Medroxyprogesterone acetate and estrogens, conjugated
Looking up MedlinePlus…
From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER and PROBABLE DEMENTIA Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.3) , and Clinical Studies (14.6 , 14.7) ] .
The Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) (0.625 mg) combined with medroxyprogesterone acetate (MPA) (2.5 mg), relative to placebo [see Warnings and Precautions (5.1) , and Clinical Studies (14.6) ] .
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 Warnings and Precautions (5.3) , Use in Specific Populations (8.5) , and Clinical Studies (14.7) ] . Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.2) , and Clinical Studies (14.6) ] .
In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins. 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. Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.
Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ] . Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 ,…
Handling and access
NIOSH hazardous drug
Table 1This product contains estrogens, conjugated, which NIOSH lists as a hazardous drug. AHFS class: 68:16.04 estrogens; 92:24 bone resorption inhibitors.
- Listed in Table 1 because it meets the NIOSH definition of a hazardous drug and is classified as a carcinogen.
- Carcinogen classification: NTP “known to be a human carcinogen”.
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
Estrogen
Dosing in kidney impairment
Renal Impairment The effects of renal impairment on the pharmacokinetics of PREMPRO or PREMPHASE have not been studied.
Dosing in liver impairment
Hepatic Impairment The effects of hepatic impairment on the pharmacokinetics of PREMPRO or PREMPHASE have not been studied.
Drug interactions
Check medroxyprogesterone acetate and estrogens, conjugated against a medication listLabel text (3 paragraphs)
Data from a single-dose drug-drug interaction study involving CE and MPA indicate that the pharmacokinetic disposition of both drugs is not altered when the drugs are coadministered. No other clinical drug-drug interaction studies have been conducted with CE plus MPA. • 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 )
7.1 Metabolic Interactions In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St. John's wort ( Hypericum perforatum ) preparations, 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.
Aminoglutethimide administered concomitantly with MPA may significantly depress the bioavailability of MPA.
Contraindications
4 CONTRAINDICATIONS PREMPRO and PREMPHASE are contraindicated in women with any of the following conditions: • Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2) ] • Breast cancer or a history of breast cancer [see Warnings and Precautions (5.2) ] • Estrogen-dependent neoplasia [see Warnings and Precautions (5.2) ] • Active DVT, PE, or a history of these conditions [see Warnings and Precautions (5.1) ] • Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions [see Warnings and Precautions (5.1) ] • Known anaphylactic reaction or angioedema with PREMPRO/PREMPHASE [see Warnings and Precautions (5.15 , 5.16 )] • Hepatic impairment or disease [see Warnings and Precautions (5.10) ] • Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders • Undiagnosed abnormal genital bleeding ( 4 ) • Breast cancer or history of breast cancer ( 4 , 5.2 ) • 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 ) • Hepatic impairment or disease ( 4 , 5.10 ) • Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for medroxyprogesterone acetate and estrogens, conjugated. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary PREMPRO and PREMPHASE are not indicated for use during pregnancy. There are no data with the use of PREMPRO and PREMPHASE in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogen and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.