Progesterone - Warnings and Precautions
The following warnings and precautions are taken directly from the US FDA-approved drug label for Progesterone. This is the same information dispensing pharmacists read.
\u26a0\ufe0f Boxed Warning (Highest FDA Alert)
WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA FOR ESTROGEN PLUS PROGESTIN THERAPY Cardiovascular Disorders and Probable Dementia Estrogens plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia (see CLINICAL STUDIES and WARNINGS, Cardiovascular disorders and Probable dementia ). The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo (see CLINICAL STUDIES and WARNINGS, Cardiovascular disorders ). The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women (see CLINICAL STUDIES and WARNINGS, Probable dementia and PRECAUTIONS, Geriatric Use ). Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer (see CLINICAL STUDIES and WARNINGS, Malignant neoplasms, Breast Cancer ). In the absence of comparable data, these risks should be assum
WARNINGS See BOXED WARNING .
Cardiovascular disorders An increased risk of pulmonary embolism, deep vein thrombosis (DVT), stroke and myocardial infarction has been reported with estrogen plus progestin therapy.
Should any of these occur or be suspected, estrogen with progestin therapy should be discontinued immediately.
Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia and obesity) and/or venous thromboembolism (for example, personal history or family history of venous thromboembolism [VTE], obesity and systemic lupus erythematosus) should be managed appropriately. a.
Stroke In the Women’s Health Initiative (WHI) estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years).
The increase in risk was demonstrated after the first year and persisted (see CLINICAL STUDIES ).
Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. b.
Coronary Heart Disease In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of coronary heart disease (CHD) events (defined as nonfatal myocardial infarction [MI], silent MI, or CHD death) reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years).
An increase in relative risk was demonstrated in year 1 and a trend toward decreasing relative risk was reported in years 2 through 5 (see CLINICAL STUDIES ).
In postmenopausal women with documented heart disease (n = 2,763, average age 66.7 years), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study [HERS]), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit.
During an average follow-up of 4.1 years, treatment with CE plus 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 plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years.
Two thousand, three hundred and twenty-one (2,321) 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 plus MPA group and the placebo group in HERS, HERS II and overall. c.
Venous Thromboembolism In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE (DVT and pulmonary embolism [PE]) was reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years).
Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated.
The increase in VTE risk was demonstrated during the first year and persisted (see CLINICAL STUDIES ).
Should a VTE occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.
If feasible, estrogens with progestins 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.
Breast Cancer The WHI substudy of daily CE (0.625 mg)- alone provided information about breast cancer in estrogen-alone users.
In the WHI estrogen-alone substudy, after an average of follow-up of 7.1 years, daily CE-alone was not associated with an increased risk of invasive breast cancer [relative risk (RR) 0.80] compared to placebo (see CLINICAL STUDIES ).
In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26 percent of the women.
The relative risk of invasive breast cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years, for CE plus MPA compared with placebo.
Applies to YOU?
Some warnings apply only to specific age groups, health conditions, or other medicines. Ask GoDavaii AI to filter which of these 59+ warnings apply to your profile.
Ask Health AI \u2192