Endo’s Lidoderm Mailings Draw FDA Warning Letter For Unsubstantiated Claims

FDA asks Endo to disseminate “corrective messages” to doctors who received the violative promotional materials, which the agency says omit risk information and contain unsubstantiated effectiveness claims.

Two professional direct mail pieces used by Endo to promote Lidoderm contain unsubstantiated effectiveness claims, omit and minimize risk information and fail to communicate an indication limitation, FDA says.

In a June 28 ^FDL-1 warning letter to Endo, FDA's Division of Drug Marketing, Advertising & Communications stated the promotional materials for Lidoderm (lidocaine patch 5%) "may encourage use of Lidoderm in circumstances other than those in which the drug has been shown to be safe and effective."

One of the two flyers was distributed to primary care physicians beginning in June, while the other was mailed to pain management specialists and primary care physicians in 2004, according to Endo.

Both pieces make effectiveness claims that "have not been demonstrated by substantial evidence or substantial clinical experience," the warning letter says.

For example, the more recent flyer includes the statements: "2 out of 3 patients (n=310) achieved reduction in pain intensity at week 1," "continue with Lidoderm and more of your patients may respond" and "4 our of 5 patients (n=310) achieved reduction in pain intensity at week 2, with efficacy sustained for the duration of the trial."

However, FDA said the study used to support the claims was an open-label, single-arm study without a control group, rather than a well-controlled study.

"Without a control group and blinding to reduce the possibility of bias, subjective endpoints such as 'pain intensity' and 'quality of life' cannot be properly assessed," the ad division said.

General effectiveness claims, such as statements that Lidoderm provides "improvement in pain intensity" and "improvement in quality of life," fail to reveal important risks associated with the product and presented in labeling, the letter adds.

Both pieces, for example, omit serious warnings in labeling regarding accidental exposure in children and excessive dosing that could lead to high blood concentrations and serious adverse events, FDA said.

The agency already cited Endo for omitting risk information in a previous sales aid for Lidoderm; DDMAC sent the company an "untitled" letter in November 1999, the letter states.

"In addition to omitting important risk information, the direct mailing pieces also misleadingly minimize the risks they do mention," the letter continues. Both pieces point solely to localized rash as the most common adverse event associated with Lidoderm.

However, FDA said, "these statements are insufficient to describe the myriad of application site reactions associated with Lidoderm use" in labeling.

Claims used in the flyers that Lidoderm is for "the neuropathic pain of postherpetic neuralgia (PHN)" fail to communicate an important limitation in the approved indication for Lidoderm, that the product "should be applied only to intact skin," the letter adds.

"By failing to adequately communicate Lidoderm's approved indication, the direct mailing pieces fail to appropriately caution against unsafe use of Lidoderm," including application to broken or inflamed skin," FDA said.

The ad division requested that Endo immediately discontinue distribution of violative promotional material for Lidoderm, including the two direct mail pieces, and submit a response to the agency by July 13.

FDA also asks the company to propose a plan for contacting physicians who received the mailings at issue.

"We request, further, that your submission include a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective messages about the issues discussed in this letter to the audience(s) that received the violative promotional materials," the letter states.

Endo said it has not yet decided how it will respond to DDMAC's letter.

- Andrew Dove