Varenicline Label Changes Downplay Suicide Risk

Megan Brooks

September 30, 2014

Label changes for the smoking cessation drug varenicline (Chantix, Pfizer Inc), requested by Pfizer and approved by the US Food and Drug Administration (FDA), suggest that the risk for suicidal behavior is lower than initially thought.

In a statement, Pfizer said new data from clinical trials and observational study data that further evaluate the neuropsychiatric safety profile of varenicline have been added to the label.

The updated label includes results from a Pfizer meta-analysis of 5 clinical trials that showed no increased risk in the incidence of suicidal ideation and/or behavior in patients treated with varenicline compared with patients treated with placebo, the company said.

The label also includes results from a Pfizer pooled analysis of 18 clinical trials, which showed a similar incidence of common psychiatric events of anxiety, depressed mood, and other mood disorders in patients treated with varenicline compared with patients treated with placebo.

The updated label also includes results from 4 independently conducted, large observational studies, each of which included 10,000 to 30,000 varenicline-treated patients with and without a psychiatric history. The studies assessed the risk for selected serious neuropsychiatric events between varenicline users and uses of prescription nicotine replacement therapy (NRT) or bupropion.

Two studies found no difference in risk for neuropsychiatric hospitalizations between varenicline users and nicotine patch users. However, neither study validated the diagnostic codes used to identify outcomes against medical records, the label notes.

A third study reported no difference in risk for psychiatric adverse events diagnosed during an emergency department visit or inpatient admission between varenicline users and bupropion users.

A fourth study assessed risk for fatal and nonfatal self-harm in users of varenicline compared with users of NRT. Although the occurrence of detected suicide was rare during the 3 months after patients initiated any drug treatment, "this study has important limitations," the label notes.

Revisiting Black Box Warning

Varenicline has been shown to help adults quit smoking and increase their chances of staying abstinent for as long as 1 year compared with placebo. The drug has been prescribed to more than 10 million smokers in the United States, according to Pfizer.

On the basis of the new data, the company has asked the FDA to remove the boxed warning on varenicline regarding serious neuropsychiatric events. The boxed warning was added to the label in 2009 and relates to postmarketing reports of serious neuropsychiatric events in patients treated with varenicline.

The FDA will take up the matter on October 16 at a joint meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee.

According to a statement on the FDA Web site, the committees will discuss safety data from observational studies and a meta-analysis of randomized controlled clinical trials that have been conducted since the original signal of serious neuropsychiatric adverse events with varenicline emerged. The committees will also discuss whether any action needs to be taken regarding how this risk is described in product labeling.

Additional Label Updates

According to Pfizer, the warnings and precautions section of the varenicline label has also been updated to include information on postmarketing reports of increased intoxicating effects of alcohol in patients taking the drug. "Patients are instructed to reduce the amount of alcohol they consume during treatment with Chantix until they know whether Chantix affects their tolerance for alcohol," Pfizer said.

The warnings and precautions section of the drug label has also been updated to include information about new or worsening seizures observed in patients treated with varenicline during clinical trials and in the postmarketing experience. The label advises that the drug be used cautiously in patients with a history of seizures or other factors that can lower the seizure threshold, Pfizer said.

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