Keep Chantix Black Box Warning, FDA Panel Says

Megan Brooks

October 17, 2014

The black box warning on antismoking drug varenicline (Chantix, Pfizer Inc) should not be removed at this time, a US Food and Drug Administration (FDA) panel recommends.

On the basis of updated data on the risk for serious neuropsychiatric adverse events with varenicline that were provided by Pfizer, 11 panel members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted to retain the current boxed warning statements and to reassess after the ongoing postmarketing randomized controlled trial designed to capture serious neuropsychiatric adverse events is complete.

Six panel members voted to modify the language in the black box warning, and one voted to remove the black box warning statements regarding the risk for serious neuropsychiatric adverse events.

Since it was approved as a smoking cessation aid in 2006, varenicline has been linked to serious neuropsychiatric events, including suicidal thoughts and behavior and aggressive/irrational behavior. The FDA placed a black box warning on the product in 2009, highlighting this risk.

Observational studies and a Pfizer-sponsored meta-analysis of five clinical trials conducted since the original signal of neuropsychiatric side effects with varenicline emerged suggest that the risk for suicidal behavior is lower than initially thought, Pfizer said.

Last month, the FDA approved several updates to the Chantix label requested by Pfizer to reflect the new data.

Time to "Unring the Bell"?

Pfizer also asked the FDA revisit the black box warning on the Chantix label, in the hopes of getting it removed.

At the meeting, Pfizer's Christopher Wohlberg, MD, PhD, said that on the basis of "convergence" of the new data, "it's time to unring the alarm bell" on varenicline. "We think the available evidence is inconsistent with a boxed warning."

Most of the panel members disagreed.

In a report issued earlier this week ahead of today's committee meeting, FDA reviewers also recommended that the black box warning on varenicline remain.

The reviewers had "concerns about the validity of the findings from Pfizer's meta-analyses and published observational studies."

They noted that observational postmarketing studies submitted by Pfizer "had a number of study design limitations" and noted that these limitations may "underestimate" the actual incidence of neuropsychiatric adverse events associated with varenicline.

The reviewers also felt that removing the black box warning "could be interpreted as confirming 'no association' between varenicline use and neuropsychiatric risk, which is not supported by currently available observational data."

They said it might be "more reasonable" to decide on the black box issue after completion of a phase 4 trial of varenicline's neuropsychiatric safety, due in August 2016.

Most of the panel members agreed it would be wise to wait for the phase 4 data before removing the black box warning on varenicline.

The panel voiced "excitement about being on the cusp about getting good data" on this issue, noted panel moderator Ruth Parker, MD, of Emory University School of Medicine, Atlanta, Georgia.

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