J&J Ortho Evra Patch New Warning May Prompt Changes To Lauded TV Ad

Johnson & Johnson may have to modify its novel direct-to-consumer TV commercial for Ortho Evra because of the addition of a bolded warning to labeling for the contraceptive patch.

J&J's Ortho-McNeil division announced Nov. 10 that it would include a warning in Ortho Evra (norelgestromin/ ethinyl estradiol) labeling on increased estrogen exposure with the product.

Updated prescribing information includes a bolded warning stating that "AUC and average concentration at steady state of ethinyl estradiol (EE) are approximately 60% higher in women using Ortho Evra compared with women using an oral contraceptive containing EE 35 mcg."

"However, it is not known whether there are changes in the risk of serious adverse events based on the differences in pharmacokinetic profiles of EE in women using Ortho Evra compared with women using oral contraceptives," the warning notes.

The addition of warning language was based on an FDA and Ortho-McNeil analysis that compared levels of estrogen and progestin hormones in users of Ortho Evra and typical oral contraceptives, the agency said.

"In general, increased estrogen exposure may increase the risk of blood clots," FDA said.

J&J said that it is not currently running any DTC advertisements for Ortho Evra and offered no comment on its future promotional plans.

The firm's recent commercial for the Ortho Evra patch featured a "question and answer" segment between a physician and a patient. Pfizer CEO Hank McKinnell and Abbott CEO Miles White have praised the spot for its direct delivery of risk/benefit information (¹ (Also see "FDA’s Crawford Praises DTC Advertising; PhRMA’s Tauzin Pushes For Change" - Pink Sheet, 2 May, 2005.), p. 12).

The ad discussed the "serious risks" of heart attack, stroke and blood clots with hormonal birth control and emphasized that such risks are increased by smoking. However, it did not include a discussion of increased exposure to estrogen with the patch versus oral contraceptives.

FDA generally requires the "most serious risks" of a product be included in DTC advertising, although information disclosure requirements for promotional advertising are managed on a "case-by-case" basis, the agency said.

Ortho Evra labeling previously included a statement in the Description section about increased estrogen exposure with the patch versus oral contraceptives, as well as a discussion of estrogen exposure in the Pharmacokinetics - Absorption section.

"This level of transdermal release of EE results in exposure to EE greater than that produced by an oral contraceptive product containing 20 micrograms of EE," labeling previously stated.

A possible increased risk of blood clots with Ortho Evra was raised in July in an Associated Press article alleging that the patch may have contributed to the deaths of 12 women from blood clots in 2004.

In responding to the article during its second quarter earnings call, J&J said there were "no fatal events" linked to the patch during clinical trials for the product and pointed to "several inaccuracies" in the story.

Updated labeling for Ortho Evra includes a new section, Transdermal Versus Oral Contraceptives, that compares the pharmacokinetics of the two forms of birth control. In addition, discussion of estrogen exposure was added to the Indications and Usage, Description, Dosage and Administration, and Clinical Pharmacology sections, as well as to the patient package insert.

Ortho-McNeil plans a "Dear Healthcare Professional" letter on the labeling update. The company will also conduct further studies to assess the risk of blood clots in women who use the patch versus those who use oral contraceptives.

In a Nov. 11 press release, Public Citizen lambasted FDA for its actions on Ortho Evra, saying the agency "belatedly acknowledges the increased dangers of using the drug." Public Citizen noted that it issued an alert two months ago on its worstpills.org website warning against Ortho Evra's "increased risk of life-threatening blood clots." The consumer group also pointed to discussion of blood clot risk by an FDA reviewer before the drug was approved.