Synthetic conjugated estrogens, A tablets contain a blend of nine (9) synthetic estrogenic substances. The estrogenic substances are sodium estrone sulfate, sodium equilin sulfate, sodium 17α-dihydroequilin sulfate, sodium 17α-estradiol sulfate, sodium 17β-dihydroequilin sulfate, sodium 17α-dihydroequilenin sulfate, sodium 17β-dihydroequilenin sulfate, sodium equilenin sulfate and sodium 17β-estradiol sulfate.

The structural formulae for these estrogens are:

Tablets for oral administration, are available in 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg and 1.25 mg strengths of synthetic conjugated estrogens, A. Tablets also contain the following inactive ingredients: ethylcellulose, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polysorbate 80, pregelatinized starch, titanium dioxide, and triethyl citrate.

-0.3 mg tablets also contain FD&C Blue No. 2 aluminum lake and D&C Yellow No. 10 aluminum lake.

-0.45 mg tablets also contain FD&C Yellow No. 6/Sunset Yellow FCF lake.

-0.625 mg tablets also contain FD&C Red No. 40 aluminum lake.

-0.9 mg tablets do not contain additional color additives.

-1.25 mg tablets also contain FD&C Blue No. 2 aluminum lake.

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 by 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 follicle stimulating hormone (FSH) through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.

Cenestin (Estrogens, conjugated synthetic a) therapy is indicated for the:

1. Treatment of moderate-to-severe vasomotor symptoms associated with the menopause.

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.

Cenestin (Estrogens, conjugated synthetic a) should not be used in women with any of the following conditions:

See

See and

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 (Estrogens, conjugated synthetic a) and 48 women treated with placebo, adverse events that occurred at a rate of ≥ 5% are summarized in .

In a second 12-week clinical trial that included 52 women treated with 0.45 mg Cenestin (Estrogens, conjugated synthetic a) and 51 women treated with placebo, adverse events that occurred at a rate of >5% are summarized in .

P-value by Fisher's Exact (2-tail) Test

If a subject experiences the same event more than once, the first occurrence is tabulated.

The following additional adverse reactions have been reported with estrogen and/or progestin therapy:

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.

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 and ). 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.

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 (Estrogens, conjugated synthetic a) (synthetic conjugated estrogens, A) Tablets are available as:

Store at 20-25°C (68-77°F); excursions are permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature].

Dispense in tight container.

Dispense in child-resistant packaging.

Pharmacist: Include one “Information for the patient” leaflet with each package dispensed.

Read this PATIENT INFORMATION before you start taking Cenestin (Estrogens, conjugated synthetic a) and read what you get each time you refill Cenestin (Estrogens, conjugated synthetic a) . There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

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Cenestin (Estrogens, conjugated synthetic a)

(synthetic conjugated estrogens, A) Tablets

1.25 mg

Rx only

Each tablet contains:Synthetic conjugated estrogens, A..........1.25 mg

Usual Dosage: See accompanying prescribing information.

Dispense in tight container.

Store at 20-25°C (68-77°F); excursions are permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature].

Pharmacist: Include one "Information for the patient" leaflet with each package dispensed. Dispense in child-resistant packaging.

Keep out of the reach of children.