FDA panel okays revised osteoporosis indication for PremPro: discussion of WHI data.(News)

BETHESDA, MD. -- An independent expert panel convened by the Food and Drug Administration has agreed that the revised osteoporosis indication for PremPro, changed earlier this year to reflect the findings of the Women's Health Initiative, is adequate.

The FDA's Endocrinologic and Metabolic Drugs Advisory Committee panel came to this consensus at the end of a meeting called by the agency to review data from the trial and consider the implications of long-term use of these products for the prevention and/or treatment of postmenopausal osteoporosis.

This was the first time Women's Health Initiative (WHI) data have been discussed at an FDA advisory panel meeting.

In January, the osteoporosis indication for PremPro (conjugated estrogens/medroxyprogesterone, 0.625 / 2.5 and 0.625 / 5) and Premarin (conjugated estrogens) was updated to include the statement that when these products are prescribed "solely" for the prevention of postmenopausal osteoporosis, approved nonestrogen treatment should be carefully considered, and estrogens and combined estrogen-progestin products should be considered only for women with a significant risk of osteoporosis that outweighs the risks of the drug.

The same label changes applied to the lower dose formulations of PremPro (0.45 mg/1.5 mg and 0.3 mg/1.5 mg) when they were approved in April and June, respectively.

"Collectively, we can't think of a better way" to state the information on the osteoporosis indication, said acting panel chair Michael McClung, director of the Oregon Osteoporosis Center, Portland. The changes clarify that the use is for prevention and not treatment, he said, and the reminder that there are alternative therapies for preventing bone loss represents "great progress."

At the meeting, principal investigators from the WHI trial of estrogen and progestin in postmenopausal women and officials from the FDA and Wyeth, the maker of PremPro, made presentations on the data and implications of the estrogen-progestin arm of the WHI, including a recently published analysis of the osteoporosis data. (See story on p. 1, continued above.) That study concluded that, despite the increased bone mineral density and reduction in fracture risk associated with the use of PremPro in postmenopausal women, it should not be recommended for preventing or treating osteoporosis in women who don't have vasomotor symptoms, "given the overall unfavorable risk-benefit ratio and the availability of other agents" (JAMA 290[13]: 1729-38, 2003).