Estrogens/Conjugated Synthetic B (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ENJUVIA
Boxed Warning
Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of “natural” estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses. (See WARNINGS, Malignant neoplasms, Endometrial cancer .) CARDIOVASCULAR AND OTHER RISKS Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders and Dementia .) The estrogen alone substudy of the Women’s Health Initiative (WHI) reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 6.8 years and 7.1 years, respectively, of treatment with oral conjugated estrogens (CE 0.625 mg) alone per day, relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders .) The estrogen-plus-progestin substudy of the WHI reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) per day, relative to placebo. (See CLINICAL STUDIES, and WARNINGS, Cardiovascular disorders and Malignant neoplasms, Breast cancer ). The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI study, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with CE 0.625 mg alone and during 4 years of treatment with CE 0.625 mg combined with MPA 2.5 mg, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINI
Indications and Usage
ENJUVIA tablets are indicated in the: Treatment of moderate to severe vasomotor symptoms associated with menopause. Treatment of moderate to severe vaginal dryness and pain with intercourse, symptoms of vulvar and vaginal atrophy, associated with menopause. When prescribing solely for the treatment of moderate to severe vaginal dryness and pain with intercourse, topical vaginal products should be considered.
Dosage and Administration
When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. 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. Patients should be re-evaluated periodically as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary (see BOXED WARNINGS and WARNINGS). For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding. ENJUVIA tablets are taken orally, once daily for: The treatment of moderate to severe vasomotor symptoms, associated with menopause. ENJUVIA 0.3 mg ENJUVIA 0.45 mg ENJUVIA 0.625 mg ENJUVIA 0.9 mg ENJUVIA 1.25 mg The treatment of moderate to severe vaginal dryness and pain with intercourse, symptoms of vulvar and vaginal atrophy, associated with menopause. When prescribing solely for the treatment of moderate to severe vaginal dryness and pain during intercourse, topical vaginal products should be considered. ENJUVIA 0.3 mg Patients should be started at the lowest approved dose of 0.3 mg ENJUVIA daily. Subsequent dosage adjustment (which will differ depending on the indication) may be made based upon the individual patient response. This dose should be periodically reassessed by the healthcare provider.
Contraindications
ENJUVIA tablets should not be used in women with any of the following conditions: Undiagnosed abnormal genital bleeding. Known, suspected, or history of cancer of the breast. Known or suspected estrogen-dependent neoplasia. Active deep vein thrombosis, pulmonary embolism or a history of these conditions. Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction). Liver dysfunction or disease. Known hypersensitivity to the ingredients of ENJUVIA Tablets. Known or suspected pregnancy. There is no indication for ENJUVIA in pregnancy. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins from oral contraceptives inadvertently during early pregnancy. (See PRECAUTIONS.)
Adverse Reactions
See BOXED WARNINGS, WARNINGS and PRECAUTIONS . Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. In a 12-week clinical trial, 209 postmenopausal women with vasomotor symptoms were treated with ENJUVIA. Adverse events that occurred in the study at a rate greater than or equal to 5% and greater than placebo, regardless of relationship to study drug, are summarized in Table 8. Table 8. ENJUVIA Tablets – Number (%) of Patients Reporting Aderse Events* with ≥ 5% Occurrence Rate by Body System Treatment-emergent adverse events, regardless of relationship to study drug Body System/Adverse Event 0.3 mg n=68 0.625 mg n=72 1.25 mg n=69 Placebo n=72 Number of Patients in Safety Sample (%) 68 (100) 72 (100) 69 (100) 72 (100) Number of Patients with Adverse Events (%) 49 (72) 55 (76) 56 (81) 51 (71) Number of Patients without Adverse Events (%) 19 (28) 17 (24) 13 (19) 21 (29) Body as a Whole Abdominal Pain 3 (4) 11 (15) 3 (4) 7 (10) Accidental Injury 6 (8) 2 (3) 3 (4) 5 (7) Flu Syndrome 4 (6) 3 (4) 5 (7) 3 (4) Headache 10 (15) 18 (25) 11 (16) 15 (21) Pain 10 (15) 14 (19) 7 (10) 6 (8) Digestive System Flatulence 3 (4) 5 (7) 3 (4) 2 (3) Nausea 5 (7) 7 (10) 8 (12) 6 (8) Nervous System Dizziness 5 (7) 3 (4) 1 (1) 3 (4) Paresthesia 0 4 (6) 1 (1) 0 Respiratory System Bronchitis 0 3 (4) 5 (7) 3 (4) Rhinitis 3 (4) 4 (6) 5 (7) 4 (6) Sinusitis 2 (3) 3 (4) 5 (7) 2 (3) Urogenital System Breast Pain 0 9 (12) 10 (14) 3 (4) Dysmenorrhea 1 (2) 6 (8) 1 (1) 2 (3) Vaginitis 1 (2) 5 (7) 2 (3) 3 (4) In a second 12-week clinical trial, 310 women with symptoms of vulvar and vaginal atrophy were treated (15
Overdosage
Serious ill effects have not been reported following acute ingestion of large doses of estrogen-containing products by young children. Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females.