Jane S. Ricciuti, RPh, MS

Disclosures

February 19, 2003

In This Article

Estrogens

Premarin
(conjugated estrogens) Tablets

Manufacturer: Wyeth-Ayerst

Drug Approval Classification: Supplemental NDA (approval date: 1/7/03)

New Indications: The revised indications for Premarin reserve its use for the following:

Treatment of moderate to severe vasomotor symptoms (such as "hot flashes") associated with the menopause. (This indication has not changed.)

  • Treatment of moderate to severe symptoms of vulvar and vaginal atrophy (dryness and irritation) associated with the menopause. When these products are being prescribed solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.

  • Prevention of postmenopausal osteoporosis (weak bones). When these products are being prescribed solely for the prevention of postmenopausal osteoporosis, approved nonestrogen treatments should be carefully considered, and estrogens and combined estrogen-progestin products should only be considered for women with significant risk of osteoporosis that outweighs the risks of the drug.

  • Premarin is no longer indicated for the prevention of heart disease.

    Clinical Summary: In a series of risk management efforts by the FDA, it has approved labeling changes for a second time for all estrogen and estrogen plus progestin products for use in postmenopausal women in response to the results from the Women's Health Initiative Studies (WHI) ). [1,2,3,4,5] Labeling changes include a new boxed warning describing the increased risk of cardiovascular disease and cancer.

    1. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002;288:49-57. Abstract.

    2. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-333. Abstract.

    3. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA. 2002;288:872-881. Abstract.

    4. Humphrey LL, Chan BK, Sox HC. Postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease. Ann Intern Med. 2002;137:273-284. Abstract.

    5. Mosca L, Collins P, Herrington DM, et al. Hormone replacement therapy and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 2001;104:499-503. Abstract.

    Adverse Effects: A new boxed warning to the Premarin labeling has been added. It states:

    • Cardiovascular and Other Risks

      -- Estrogens with or without progestins should not be used for the prevention of cardiovascular disease.

      -- The Women's Health Initiative (WHI) reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women during 5 years of treatment with conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo. Other doses of conjugated estrogens and medroxyprogesterone acetate, and other combinations of estrogens and progestins were not studied in the WHI and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

    Premarin (conjugated estrogens) Tablets Labeling

    Premarin (conjugated estrogens) Tablets

    Prempro
    and Premphase
    (conjugated estrogens /medroxyprogesterone acetate) Tablets

    Manufacturer: Wyeth-Ayerst

    Drug Approval Classification: Supplemental NDA (approval date: 1/7/03)

    Indication: The revised indications for Prempro and Premphase reserve its use for the following:

    • Treatment of moderate to severe vasomotor symptoms (such as "hot flashes") associated with the menopause. (This indication has not changed.)

    • Treatment of moderate to severe symptoms of vulvar and vaginal atrophy (dryness and irritation) associated with the menopause. When these products are being prescribed solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.

    • Prevention of postmenopausal osteoporosis (weak bones). When these products are being prescribed solely for the prevention of postmenopausal osteoporosis, approved nonestrogen treatments should be carefully considered, and estrogens and combined estrogen-progestin products should only be considered for women with significant risk of osteoporosis that outweighs the risks of the drug.

    Prempro and Premphase are no longer indicated for the prevention of heart disease.

    Adverse Effects: The following information is included in the boxed warning added to the Prempro and Premphase labeling.

    • Warning

      -- Estrogens and progestins should not be used for the prevention of cardiovascular disease. The Women's Health Initiative (WHI) reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women during 5 years of treatment with conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo. Other doses of conjugated estrogens and medroxyprogesterone acetate, and other combinations of estrogens and progestins were not studied in the WHI and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens and progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

    Prempro and Premphase (conjugated estrogens/medroxyprogesterone acetate) Tablets Labeling

    Prempro and Premphase (conjugated estrogens/medroxyprogesterone acetate) Tablets

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