Drug Class: Sex hormone combinations
Usual Adult Dose for Postmenopausal Symptoms
Esterified estrogens-medroxyprogesterone 1.25 mg-2.5 mg oral tablets: one tablet orally once a day
or
Esterified estrogens-medroxyprogesterone 0.625 mg-1.25 mg oral tablets: one or two tablets orally once a day
Comments:
- Administration should be cyclic (e.g., three weeks on and one week off); women with a uterus should receive a progestin to reduce the risk of endometrial cancer.
- This drug should be used at the lowest dose that will control symptoms for the shortest duration consistent with treatment goals; attempts to discontinue or taper medication should be made at 3 to 6 month intervals.
- There is no evidence that estrogens are effective for nervous symptoms or depression without associated vasomotor symptoms, and they should not be used to treat such conditions.
Use: For treatment of moderate to severe vasomotor symptoms associated with the menopause in patients not improved by estrogen alone.
Renal Dose Adjustments
Data not available
Liver Dose Adjustments
Contraindicated in liver dysfunction or disease
Precautions
US BOXED WARNINGS: ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER, CARDIOVASCULAR AND OTHER RISKS
- ENDOMETRIAL CANCER: Estrogens increase the risk of endometrial cancer. Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses.
- CARDIOVASCULAR: Estrogen with or without progestins should not be used for prevention of cardiovascular disease. The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo.
- DEMENTIA: The WHI Memory Study (WHIMS) study, a substudy of WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens/medroxyprogesterone relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or women taking estrogen alone therapy.
- Other doses of conjugated estrogens with medroxyprogesterone, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Due to these risks, 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.
CONTRAINDICATIONS:
- Undiagnosed abnormal genital bleeding
- Known, suspected, or a history of breast cancer
- Known or suspected estrogen-dependent neoplasia
- Active or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE)
- Active, or within last year, arterial thromboembolic disease (e.g., stroke and MI)
- Liver disease or dysfunction
- Hypersensitivity to the active components or any of the ingredients
- Known or suspected pregnancy
This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA; this drug is not indicated in pediatric patients.
Consult WARNINGS section for additional precautions.
US Controlled Substance: Schedule CIII
Dialysis
Data not available
Other Comments
Administration advice:
Take orally, administer cyclically (e.g., 3 weeks on and 1 week off)
General:
- For postmenopausal woman with a uterus, a progestin should be added to reduce the risk of endometrial cancer.
- This drug should be given at the lowest effective dose and for the shortest duration necessary; periodically reevaluate if treatment is still necessary.
Monitoring:
- Monitor blood pressure
- Monitor thyroid function in patients receiving thyroid replacement
- Monitor glycemic control in patients with diabetes
- Monitor for signs of virilization
- Women with disseminated breast cancer should have frequent determinations of calcium levels
- Monitor liver function tests
Patient advice:
- Patients should be instructed to read the US FDA-approved patient labeling (Patient Information).
- Patients should be instructed to immediately report any unusual vaginal bleeding, breast lumps, signs or symptoms of stroke, myocardial infarction, severe headaches/migraines, or changes in vision.
- Patients should report any signs or symptoms of liver dysfunction or virilization.
