Synthetic conjugated estrogens (Cenestin)
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Synthetic conjugated estrogens (Cenestin)

Cenestin®
(synthetic conjugated estrogens, A) Tablets

ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER

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. (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.

DRUG DESCRIPTION

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:

Cenestin Structural formula Illustration

Tablets for oral administration, are available in 0.3 mg, 0.45mg, 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.

What are the possible side effects of conjugated estrogens (Cenestin, Enjuvia, Premarin)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking this medication and call your doctor at once if you have any of these serious side effects:

  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden headache, confusion, problems with vision, speech, or balance;
  • pain or...

Read All Potential Side Effects and See Pictures of Cenestin »

What are the precautions when taking synthetic conjugated estrogens (Cenestin)?

Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: vaginal bleeding of unknown cause, certain cancers (such as breast cancer, cancer of the uterus/ovaries), blood clots, stroke, heart disease (such as heart attack), liver disease, kidney disease, family medical history (especially breast lumps, cancer, blood clots, angioedema), blood clotting disorders (such as protein C or protein S deficiency), high blood pressure, diabetes, high cholesterol/triglyceride levels,...

Read All Potential Precautions of Cenestin »

Last reviewed on RxList: 10/16/2008
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Cenestin (synthetic conjugated estrogens) therapy is indicated for the:

  1.  Treatment of moderate to severe vasomotor symptoms associated with the menopause.
    •  0.45 mg Cenestin (synthetic conjugated estrogens)
    •  0.625 mg Cenestin (synthetic conjugated estrogens)
    •  0.9 mg Cenestin (synthetic conjugated estrogens)
    •  1.25 mg Cenestin (synthetic conjugated estrogens)
  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 (synthetic conjugated estrogens)

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 (synthetic conjugated estrogens) 0.45 mg
    •  Cenestin (synthetic conjugated estrogens) 0.625 mg
    •  Cenestin (synthetic conjugated estrogens) 0.9 mg
    •  Cenestin (synthetic conjugated estrogens) 1.25 mg
      Patients should be started with Cenestin (synthetic conjugated estrogens) 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 (synthetic conjugated estrogens) 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 (synthetic conjugated estrogens) 0.3 mg daily

HOW SUPPLIED

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

0.3 mg: Round, green, film-coated, and are debossed with letters, dp, and number, 41.

Available in bottles of:

30 NDC 51285-441-30
100 NDC 51285-441-02
1000 NDC 51285-441-05

0.45 mg: Round, orange, film-coated, and are debossed with letters, dp, and number, 46.

Available in bottles of:

30 NDC 51285-446-30
100 NDC 51285-446-02
1000 NDC 51285-446-05

0.625 mg: Round, red, film-coated, and are debossed with letters, dp, and number, 42.

Available in bottles of:

30 NDC 51285-442-30
100 NDC 51285-442-02
1000 NDC 51285-442-05

0.9 mg: Round, white, film-coated, and are debossed with letters, dp, and number, 43.

Available in bottles of:

30 NDC 51285-443-30
100 NDC 51285-443-02
1000 NDC 51285-443-05

1.25 mg: Round, blue, film-coated, and are debossed with letters, dp, and number, 44.

Available in bottles of:

30 NDC 51285-444-30
100 NDC 51285-444-02
1000 NDC 51285-444-05

Store at 20-25°C (68-77°F); excursions are permitted to15-30°C (59-86°F) [See USP Controlled Room Temperature].

Keep out of the reach of children. Dispense in tight container. Dispense in child-resistant packaging.

Keep out of the reach of children.

Manufactured By: Duramed Pharmaceuticals, Inc. Subsidiary of Barr Pharmaceuticals, Inc. Pomona, NY 10970. Revised SEPTEMBER 2004. FDA rev date: 10/28/2004

Last reviewed on RxList: 10/16/2008
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

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 (synthetic conjugated estrogens) 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 (33)
    Vertigo 12 (17) 12 (25) 24 (20)
Respiratory System
    Cough Increased 4 (6) 1 (2) 5 (4)
    Pharyngitis 6 (8) 4 (8) 10 (8)
    Rhinitis 6 (8) 7(15) 13 (11)
Skin and Appendages      
    Rash 3 (4) 3 (6) 6 (5)
Urogenital System
    Breast Pain 21 (29) 7 (15) 28 (23)
    Dysmenorrhea 4 (6) 3 (6) 7 (6)
    Metrorrhagia 10 (14) 3 (6) 13 (11)
* Combined results for 0.625 mg and 2 x 0.625 mg Cenestin Tablets

In a second 12-week clinical trial that included 52 women treated with 0.45 mg Cenestin (synthetic conjugated estrogens) and 51 women treated with placebo, adverse events that occurred at a rate of > 5% are summarized in Table 6

Table 6
Number (%) of Patients with a > 5% Occurrence Rate by Body System and Treatment Group

Body System and Term Cenestin 0.45 mg Control p-value
Any Adverse Event (%) 40 (75.5%) 39 (76.5%) 1.0000
Body as a whole 20 (37.7%) 24 (47.1%) 0.4275
    Asthenia 6 (11.3%) 7 (13.7%) 0.7731
    Headache 6 (11.3%) 8 (15.7%) 0.5748
    Infection 1 (1.9%) 6 (11.8%) 0.0576
    Pain 6 (11.3%) 1 (2.0%) 0.1128
    Pain abdominal 5 (9.4%) 3 (5.9%) 0.7159
Cardiovascular 5 (9.4%) 10 (19.6%) 0.1695
    Palpitations 3 (5.7%) 3 (5.9%) 1.0000
    Vasodilations 2 (3.8%) 4 (7.8%) 0.4324
Digestive 8 (15.1%) 7 (13.7%) 1.0000
    Nausea 5 (9.4%) 2 (3.9%) 0.4374
Metabolic and nutritional 5 (9.4%) 3 (5.9%) 0.7159
    Weight increase 3 (5.7%) 2 (3.9%) 1.0000
Musculoskeletal 5 (9.4%) 6 (11.8%) 0.7582
    Arthralgia 5 (9.4%) 5 (9.8%) 1.0000
    Myalgia 2 (3.8%) 6 (11.8%) 0.1566
Neurological 15 (28.3%) 19 (37.3%) 0.4044
    Anxiety 3 (5.7%) 1 (2.0%) 0.6179
    Depression 2 (3.8%) 7 (13.7%) 0.0895
    Insomnia 3 (5.7%) 5 (9.8%) 0.4839
    Nervousness 2 (3.8%) 7 (13.7%) 0.0895
    Paresthesia 4 (7.5%) 3 (5.9%) 1.0000
    Vertigo 3 (5.7%) 3 (5.9%) 1.0000
Respiratory 10 (18.9%) 6 (11.8%) 0.4173
    Upper Respiratory Tract Infection 7 (13.2%) 1 (2.0%) 0.0603
    Rhinitis 3 (5.7%) 2 (3.9%) 1.0000
    Pharyngitis 1 (1.9%) 3 (5.9%) 0.3581
Urogenital 19 (35.8%) 7 (13.7%) 0.0124
    Endometrial thickening 10 (18.9%) 4 (7.8%) 0.1503
    Vaginitis 4 (7.5%) 1 (2.0%) 0.3632
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:

Genitourinary system

Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer.

Breasts

Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.

Cardiovascular

Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.

Gastrointestinal

Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis, enlargement of hepatic hemangiomas

Skin

Chloasma or melasma, which may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash.

Eyes

Retinal vascular thrombosis; intolerance to contact lenses.

Central nervous system

Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia.

Miscellaneous

Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaplylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.

Read the Cenestin (synthetic conjugated estrogens) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Drug/Laboratory Test Interactions

  1.  Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.
  2.  Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels, as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.
  3.  Other binding proteins may be elevated in serum (i.e., corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG)) leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
  4.  Increased plasma HDL and HDL2 cholesterol subfraction concentrations, reduced LDL cholesterol concentration, increased triglyceride levels.
  5.  Impaired glucose tolerance.
  6.  Reduced response to metyrapone test.

Last reviewed on RxList: 10/16/2008
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

See BOXED WARNINGS.

Cardiovascular disorders.

Estrogen and estrogen/progestin therapy has been associated with an increased risk of cardiovascular events such as myocardial infarction and stroke, as well as venous thrombosis and pulmonary embolism (venous thromboembolism or VTE). Should any of these occur or be suspected, estrogens should be discontinued immediately.

Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.

a. Coronary heart disease and stroke. In the Women's Health Initiative (WHI) study, an increase in the number of strokes has been observed in women receiving CE compared to placebo.

In the CE/MPA substudy of WHI, an increased risk of coronary heart disease (CHD) events (defined as non-fatal myocardial infarction and CHD death) was observed in women receiving CE/MPA compared to women receiving placebo (37 vs. 30 per 10,000 women- years). The increase in risk was observed in year one and persisted. (See CLINICAL PHARMACOLOGY, Clinical Studies.)

In the same substudy of WHI, an increased risk of stroke was observed in women receiving CE/MPA compared to women receiving placebo (29 vs. 21 per 10,000 women-years). The increase in risk was observed after the first year and persisted.

In postmenopausal women with documented heart disease (n = 2,763, average age 66.7 years) a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS) treatment with CE/MPA (0.625mg/2.5mg per day) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE/MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE/MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand three hundred and twenty one women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE/MPA group and the placebo group in HERS, HERS II, and overall.

Large doses of estrogen (5 mg conjugated estrogens per day), comparable to those used to treat cancer of the prostate and breast, have been shown in a large prospective clinical trial in men to increase the risks of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis.

b. Venous thromboembolism (VTE). In the Women's Health Initiative (WHI) study, an increase in VTE has been observed in women receiving CE compared to placebo.

In the CE/MPA substudy of WHI, a 2-fold greater rate of VTE, including deep venous thrombosis and pulmonary embolism, was observed in women receiving CE/MPA compared to women receiving placebo. The rate of VTE was 34 per 10,000 women-years in the CE/MPA group compared to 16 per 10,000 women-years in the placebo group. The increase in VTE risk was observed during the first year and persisted. (See CLINICAL PHARMACOLOGY, Clinical Studies.)

If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.

Malignant neoplasms

a. Endometrial cancer. The use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than one year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for five to ten years or more and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued.

Clinical surveillance of all women taking estrogen/progestin combinations 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 of equivalent estrogen dose. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.

b. Breast cancer. The use of estrogens and progestins by postmenopausal women has been reported to increase the risk of breast cancer. The most important randomized clinical trial providing information about this issue is the Women's Health Initiative (WHI) substudy of CE/MPA (see CLINICAL PHARMACOLOGY, Clinical Studies). The results from observational studies are generally consistent with those of the WHI clinical trial and report no significant variation in the risk of breast cancer among different estrogens or progestins, doses, or routes of administration.

The CE/MPA sub-study of WHI reported an increased risk of breast cancer in women who took CE/MPA for a mean follow-up of 5.6 years. Observational studies have also reported an increased risk for estrogen/progestin combination therapy, and a smaller increased risk for estrogen alone therapy, after several years of use. In the WHI trial and from observational studies, the excess risk increased with duration of use. From observational studies, the risk appeared to return to baseline in about five years after stopping treatment. In addition, observational studies suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen/progestin combination therapy as compared to estrogen alone therapy.

In the CE/MPA sub-study, 26% of the women reported prior use of estrogen alone and/or estrogen/progestin combination hormone therapy. After a mean follow-up of 5.6 years during the clinical trial, the overall relative risk of invasive breast cancer was 1.24 (95% confidence interval 1.01-1.54), and the overall absolute risk was 41 vs. 33 cases per 10,000 women-years, for CE/MPA compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 vs. 25 cases per 10,000 women-years, for CE/MPA compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 vs. 36 cases per 10,000 women-years for CE/MPA compared with placebo. In the same sub-study, invasive breast cancers were larger and diagnosed at a more advanced stage in the CE/MPA group compared with the placebo group. Metastatic disease was rare with no apparent difference between the two groups. Other prognostic factors such as histologic subtype, grade and hormone receptor status did not differ between the groups.

The use of estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.

Dementia

In the Women's Health Initiative Memory Study (WHIMS), 4,532 generally healthy postmenopausal women 65 years of age and older were studied, of whom 35% were 70 to 74 years of age and 18% were 75 or older. After an average follow-up of 4 years, 40 women being treated with CE/MPA (1.8%, n = 2,229) and 21 women in the placebo group (0.9%, n = 2,303) received diagnoses of probable dementia. The relative risk for CE/MPA versus placebo was 2.05 (95% confidence interval 1.21 - 3.48), and was similar for women with and without histories of menopausal hormone use before WHIMS. The absolute risk of probable dementia for CE/MPA versus placebo was 45 versus 22 cases per 10,000 women-years, and the absolute excess risk for CE/MPA was 23 cases per 10,000 women-years. It is unknown whether these findings apply to younger postmenopausal women. (See CLINICAL PHARMACOLOGY, Clinical Studies and PRECAUTIONS, Geriatric Use.)

Gallbladder disease

A 2 to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

Hypercalcemia

Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level.

Visual abnormalities

Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or renal vascular lesions, estrogens should be permanently discontinued.

PRECAUTIONS

General

  1. Addition of a progestin when a woman has not had a hysterectomy. Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer.
    There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include a possible increased risk of breast cancer.
  2. Elevated blood pressure. In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo controlled clinical trial, a generalized effect of estrogens on blood pressure was not seen. Blood pressure should be monitored at regular intervals with estrogen use.
  3. Hypertriglyceridemia. In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications.
  4. Impaired liver function and past history of cholestatic jaundice. Estrogens may be poorly metabolized in patients with impaired liver function. For patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised and in the case of recurrence, medication should be discontinued.
  5. Hypothyroidism. Estrogen administration leads to increased thyroid-binding globulin (TBG) levels.
    Patients with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.
  6. Fluid retention. Because estrogens may cause some degree of fluid retention, patients with conditions that might be influenced by this factor, such as a cardiac or renal dysfunction, warrant careful observation when estrogens are prescribed.
  7. Hypocalcemia. Estrogens should be used with caution in individuals with severe hypocalcemia.
  8. Ovarian cancer. The CE/MPA substudy of WHI reported that estrogen plus progestin increased the risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE/MPA versus placebo was 1.58 (95% confidence interval 0.77 - 3.24) but was not statistically significant. The absolute risk for CE/MPA versus placebo was 4.2 versus 2.7 cases per 10,000 women-years. In some epidemiologic studies, the use of estrogen alone, in particular for ten or more years, has been associated with an increased risk of ovarian cancer. Other epidemiologic studies have not found these associations.
  9. Exacerbation of endometriosis. Endometriosis may be exacerbated with administration of estrogens.
    A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen alone therapy. For patients known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.
  10. Exacerbation of other conditions. Estrogens may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

Patient Information

Physicians are advised to discuss the PATIENT INFORMATION leaflet with patients for whom they prescribe Cenestin (synthetic conjugated estrogens) .

Laboratory Tests

Estrogen administration should be initiated at the lowest dose approved for the_indication and then guided by clinical response, rather than by serum hormone levels (e.g., estradiol, FSH).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term continuous administration of estrogen, with and without progestin, in women, with and without a uterus, has shown an increased risk of endometrial cancer, breast cancer, and ovarian cancer. (See BOXED WARNINGS, WARNINGS and PRECAUTIONS.)

Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.

 Pregnancy

Cenestin should not be used during pregnancy. (See CONTRAINDICATIONS.)

Nursing Mothers

Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk. Detectable amounts of estrogens have been identified in the milk of mothers receiving this drug. Caution should be exercised when Cenestin (synthetic conjugated estrogens) is administered to a nursing woman.

Pediatric Use

Cenestin (synthetic conjugated estrogens) is not indicated in children.

Geriatric Use

There have not been sufficient numbers of geriatric patients involved in studies utilizing Cenestin (synthetic conjugated estrogens) to determine whether those over 65 years of age differ from younger subjects in their response to Cenestin (synthetic conjugated estrogens) .

In the Women's Health Initiative Memory Study, including 4,532 women 65 years of age and older, followed for an average of 4 years, 82% (n = 3,729) were 65 to 74 while 18% (n = 803) were 75 and over. Most women (80%) had no prior hormone therapy use. Women treated with conjugated estrogens plus medroxyprogesterone acetate were reported to have a two-fold increase in the risk of developing probable dementia. Alzheimer's disease was the most common classification of probable dementia in both the conjugated estrogens plus medroxyprogesterone acetate group and the placebo group. Ninety percent of the cases of probable dementia occurred in the 54% of women that were older than 70. (See WARNINGS, Dementia.)

Last reviewed on RxList: 10/16/2008
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

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.

CONTRAINDICATIONS

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

  1.  Undiagnosed abnormal genital bleeding.
  2.  Known, suspected, or history of cancer of the breast.
  3.  Known or suspected estrogen-dependent neoplasia.
  4.  Active deep vein thrombosis, pulmonary embolism or a history of these conditions.
  5.  Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction).
  6.  Liver dysfunction or disease.
  7.  Cenestin (synthetic conjugated estrogens) therapy should not be used in patients with known hypersensitivity to its ingredients.
  8.  Known or suspected pregnancy. There is no indication for Cenestin (synthetic conjugated estrogens) 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.)

Last reviewed on RxList: 10/16/2008
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

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.

Pharmacokinetics

Absorption

Synthetic conjugated estrogens, A are soluble in water and are well absorbed from the gastrointestinal tract after release from the drug formulation. The Cenestin tablet releases the synthetic conjugated estrogens, A slowly over a period of several hours. The effect of food on the bioavailability of synthetic conjugated estrogens, A from Cenestin (synthetic conjugated estrogens) has not been studied.

Table 1
PHARMACOKINETIC PARAMETERS FOR UNCONJUGATED AND CONJUGATED ESTROGENS IN HEALTHY POSTMENOPAUSAL WOMEN UNDER FASTING CONDITIONS
Pharmacokinetic Parameters of Unconjugated Estrogens Following a Dose of 2 x 0.625 mg Cenestin (synthetic conjugated estrogens)

Drug C max
(pg/mL)
CV%
tmax
(h)
CV%
AUC 0-72h
(pg-hr/mL)
CV%
Baseline-corrected estrone 84.5 (41.7) 8.25 (35.6) 1749 (43.8)
Equilin 45.6 (47.3) 7.78 (28.8) 723 (67.9)

Pharmacokinetic Parameters of Conjugated Estrogens Following a Dose of 2 x 0.625 mg Cenestin (synthetic conjugated estrogens)

Drug C max
(ng/mL) CV%
tmax
(h)
CV%

(h)
CV%
AUC0_72h
(ng-hr/mL)
CV%
Baseline-corrected estrone 4.43 (40.4) 7.7 (30.3) 10.6 (25.4) 69.89 (39.2)
Equilin 3.27 (43.5) 5.8 (31.1) 9.7 (23.0) 46.46 (47.5)

Figure 1
Mean Plasma Concentration of Unconjugated Estrogens After a 2 x 0.625 mg Cenestin (synthetic conjugated estrogens) Dose Under Fasting Conditions

Mean Plasma Concentration of Unconjugated Estrogens After a 2 x 0.625 mg Cenestin Dose Under Fasting Conditions - illustration

Distribution

The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin.

Metabolism

Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women a significant portion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.

Excretion

Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

Special Populations

Cenestin (synthetic conjugated estrogens) was investigated in postmenopausal women. No pharmacokinetic studies were conducted in special populations, including patients with renal or hepatic impairment.

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.

Clinical Studies

Effects on vasomotor symptoms

A randomized, placebo-controlled multicenter clinical study was conducted evaluating the effectiveness of Cenestin (synthetic conjugated estrogens) for the treatment of moderate to severe vasomotor symptoms in 120 postmenopausal women between 38 and 66 years of age (68% were Caucasian). Patients were randomized to receive either placebo or 0.625 mg Cenestin (synthetic conjugated estrogens) daily for 12 weeks. Dose titration was allowed after one week of treatment. The starting dose was either doubled (2 x 0.625 mg Cenestin (synthetic conjugated estrogens) or placebo taken daily) or reduced (0.3 mg Cenestin (synthetic conjugated estrogens) or placebo taken daily), if necessary. Efficacy was assessed at 4 and 12 weeks of treatment. By week 12, 10% of the study participants remained on a single 0.625 mg Cenestin (synthetic conjugated estrogens) tablet daily while 77% required two (0.625 mg) tablets daily. The results in Table 2 indicate that compared to placebo, Cenestin (synthetic conjugated estrogens) produced a reduction in moderate to severe vasomotor symptoms at weeks 4 and 12.

A second randomized, placebo-controlled multicenter clinical study was conducted evaluating the effectiveness of 0.45 mg Cenestin (synthetic conjugated estrogens) tablets, for the treatment of moderate to severe vasomotor symptoms in 104 menopausal women between 52 and 74 years of age (76% were Caucasian). Patients were randomized to receive either placebo or 0.45 mg Cenestin (synthetic conjugated estrogens) daily for 12 weeks. Efficacy was assessed at 4 and 12 weeks of treatment. The mean change in the number of moderate to severe hot flushes per week shown in Table 3 indicate that compared to placebo, 0.45 mg Cenestin (synthetic conjugated estrogens) produced a reduction in moderate to severe vasomotor symptoms at weeks 4 and 12. A corresponding reduction in the severity of hot flushes was demonstrated at weeks 5 and 12.

Table 2
Clinical Response*a
Mean Change in the Number of Moderate to Severe Hot Flushes Per Week,
0.625 mg and 2 x 0.625 mg Cenestin (synthetic conjugated estrogens) , ITT Population

  Cenestin (synthetic conjugated estrogens) b 0.625 mg and 2 x 0.625 mg
(n=70)
Placebo
(n=47)
Baseline
Mean # (SD) 96.8 (42.6) 94.1 (33.9)
Week 4
Mean # (SD) 28.7 (28.8) 45.7 (36.8)
Mean Change from Baseline (SD) -68.1 (43.9) -48.4 (46.2)
P-value vs. Placebo p=.022  
Week 12
Mean # (SD) 16.5 (25.7) 37.8 (38.7)
Mean Change from Baseline (SD) -80.3 (50.3) -56.3 (48.0)
P-value vs. Placebo p=.010  
Mean = Arithmetic Mean, SD = Standard Deviation
a Intent-to-treat population = 117
b: Combined results for 0.625 mg and 0.625 mg Cenestin (synthetic conjugated estrogens) tablets

Table 3
Clinical Response* Mean Change in the Number of Moderate to Severe Hot Flushes Per Week, 0.45 mg Cenestin (synthetic conjugated estrogens) , ITT Population

  Cenestin 0.45 mg
(n=53)
Placebo
(n=51)
Baseline
Mean # (SD) 95.9 (37.0) 95.9 (41.6)
Week 4
Mean # (SD) 45.7 (45.9) 59.4 (46.2)
Mean Change from Baseline (SD) -50.3 (35.4) -36.5 (42.9)
P-value vs. Placebo p=.014  
Week 12
Mean # (SD) 26.1 (43.0) 50.5 (48.4)
Mean Change from Baseline (SD) -69.9 (38.1) -45.4 (44.7)
p-value vs. Placebo p < .001  
Mean = Arithmetic Mean, SD = Standard Deviation
*Intent-to-treat population = 104

Effects on vulvar and vaginal atrophy

The effects of 0.3 mg Cenestin (synthetic conjugated estrogens) on moderate to severe symptoms of vulvar and vaginal atrophy were confirmed in a 16-week, randomized, placebo-controlled, multicenter clinical study in 72 postmenopausal women between 30 and 77 years of age (53% were Caucasian). Patients were randomized to receive either placebo or 0.3 mg Cenestin (synthetic conjugated estrogens) daily for 16 weeks. Efficacy was assessed at weeks 12 and 16 for vaginal wall cytology and week 16 for vaginal pH. Results for percent of superficial cells from a maturation index of the vaginal mucosa are shown in Figure 2. Mean vaginal pH decreased from a baseline of 6.20 to 5.14 for Cenestin (synthetic conjugated estrogens) and increased to 6.15 from a baseline of 6.03 for placebo.

Figure 2
Summary of % Superficial Cells Results in Patients Following 16 Weeks of Treatment with Cenestin (synthetic conjugated estrogens) 0.3 mg Mean +/- SE

Summary of % Superficial Cells Results in Patients Following 16 Weeks of Treatment with Cenestin 0.3 mg - illustration

Women's Health Initiative Studies.

The Women's Health Initiative (WHI) enrolled a total of 27,000 predominantly healthy postmenopausal women to assess the risks and benefits of either the use of oral 0.625 mg conjugated equine estrogens (CE) per day alone or the use of oral 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate (MPA) per day compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome studied. A "global index" included the earliest occurrence of CHD, invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, or death due to other cause. The study did not evaluate the effects of CE or CE/MPA on menopausal symptoms.

The CE/MPA substudy was stopped early because, according to the predefined stopping rule, the increased risk of breast cancer and cardiovascular events exceeded the specified benefits included in the "global index". Results of the CE/MPA substudy, which included 16,608 women (average age of 63 years range 50 to 79; 83.9% White, 6.5% Black, 5.5% Hispanic), after an average follow-up of 5.2 years are presented in Table 4 below:

Table 4
Relative and Absolute Risk Seen in the Estrogen/Progestin Substudy of the WHIa

Eventc Relative Risk Conjugated Equine Estrogens/Medroxyproge sterone Acetate vs Placebo at 5.2 years (95% Cl*) Placebo
n = 8102
CE/MPA
n = 8506
Absolute Risk per 10,000 Person-years
   
CHD events
  Non-fatal MI
  CHD death
1.29 (1.02-1.63)
1.32 (1.02-1.72)
1.18 (0.70-1.97)
30
23
6
37
30
7
Invasive breast cancerb 1.26 (1.00-1.59) 30 38
Stroke 1.41 (1.07-1.85) 21 29
Pulmonary embolism 2.13 (1.39-3.25) 8 16
Colorectal cancer 0.63 (0.43-0.92) 16 10
Endometrial cancer 0.83 (0.47-1.47) 6 5
Hip fracture 0.66 (0.45-0.98) 15 10
Death due to causes other than the events above 0.92 (0.74-1.14) 40 37
Global indexc 1.15 (1.03-1.28) 151 170
Deep vein thrombosisd 2.07 (1.49-2.87) 13 26
Vertebral fracturesd 0.66 (0.44-0.98) 15 9
Other osteoporotic fracturesd 0.77 (0.69-0.86) 170 131
aadapted from JAMA, 2002; 288:321-333.
b
includes metastatic and non-metastatic breast cancer with the exception of in situ breast cancer.
ca subset of the events was combined in a "global index", defined as the earliest occurrence of CHD events, invasive breast cancer,stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes.dnot included in Global Index.
*
nominal confidence intervals unadjusted for multiple looks and multiple comparisons. CE - conjugated estrogens

For those outcomes included in the "global index," the absolute excess risks per 10,000 person-years in the group treated with CE/MPA were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10,000 women-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the "global index" was 19 per 10,000 women-years. There was no difference between the groups in terms of all-cause mortality. (See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.)

Women's Health Initiative Memory Study

The Women's Health Initiative Memory Study (WHIMS), a sub-study of WHI, enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47% were age 65 to 69 years, 35% were 70 to 74 years, and 18% were 75 years of age and older) to evaluate the effects of CE/MPA (0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate) on the incidence of probable dementia (primary outcome) compared with placebo.

After an average follow-up of 4 years, 40 women in the estrogen/progestin group (45 per 10,000 women-years) and 21 in the placebo group (22 per 10,000 women-years) were diagnosed with probable dementia. The relative risk of probable dementia in the hormone therapy group was 2.05 (95% CI, 1.21 to 3.48) compared to placebo. Differences between groups became apparent in the first year of treatment. It is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNING and WARNINGS, Dementia.)

Last reviewed on RxList: 10/16/2008
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Revised MAY 2004

Cenestin®
(synthetic conjugated estrogens, A) Tablets

Read this PATIENT INFORMATION before you start taking Cenestin (synthetic conjugated estrogens) and read what you get each time you refill Cenestin (synthetic conjugated estrogens) . 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.

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT CENESTIN (synthetic conjugated estrogens)
(SYNTHETIC ESTROGEN MIXTURE)?

  •  Estrogens increase the chances of getting cancer of the uterus.

Report any unusual vaginal bleeding right away while you are taking estrogens. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

  •  Do not use estrogens with or without progestins to prevent heart disease, heart attacks, or strokes.

Using estrogens with or without progestins may increase your chances of getting heart attacks, strokes, breast cancer, and blood clots. Using estrogens with progestins may increase your risk of dementia. You and your healthcare provider should talk regularly about whether you still need treatment with Cenestin (synthetic conjugated estrogens) .

What is Cenestin (synthetic conjugated estrogens) ?

Cenestin (synthetic conjugated estrogens) is a medicine that contains a mixture of synthetic estrogens made from a plant source.

What is Cenestin (synthetic conjugated estrogens) used for?

Cenestin (synthetic conjugated estrogens) is used after menopause to:

  •  reduce moderate to severe hot flashes.
    Estrogens are hormones made by a woman's ovaries. The ovaries normally stop making estrogens when a woman is between 45 to 55 years old. This drop in body estrogen levels causes the "change of life" or menopause (the end of monthly menstrual periods). Sometimes, both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes "surgical menopause".
    When estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating ("hot flashes" or "hot flushes"). In some women, the symptoms are mild, and they will not need estrogens. In other women, symptoms can be more severe. You and your healthcare provider should talk regularly about whether you still need treatment with Cenestin (synthetic conjugated estrogens) .
  •  treat moderate to severe dryness, itching, and burning in and around the vagina.
    You and your healthcare provider should talk regularly about whether you still need treatment with Cenestin (synthetic conjugated estrogens) to control these problems. If you use Cenestin (synthetic conjugated estrogens) only to treat your dryness, itching, and burning in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you.

Who Should Not Take Cenestin (synthetic conjugated estrogens) ?

Do not start taking Cenestin (synthetic conjugated estrogens) if you:

  •  have unusual vaginal bleeding.
  •  currently have or have had certain cancers.
    Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or had cancer, talk with your healthcare provider about whether you should take Cenestin (synthetic conjugated estrogens) .
  •  had a stroke or heart attack in the past year.
  •  currently have or have had blood clots.
  •  currently have or have had liver problems.
  •  are allergic to Cenestin (synthetic conjugated estrogens) or any of its ingredients.
    See the end of this leaflet for a list of ingredients in Cenestin (synthetic conjugated estrogens) .
  •  If you think you may be pregnant.

Tell your healthcare provider:

  •  if you are breastfeeding.
    The synthetic estrogen hormones in Cenestin (synthetic conjugated estrogens) can pass into your milk.
  •  about all of your medical problems.
    Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), migraine, endometriosis, lupus, or problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
  •  about all the medicines you take.
    This includes prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how Cenestin (synthetic conjugated estrogens) works. Cenestin (synthetic conjugated estrogens) may also affect how your other medicines work.
  •  if you are going to have surgery or will be on bedrest.
    You may need to stop taking estrogens.

How Should I Take Cenestin (synthetic conjugated estrogens) ?

Take one Cenestin (synthetic conjugated estrogens) tablet each day at about the same time. If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at the same time.

Start at the lowest dose and talk to your healthcare provider about how well that dose is working for you. Estrogens should be used only as long as needed. You and your healthcare provider should talk regularly (for example every 3 to 6 months) about whether you still need treatment with Cenestin (synthetic conjugated estrogens) .

What are the possible side effects of estrogens?

Less common but serious side effects include:

  •  Breast cancer
  •  Cancer of the uterus
  •  Stroke
  •  Heart attack
  •  Blood clots
  •  Dementia
  •  Gallbladder disease
  •  Ovarian cancer

These are some of the warning signs of serious side effects:

  •  Breast lumps
  •  Unusual vaginal bleeding
  •  Dizziness and faintness
  •  Changes in speech
  •  Severe headaches
  •  Chest pain
  •  Shortness of breath
  •  Pains in your legs
  •  Changes in vision
  •  Vomiting

Call your healthcare provider right away if you get any of these warning signs, or any other unusual symptom that concerns you.

Common side effects include:

Other side effects include:

These are not all the possible side effects of Cenestin (synthetic conjugated estrogens) . For more information, ask your health care provider or pharmacist.

What can I do to lower my chances of a serious side effect with Cenestin (synthetic conjugated estrogens) ?

  •  Talk with your healthcare provider regularly about whether you should continue taking Cenestin (synthetic conjugated estrogens) .
  •  If you have a uterus, talk to your healthcare provider about whether the addition of a progestin is right for you.
  •  See your healthcare provider right away if you get vaginal bleeding while taking Cenestin (synthetic conjugated estrogens) .
  •  Have a breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
  •  If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease. Ask your healthcare provider for ways to lower your chances for getting heart disease.

General information about safe and effective use of Cenestin (synthetic conjugated estrogens) .

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not take Cenestin (synthetic conjugated estrogens) for conditions for which it was not prescribed. Do not give Cenestin (synthetic conjugated estrogens) to other people, even if they have the same symptoms you have. It may harm them.

Keep Cenestin (synthetic conjugated estrogens) out of the reach of children.

This leaflet provides a summary of the most important information about Cenestin (synthetic conjugated estrogens) . If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about Cenestin (synthetic conjugated estrogens) that is written for health professionals. You can get more information by calling the toll free number 877-405-0369.

What are the ingredients in Cenestin (synthetic conjugated estrogens) ?

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 any additional color additives.
-1.25 mg tablets also contain FD&C Blue No. 2 aluminum lake.

Last reviewed on RxList: 10/16/2008
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

Revised MAY 2004

Cenestin®
(synthetic conjugated estrogens, A) Tablets

Read this PATIENT INFORMATION before you start taking Cenestin (synthetic conjugated estrogens) and read what you get each time you refill Cenestin (synthetic conjugated estrogens) . 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.

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT CENESTIN (synthetic conjugated estrogens)
(SYNTHETIC ESTROGEN MIXTURE)?

  •  Estrogens increase the chances of getting cancer of the uterus.

Report any unusual vaginal bleeding right away while you are taking estrogens. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

  •  Do not use estrogens with or without progestins to prevent heart disease, heart attacks, or strokes.

Using estrogens with or without progestins may increase your chances of getting heart attacks, strokes, breast cancer, and blood clots. Using estrogens with progestins may increase your risk of dementia. You and your healthcare provider should talk regularly about whether you still need treatment with Cenestin (synthetic conjugated estrogens) .

What is Cenestin (synthetic conjugated estrogens) ?

Cenestin (synthetic conjugated estrogens) is a medicine that contains a mixture of synthetic estrogens made from a plant source.

What is Cenestin (synthetic conjugated estrogens) used for?

Cenestin (synthetic conjugated estrogens) is used after menopause to:

  •  reduce moderate to severe hot flashes.
    Estrogens are hormones made by a woman's ovaries. The ovaries normally stop making estrogens when a woman is between 45 to 55 years old. This drop in body estrogen levels causes the "change of life" or menopause (the end of monthly menstrual periods). Sometimes, both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes "surgical menopause".
    When estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating ("hot flashes" or "hot flushes"). In some women, the symptoms are mild, and they will not need estrogens. In other women, symptoms can be more severe. You and your healthcare provider should talk regularly about whether you still need treatment with Cenestin (synthetic conjugated estrogens) .
  •  treat moderate to severe dryness, itching, and burning in and around the vagina.
    You and your healthcare provider should talk regularly about whether you still need treatment with Cenestin (synthetic conjugated estrogens) to control these problems. If you use Cenestin (synthetic conjugated estrogens) only to treat your dryness, itching, and burning in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you.

Who Should Not Take Cenestin (synthetic conjugated estrogens) ?

Do not start taking Cenestin (synthetic conjugated estrogens) if you:

  •  have unusual vaginal bleeding.
  •  currently have or have had certain cancers.
    Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or had cancer, talk with your healthcare provider about whether you should take Cenestin (synthetic conjugated estrogens) .
  •  had a stroke or heart attack in the past year.
  •  currently have or have had blood clots.
  •  currently have or have had liver problems.
  •  are allergic to Cenestin (synthetic conjugated estrogens) or any of its ingredients.
    See the end of this leaflet for a list of ingredients in Cenestin (synthetic conjugated estrogens) .
  •  If you think you may be pregnant.

Tell your healthcare provider:

  •  if you are breastfeeding.
    The synthetic estrogen hormones in Cenestin (synthetic conjugated estrogens) can pass into your milk.
  •  about all of your medical problems.
    Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), migraine, endometriosis, lupus, or problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
  •  about all the medicines you take.
    This includes prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how Cenestin (synthetic conjugated estrogens) works. Cenestin (synthetic conjugated estrogens) may also affect how your other medicines work.
  •  if you are going to have surgery or will be on bedrest.
    You may need to stop taking estrogens.

How Should I Take Cenestin (synthetic conjugated estrogens) ?

Take one Cenestin (synthetic conjugated estrogens) tablet each day at about the same time. If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at the same time.

Start at the lowest dose and talk to your healthcare provider about how well that dose is working for you. Estrogens should be used only as long as needed. You and your healthcare provider should talk regularly (for example every 3 to 6 months) about whether you still need treatment with Cenestin (synthetic conjugated estrogens) .

What are the possible side effects of estrogens?

Less common but serious side effects include:

  •  Breast cancer
  •  Cancer of the uterus
  •  Stroke
  •  Heart attack
  •  Blood clots
  •  Dementia
  •  Gallbladder disease
  •  Ovarian cancer

These are some of the warning signs of serious side effects:

  •  Breast lumps
  •  Unusual vaginal bleeding
  •  Dizziness and faintness
  •  Changes in speech
  •  Severe headaches
  •  Chest pain
  •  Shortness of breath
  •  Pains in your legs
  •  Changes in vision
  •  Vomiting

Call your healthcare provider right away if you get any of these warning signs, or any other unusual symptom that concerns you.

Common side effects include:

Other side effects include:

These are not all the possible side effects of Cenestin (synthetic conjugated estrogens) . For more information, ask your health care provider or pharmacist.

What can I do to lower my chances of a serious side effect with Cenestin (synthetic conjugated estrogens) ?

  •  Talk with your healthcare provider regularly about whether you should continue taking Cenestin (synthetic conjugated estrogens) .
  •  If you have a uterus, talk to your healthcare provider about whether the addition of a progestin is right for you.
  •  See your healthcare provider right away if you get vaginal bleeding while taking Cenestin (synthetic conjugated estrogens) .
  •  Have a breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
  •  If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease. Ask your healthcare provider for ways to lower your chances for getting heart disease.

General information about safe and effective use of Cenestin (synthetic conjugated estrogens) .

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not take Cenestin (synthetic conjugated estrogens) for conditions for which it was not prescribed. Do not give Cenestin (synthetic conjugated estrogens) to other people, even if they have the same symptoms you have. It may harm them.

Keep Cenestin (synthetic conjugated estrogens) out of the reach of children.

This leaflet provides a summary of the most important information about Cenestin (synthetic conjugated estrogens) . If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about Cenestin (synthetic conjugated estrogens) that is written for health professionals. You can get more information by calling the toll free number 877-405-0369.

What are the ingredients in Cenestin (synthetic conjugated estrogens) ?

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 any additional color additives.
-1.25 mg tablets also contain FD&C Blue No. 2 aluminum lake.

Last reviewed on RxList: 10/16/2008
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Cenestin Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

ESTROGENS - ORAL

(ES-troe-jenz)

COMMON BRAND NAME(S): Cenestin, Enjuvia, Estrace, Femtrace, Ogen, Premarin

WARNING: Estrogens, either used alone or with another hormone (progestin), have rarely caused very serious side effects. Discuss the risks and benefits of hormone treatment with your doctor. Estrogens should not be used to prevent heart disease or dementia.

Estrogens can increase the risk of cancer of the uterus (endometrial cancer). Taking a progestin as directed by your doctor can help decrease this risk. Tell your doctor right away if you have any unusual vaginal bleeding.

In postmenopausal women, estrogens can increase the risk of cancer of the ovaries, stroke, dementia, and serious blood clots in the legs. Estrogens alone do not appear to increase the risk of breast cancer when used for up to 7 years. Estrogen, when used with a progestin, can increase the risk of heart disease (such as heart attacks), stroke, serious blood clots in the lungs/legs, dementia, and cancer of the breast/ovaries.

The risk for serious side effects may depend on the dose of estrogen and the length of time it is used. Therefore, this medication should be used at the lowest effective dose and for the shortest amount of time. Discuss the use of this medication with your doctor and check with him/her regularly (for example, every 3 to 6 months) to see if you still need to take this medication. If you will be taking this medication long-term, you should have regular complete physical exams (for example, once a year) as directed by your doctor. See also Notes section.

USES: This medication is a female hormone. It is used by women to help reduce symptoms of menopause (such as hot flashes, vaginal dryness). These symptoms are caused by the body making less estrogen. If you are using this medication to treat symptoms only in and around the vagina, products applied directly inside the vagina should be considered before medications that are taken by mouth, absorbed through the skin, or injected.

Certain estrogen products may also be used by women after menopause to prevent bone loss (osteoporosis). However, there are other medications (such as raloxifene, bisphosphonates including alendronate) that are also effective in preventing bone loss and may be safer. These medications should be considered for use before estrogen treatment.

Certain estrogen products may also be used by men and women to treat cancers (certain types of prostate cancer, breast cancer that has spread to other parts of the body) and by women who are not able to produce enough estrogen (for example, due to hypogonadism, primary ovarian failure).

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using this medication and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food as directed by your doctor. You may take it with food or right after a meal to prevent stomach upset.

The dosage is based on your medical condition and response to treatment.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day as directed. Follow your dosing schedule carefully. Do not increase your dose or take this medication more often or for a longer time than directed.

Tell your doctor if your condition does not improve or if it worsens.

Disclaimer

Cenestin Consumer (continued)

SIDE EFFECTS: See also Warning section.

Stomach upset, nausea/vomiting, bloating, breast tenderness, headache, or weight changes may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Tell your doctor promptly if you see the tablet in your stool.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as depression, memory loss), breast lumps, unusual vaginal bleeding (such as spotting, breakthrough bleeding, prolonged/recurrent bleeding), increased or new vaginal irritation/itching/odor/discharge, severe stomach/abdominal pain, persistent nausea/vomiting, yellowing eyes/skin, dark urine, swelling hands/ankles/feet, increased thirst/urination.

This medication may rarely cause serious problems from blood clots (such as heart attacks, strokes, deep vein thrombosis, pulmonary embolism). Get medical help right away if you have any serious side effects, including: chest/jaw/left arm pain, unusual sweating, sudden/severe headache, weakness on one side of the body, confusion, slurred speech, sudden vision changes (such as partial/complete blindness), pain/redness/swelling of legs, tingling/weakness/numbness in the arms/legs, trouble breathing, coughing up blood, sudden dizziness/fainting.

A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Cenestin (synthetic conjugated estrogens) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: vaginal bleeding of unknown cause, certain cancers (such as breast cancer, cancer of the uterus/ovaries), blood clots, stroke, heart disease (such as heart attack), liver disease, kidney disease, family medical history (especially breast lumps, cancer, blood clots, angioedema), blood clotting disorders (such as protein C or protein S deficiency), high blood pressure, diabetes, high cholesterol/triglyceride levels, obesity, lupus, underactive thyroid (hypothyroidism), mineral imbalance (low or high level of calcium in the blood), a certain hormone problem (hypoparathyroidism), uterus problems (such as fibroids, endometriosis), gallbladder disease, asthma, seizures, migraine headaches, a certain blood disorder (porphyria), mental/mood disorders (such as dementia, depression).

Do not smoke or use tobacco. Estrogens combined with smoking further increases your risk of stroke, blood clots, high blood pressure, and heart attack, especially in women older than 35.

Tell your doctor if you just had or will be having surgery, or if you will be confined to a chair or bed for a long time (such as a long plane flight). These conditions increase your risk of getting blood clots, especially if you are taking an estrogen product. You may need to stop this medication for a time or take special precautions.

This drug may cause blotchy, dark areas of the skin on the face (melasma). Sunlight may worsen this effect. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

If you are nearsighted or wear contact lenses, you may develop vision problems or trouble wearing your contact lenses. Contact your eye doctor if these problems occur.

Children may be more sensitive to the side effects of this drug. It may affect their growth/development. Discuss the possible effects of this medication with the doctor, and monitor your child's growth periodically.

This medication must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor immediately.

This medication passes into breast milk. It may reduce the quality and amount of breast milk produced. Consult your doctor before breast-feeding.

Disclaimer

Cenestin Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: aromatase inhibitors (such as anastrozole, exemestane, letrozole), fulvestrant, raloxifene, tamoxifen, toremifene.

This medication may interfere with certain laboratory tests (including metyrapone test), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe nausea/vomiting, unusual vaginal bleeding.

NOTES: Do not share this medication with others.

Keep all regular medical and laboratory appointments. You should have regular complete physical exams (for example, once a year) which include laboratory and medical tests (such as blood pressure, breast exam/mammogram, pelvic exam, pap smear) to monitor your progress and check for side effects. Follow your doctor's instructions for examining your own breasts, and report any lumps right away. Consult your doctor for more details.

Preventing or controlling high blood pressure, high cholesterol, and diabetes can help to reduce your chances of heart disease and stroke. Lifestyle changes that can help to control or prevent these diseases include reducing stress, eating a low fat/salt diet, losing weight if overweight, exercising regularly, and stopping smoking. Keep your mind active with mental exercises (such as reading, solving crossword puzzles) to help prevent dementia. Talk to your doctor about lifestyle changes that might benefit you.

Lifestyle changes that may help reduce hot flashes include stopping smoking, dressing lightly or in layers, avoiding/limiting certain foods (spicy foods, caffeine, alcohol), reducing stress, and exercising regularly.

Lifestyle changes that help promote healthy bones include increasing weight-bearing exercise, stopping smoking, limiting alcohol, and eating well-balanced meals that contain adequate calcium and vitamin D. Since you may also need to take calcium and vitamin D supplements and make lifestyle changes, consult your doctor for specific advice.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Information last revised December 2011. Copyright(c) 2011 First Databank, Inc.

Cenestin Patient Information Including Side Effects

Brand Names: Cenestin, Enjuvia, Premarin

Generic Name: conjugated estrogens (oral) (Pronunciation: KON joo gay ted ES troe jenz)

What are conjugated estrogens (Cenestin)?

Estrogen is a female sex hormone produced by the ovaries. Estrogen is necessary for many processes in the body.

Conjugated estrogens are a mixture of estrogen hormones used to treat symptoms of menopause such as hot flashes, and vaginal dryness, burning, and irritation. Other uses include prevention of osteoporosis in postmenopausal women, and replacement of estrogen in women with ovarian failure or other conditions that cause a lack of natural estrogen in the body. Conjugated estrogens are sometimes used as part of cancer treatment in women and men.

Conjugated estrogens should not be used to prevent heart disease or dementia, because this medication may actually increase your risk of developing these conditions.

Conjugated estrogens may also be used for other purposes not listed in this medication guide.

Cenestin 0.3 mg

round, green, imprinted with dp, 41

Cenestin 0.45 mg

round, orange, imprinted with dp, 46

Cenestin 0.625 mg

round, red, imprinted with dp, 42

Cenestin 0.9 mg

round, white, imprinted with dp, 43

Cenestin 1.25 mg

round, blue, imprinted with dp, 44

Premarin 0.3 mg

elliptical, green, imprinted with PREMARIN 0.3

Premarin 0.45 mg

oval, blue, imprinted with PREMARIN 0.45

Premarin 0.625 mg

elliptical, maroon, imprinted with PREMARIN 0.625

Premarin 0.9 mg

elliptical, white, imprinted with PREMARIN 0.9

Premarin 1.25 mg

elliptical, yellow, imprinted with PREMARIN 1.25

What are the possible side effects of conjugated estrogens (Cenestin)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking this medication and call your doctor at once if you have any of these serious side effects:

  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden headache, confusion, problems with vision, speech, or balance;
  • pain or swelling in your lower leg;
  • abnormal vaginal bleeding;
  • migraine headache;
  • pain, swelling, or tenderness in your stomach;
  • confusion, problems with memory or concentration;
  • jaundice (yellowing of the skin or eyes);
  • swelling in your hands, ankles, or feet; or
  • a breast lump.

Less serious side effects may include:

  • mild nausea, vomiting, bloating, stomach cramps;
  • breast pain, tenderness, or swelling;
  • freckles or darkening of facial skin;
  • increased hair growth, loss of scalp hair;
  • changes in weight or appetite;
  • problems with contact lenses;
  • vaginal itching or discharge;
  • changes in your menstrual periods, decreased sex drive; or
  • headache, nervousness, dizziness, tired feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Cenestin (synthetic conjugated estrogens) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about conjugated estrogens (Cenestin)?

Do not use this medication if you have any of the following conditions: a history of heart attack, stroke, or blood clot (especially in your lung or your lower body), liver disease, abnormal vaginal bleeding, or a hormone-related cancer such as breast or uterine cancer.

Long-term treatment with conjugated estrogens may increase your risk of breast cancer, heart attack, or stroke. Talk with your doctor about your individual risks before using conjugated estrogens long term, especially if you smoke or are overweight. Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment.

Have regular physical exams and self-examine your breasts for lumps on a monthly basis while using conjugated estrogens.

Conjugated estrogens should not be used to prevent heart disease or dementia, because this medication may actually increase your risk of developing these conditions.

Side Effects Centers

Cenestin Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking conjugated estrogens (Cenestin)?

Do not use conjugated estrogens if you have:

  • a history of heart attack, stroke, or blood clot (especially in your lung or your lower body);
  • abnormal vaginal bleeding that a doctor has not checked;
  • liver disease; or
  • any type of breast, uterine, or hormone-dependent cancer.

Before using conjugated estrogens, tell your doctor if you are allergic to any drugs, or if you have:

  • high blood pressure, heart disease, or circulation problems;
  • a personal or family history of stroke;
  • endometriosis;
  • kidney disease;
  • asthma;
  • epilepsy or other seizure disorder;
  • migraines;
  • diabetes;
  • underactive thyroid;
  • high cholesterol or triglycerides;
  • high or low levels of calcium in your blood;
  • porphyria;
  • systemic lupus erythematosus (SLE);
  • gallbladder disease; or
  • if you have had your uterus removed (hysterectomy).

Conjugated estrogens increase your risk of developing endometrial hyperplasia, a condition that may lead to cancer of the uterus. Taking progestins while using conjugated estrogens may lower this risk. If your uterus has not been removed, your doctor may prescribe a progestin for you to take while you are using conjugated estrogens.

Long-term conjugated estrogens treatment may increase your risk of stroke or blood clots. Talk with your doctor about your individual risks before using conjugated estrogens long term, especially if you smoke or are overweight. Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment.

FDA pregnancy category X. This medication can cause birth defects. Do not use conjugated estrogens if you are pregnant. Tell your doctor right away if you become pregnant during treatment. Use an effective form of birth control while you are using this medication.

Conjugated estrogens can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast-feeding a baby.

Do not give this medication to anyone under 18 years old without the advice of a doctor.

How should I take conjugated estrogens (Cenestin)?

Take this medication exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor.

Conjugated estrogens are sometimes taken on a daily basis. For certain conditions, the medication is given in a cycle, such as 3 weeks on followed by 1 week off. Follow the directions on your prescription label.

Take this medication with a full glass of water.

You may take conjugated estrogens with or without food. Try to take the medicine at the same time each day.

Have regular physical exams and self-examine your breasts for lumps on a monthly basis while using conjugated estrogens.

It is important to take conjugated estrogens regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

To be sure this medication is not causing harmful effects, your blood will need to be tested on a regular basis. Your thyroid function may also need to be tested. Do not miss any scheduled appointments.

If you need to have any type of surgery, tell the surgeon ahead of time that you are taking conjugated estrogens. You may need to stop using the medicine for a short time.

This medication can affect the results of certain medical tests. Tell any doctor who treats you that you are using conjugated estrogens.

Store conjugated estrogens at room temperature away from moisture and heat. Keep the medicine container tightly closed.

Side Effects Centers

Cenestin Patient Information including If I Miss a Dose

What happens if I miss a dose (Cenestin)?

Take the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Cenestin)?

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include nausea, vomiting, or vaginal bleeding.

What should I avoid while taking conjugated estrogens (Cenestin)?

Do not smoke while using this medication. Smoking can increase your risk of blood clots, stroke, or heart attack caused by conjugated estrogens.

What other drugs will affect conjugated estrogens (Cenestin)?

Before taking conjugated estrogens, tell your doctor if you are taking any of the following medicines:

  • a blood thinner such as warfarin (Coumadin);
  • a thyroid medication such as levothyroxine (Synthroid);
  • insulin or diabetes medicine taken by mouth;
  • rifampin (Rifadin, Rifater, Rifamate, Rimactane);
  • ketoconazole (Nizoral) or itraconazole (Sporanox);
  • seizure medicines such as phenytoin (Dilantin), carbamazepine (Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), or primidone (Mysoline);
  • a barbiturate such as amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), secobarbital (Seconal), or phenobarbital (Luminal, Solfoton); or
  • antidepressants such as amitriptyline (Elavil, Etrafon), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Janimine, Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), or trimipramine (Surmontil).

This list is not complete and there may be other drugs that can interact with conjugated estrogens. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about conjugated estrogens.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 7.03. Revision date: 12/15/2010.

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