Usual Adult Dose for Osteoporosis

1 tablet orally once a day

Two regimens available, either

• Regimen 1: A combined conjugated estrogen-medroxyprogesterone tablet taken once a day [Prempro(R)])
• Available in various strengths (0.3 mg-1.5 mg; 0.45 mg/1.5 mg; 0.625 mg-2.5 mg; or 0.625 mg-5 mg)

-OR-

• Regimen 2: Two separate tablets taken sequentially (Premphase[R]:
• Conjugated estrogen taken once a day on days 1 through 14 (conjugated estrogen 0.625 mg)
• Combined conjugated estrogen-medroxyprogesterone taken once a day on days 15 through 28 (conjugated estrogen 0.625 mg-medroxyprogesterone 5 mg)

Comments:

• This drug should be considered for the prevention of postmenopausal osteoporosis only after considering non-estrogen therapies, and then used only for women at significant risk of osteoporosis.
• Use the lowest effective dose for the shortest duration consistent with treatment goals and risks for the individual woman; periodically re-evaluate as clinically indicated to determine if treatment is still necessary.

Use: Prevention of Postmenopausal Osteoporosis

Usual Adult Dose for Postmenopausal Symptoms

1 tablet orally once a day

Two regimens available, either

• Regimen 1: A combined conjugated estrogen-medroxyprogesterone tablet taken once a day [Prempro(R)])
• Available in various strengths (0.3 mg-1.5 mg; 0.45 mg/1.5 mg; 0.625 mg-2.5 mg; or 0.625 mg-5 mg)

-OR-

• Regimen 2: Two separate tablets taken sequentially (Premphase[R]:
• Conjugated estrogen taken once a day on days 1 through 14 (conjugated estrogen 0.625 mg)
• Combined conjugated estrogen-medroxyprogesterone taken once a day on days 15 through 28 (conjugated estrogen 0.625 mg-medroxyprogesterone 5 mg)

Comments:

• Use the lowest effective dose for the shortest duration consistent with treatment goals and risks for the individual woman; periodically re-evaluate as clinically indicated to determine if treatment is still necessary.

Use: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

Usual Adult Dose for Atrophic Urethritis

1 tablet orally once a day

Two regimens available, either

• Regimen 1: A combined conjugated estrogen-medroxyprogesterone tablet taken once a day [Prempro(R)])
• Available in various strengths (0.3 mg-1.5 mg; 0.45 mg/1.5 mg; 0.625 mg-2.5 mg; or 0.625 mg-5 mg)

-OR-

• Regimen 2: Two separate tablets taken sequentially (Premphase[R]:
• Conjugated estrogen taken once a day on days 1 through 14 (conjugated estrogen 0.625 mg)
• Combined conjugated estrogen-medroxyprogesterone taken once a day on days 15 through 28 (conjugated estrogen 0.625 mg-medroxyprogesterone 5 mg)

Comments:

• Topical vaginal products should be considered prior to use of this drug solely for the treatment of moderate to severe vulvar and vaginal atrophy.
• Use the lowest effective dose for the shortest duration consistent with treatment goals and risks for the individual woman; periodically re-evaluate as clinically indicated to determine if treatment is still necessary.

Use: Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due to Menopause

Usual Adult Dose for Atrophic Vaginitis

1 tablet orally once a day

Two regimens available, either

• Regimen 1: A combined conjugated estrogen-medroxyprogesterone tablet taken once a day [Prempro(R)])
• Available in various strengths (0.3 mg-1.5 mg; 0.45 mg/1.5 mg; 0.625 mg-2.5 mg; or 0.625 mg-5 mg)

-OR-

• Regimen 2: Two separate tablets taken sequentially (Premphase[R]:
• Conjugated estrogen taken once a day on days 1 through 14 (conjugated estrogen 0.625 mg)
• Combined conjugated estrogen-medroxyprogesterone taken once a day on days 15 through 28 (conjugated estrogen 0.625 mg-medroxyprogesterone 5 mg)

Comments:

• Topical vaginal products should be considered prior to use of this drug solely for the treatment of moderate to severe vulvar and vaginal atrophy.
• Use the lowest effective dose for the shortest duration consistent with treatment goals and risks for the individual woman; periodically re-evaluate as clinically indicated to determine if treatment is still necessary.

Use: Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due to Menopause

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Known liver dysfunction or disease: Use is contraindicated

Precautions

US BOXED WARNINGS: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER, and PROBABLE DEMENTIA:
Estrogen Plus Progestin Therapy:

• Cardiovascular Disorders and Probable Dementia: Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens 0.625 mg combined with medroxyprogesterone acetate 2.5 mg, relative to placebo. The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age of older during 4 years of treatment with daily conjugated estrogens 0.625 mg combined with medroxyprogesterone acetate 2.5 mg, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
• Breast Cancer: The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer. In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins. 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.

Estrogen-Alone Therapy:

• Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who use unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
• Cardiovascular Disorders and Probable Dementia: Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia. The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogen 0.625 mg alone, relative to placebo. The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily conjugated estrogen alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and other dosage forms of estrogens. 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.

CONTRAINDICATIONS:

• Undiagnosed abnormal genital bleeding
• Known, suspected, or a history of breast cancer
• Known or suspected estrogen-dependent neoplasia
• Active or history of DVT or PE
• Active or history of arterial thromboembolic disease (e.g., stroke, MI)
• Known anaphylactic reaction, angioedema to active substance or any product ingredients
• Liver dysfunction or disease
• Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
• Pregnancy

Safety and efficacy have not been established in premenopausal women.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally once a day with or without food

Missed dose: If a dose is missed, it should be taken as soon as remembered; if it is close to the next dose, skip the missed dose and resume normal schedule

General:

• Due to risks of cardiovascular disorders, breast cancer, endometrial cancer, and probable dementia, estrogens with or without progestins should be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.

Monitoring:

• Monitor thyroid function in women on thyroid hormone replacement therapy

Patient advice:
Read the US FDA-approved patient labeling (Patient Information).

• Women should be instructed to report abnormal vaginal bleeding to their healthcare provider as soon as possible.
• Women should understand the serious risks of therapy including cardiovascular disorders, malignant neoplasms, and dementia.