Overview
11 DESCRIPTION PREMARIN ® (conjugated estrogens tablets, USP) for oral administration contains a mixture of CE purified from pregnant mares' urine and consists of the sodium salts of water-soluble estrogen sulfates blended to represent the average composition of material derived from pregnant mares' urine. It is a mixture of sodium estrone sulfate and sodium equilin sulfate.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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.
Indications
- 1 INDICATIONS AND USAGE PREMARIN is a mixture of estrogens indicated for: • Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) • Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due to Menopause ( 1.2 ) • Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure ( 1.3 ) • Treatment of Breast Cancer (for Palliation Only) in Appropriately Selected Women and Men with Metastatic Disease ( 1.4 ) • Treatment of Advanced Androgen-Dependent Carcinoma of the Prostate (for Palliation Only) ( 1.
Common Doses
- 1.25 mg
- 0.3 mg
- 0.625 mg
- 10 mg
Dosage
2 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...
Black Box Warning
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA See full prescribing information for complete boxed warning. Estrogen-Alone Therapy • There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens ( 5.2 ) • Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia ( 5.1 , 5.
Contraindications
- 4 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.
Side Effects
- 6 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) ] Most common adverse reactions (≥5%) are: abdominal pain, asthenia, pain, back pain, headache, flatulence, nausea, depression, insomnia, breast pain, endometrial hyperplasia, leucorrhea, vaginal hemorrhage, and vaginitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.
Interactions
- 7 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. Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism ( 7.1 ) 7.1 Metabolic Interactions In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.