Version May 2024
There is an increased risk of endometrial cancer in a patient with a uterus who uses unopposed estrogens. Conjugated estrogens/bazedoxifene has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal patients with undiagnosed persistent or recurring abnormal genital bleeding.
Do not use estrogen therapy for the prevention of cardiovascular disease.
The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal patients (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (0.625 mg) alone, relative to placebo.
Do not use estrogen therapy for the prevention of dementia. The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal patients ≥65 years of age during 5.2 years of treatment with daily conjugated estrogens (0.625 mg) alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal patients.
Patients taking conjugated estrogens/bazedoxifene should not take additional estrogens. Only daily oral conjugated estrogen (0.625 mg) was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower conjugated estrogen doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risk of estrogen-alone therapy, taking into account the patient’s individual risk profile. Estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual patient.
Osteoporosis, postmenopausal, prevention (alternative agent):
Note: May be used as an alternative to first-line therapies to prevent bone loss in patients with a uterus who have moderate to severe vasomotor symptoms of menopause (AACE [Camacho 2020]; NAMS 2021; NOF [Cosman 2014]). In patients without menopausal vasomotor symptoms who require fracture risk reduction, other first-line therapies are preferred. Avoid use in patients >60 years of age or who are >10 years beyond menopause (NAMS 2021; NOF [Cosman 2014]). Ensure adequate calcium and vitamin D intake during therapy.
Oral: Conjugated estrogens 0.45 mg and bazedoxifene 20 mg once daily.
Duration of therapy: The optimal duration of therapy has not been established. Estrogens should be used for the shortest duration possible consistent with treatment goals (AACE/ACE [Camacho 2020]; NOF [Cosman 2014]; manufacturer’s labeling). Extended use may be considered in patients in whom alternative therapies are not appropriate and when benefits of therapy are expected to outweigh risks (NAMS 2021).
Discontinuation of therapy: If continued osteoporosis preventive therapy is necessary, switch to antiresorptive therapy (eg, with a bisphosphonate) following discontinuation (NAMS 2021; NOF [Cosman 2014]).
Vasomotor symptoms associated with menopause (alternative agent): Note: For use in symptomatic patients who are <60 years of age or within 10 years of menopause (NAMS 2022). Combination products are only indicated for patients with a uterus; the selective estrogen receptor modulator component prevents estrogen therapy-associated endometrial hyperplasia. Generally reserved for patients unable to tolerate oral progestogens or patients who experience breast tenderness with standard hormone therapy (Martin 2022).
Oral: Conjugated estrogens 0.45 mg/bazedoxifene 20 mg once daily.
Duration of therapy: Not clearly established; continued use may be appropriate in patients ≥60 years of age or >10 years after menopause with a low risk of cardiovascular disease and breast cancer and with persistent vasomotor symptoms after attempted taper/discontinuation of estrogen and trial of alternative therapies. Evaluate routinely for comorbidities and appropriateness of lower doses, nonoral routes of administration (preferred in patients ≥60 years of age), and discontinuation of therapy (NAMS 2022).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use is not recommended.
Use is contraindicated with hepatic dysfunction or disease.
Note: The Beers Criteria recommends avoiding systemic estrogen therapy in postmenopausal patients ≥65 years of age (independent of diagnosis or condition). In older postmenopausal patients already taking systemic estrogens, consider deprescribing (Ref). Duration of use is not clearly established; continued use may be appropriate in patients ≥60 years of age or >10 years after menopause with a low risk of cardiovascular disease and breast cancer with persistent vasomotor symptoms after attempted taper/discontinuation of estrogen and trial of alternative therapies. Evaluate routinely for comorbidities and appropriateness of lower doses, nonoral routes of administration (preferred in patients ≥60 years of age), choice of progestogen, and discontinuation of therapy (NAMS 2022).
Refer to adult dosing. Use in females >75 years of age is not recommended (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages as reported with combination product.
1% to 10%:
Central nervous system: Dizziness (5%)
Gastrointestinal: Diarrhea (8%), nausea (8%), dyspepsia (7%), upper abdominal pain (7%)
Neuromuscular & skeletal: Muscle spasm (9%), neck pain (5%)
Respiratory: Oropharyngeal pain (7%)
Hypersensitivity to estrogens, bazedoxifene, or any component of the formulation; undiagnosed abnormal uterine bleeding; active or past history of venous thromboembolism (VTE) (eg, PE, DVT); active or history of arterial thromboembolic disease (eg, stroke, MI); carcinoma of the breast (known, suspected or history of); estrogen-dependent tumor (known or suspected); hepatic impairment or disease; known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders; pregnancy.
Canadian labeling: Additional contraindications (not in US labeling): Active thrombophlebitis; endometrial hyperplasia; partial or complete loss of vision due to ophthalmic vascular disease.
Concerns related to adverse effects:
• Breast cancer: Based on data from the Women’s Health Initiative (WHI) studies, an increased risk of invasive breast cancer was observed in females who were postmenopausal using conjugated estrogens (CE) in combination with medroxyprogesterone acetate (MPA). Observational studies noted this risk declines once therapy is discontinued. The WHI study did not observe an increased risk of invasive breast cancer in females with a hysterectomy using CE alone. The risk of breast cancer in patients who are postmenopausal receiving hormone therapy may depend upon type of estrogen and/or progestogen, dose, timing of therapy initiation, duration of therapy, route of administration, and individual patient characteristics (AACE/ACE [Cobin 2017]; NAMS 2022). Hormone therapy may be associated with increased breast density (NAMS 2022); an increase in abnormal mammogram findings requiring further evaluation has been reported with estrogen alone or in combination with progestogen therapy. Estrogen use may lead to severe hypercalcemia in patients with breast cancer and bone metastases; discontinue estrogen if hypercalcemia occurs.
• Dementia: Because the WHI memory studies were conducted in females ≥65 years of age, it is unknown if these findings apply to younger females who are postmenopausal. However, hormone therapy is not recommended at any age to prevent or treat cognitive decline or dementia (AACE [Goodman 2011]; NAMS 2022).
• Lipid effects: Estrogen compounds are generally associated with lipid effects such as increased HDL-cholesterol and decreased LDL-cholesterol. Triglycerides may also be increased; discontinue if pancreatitis occurs.
• Ovarian cancer: Available information related to the use of menopausal estrogen or estrogen/progestogen therapy and risk of ovarian cancer is inconsistent. If an association is present, the absolute risk is likely rare and may be influenced by duration of therapy (AACE [Goodman 2011]; ES [Stuenkel 2015]; NAMS 2022).
• Retinal vascular thrombosis: Estrogens may cause retinal vascular thrombosis; discontinue pending examination if migraine, loss of vision, proptosis, diplopia, or other visual disturbances occur; discontinue permanently if papilledema or retinal vascular lesions are observed on examination.
Disease-related concerns:
• Asthma: Use caution in patients with asthma; may exacerbate disease.
• Carbohydrate intolerance: May impair glucose tolerance; use caution in patients with diabetes. Prior to therapy, consider age, cardiovascular and metabolic risk factors in patients previously diagnosed with diabetes (AACE/ACE [Cobin 2017]).
• Cardiovascular disease: Estrogens and bazedoxifene are known to increase the risk of venous thromboembolism (VTE). Additional risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of VTE. Manage risk factors appropriately; discontinue use immediately if adverse cardiovascular events occur or are suspected. Due to possible lower risk of thrombotic events, transdermal administration may be preferred for treating vasomotor symptoms of menopause in patients with risk factors for cardiovascular disease (AACE/ACE [Cobin 2017]; ACOG 556 2013; ES [Stuenkel 2015]). Use is contraindicated in females with active DVT, PE, arterial thromboembolic disease (stroke and MI), or a history of these conditions.
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including cardiac or renal dysfunction.
• Endometrial hyperplasia: Risk may be increased in patients taking combination estrogens.
• Epilepsy: Use caution with epilepsy; may exacerbate disease.
• Gallbladder disease: Use of postmenopausal estrogen may be associated with an increased risk of gallbladder disease requiring surgery.
• Hepatic dysfunction: Estrogens are poorly metabolized in patients with hepatic dysfunction. Use caution with a history of cholestatic jaundice associated with prior estrogen use or pregnancy. Discontinue if jaundice develops or if acute or chronic hepatic disturbances occur. Use is contraindicated with hepatic disease.
• Hepatic hemangiomas: Use with caution in patients with hepatic hemangiomas; may exacerbate disease.
• Hereditary angioedema: Exogenous estrogens may exacerbate angioedema symptoms in females with hereditary angioedema.
• Hypoparathyroidism: Use caution in patients with hypoparathyroidism; estrogen-induced hypocalcemia may occur.
• Migraine: Use caution with migraine; may exacerbate disease.
• Porphyria: Use with caution in patients with porphyria; may exacerbate disease.
• SLE: Use with caution in patients with SLE; may exacerbate disease.
Concurrent drug therapy issues:
• Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels. Females on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens.
Special populations:
• Overweight/Obese: Bazedoxifene exposure is decreased in females with a BMI >27 kg/m2 which may be associated with an increased risk of endometrial hyperplasia. Females with a BMI >34 kg/m2 or >32.2 kg/m2 were excluded from some initial vasomotor or osteoporosis studies, respectively (Lindsay 2009; Pinkerton 2009). Regardless of BMI, monitor to rule out malignancy in females who are postmenopausal with undiagnosed persistent or recurrent abnormal genital bleeding.
• Surgery: Whenever possible, discontinue estrogens at least 4 to 6 weeks prior to elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Other warnings/precautions:
• Duration of use: Not clearly established; continued use may be appropriate in patients ≥60 years of age or >10 years after menopause with a low risk of cardiovascular disease and breast cancer with persistent vasomotor symptoms after attempted taper/discontinuation of estrogen and trial of alternative therapies. Evaluate routinely for comorbidities and appropriateness of lower doses, nonoral routes of administration (preferred in patients ≥60 years of age), choice of progestogen, and discontinuation of therapy (NAMS 2022).
• Laboratory changes: The use of estrogens and/or progestogens may change the results of some laboratory tests (eg, coagulation factors, lipids, glucose tolerance, binding proteins). The dose, route, and the specific estrogen/progestogen influences these changes.
• Osteoporosis use: In females with premature menopause, hormone therapy to prevent bone loss may be used unless otherwise contraindicated; reassess therapy when the average age of menopause is reached. It is also an appropriate bone-active therapy for females with vasomotor symptoms who are <60 years of age or within 10 years of menopause onset. Use may be considered for females at high risk of fractures who are not candidates for other osteoporosis therapies (NAMS 2022).
• Risks vs benefits: When used for the relief of menopausal symptoms or increased risk of bone fracture/loss, the benefit-risk of hormone therapy is most favorable if started in patients who have no contraindications to therapy, are <60 years of age, within 10 years of menopause onset, have a favorable lipid profile, and do not have the factor V Leiden genotype or metabolic syndrome. Consider risk factors for cardiovascular disease when evaluating therapy and route of administration (AACE/ACE [Cobin 2017]; NAMS 2022). Do not take progestogens or additional estrogen agonists/antagonists. Reevaluate patients as clinically appropriate to determine if treatment is still necessary. Available data related to treatment risks are from Women’s Health Initiative (WHI) studies, which evaluated oral CE 0.625 mg relative to placebo in females who were postmenopausal.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Duavee: Conjugated estrogens 0.45 mg and bazedoxifene acetate 20 mg
No
Tablets (Duavee Oral)
0.45-20 mg (per each): $7.88
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release, Oral:
Duavive: Conjugated estrogens 0.45 mg and bazedoxifene 20 mg
Administer without regard to meals; swallow tablets whole.
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
Osteoporosis, postmenopausal, prevention: Prevention of postmenopausal osteoporosis in females with a uterus.
Limitations of use: For use only in females at significant risk of postmenopausal osteoporosis; consider use of nonestrogen medications.
Vasomotor symptoms: Treatment of moderate to severe vasomotor symptoms associated with menopause in patients with a uterus.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Beers Criteria: Estrogens (oral or topical patch products only), with or without progestins, are identified in the Beers Criteria as potentially inappropriate medications to be avoided in postmenopausal patients ≥65 years of age (independent of diagnosis or condition) due to their carcinogenic potential (breast and endometrium) and lack of cardioprotection or cognitive protection. Starting therapy in postmenopausal patients ≥60 years of age has greater risks (eg, heart disease, stroke, blood clots, dementia) than benefits. In postmenopausal patients already taking systemic estrogens, consider deprescribing (Beers Criteria [AGS 2023]).
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Ajmaline: Estrogen Derivatives may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination
Anthrax Immune Globulin (Human): Estrogen Derivatives may enhance the thrombogenic effect of Anthrax Immune Globulin (Human). Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
C1 inhibitors: Estrogen Derivatives may enhance the thrombogenic effect of C1 inhibitors. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor therapy
Chenodiol: Estrogen Derivatives may diminish the therapeutic effect of Chenodiol. Risk C: Monitor therapy
Chlorprothixene: Estrogen Derivatives may enhance the adverse/toxic effect of Chlorprothixene. Estrogen Derivatives may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Cosyntropin: Estrogen Derivatives may diminish the diagnostic effect of Cosyntropin. Management: Discontinue estrogen containing drugs 4 to 6 weeks prior to cosyntropin (ACTH) testing. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Dantrolene: Estrogen Derivatives may enhance the hepatotoxic effect of Dantrolene. Risk C: Monitor therapy
Dehydroepiandrosterone: May enhance the adverse/toxic effect of Estrogen Derivatives. Risk X: Avoid combination
Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Fluoroestradiol F18: Selective Estrogen Receptor Modulators may diminish the diagnostic effect of Fluoroestradiol F18. Management: Image patients with fluoroestradiol F-18 prior to starting systemic endocrine therapies that block the estrogen receptor. Use of fluoroestradiol F-18 should not delay indicated treatment. Risk D: Consider therapy modification
Fosphenytoin: May decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Growth Hormone Analogs: Estrogen Derivatives may diminish the therapeutic effect of Growth Hormone Analogs. Management: Initiate somapacitan at 2 mg once weekly in patients receiving oral estrogens. Monitor for reduced efficacy of growth hormone analogs; increased doses may be required. Risk D: Consider therapy modification
Hemin: Estrogen Derivatives may diminish the therapeutic effect of Hemin. Risk X: Avoid combination
Hyaluronidase: Estrogen Derivatives may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
Hydrocortisone (Systemic): Estrogen Derivatives may increase the serum concentration of Hydrocortisone (Systemic). Estrogen Derivatives may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Immune Globulin: Estrogen Derivatives may enhance the thrombogenic effect of Immune Globulin. Risk C: Monitor therapy
Indium 111 Capromab Pendetide: Estrogen Derivatives may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
LamoTRIgine: Estrogen Derivatives may decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy
Lenalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Lenalidomide. Risk C: Monitor therapy
Melatonin: Estrogen Derivatives may increase the serum concentration of Melatonin. Risk C: Monitor therapy
MetyraPONE: Estrogen Derivatives may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking estrogen derivatives. Risk D: Consider therapy modification
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy
Mivacurium: Estrogen Derivatives may increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the thrombogenic effect of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Ospemifene: Selective Estrogen Receptor Modulators may enhance the adverse/toxic effect of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Risk X: Avoid combination
Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. Risk X: Avoid combination
PHENobarbital: May decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor therapy
Pomalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Pomalidomide. Risk C: Monitor therapy
Primidone: May decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor therapy
Protease Inhibitors: May decrease the serum concentration of Estrogen Derivatives. Protease Inhibitors may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Raloxifene: Estrogen Derivatives may enhance the adverse/toxic effect of Raloxifene. Risk X: Avoid combination
RifAMPin: May decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor therapy
ROPINIRole: Estrogen Derivatives may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy
Succinylcholine: Estrogen Derivatives may increase the serum concentration of Succinylcholine. Risk C: Monitor therapy
Tacrolimus (Systemic): Estrogen Derivatives may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Thalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Thyroid Products: Estrogen Derivatives may diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Tranexamic Acid: Estrogen Derivatives may enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination
Ursodiol: Estrogen Derivatives may diminish the therapeutic effect of Ursodiol. Risk C: Monitor therapy
This combination product is approved for use in females who are postmenopausal only. Use is contraindicated during pregnancy.
Estrogens are present in breast milk; excretion of bazedoxifene is not known.
Also refer to the Estrogens (Conjugated/Equine) monograph for additional information.
Ensure adequate calcium and vitamin D intake when used for the prevention of osteoporosis.
Prior to therapy, baseline risk for breast cancer and CVD. During therapy, age appropriate breast and pelvic exams; blood pressure; unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients who are obese, diabetic, or have a history of endometrial cancer); serum triglycerides (2 weeks after starting therapy in patients with baseline level >200 mg/dL); TSH (6 to 12 weeks after starting oral therapy in patients taking thyroid replacement) (ES [Stuenkel 2015]).
Osteoporosis, prevention: Bone density measurement
Vasomotor symptoms: Efficacy beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate. Evaluate duration of treatment at least annually (ES [Stuenkel 2015]).
Note: Monitoring of FSH and serum estradiol is not useful when managing vasomotor symptoms of menopause
Conjugated estrogens contain a mixture of estrone sulfate, equilin sulfate, 17 alpha-dihydroequilin, 17 alpha-estradiol and 17 beta-dihydroequilin. Bazedoxifene is a selective estrogen receptor modulator (SERM). Conjugated estrogens act as an estrogen agonist and bazedoxifene acts as an estrogen agonist/antagonist depending on the specific tissue. The combination of a SERM and estrogen [referred to as a tissue-selective estrogen complex (TSEC)] provides relief of vasomotor symptoms and maintenance of bone mineral density in postmenopausal females with a uterus, while reducing the risk of endometrial hyperplasia observed with estrogen use alone (Pickar 2009).
Onset:
Relief of vasomotor symptoms: A significant reduction in the number and severity of moderate/severe hot flashes was observed after 4 weeks of therapy (Pinkerton, 2009).
Osteoporosis: A significant increase in BMD measured at the lumbar spine and hip was observed at 12 months of therapy (Lindsay, 2009).
Absorption: Conjugated estrogens: Well-absorbed from the gastrointestinal tract.
Distribution: Bazedoxifene: Vd: ~15 L/kg.
Protein binding:
Bazedoxifene: 98% to 99%; does not bind to sex-hormone binding globulin.
Conjugated estrogens: Binds to sex-hormone-binding globulin and albumin.
Metabolism:
Bazedoxifene: Metabolized via glucuronidation; forms metabolites; little or no CYP mediated metabolism; undergoes hepatic recirculation.
Conjugated estrogens: Hepatic via CYP3A4; estradiol is converted to estrone and estriol; also undergoes enterohepatic recirculation; estrone sulfate is the main metabolite in females who are postmenopausal.
Bioavailability: Bazedoxifene: ~6%.
Half-life elimination: Bazedoxifene: ~30 hours; Total estrone: ~17 hours.
Time to peak: Bazedoxifene: ~2.5 hours; Total estrone: ~6.5 hours.
Excretion:
Conjugated estrogens: Urine (primarily estriol, also as estradiol, estrone, and conjugates).
Bazedoxifene: Biliary; feces (~85%); urine (<1%).
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