Usual Adult Dose for Osteoporosis

• 0.3 mg orally once a day

Comments:

• Therapy may be given continuously, with no interruption, or in cyclical regimens (e.g., 25 days on drug followed by 5 days off drug).
• Use the lowest effective dose.
• Doses may be adjusted based on individual clinical and bone mineral density responses.
• Dose adjustment should be periodically reassessed.

Use: Prevention of postmenopausal osteoporosis

Usual Adult Dose for Postmenopausal Symptoms

Initial dose: 0.3 mg orally once a day
Maintenance dose: 0.45 to 1.25 mg orally once a day

Comments:

• Dose may be adjusted based upon individual patient response.
• Dose adjustment should be periodically reassessed.
• Therapy may be given continuously, with no interruption, or in cyclical regimens (e.g., 25 days on drug followed by 5 days off drug).

Use: Treatment of moderate to severe vasomotor symptoms due to menopause

Usual Adult Dose for Atrophic Vaginitis

• 0.3 mg orally once a day

Comments:

• Topical vaginal products should be considered when prescribing solely for the treatment of moderate to severe vaginal dryness and pain during intercourse.
• Doses may be adjusted based on individual patient response.
• Dose adjustment should be periodically reassessed.
• Therapy may be given continuously, with no interruption, or in cyclical regimens (e.g., 25 days on drug followed by 5 days off drug).

Uses: Treatment of moderate to severe vaginal dryness and pain with intercourse, symptoms of vulvar and vaginal atrophy, due to menopause

Usual Adult Dose for Hypoestrogenism

• 0.3 to 0.625 mg orally once a day administered cyclically (e.g., 3 weeks on and 1 week off)

Comments:

• Doses are adjusted depending on the severity of symptoms and responsiveness of the endometrium.
• Therapy should be initiated and maintained with the lowest effective dose to achieve clinical goals.

Use: Female hypoestrogenism due to hypogonadism

Usual Adult Dose for Abnormal Uterine Bleeding

Initial dose: One injection of 25 mg IM or IV. Repeat in 6 to 12 hours if necessary.

Comments:

• Intravenous use is preferred since more rapid response can be expected.
• Follow the usual precautionary measures for IV administration.
• Injection should be administered slowly to avoid the occurrence of flushes.

Use: Short term treatment of abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology

Usual Adult Dose for Prostate Cancer

• 1.25 mg to 2.5 mg (2 x 1.25 mg) orally three times a day

Comment: The effectiveness of therapy can be judged by phosphatase determinations as well as by symptomatic improvement of the patient.

Use: Palliative treatment of advanced androgen-dependent carcinoma of the prostate

Usual Adult Dose for Primary Ovarian Failure

• 1.25 mg orally once a day administered cyclically (e.g., 3 weeks on and 1 week off)

Comments:

• Doses can be adjusted according to severity of symptoms and response of the patient.
• For maintenance, adjust dosage to the lowest effective dose.

Use: Female castration or primary ovarian failure

Usual Adult Dose for Breast Cancer-Palliative

• 10 mg orally three times a day for at least 3 months

Use: Palliative treatment of breast cancer in appropriately selected women and men with metastatic disease

Renal Dose Adjustments

Use with caution.

Liver Dose Adjustments

Contraindicated

Precautions

US BOXED WARNINGS:
ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA:
Estrogen-Alone Therapy:
Endometrial Cancer:

• There is an increased risk of endometrial cancer in a woman with a uterus who uses 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 Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo.
• The WHI Memory Study (WHIMS) estrogen-alone ancillary study of the 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 CE (0.625 mg)-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 CE 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.

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 WHI estrogen plus progestin substudy reported increased risks of 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 CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.
• The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (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 also 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 CE and MPA, 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.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• To reduce the risk of endometrial cancer, consider adding a progestin when prescribing estrogen therapy for a postmenopausal woman with a uterus.
• A woman without a uterus does not need progestin, however, hysterectomized women with a history of endometriosis may need a progestin.
• Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration.
• Periodical reevaluation is recommended as clinically appropriate to determine if treatment is still necessary.
• This drug may be taken without regard to meals.

Injection:

• IV injection provides a rapid and temporary increase in estrogen levels.
• Infusion of IV formulation with other agents is not recommended. In emergencies, however, when an infusion has already been started it may be expedient to administer the injection into the tubing just distal to the infusion needle. In this case, compatibility of solutions must be considered.
• IV formulation for this drug is compatible with normal saline, dextrose, and invert sugar solutions. It is not compatible with protein hydrolysate, ascorbic acid, or any solution with an acid pH.

Limitation of Use:

• When prescribing this drug solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis; non-estrogen medication should be carefully considered.
• When prescribing this drug solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, topical vaginal products should be considered.

Monitoring:

• Endocrine: Thyroid function
• Metabolic: Calcium levels
• Musculoskeletal: Bone density; bone maturation and effects on epiphyseal centers in patients with incomplete bone growth

Patient advice:

• Report any unusual vaginal bleeding immediately while you are using this drug. Vaginal bleeding in postmenopausal women may be a sign of cancer of the uterus. Patient's healthcare provider should check any unusual vaginal bleeding to find the cause.
• Possible serious adverse reactions of estrogen-alone therapy including cardiovascular disorders (e.g., strokes, blood clots), malignant neoplasms (e.g., cancer of the uterus), and probable dementia can occur.
• Estrogen-alone should not be used to prevent heart disease, heart attacks, or dementia.
• Possible less serious, but common adverse reactions of estrogen-alone therapy such as headaches, breast pain and tenderness, nausea, and vomiting can occur.