Dosing and uses of Premphase, Prempro (conjugated estrogens/medroxyprogesterone)
Adult dosage forms and strengths
conjugated estrogens/medroxyprogesterone
tablet
- 0.3 mg/1.5mg
- 0.45 mg/1.5mg
- 0.625 mg/2.5mg
- 0.625 mg/5mg
- 0.625 mg/5mg plus conjugated estrogen 0.625 mg (Premphase)
Menopause
Indicated in women who have a uterus for the treatment of moderate-to-severe vasomotor symptoms or vulvar and vaginal atrophy associated with the menopause
Also indicated for prevention of postmenopausal osteoporosis; when prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and nonestrogen medications should be carefully considered
Premphase (biphasic regimen)
- 1 pure estrogen tablet qDay Days 1-14, THEN
- 1 combo tablet PO qDay on days 15-28 of cycle
Prempro
- 1 tablet PO qDay
Pediatric dosage forms and strengths
Not recommended
Premphase, Prempro (conjugated estrogens/medroxyprogesterone) adverse (side) effects
>10%
Abdominal pain
Breast enlargement
Breast tenderness
Bloating
Nausea/vomiting
Peripheral edema
Frequency not defined
Amenorrhea
Breakthrough bleeding
Depression
Headache
Melasma
Spotting
Weight changes
Postmarketing Reports
Ischemic colitis
Growth potentiation of benign meningioma
Warnings
Contraindications
Known anaphylactic reaction or angioedema
Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Pregnancy
Estrogen-dependent neoplasia
Current/history of DVT/PE, arterial thromboembolic disease, breast cancer, liver disease/tumors
Undiagnosed abnormal vaginal bleeding
Cautions
Bone mineral density changes, current/history of depression, diabetes mellitus, HTN, hyperlipidemia, hypertriglyceridemia, obesity, endometriosis, family history of breast cancer and/or DVT/PE, smoking, severe hypocalcemia, ovarian cancer
Discontinue if the following develop: jaundice, visual problems, 4 wk before major surgery or prolonged immobilization, any symptoms of VTE, massive BP increase, unusually severe migraines or first-time migraines, depression
Increased risk of post-op thromboembolic complications, MI, stroke, pulmonary emboli, DVT, Alzheimer's disease, cardiovascular disorders, probable dementia, and endometrial cancer
Conditions exacerbated by fluid retention (eg, asthma, migraine, cardiac/renal dysfunction, epilepsy)
Patients on warfarin/oral anticoagulants: estrogens increase thromboembolic risk; increase in anticoagulant dose may be warranted
Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema
Pregnancy and lactation
Pregnancy category: X
Lactation: controversial; estrogens are excreted into breast milk in small quantities, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Premphase, Prempro (conjugated estrogens/medroxyprogesterone)
Mechanism of action
Estradiol: Endogenous estrogen; reduces the release of gonadotropin-releasing hormone from hypothalamus, reduces release of LH and FSH from pituitary gland; increases synthesis of DNA, RNA, and various proteins in target tissues
Medroxyprogestin: Progestin; inhibits secretion of gonadotropins from pituitary gland; prevents follicular maturation and ovulation, stimulates growth of mammary tissues
Absorption
Bioavailability: Readily absorbed from GI tract (conjugated estrogens)
Onset: 2-4 wk (conjugated estrogens)
Peak Plasma: 8 hr (conjugated estrogens)
Distribution
Protein Bound: 80% (conjugated estrogens); 90% (medroxyprogesterone)
Metabolism
Conjugated estrogens metabolized in liver to inactive sulfates and glucuronides
Medroxyprogesterone metabolized in liver
Metabolites: Estradiol, estrone, estriol (conjugated estrogens)
Elimination
Excretion (conjugated estrogens): Urine, most estrogens are also excreted in bile and undergo enterohepatic recycling
Excretion (medroxyprogesterone): Urine
