The U.S. Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) met recently to discuss the use of Wyeth's estrogen plus progestin (E+P) hormone therapy product, Prempro (conjugated estrogens/medroxyprogesterone acetate tablets), for the prevention of postmenopausal osteoporosis. After a review of available data, including presentations by the Women's Health Initiative (WHI) investigators, the consensus of the Committee was that the current labeling for Prempro provides appropriate guidance for its use in the prevention of postmenopausal osteoporosis and does not require modification.
Estrogen and E+P therapies are important therapeutic options because they are the only therapies proven both to relieve menopausal symptoms, such as hot flashes, night sweats, and vaginal atrophy, as well as to concomitantly prevent postmenopausal osteoporosis. "We continue to support the appropriate use of hormone therapy and believe that the availability of estrogen and E+P therapies for the prevention of osteoporosis provides clinicians with a range of therapeutic options for use in individualizing therapy," says Dr. Joseph Camardo, Senior Vice President, Clinical Research and Development for Wyeth Pharmaceuticals, who addressed the Committee on behalf of Wyeth. "A woman's decision to take hormone therapy should be individualized and made in consultation with her doctor, based on her treatment goals and personal health history."
A recent examination of fracture data from the combination E+P arm of WHI, as published in the October 1, 2003 issue of the Journal of the American Medical Association, is consistent with the WHI data initially published in July 2002, finding that women on E+P therapy had a relative risk of hip, spine, and total fractures that was lower by 33 per cent, 35 per cent, and 24 per cent, respectively. The WHI data also show that E+P therapy increases bone mineral density, the primary criterion for defining the prevention of osteoporosis.
Prevalence data from the National Osteoporosis Foundation show that an estimated 44 million Americans are at risk for osteoporosis and low bone mass, 30 million of which are women. At an annual public health cost of more than $17 billion, osteoporosis and low bone mass, characterized by fragile bones and fracture susceptibility, are major public health issues.
Wyeth recently introduced two new low dose hormone therapy products, Prempro(tm) 0.45 mg/1.5 mg and Premarin (conjugated estrogens tablets, USP) 0.45 mg, expanding dosing options to better individualize treatment. FDA and other health experts recommend that postmenopausal hormone therapy be used at the lowest dose for the shortest duration consistent with treatment goals and risks for the individual woman.
Wyeth regularly reviews and updates its product labeling based on new information.
A separate study arm of WHI evaluating the effects of estrogen alone continues, and is scheduled for completion in 2005.
What is the most important information a woman should know about Premarin (a mixture of estrogen hormones) or Prempro(combination of estrogens and a progestin)?
Estrogens increase the chances of getting cancer of the uterus. A woman should report any unusual vaginal bleeding right away while taking these products. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Her health care provider should check any unusual vaginal bleeding to find out the cause.
Do not use estrogens with or without progestins to prevent heart disease, heart attacks, or strokes. Using estrogens with or without progestins may increase a woman's chances of getting heart attacks, strokes, breast cancer, and blood clots. A woman and her health care provider should talk regularly about whether she still needs treatment with estrogens.
Premarin is used after menopause to reduce moderate to severe hot flashes; to treat moderate to severe dryness, itching, and burning in or around the vagina; and to help reduce a woman's chances of getting osteoporosis (thin, weak bones).
Prempro is used after menopause in women with a uterus to reduce moderate to severe hot flashes; to treat moderate to severe dryness, itching, and burning in or around the vagina; and to help reduce a woman's chances of getting osteoporosis (thin, weak bones).
Premarin and Prempro should be used for the shortest duration consistent with a woman's treatment goals and risks. If a woman does not have symptoms, non-estrogen treatments should be carefully considered before taking Premarin or Prempro solely for the prevention of postmenopausal osteoporosis.
In a clinical trial, the most commonly reported side effects (>5%) of Premarin were vaginitis, vaginal bleeding, painful menstruation, and leg cramps.
In a clinical trial, the most commonly reported side effects (>5%) of Prempro 0.45 mg/1.5 mg and Prempro 0.625 mg/2.5 mg were breast pain/enlargement, vaginitis, leg cramps, vaginal spotting/bleeding, and painful menstruation.
Premarin and Prempro should not be used if a woman has unusual vaginal bleeding, has or had cancer of the breast or uterus, had a stroke or heart attack in the past year, has or had blood clots, has liver problems, is allergic to any of the ingredients in Premarin or Prempro or thinks she may be pregnant.