Estrogens/Conjugated (11 brand names, 3 dosage forms, 4 routes)
Available dosage forms: CREAM, INJECTABLE, TABLET.
Routes of administration: TOPICAL, VAGINAL, INJECTION, ORAL-28, ORAL.
Brand Names
- CONJUGATED ESTROGENS
- DUAVEE
- MILPREM-200
- MILPREM-400
- PMB 200
- PMB 400
- PREMARIN
- PREMPHASE (PREMARIN;CYCRIN 14/14)
- PREMPHASE 14/14
- PREMPRO
- PREMPRO (PREMARIN;CYCRIN)
Dosage and Administration
Generally, when estrogen therapy is prescribed for a postmenopausal woman with a uterus, a progestin should be considered to reduce the risk of endometrial cancer [see Boxed Warning]. A woman without a uterus does not need progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions (5.2, 5.16)]. Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. PREMARIN may be taken without regard to meals.
Contraindications
PREMARIN therapy is contraindicated in individuals with any of the following conditions: •Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2)] •Breast cancer or a history of breast cancer except in appropriately selected patients being treated for metastatic disease [see Warnings and Precautions (5.2)] •Estrogen-dependent neoplasia [see Warnings and Precautions (5.2)] •Active DVT, PE, or a history of these conditions [see Warnings and Precautions (5.1)] •Active arterial thromboembolic disease (for example stroke and MI), or a history of these conditions [see Warnings and Precautions (5.1)] •Known anaphylactic reaction or angioedema with PREMARIN [see Warnings and Precautions (5.7, 5.15)] •Hepatic impairment or disease [see Warnings and Precautions (5.11)] •Protein C, protein S or antithrombin deficiency, or other known thrombophilic disorders.
Adverse Reactions
The following serious adverse reactions are discussed elsewhere in labeling: • Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions (5.1)] • Malignant Neoplasms [see Boxed Warning, Warnings and Precautions (5.2)]
Drug Interactions
Data from a single-dose drug-drug interaction study involving CE and MPA indicate that the pharmacokinetic disposition of both drugs is not altered when the drugs are coadministered. No other clinical drug-drug interaction studies have been conducted with CE.
Mechanism of Action
Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH, through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these gonadotropins seen in postmenopausal women.
Overdosage
Overdosage of estrogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of PREMARIN therapy with institution of appropriate symptomatic care.