PREMPRO/PREMPHASE is an estrogen plus progestin indicated in a woman with a uterus for:

• Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause (1.1)
• Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due to Menopause (1.2)
• Prevention of Postmenopausal Osteoporosis (1.3)

PREMPRO: one tablet containing conjugated estrogens (CE) plus medroxyprogesterone acetate (MPA) taken orally once daily. (2)

PREMPHASE: one maroon tablet containing 0.625 mg CE taken orally on days 1 through 14, and one light-blue tablet containing 0.625 mg CE plus 5.0 mg MPA taken orally on days 15 through 28. (2)

PREMPRO Tablets: 0.3 mg CE plus 1.5 mg MPA, 0.45 mg CE plus 1.5 mg MPA, 0.625 mg CE plus 2.5 mg MPA, 0.625 mg CE plus 5 mg MPA.

PREMPHASE Tablets: 0.625 mg CE, 0.625 mg CE plus 5 mg MPA. (3)

• Undiagnosed abnormal genital bleeding (4)
• Known, suspected, or history of breast cancer (4, 5.2)
• Known or suspected estrogen-dependent neoplasia (4, 5.2)
• Active DVT, PE, or a history of these conditions (4, 5.1)
• Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions (4, 5.1)
• Known anaphylactic reaction or angioedema to PREMPRO/PREMPHASE (5.15, 5.16)
• Known liver dysfunction or disease (4, 5.10)
• Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders (4)
• Known or suspected pregnancy (4, 8.1)

• Estrogens increase the risk of gallbladder disease (5.4)
• Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs (5.5, 5.6, 5.9, 5.10)
• Monitor thyroid function in women on thyroid replacement therapy (5.11, 5.19)

In two prospective, randomized clinical studies, the most common adverse reactions > 5 percent are abdominal pain, asthenia, back pain, headache, flatulence, nausea, depression, pruritus, breast pain, dysmenorrhea, and leukorrhea. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism (7.1)
• Aminoglutethimide administered concomitantly with MPA may significantly depress the bioavailability of medroxyprogesterone acetate (7.1)

• Nursing Mothers: Estrogen administration to nursing women has been shown to decrease the quantity and quality of breast milk (8.3)
• Geriatric Use: An increased risk of probable dementia in women over 65 years of age was reported in the Women's Health Initiative Memory ancillary studies of the Women's Health Initiative (5.3, 8.5)