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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.

During the first year of a 2-year clinical trial with 2,333 postmenopausal women between 40 and 65 years of age (88 percent Caucasian), 1,012 women were treated with conjugated estrogens and 332 were treated with placebo. Table 6 summarizes adverse events that occurred at a rate of ≥ 5 percent.

TABLE 6. NUMBER (%) OF PATIENTS REPORTING ≥ 5 PERCENT TREATMENT EMERGENT ADVERSE EVENTS

Body System
  Adverse event
--Conjugated Estrogens Treatment Group--
0.625 mg
(n = 348)
0.45 mg
(n = 338)
0.3 mg
(n = 326)
Placebo
(n = 332)
Any adverse event 323 (93%) 305 (90%) 292 (90%) 281 (85%)
Body as a Whole
  Abdominal pain 56 (16%) 50 (15%) 54 (17%) 37(11%)
  Accidental injury 21 (6%) 41 (12%) 20 (6%) 29 (9%)
  Asthenia 25 (7%) 23 (7%) 25 (8%) 16 (5%)
  Back pain 49 (14%) 43 (13%) 43 (13%) 39 (12%)
  Flu syndrome 37(11%) 38(11%) 33 (10%) 35(11%)
  Headache 90 (26%) 109 (32%) 96 (29%) 93 (28%)
  Infection 61 (18%) 75 (22%) 74 (23%) 74 (22%)
  Pain 58 (17%) 61 (18%) 66 (20%) 61 (18%)
Digestive System
  Diarrhea 21 (6%) 25 (7%) 19 (6%) 21 (6%)
  Dyspepsia 33 (9%) 32 (9%) 36(11%) 46 (14%)
  Flatulence 24 (7%) 23 (7%) 18(6%) 9 (3%)
  Nausea 32 (9%) 21 (6%) 21 (6%) 30 (9%)
Musculoskeletal System
  Arthralgia 47 (14%) 42 (12%) 22 (7%) 39 (12%)
  Leg cramps 19 (5%) 23 (7%) 11(3%) 7 (2%)
  Myalgia 18(5%) 18(5%) 29 (9%) 25 (8%)
Nervous System
  Depression 25 (7%) 27 (8%) 17 (5%) 22 (7%)
  Dizziness 19 (5%) 20 (6%) 12 (4%) 17 (5%)
  Insomnia 21 (6%) 25 (7%) 24 (7%) 33 (10%)
  Nervousness 12 (3%) 17 (5%) 6 (2%) 7 (2%)
Respiratory System
  Cough increased 13 (4%) 22 (7%) 14 (4%) 14 (4%)
  Pharyngitis 35 (10%) 35 (10%) 40 (12%) 38(11%)
  Rhinitis 21 (6%) 30 (9%) 31 (10%) 42 (13%)
  Sinusitis 22 (6%) 36(11%) 24 (7%) 24 (7%)
  Upper respiratory infection 42 (12%) 34 (10%) 28 (9%) 35(11%)
Skin and Appendages
  Pruritus 14 (4%) 17 (5%) 16(5%) 7 (2%)
Urogenital System
  Breast pain 38(11%) 41 (12%) 24 (7%) 29 (9%)
  Leukorrhea 18(5%) 22 (7%) 13 (4%) 9 (3%)
  Vaginal hemorrhage 47 (14%) 14 (4%) 7 (2%) 0
  Vaginal moniliasis 20 (6%) 18(5%) 17 (5%) 6 (2%)
  Vaginitis 24 (7%) 20 (6%) 16(5%) 4 (1%)

Postmarketing Experience

The following additional adverse reactions have been identified during post approval use of PREMARIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Genitourinary System

Abnormal uterine bleeding, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis, including vaginal candidiasis, change in cervical secretion, ovarian cancer, endometrial hyperplasia, endometrial cancer, leukorrhea.

Breast

Tenderness, enlargement, pain, discharge, galactorrhea, fibrocystic breast changes, breast cancer, gynecomastia in males.

Cardiovascular

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

Gastrointestinal

Nausea, vomiting, abdominal pain, bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, enlargement of hepatic hemangiomas, ischemic colitis.

Skin

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

Eyes

Retinal vascular thrombosis, intolerance to contact lenses.

Central Nervous System

Headache, migraine, dizziness, mental depression, nervousness, mood disturbances, irritability, exacerbation of epilepsy, dementia, possible growth potentiation of benign meningioma.

Miscellaneous

Increase or decrease in weight, glucose intolerance, aggravation of porphyria, edema, arthralgias, leg cramps, changes in libido, urticaria, exacerbation of asthma, increased triglycerides, hypersensitivity.

Additional postmarketing adverse reactions have been reported in patients receiving other forms of hormone therapy.