FDA Warns Pfizer Over Zithromax Brochure

File this under 'let's see if anyone at the FDA is paying attention.' Before distributing or airing various promotional materials, drugmakers are required to submit these items to the FDA for review. Why? The agency wants to make sure the materials include all the necessary safety and efficacy information. Every drugmakers knows this - and certainly, the largest drugmakers have regulatory and marketing personnel to plan for these submissions accordingly.

Pfizer, nonetheless, managed to run afoul of the FDA with a promotional brochure for its Zithromax antibiotic. And Pfizer ran afoul in a big way. Its brochure was deemed false or misleading because it omitted and minimized important risk information, made unsubstantiated superiority claims, omitted material facts, broadened the indication for the drug product, made misleading efficacy claims and made unsubstantiated claims, according to a June 19 untitled letter. Another way of looking at this is what did Pfizer not do incorrectly?

For instance, the brochure contains info about the most commonly reported adverse events, but "fails to include information regarding a serious warning and precaution" the FDA writes. "Specifically, the brochure omits the important risk of QT prolongation associated with Zmax use." The brochure also minimizes risks associated with usage by failing to disclose that severe and fatal allergic and skin reactions have been observed" with Zithromax, which was called Zmax.

The Pfizer team also managed to emphasize efficacy over risk. How so? "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," the FDA notes. "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." As a result, the "overall effect... undermines the communication of important risk information" and misleadingly suggests Zmax is safer than demonstrated.

Then there was an unsubstantiated safety claim. The brochures says: "Zmax is different from other drugs, because it’s not released in the stomach. Zmax goes to work in the small intestine so it’s easier on the stomach. Unlike many other drugs, you should take Zmax on an empty stomach.” But there are no head-to-head studies to support the contention and the prescribing information states that vomiting, diarrhea, loose stools, and abdominal pain were the most common adverse events reported in the pediatric studies. The brochure is aimed at adults and children.

There is, in fact, a laundry list of problems with the brochure: Pfizer broadened the indication by implying Zmax is suitable for combating infections beyond what was approved and suggested the antibiotic works against the common cold and flu; made an unsubstantiated superiority claim based on dosing and also failed to support claims that were made based on telephone surveys.

In this case, the brochure states that 84 percent of adult patients said they would most likely take Zmax again for the same infection and 78 percent of parents said they would most likely use Zmax to treat their children again. But the FDA counters that such responses are "not sufficient to support the outcomes claimed" because these cannot "adequately assess all of the various factors," such as all aspects of efficacy, adverse events, and cost, which may influence patient or caretaker decisions to take any particular medication again.

The FDA told Pfizer to respond by July 3 and we have written the drugmaker for comment. We will update you accordingly. Meanwhile, YOU CAN READ THE LETTER AND SEE THE BROCHURE RIGHT HERE.

[UPDATE: A Pfizer spokesman wrote us this: "Pfizer discontinued from use the Zmax Patient Education Brochure cited in the Office of Prescription Drug Promotion letter prior to the issuance of the Notice of Violation. We are working to address the FDA’s concerns about the brochure. Pfizer is committed to educating physicians and patients about our medicines. We recognize the importance of fair and balanced patient education materials for our medicines."]