SILVER SPRING, MD. – The boxed warning about the risk of serious neuropsychiatric effects associated with the smoking cessation drug varenicline should remain on the drug’s label, and the need for this warning can be reevaluated when the results of a postmarketing safety study become available next year, according to the majority of a Food and Drug Administration advisory panel.
On Oct. 16, at a joint meeting of the FDA’s Psychopharmacologic Drugs and the Drug Safety and Risk Management Advisory committees, 11 of the 18 panelists voted to retain the boxed warning about neuropsychiatric symptoms and suicidality, agreeing that a decision about whether to retain the warning should not be made until the results of the study are available.
Pfizer, which manufactures varenicline, a nicotinic receptor partial agonist in a tablet formulation, as Chantix, is conducting the prospective, randomized, double-blind study comparing neuropsychiatric events in 8,000 smokers, with and without a psychiatric history, treated with varenicline, nicotine replacement therapy, bupropion, or placebo. Although the results are expected in 2015, the company maintained that the boxed warning is no longer justified and can be put in the warnings and precautions section, based on analyses of observational studies and randomized clinical trials. The company submitted those analyses to the FDA earlier this year.
The boxed warning in the drug’s prescribing information states that the serious events reported in patients taking the drug include but “are not limited to” depression, suicidal ideation, suicide attempts, and completed suicides; and that some cases “may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking.” The reason the boxed warning is used for this drug is that there is a “serious adverse reaction that can be prevented or reduced in frequency or severity,” the FDA said.
Because the precedent for removing a boxed warning from a drug label is limited and the FDA’s view that the decision should consider the final results of the postmarketing trial, the agency convened the joint meeting to review the analyses submitted by the company. Overall, the panelists were not convinced by the analyses. They cited various weaknesses in the observational studies and the meta-analysis, including questions about whether the correct outcomes were being captured.