also identified some of the common characteristics among people using the pill and their subsequent behavior (see this).
Two of the authors of these studies, by the way, are also on the ISMP Quarter Watch staff that reviews the FDA adverse event reporting system. One of them, Thomas Moore, recently agreed to serve as a consulting expert in the civil litigation regarding Chantix. For that reason, Pfizer declined to respond to
ISMP prior to the release of its report. In the past, ISMP says Pfizer regularly declined to comment, but did not offer any reason.
[UPDATE: On May 19, the FDA issued a statement; here is an excerpt: "In July 2010, Pfizer, at the request of FDA, resubmitted a large number of adverse event reports that were initially sent to the agency in a way that did not allow for comprehensive evaluation. Although this resubmission included thousands of
reports of potential adverse events, these events were spread out over a number of years, and had been reported to the agency periodically in summary safety reports. These reports confirm what we already knew about Chantix and would not have changed the Agency's position on the drug's risks and benefits, given that
the data in these reports were consistent with those that led to the 2009 labeling change. At this point, based on the data, FDA does not have any new safety concerns with Chantix, though those that have been established remain under active review" (read the complete statement here).
Chantix lawsuits regularly make headlines. The latest was filed earlier this month by the children of a Pittsburgh man who killed his wife and himself in 2009 while taking the pill. According to the complaint, Sean Wain, 34, had been using Chantix for up to two weeks before he began experiencing side effects that
allegedly prompted him to kill his wife and himself. The murder-suicide left behind four minor children (you can read the lawsuit here).
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