Duavee Drug Information
Generic name: CONJUGATED ESTROGENS/BAZEDOXIFENE
Estrogen [EPC]
Uses of Duavee
Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause
Prevention of Postmenopausal Osteoporosis
Important Limitations of Use • Use DUAVEE for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. • When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medication should be carefully considered.
Dosage & Administration of Duavee
Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause The recommended dosage is one DUAVEE tablet daily.
General Dosing Information Take
DUAVEE once daily, without regard to meals. Tablets should be swallowed whole.
Recommendations for Calcium and Vitamin D Supplementation
Women taking DUAVEE for prevention of postmenopausal osteoporosis should add supplemental calcium and/or vitamin D to their diet if daily intake is inadequate.
Administration Instructions for Missed Doses If a dose of DUAVEE is missed, instruct patients to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time.
Use in Patients with Renal Impairment
The pharmacokinetics of DUAVEE have not been evaluated in patients with renal impairment. Use in patients with renal impairment is not recommended.
Use in the Elderly DUAVEE has not been studied in women over 75 years of age. Use in women over 75 years of age is not recommended.
Side Effects of Duavee
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 1,224 patients were treated with DUAVEE and 1,069 patients received placebo. The incidence of all-cause mortality was 0.0% in the DUAVEE group and 0.2% in the placebo group.
The incidence of serious adverse reactions was 3.5% in the DUAVEE group and 4.8% in the placebo group. The percentage of patients who withdrew from treatment due to adverse reactions was 7.5% in the DUAVEE group and 10.0% in the placebo group. The most common adverse reactions leading to discontinuation were hot flush, abdominal pain upper, and nausea.
The most commonly observed adverse reactions (incidence ≥ 5%) more frequently reported in women treated with DUAVEE than placebo are presented in Table 1. Table 1: Adverse Reactions (Incidence ≥ 5%) More Common in the DUAVEE Treatment Group in Placebo-controlled Trials 80 61 Venous thromboembolism: In the clinical studies with DUAVEE, the reporting rates for venous thromboembolism (deep venous thrombosis, pulmonary embolism, and retinal vein thrombosis) were low in all treatment groups. Adverse reactions of venous thromboembolism were reported in 0.0% of patients treated with DUAVEE and 0.1% of patients treated with placebo.
Due to the low rate of events in both groups, it is not possible to conclude that the risk of venous thromboembolism with DUAVEE is different from that seen with other estrogen therapies.
| DUAVEE (N=1224) n (%) | Placebo (N=1069) n (%) | |
|---|---|---|
| Gastrointestinal disorders | ||
| Nausea | 100 (8) | 58 (5) |
| Diarrhea | 96 (8) | 57 (5) |
| Dyspepsia | 84 (7) | 59 (6) |
| Abdominal pain upper | 81 (7) | 58 (5) |
| Musculoskeletal and connective tissue disorders | ||
| Muscle spasms | 110 (9) | 63 (6) |
| Neck pain | 62 (5) | 46 (4) |
| Nervous system disorders | ||
| Dizziness | 65 (5) | 37 (3) |
| Respiratory, thoracic, and mediastinal disorders | ||
| Oropharyngeal pain | 80 (7) | 61 (6) |
Warnings & Cautions for Duavee
Drugs Containing Progestins, Estrogens or Estrogen Agonist/Antagonists DUAVEE contains conjugated estrogens and bazedoxifene, an estrogen agonist/antagonist. Women taking DUAVEE should not take progestins, additional estrogens or additional estrogen agonist/antagonists.
Cardiovascular Disorders
Estrogen agonist/antagonists (including bazedoxifene, a component of DUAVEE) and estrogens individually are known to increase the risk of VTE. An increased risk of stroke and DVT has been reported with estrogen-alone therapy. Should any of these occur or be suspected, DUAVEE should be discontinued immediately.
Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or VTE (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. The increase in risk was demonstrated in year 1 and persisted. Should a stroke occur or be suspected, DUAVEE should be discontinued immediately.
Coronary Heart Disease In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal myocardial infarction, silent myocardial infarction, or CHD death) was reported in women receiving estrogen-alone compared to placebo. The increase in VTE risk was demonstrated during the first 2 years. If feasible, DUAVEE 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.
Because immobilization increases the risk for venous thromboembolic events independent of therapy, DUAVEE should be discontinued prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest) and DUAVEE therapy should be resumed only after the patient is fully ambulatory. In addition, women taking DUAVEE should be advised to move about periodically during travel involving prolonged immobilization.
Malignant Neoplasms Endometrial Cancer
An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in women with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than 1 year.
The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more of treatment. This risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. DUAVEE contains an estrogen agonist/antagonist.
This component reduces the risk of endometrial hyperplasia that can occur with the conjugated estrogens component. Endometrial hyperplasia may be a precursor to endometrial cancer. Women taking DUAVEE should not take additional estrogens as this may increase the risk of endometrial hyperplasia.
Clinical surveillance of all women taking DUAVEE is important. 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. Breast Cancer The WHI substudy of daily conjugated estrogens (0.625 mg)-alone provided information about breast cancer in estrogen‑alone users.
In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily conjugated estrogen (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer (relative risk 0.80). The use of estrogen-alone has been reported to result in an increase in abnormal mammograms requiring further evaluation. The effect of treatment with DUAVEE on the risk of breast cancer is unknown.
All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results. Ovarian Cancer A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer.
The primary analysis, using case-control comparisons, included 12,110 cancer cases from the 17 prospective studies. The relative risk associated with combined current and recent use (discontinued use within 5 years before cancer diagnosis) was 1.37 (95% CI 1.27–1.48), and the elevated risk was significant for both estrogen-alone and estrogen plus progestin products. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown.
Probable Dementia In the WHIMS estrogen-alone ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg)-alone or placebo. After an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83–2.66).
The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years.
Gallbladder Disease A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
Visual Abnormalities
Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, DUAVEE should be permanently discontinued.
Elevated Blood Pressure In a small number of case reports in women receiving estrogens, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical study, a generalized effect of estrogens on blood pressure was not seen.
Hypertriglyceridemia
In women with pre-existing hypertriglyceridemia, treatment with estrogens may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of DUAVEE if pancreatitis occurs.
Hepatic Impairment and Past History of Cholestatic Jaundice DUAVEE has not been studied in women with impaired liver function or past history of cholestatic jaundice. Estrogens may be poorly metabolized in women with impaired liver function. On average, women with hepatic impairment treated with bazedoxifene alone showed a 4.3-fold increase in overall exposures compared with controls.
For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised; and in the case of recurrence, DUAVEE should be discontinued. Use of DUAVEE in patients with hepatic impairment is contraindicated.
Hypothyroidism
Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy.
These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.
Fluid Retention Estrogens may cause some degree of fluid retention. Because of this, patients who have conditions that might be influenced by this factor, such as cardiac dysfunction or renal impairment, warrant careful observation when estrogens are prescribed. Use of DUAVEE in patients with renal impairment is not recommended.
Hypocalcemia
Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.
Hereditary Angioedema
Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.
Exacerbation of Other Conditions Estrogens may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.
Premenopausal Women There is no indication for premenopausal use of DUAVEE. The efficacy and safety of DUAVEE in premenopausal women have not been established, and its use is not recommended. Additionally, there is concern regarding inadvertent drug exposure in pregnancy in women of reproductive potential who become pregnant, due to risk of fetal harm.
Laboratory Tests
Serum follicle stimulating hormone (FSH) and estradiol levels have not been shown to be useful in the management of moderate to severe vasomotor symptoms.
Drug-Laboratory Test Interactions
Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay), or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reflecting the elevated TBG.
Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, for example, corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased.
Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin). Increased plasma high-density lipoprotein (HDL) and HDL2 cholesterol subfraction concentrations, reduced low-density lipoprotein (LDL) cholesterol concentrations, increased triglyceride levels. Impaired glucose tolerance.
Drug Interactions with Duavee
Cytochrome P450 (CYP)
In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Concomitant administration of itraconazole, a strong CYP3A4 inhibitor, with DUAVEE, resulted in increases in bazedoxifene exposure (40%) and, to a lesser extent, conjugated estrogens exposure (9% for baseline-adjusted total estrone, 5% for total equilin), compared to DUAVEE alone. Inducers of CYP3A4, such as St.
John's Wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of some estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Bazedoxifene does not induce or inhibit the activities of major CYP isoenzymes. In vitro data suggest that bazedoxifene is unlikely to interact with co-administered drugs via CYP-mediated metabolism.
Uridine Diphosphate Glucuronosyltransferase (UGT)
Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver. The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs, such as rifampin, phenobarbital, carbamazepine, and phenytoin. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia.
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.
Atorvastatin
Concomitant administration of bazedoxifene (40 mg daily) and atorvastatin (20 mg, single-dose) to healthy postmenopausal women did not affect the pharmacokinetics of bazedoxifene, atorvastatin or its active metabolites.
Pregnancy Safety for Duavee
Pregnancy Risk Summary DUAVEE is contraindicated for use in pregnant women and is not indicated for use in females of reproductive potential. Conjugated Estrogens (CE) There are no data with the use of conjugated estrogens in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital and non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives before conception or during early pregnancy. Bazedoxifene There are no available data on bazedoxifene use in pregnant women to inform a drug associated risk of adverse developmental outcomes.
Animal studies have shown that oral bazedoxifene administered during the period of organogenesis to pregnant rats or rabbits at 0.3 and 2 times, respectively, the exposure at the maximum recommended dose, can cause fetal harm. Based on mechanism of action, bazedoxifene may block the important functions that estrogen has during all stages of pregnancy. Data Animal data Bazedoxifene Administration of bazedoxifene to rats at maternally toxic dosages ≥1 mg/kg/day (≥ 0.3 times the human area under the curve (AUC) at the 20 mg dose) resulted in reduced numbers of live fetuses and/or reductions in fetal body weights.
No fetal developmental anomalies were observed. In studies conducted with pregnant rabbits treated with bazedoxifene, abortion and an increased incidence of heart (ventricular septal defect) and skeletal system (ossification delays, misshapen or misaligned bones, primarily of the spine and skull) anomalies in the fetuses were present at maternally toxic dosages of ≥ 0.5 mg/kg/day (≥ 2 times the human AUC at the 20 mg dose).
Pediatric Use of Duavee
Pediatric Use DUAVEE is not indicated for use in children.
Contraindications for Duavee
- DUAVEE is contraindicated in women with any of the following conditions:
- Undiagnosed abnormal uterine bleeding
- Known, suspected, or past history of breast cancer
- Known or suspected estrogen-dependent neoplasia
- Active deep venous thrombosis, pulmonary embolism, or history of these conditions
- Active arterial thromboembolic disease (for example, stroke, myocardial infarction) or history of these conditions
- Hypersensitivity (for example, anaphylaxis, angioedema) to estrogens, bazedoxifene, or any ingredients
- Known hepatic impairment or disease
- Known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders
- Pregnancy, as DUAVEE may cause fetal harm.
- Undiagnosed abnormal uterine bleeding
- Active or past history of venous thromboembolism
- Active or past history of arterial thromboembolism
- Pregnancy
Overdosage Information for Duavee
In case of overdosage, there is no specific antidote, and the treatment should be symptomatic. Symptoms of overdosage of estrogen-containing products in adults and children may include nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue; withdrawal bleeding may occur.
Clinical Studies of Duavee
Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause in Women with a Uterus The safety and efficacy of DUAVEE as a treatment for moderate to severe vasomotor symptoms associated with menopause was established in a 12-week randomized, double-blind, placebo-controlled study (Study 3). The mean number of years since menopause was 4.5 years with all women undergoing natural menopause. A total of 127 women were assigned to DUAVEE and 63 women were assigned to placebo.
In Study 3, DUAVEE significantly reduced the number and severity of moderate to severe hot flushes, as measured by the daily severity score, compared with placebo at Weeks 4 and 12. The change from baseline in the number and severity of moderate to severe hot flushes observed and the difference from placebo in Study 3 are shown in Table 3. Study 1 was a 24-month, double-blind, randomized, placebo- and active-controlled study evaluating the safety and efficacy of multiple combinations of conjugated estrogen/bazedoxifene (including conjugated estrogens 0.45 mg/bazedoxifene 20 mg) compared to placebo.
The primary endpoint of the study was the incidence of endometrial hyperplasia at Year 1. Bone mineral density change at the lumbar spine at Year 2 was the key secondary endpoint, assessed in two subsets of patients (Substudy I and Substudy II). Patients enrolled into Substudy I had to be more than 5 years postmenopausal, have a lumbar spine or total hip T-score of -1 to -2.5, and have at least one additional risk factor for osteoporosis (e.g., Caucasian race, family history of osteoporosis, early menopause, thin/small frame, inactive lifestyle, tobacco abuse).
Those enrolled into Substudy II had to be 1–5 years postmenopausal with at least one additional risk factor for osteoporosis. A total of 3,397 women age 40–75 (mean age of 56 years) were enrolled in the overall study. Women also took calcium (600–1200 mg) and vitamin D (200–400 IU) daily.
In these substudies, treatment with DUAVEE significantly increased lumbar spine bone mineral density (BMD) at 24 months compared to placebo in both groups of postmenopausal women (Table 4). Table 4: Lumbar Spine Bone Mineral Density Results at also significantly increased total hip BMD. Study 2 was a 12-month, double-blind, randomized, placebo- and active-controlled study.
The primary endpoint was the incidence of endometrial hyperplasia at 12 months. The prevention of osteoporosis was assessed in a substudy that enrolled women (n=590) who were less than 5 years postmenopausal (mean 2.5 years). The mean baseline T-score in the substudy was -0.91 in the DUAVEE group and -0.95 in the placebo group.
The mean age of women (n=135) taking DUAVEE was 53 years (range 46–60 years). Treatment with DUAVEE also increased total hip BMD. The Efficacy Evaluable population included patients who had taken at least one dose of DUAVEE, had baseline and post baseline endometrial biopsies, or had been diagnosed with hyperplasia.
By endometrial biopsy, the incidence of endometrial hyperplasia or malignancy for DUAVEE was below 1% in both studies (see Table 5 ). In Study 2, cumulative amenorrhea at Year 1 was 88% in women treated with DUAVEE and 84% in women who received placebo.
Women's Health Initiative Studies The WHI enrolled approximately 11,000 predominantly healthy postmenopausal women to assess the risks and benefits of daily oral conjugated estrogens 0.625 mg compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of CHD (defined as nonfatal MI, silent MI and CHD death), with invasive breast cancer as the primary adverse outcome. A "global index" included the earliest occurrence of CHD, invasive breast cancer, stroke, PE, colorectal cancer, hip fracture, or death due to other cause.
These substudies did not evaluate the effects of conjugated estrogens on menopausal symptoms. The WHI estrogen-alone substudy was stopped early because an increased risk of stroke was observed, and it was deemed that no further information would be obtained regarding the risks and benefits of estrogen-alone in predetermined primary endpoints. Table 6: Relative and Absolute Risk Seen in the Estrogen Alone Substudy of WHI Adapted from numerous WHI publications.
WHI publications can be viewed at www.nhlbi.nih.gov/whi. For those outcomes included in the WHI "global index" that reached statistical significance, the absolute excess risk per 10,000 women-years in the group treated with CE-alone was 12 more strokes, while the absolute risk reduction per 10,000 women-years was 7 fewer hip fractures. The absolute excess risk of events included in the "global index" was a non-significant 5 events per 10,000 women-years.
There was no difference between the groups in terms of all-cause mortality. No overall difference for primary CHD events (nonfatal MI, silent MI and CHD death) and invasive breast cancer incidence in women receiving conjugated estrogens-alone compared to placebo was reported in final centrally adjudicated results from the estrogen-alone substudy, after an average follow-up of 7.1 years. Centrally adjudicated results for stroke events from the estrogen-alone substudy, after an average follow-up of 7.1 years, reported no significant differences in distribution of stroke subtype or severity, including fatal strokes, in women receiving conjugated estrogens-alone compared to placebo.
Estrogen-alone increased the risk for ischemic stroke, and this excess risk was present in all subgroups of women examined. Timing of the initiation of estrogen-alone therapy relative to the start of menopause may affect the overall risk benefit profile. The absolute risk of probable dementia for conjugated estrogens-alone versus placebo was 37 versus 25 cases per 10,000 women-years.
Probable dementia as defined in this study included Alzheimer's disease (AD), vascular dementia (VaD) and mixed type (having features of both AD and VaD). The most common classification of probable dementia in the treatment group and the placebo group was AD. Since the ancillary study was conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women.
| Frequency | Severity | |||
|---|---|---|---|---|
| DUAVEE | Placebo | DUAVEE | Placebo | |
| N | 122 | 63 | 122 | 63 |
| Baseline | 10.3 | 10.5 | 2.3 | 2.3 |
| Week 4 | ||||
| Mean Change Change from baseline using ANCOVA model | -5.9 | -2.8 | -0.6 | -0.1 |
| Treatment Difference Based on raw data analysis using ANCOVA model: Difference= Treatment + Baseline + Site | -3.1 (-4.4, -1.7) p<0.001 | -- | -0.5 (-0.7, -0.3) | -- |
| Week 12 | ||||
| Mean Change | -7.6 | -4.9 | -0.9 | -0.3 |
| Treatment Difference | -2.7 (-3.8, -1.6) | -- | -0.6 (-0.9, -0.4) | -- |
| DUAVEE | Placebo | |
|---|---|---|
| Adjusted mean changes, confidence intervals, and p-values based on an ANCOVA model with treatment and region (U.S. or non-U.S.) as factors and baseline BMD value and years since menopause as covariates using the Modified Intention to Treat population with Last Observation Carried Forward. Study 1 excludes those subjects with missing source documentation. | ||
| Between 1 and 5 Years Postmenopausal | ||
| N | 95 | 95 |
| % Mean Change | 1.72 | -1.90 |
| Difference from Placebo (95% C.I.) | 3.62 (2.64, 4.60) p-value < 0.001 | |
| More Than 5 Years Postmenopausal | ||
| N | 155 | 151 |
| % Mean Change | 1.64 | -1.47 |
| Difference from Placebo (95% C.I.) | 3.11 (2.29, 3.93) | – |
| STUDY 1 = Efficacy Evaluable population | STUDY 2 | ||||
|---|---|---|---|---|---|
| Treatment Group | Month | % (n/N) | 1 – Sided 95% UL | % (n/N) | 1 – Sided 95% UL |
| UL = Upper limit | |||||
| DUAVEE | 12 | 0.00% (0/336) | 0.89 | 0.30% (1/335) | 1.41 |
| 24 | 0.68% (2/294) | 2.13 | -- | -- | |
| Event | Relative Risk CE vs. Placebo (95% nCI Nominal confidence intervals unadjusted for multiple looks and multiple comparisons. ) | CE n = 5,310 | Placebo N = 5,429 |
|---|---|---|---|
| Absolute Risk per 10,000 Women-Years | |||
| CHD events Results are based on centrally adjudicated data for an average follow-up of 7.1 years. | 0.95 (0.78–1.16) | 54 | 57 |
| Non-fatal MI | 0.91 (0.73–1.14) | 40 | 43 |
| CHD death | 1.01 (0.71–1.43) | 16 | 16 |
| All strokes | 1.33 (1.15–1.68) | 45 | 33 |
| Ischemic stroke | 1.55 (1.19–2.01) | 38 | 25 |
| Deep vein thrombosis, Not included in "global index". | 1.47 (1.06–2.06) | 23 | 15 |
| Pulmonary embolism | 1.37 (0.90–2.07) | 14 | 10 |
| Invasive breast cancer | 0.80 (0.62–1.04) | 28 | 34 |
| Colorectal cancer Results are based on an average follow-up of 6.8 years. | 1.08 (0.75–1.55) | 17 | 16 |
| Hip fracture | 0.65 (0.45–0.94) | 12 | 19 |
| Vertebral fractures, | 0.64 (0.44–0.93) | 11 | 18 |
| Lower arm/wrist fractures, | 0.58 (0.47–0.72) | 35 | 59 |
| Total fractures, | 0.71 (0.64–0.80) | 144 | 197 |
| Death due to other causes, All deaths, except from breast or colorectal cancer, definite or probable CHD, PE, or cerebrovascular disease. | 1.08 (0.88–1.32) | 53 | 50 |
| Overall mortality, | 1.04 (0.88–1.22) | 79 | 75 |
| Global Index A subset of the events was combined in a "global index", defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, PE, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes. | 1.02 (0.92–1.13) | 206 | 201 |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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