The US Food and Drug Administration's (FDA) Office of Prescription Drug Promotion (OPDP) recently sent an untitled letter to pharmaceutical manufacturing giant Pfizer for allegedly marketing its extended-released antibiotic Zmax (azithromycin) using misleading, unproven and incomplete information.
The 19 June untitled letter focuses on a brochure produced by Pfizer to promote Zmax.
FDA claims the company minimized several risks factors-including severe and potentially fatal allergic and skin reactions-by failing to present information about the risks in a prominent or easily readable way.
"The brochure prominently presents efficacy claims in large bolded font size and in colorful text and graphics surrounded by a significant amount of white space; in contrast, the risk information is placed in obscure locations, in block paragraph format, without the use of headers or other signals to alert readers to its significance," FDA explained. "The overall effect of this presentation undermines the communication of important risk information, minimizing the risks associated with Zmax, and misleadingly suggests that Zmax is safer than has been demonstrated."
Another potentially dangerous cardiovascular problem resulting from QT prolongation was omitted, which FDA said "misleadingly suggests that the drug is safer than has been demonstrated."
Pfizer was also chided by FDA for allegedly suggesting Zmax "demonstrates a superior safety profile when compared to other antibiotics due to the supposed superior tolerability of the drug." FDA said it had not seen any studies supporting the "implication" contained within the advertisement, and was in fact aware of some data contesting its claim that pediatric patients tolerated the drug well.
'Omission of Material Facts'
OPDP's letter goes on to cite Pfizer for five additional alleged violations: omitting "material facts," suggesting off-label uses for Zmax, presenting unsubstantiated superiority claims, making misleading efficacy claims and other unsubstantiated claims.
FDA said the advertisement fails to include information on the recommended course of action to take if a patient vomits after taking the drug, information about which antibiotics it is comparable to in studies, or substantiate claims for proving clinical superiority.
In addition, OPDP said Pfizer's advertisement claimed Zmax is indicated to treat a broad range of infections "when this is not the case." FDA honed in on the advertisement's use of the word "including" to mean a nearly limitless variety of indications when instead the company had only listed its two approved indications after the word. The agency took this to be a broadening of the label and potentially off-label promotion.
Finally, US regulators took aim at claims used by Pfizer that highlighted the views of consumers. The company asked consumers whether they would use Zmax again if they had the same infection, whether they would use Zmax to treat the same infection in their children and if the product "made it much easier to complete treatment as directed." OPDP said the claims were misleading in that they "are not supported by substantial evidence or substantial clinical experience."
"Specifically, the support for these claims is based on patient and caretaker responses to … telephone survey questions approximately 5-10 days after taking Zmax," explained FDA. "The use of responses to these survey questions is not sufficient to support the outcomes claimed because these survey questions cannot adequately assess all of the various factors which may influence patients' or caretakers' decision to take any particular treatment again."
FDA said it is requesting that Pfizer "immediately cease the dissemination of violative promotional materials for Zmax such as those described [in the letter]," and required a response to the claims by 3 July.
Regulatory Focus reached out to Pfizer for comment but had not received a response by the time of publication.
FDA's Letter to Pfizer
Pfizer's Zmax Advertisement