FDA Drug Ad Warning Letters Total Four In September; J&J Cited Three Times

FDA's drug ad division posted four warning letters to its website in the second half of September, three for Johnson & Johnson ads.

The uptick in warning letters over the period appears to be more a coincidence in timing than indicative of a higher degree of enforcement by agency.

Division of Drug Marketing, Advertising & Communications said the issuance of several letters quickly is a matter of when final steps in the review process are completed.

As to the concentration of letters for J&J products, "this is the result of DDMAC acting on the violations that are occurring in the promotion of prescription drugs," FDA said.

The most recent J&J letter concerns a patient promotional aid for the advanced prostate cancer treatment Viadur (leuprolide acetate implant).

FDA cited a Viadur "patient disc puzzle" for failing to include labeled risks or adequate directions for use.

"The statement 'Please see patient safety information at viadur.com or call 1-866-2VIADUR' does not substitute for the PI," the Sept. 21 ¹ Viadur letter states.

Bayer has marketed and distributed Viadur for J&J since March 2001 and says that labeling was delivered with the promotional materials.

The patient disc puzzle includes the following statements: "For the treatment of symptoms of advanced prostate cancer"; "Hey, you got a choice of 3, 4, or 12 injections or a 1-year implant"; and "The only once-a-year hormone therapy for advanced prostate cancer."

"The patient disc puzzle includes none of the risk information" from labeling, the letter states.

The materials were distributed by Bayer sales reps between April and May of 2004. Each rep received 100 disc puzzles which Bayer said were intended for physicians only.

J&J must provide FDA with a written response to the Viadur warning letter that includes "a plan of action to disseminate truthful, non-misleading, and complete information to the audience(s) that received the violative promotional materials," the agency said.

The two companies will work together to address the issue and will respond to the FDA's letter with a corrective action plan by the Oct. 5 deadline set by the agency. Distribution of the aid has ceased.

The Viadur letter followed two others issued on J&J products in recent weeks.

The Topamax website and a sales aid were cited for insufficient safety information (² (Also see "Topamax Draws FDA Warning Letter For Promoting Unsafe Use In Children" - Pink Sheet, 27 Sep, 2004.), p. 8).

J&J was also warned Sept. 2 about Duragesic promotions that FDA said used inappropriate data to make comparative claims to other pain agents (³ (Also see "FDA Cites J&J Duragesic Promotion For Misleading Safety Profile" - Pink Sheet, 14 Sep, 2004.), p. 24).

The fourth September ad division warning letter went to Boehringer Ingelheim for an ad for Atrovent (ipratropium) and Combivent (ipratropium/albuterol).

The labeling piece reviewed by FDA "is false or misleading because it makes unsubstantiated effectiveness claims for, and omits material facts about Atrovent and Combivent," a Sept. 23 warning letter states.

The ad features birthday candles being blown out and includes the following efficacy claims for treatment of chronic obstructive pulmonary disease: "Anticholinergics. Essential for COPD" and "The COPD Essentials."

"These claims suggest that anticholinergics are essential for the treatment of COPD, and that COPD is not appropriately treated without an anticholinergic," FDA said.

This is false or misleading, because COPD can be treated without using anticholinergics," the ⁴ BI letter states.

The agency said the ad also fails to present material facts concerning limitations on the safety and effectiveness of Atrovent and Combivent in COPD.

"Specifically, it fails to disclose that Atrovent is indicated as a bronchodilatory only for maintenance treatment for bronchospasm in patients with COPD, and that Combivent is only indicated for use in patients with COPD who are on a regular bronchodilator and who continue to have evidence of bronchospasm and require a second bronchodilator."

The agency noted that "the asterisked statement, 'Maintenance therapy,' which is presented in small type at the bottom left-hand side of the page, does not remedy this misleading presentation."

The ad refers viewers to a website for more information and contains the statement, "Please see Brief Summaries of Prescribing Information on accompanying pages."

But the ad itself "provides no information about the risks" described in labeling for the two products.

"For the piece to be truthful and non-misleading, it must contain risk information in each part as necessary to qualify any safety or effectiveness claims made in that part," FDA said.

Atrovent is contraindicated in patients with a history of hypersensitivity to soya lecithin or related food products and contains a warning about hypersensitivity reactions.

Combivent labeling says the drug "can produce paradoxical bronchospasm that can be life threatening" and bears a warning on cardiovascular effects.

The agency requests immediate discontinuation of the promotional materials and a response to its letter by Oct. 7.

BI said the ⁵ ad, which appeared in a publication distributed to consumers by the company, is no longer in use.

BI also received an "untitled letter" from FDA citing improper Viramune (nevirapine) ads Sept. 22 (⁶ 'The Pink Sheet' Sept. 27, 2004, In Brief).