PREMPRO® AND PREMPHASE® Highlights

(conjugated estrogens and medroxyprogesterone acetate)

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use PREMPRO/PREMPHASE safely and effectively. See full prescribing information for PREMPRO/PREMPHASE.

PREMPRO (conjugated estrogens/medroxyprogesterone acetate tablets) PREMPHASE (conjugated estrogens plus medroxyprogesterone acetate tablets)
Initial U.S. Approval: 1995

WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER and PROBABLE DEMENTIA

See full prescribing information for complete boxed warning.

Estrogen Plus Progestin Therapy

•
Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia (5.1, 5.3)
•
The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) (5.1)
•
The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer (5.2)
•
The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older (5.3)

Estrogen-Alone Therapy

•
There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens (5.2)
•
Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia (5.1, 5.3)
•
The WHI estrogen-alone substudy reported increased risks of stroke and DVT (5.1)
•
The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older (5.3)

RECENT MAJOR CHANGES

Warnings and Precautions, Malignant Neoplasms (5.2)

2/2024

INDICATIONS AND USAGE

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)

DOSAGE AND ADMINISTRATION

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)

DOSAGE FORMS AND STRENGTHS

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)

CONTRAINDICATIONS

•
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)

WARNINGS AND PRECAUTIONS

•
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)

ADVERSE REACTIONS

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.

DRUG INTERACTIONS

•
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)

USE IN SPECIFIC POPULATIONS

•
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)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 2/2024

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Highlights

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use PREMPRO/PREMPHASE safely and effectively. See full prescribing information for PREMPRO/PREMPHASE.

PREMPRO (conjugated estrogens/medroxyprogesterone acetate tablets) PREMPHASE (conjugated estrogens plus medroxyprogesterone acetate tablets)
Initial U.S. Approval: 1995

WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER and PROBABLE DEMENTIA

See full prescribing information for complete boxed warning.

Estrogen Plus Progestin Therapy

•
Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia (5.1, 5.3)
•
The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) (5.1)
•
The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer (5.2)
•
The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older (5.3)

Estrogen-Alone Therapy

•
There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens (5.2)
•
Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia (5.1, 5.3)
•
The WHI estrogen-alone substudy reported increased risks of stroke and DVT (5.1)
•
The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older (5.3)

RECENT MAJOR CHANGES

Warnings and Precautions, Malignant Neoplasms (5.2)

2/2024

INDICATIONS AND USAGE

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)

DOSAGE AND ADMINISTRATION

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)

DOSAGE FORMS AND STRENGTHS

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)

CONTRAINDICATIONS

•
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)

WARNINGS AND PRECAUTIONS

•
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)

ADVERSE REACTIONS

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.

DRUG INTERACTIONS

•
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)

USE IN SPECIFIC POPULATIONS

•
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)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 2/2024
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