Estrogens/Conjugated Synthetic A (2 brand names, 2 dosage forms, 2 routes)
Available dosage forms: TABLET, CREAM.
Routes of administration: ORAL, VAGINAL.
Brand Names
- CENESTIN
- SYNTHETIC CONJUGATED ESTROGENS A
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 and without progestins should not be used for the prevention of cardiovascular disease. (See WARNINGS, Cardiovascular disorders .) The Women’s Health Initiative (WHI) study 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 years of treatment with oral conjugated equine estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. (See CLINICAL PHARMACOLOGY, Clinical Studies .) The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL PHARMACOLOGY, Clinical Studies .) Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, 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.
Indications and Usage
Cenestin therapy is indicated for the: 1. Treatment of moderate-to-severe vasomotor symptoms associated with the menopause. 0.45 mg Cenestin 0.625 mg Cenestin 0.9 mg Cenestin 1.25 mg Cenestin 2. Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered. 0.3 mg Cenestin
Dosage and Administration
When estrogen is prescribed for a postmenopausal woman with a uterus, 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 reevaluated 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. 1. For treatment of moderate to severe vasomotor symptoms associated with the menopause. Cenestin 0.45 mg Cenestin 0.625 mg Cenestin 0.9 mg Cenestin 1.25 mgPatients should be started at Cenestin 0.45 mg daily. Subsequent dosage adjustment may be made based upon the individual patient response. This dose should be periodically reassessed by the healthcare provider. The lowest effective dose of Cenestin for the treatment of moderate to severe vasomotor symptoms has not been determined. 2. For treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered. Cenestin 0.3 mg daily
Contraindications
Cenestin 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. Cenestin therapy should not be used in patients with known hypersensitivity to its ingredients. Known or suspected pregnancy. There is no indication for Cenestin 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 that included 72 women treated with 0.625 mg and 2 x 0.625 mg Cenestin and 48 women treated with placebo, adverse events that occurred at a rate of ≥ 5% are summarized in Table 5. Table 5 Number (%) of Patients with Adverse Events With ≥ 5% Occurrence Rate By Body System and Treatment Group Body System Adverse Event Cenestin 0.625 mg and 2 x 0.625 mg n (%) Placebo n (%) Total n (%) Number of Patients Who Received Medication 72 (100) 48 (100) 120 (100) Number of Patients With Adverse Events 68 (94) 43 (90) 111 (93) Number of Patients Without Any Adverse Events 4 (6) 5 (10) 9 (8) Body As A Whole Abdominal Pain 20 (28) 11 (23) 31 (26) Asthenia 24 (33) 20 (42) 44 (37) Back Pain 10 (14) 6 (13) 16 (13) Fever 1 (1) 3 (6) 4 (3) Headache 49 (68) 32 (67) 81 (68) Infection 10 (14) 5 (10) 15 (13) Pain 8 (11) 9 (19) 17 (14) Cardiovascular System Palpitation 15 (21) 13 (27) 28 (23) Digestive System Constipation 4 (6) 2 (4) 6 (5) Diarrhea 4 (6) 0 (0) 4 (3) Dyspepsia 7 (10) 3 (6) 10 (8) Flatulence 21 (29) 14 (29) 35 (29) Nausea 13 (18) 9 (19) 22 (18) Vomiting 5 (7) 1 (2) 6 (5) Metabolic and Nutritional Peripheral Edema 7 (10) 6 (13) 13 (11) Musculoskeletal System Arthralgia 18 (25) 13 (27) 31 (26) Myalgia 20 (28) 15 (31) 35 (29) Nervous System Depression 20 (28) 18 (38) 38 (32) Dizziness 8 (11) 5 (10) 13 (11) Hypertonia 4 (6) 0 (0) 4 (3) Insomnia 30 (42) 23 (48) 53 (44) Leg Cramps 7 (10) 3 (6) 10 (8) Nervousness 20 (28) 20 (42) 40 (33) Paresthesia 24 (33) 15 (31) 39
Drug Interactions
In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John’s Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.
Overdosage
Serious ill effects have not been reported following acute ingestion of large doses of estrogen containing drug products by young children. Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females.