DUAVEE- conjugated estrogens/bazedoxifene tablet, film coated

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

ESTROGENS, CONJUGATED (UNII: IU5QR144QX) (ESTROGENS, CONJUGATED - UNII:IU5QR144QX), BAZEDOXIFENE ACETATE (UNII: J70472UD3D) (BAZEDOXIFENE - UNII:Q16TT9C5BK)

Tilgjengelig fra:

Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.

INN (International Name):

ESTROGENS, CONJUGATED

Sammensetning:

ESTROGENS, CONJUGATED 0.45 mg

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

DUAVEE is indicated in women with a uterus for: DUAVEE is contraindicated in women with any of the following conditions: Risk Summary DUAVEE is contraindicated for use in pregnant women and is not indicated for use in females of reproductive potential [see Contraindications (4), Warnings and Precautions (5.15)]. 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 [see Data]. Based on mechanism of action, bazedoxifene may block the important functions that estrogen has during all stages of pregnancy [see Clinical Pharmacology (12.1)] . 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). Risk Summary DUAVEE is not indicated for use in females of reproductive potential [see Warnings and Precautions (5.15)] . Conjugated Estrogens Estrogens are present in human milk and can reduce milk production in breast-feeding females. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. Bazedoxifene There are no data on the presence of bazedoxifene in either human or animal breast milk, the effect on the breastfed infant, or the effects on milk production. Based on mechanism of action, bazedoxifene may block the important functions that estrogen has in mammary tissue during lactation [see Clinical Pharmacology (12.1)]. Infertility Bazedoxifene Based on animal data, bazedoxifene administration may adversely affect female fertility. However, clinical fertility studies with bazedoxifene have not been conducted [see Nonclinical Toxicology (13.1)] . DUAVEE is not indicated for use in children [see Indications and Usage (1)] . DUAVEE is not recommended for use in women greater than 75 years of age [see Dosage and Administration (2.7) and Clinical Pharmacology 12.3)] . Of the total number of women in phase 3 clinical studies who received DUAVEE, 4.60% (n=224) were 65 years and over. DUAVEE was not studied in women aged 75 and over. No overall differences in safety or effectiveness were observed between women 65–74 years of age and younger women, and other reported clinical experience has not identified differences in responses between the elderly and younger women, but greater sensitivity of some older women cannot be ruled out. An increased risk of probable dementia in women over 65 years of age was reported in the Women's Health Initiative Memory ancillary studies of the Women's Health Initiative using daily conjugated estrogens (0.625 mg) [see Clinical Studies (14.6)]. DUAVEE is not recommended for use in patients with renal impairment [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3)]. The pharmacokinetics, safety, and efficacy of DUAVEE have not been evaluated in women with renal impairment. DUAVEE is contraindicated in patients with hepatic impairment [see Contraindications (4) and Clinical Pharmacology (12.3)]. The pharmacokinetics, safety, and efficacy of DUAVEE have not been evaluated in women with hepatic impairment. In a pharmacokinetics study of bazedoxifene 20 mg alone, the Cmax and AUC of bazedoxifene increased 67% and 143%, respectively, in women with mild hepatic impairment (Child Pugh Class A), compared to healthy women. The Cmax and AUC of bazedoxifene increased 32% and 109%, respectively, in women with moderate hepatic impairment (Child Pugh Class B). The Cmax and AUC of bazedoxifene increased 20% and 268%, respectively, in women with severe hepatic impairment (Child Pugh Class C). No pharmacokinetic studies with conjugated estrogens were conducted in women with hepatic impairment. Following DUAVEE administration, the systemic exposures of conjugated estrogens and bazedoxifene were lower in obese subjects, compared to non-obese subjects [see Pharmacokinetics (12.3)] . A single dose of DUAVEE (conjugated estrogens 0.45 mg/bazedoxifene 20 mg) was administered to 12 obese BMI ≥ 30 [mean (SD) = 32.7 (2.7) kg/m2 ] and 12 non-obese BMI < 30 [mean (SD) 25.3 (2.6) kg/m2 ] postmenopausal women. In obese subjects, systemic exposures of total estrone, total equilin, and bazedoxifene were 2%, 32%, and 13% lower, respectively, compared to non-obese subjects. A greater reduction in bazedoxifene exposure compared to conjugated estrogens may be associated with decreased protection from endometrial hyperplasia. Monitor and evaluate women with postmenopausal or unexplained genital bleeding for possible endometrial hyperplasia or malignancy [see Warnings and Precautions (5.3)] .

Produkt oppsummering:

DUAVEE tablets contain 0.45 mg conjugated estrogens and 20 mg bazedoxifene. The tablets are oval, biconvex, and pink, branded with "0.45/20" in black ink on one side. DUAVEE® tablets are supplied as follows: Conjugated estrogens 0.45 mg/bazedoxifene 20 mg 2 blisters of 15 tablets each NDC 0008-1123-12 Storage Blisters DUAVEE tablets should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). See USP Controlled Room Temperature. Dispense product in the original package. Tablets should not be removed from blisters until immediately before use. Protect from moisture. After opening foil pouch, product must be used within 60 days.

Autorisasjon status:

New Drug Application

Preparatomtale

DUAVEE- CONJUGATED ESTROGENS/BAZEDOXIFENE TABLET, FILM COATED
WYETH PHARMACEUTICALS LLC, A SUBSIDIARY OF PFIZER INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DUAVEE SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR DUAVEE.
DUAVEE (CONJUGATED ESTROGENS/BAZEDOXIFENE) TABLETS FOR ORAL USE
INITIAL U.S. APPROVAL: 2013
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, AND PROBABLE
DEMENTIA
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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RECENT MAJOR CHANGES
Warnings and Precautions, Malignant Neoplasms
(5.3)
03/2024
INDICATIONS AND USAGE
DUAVEE is a combination of conjugated estrogens with an estrogen
agonist/antagonist indicated for
treatment of the following conditions in women with a uterus:
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Limitation of Use: DUAVEE should be used for the shortest duration
consistent with treatment goals and
risks for the individual woman (1.3)
DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
Tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg
(3)
CONTRAINDICATIONS
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®
WOMEN TAKING DUAVEE SHOULD NOT TAKE ADDITIONAL ESTROGENS (5.1)
THERE IS AN INCREASED RISK OF ENDOMETRIAL CANCER IN A WOMAN WITH A
UTERUS WHO
USES UNOPPOSED ESTROGENS (5.1, 5.3)
ESTROGEN THERAPY SHOULD NOT BE USED FOR THE PREVENTION OF
CARDIOVASCULAR DISEASE
OR DEMENTIA (5.2, 5.4)
THE WOMEN'S HEALTH INITIATIVE (WHI) ESTROGEN-ALONE SUBSTUDY REPORTED
INCREASED
RISKS OF STROKE AND DEEP VEIN THROMBOSIS (DVT) (5.2)
THE WHI MEMORY STUDY (WHIMS) ESTROGEN-ALONE ANCILLARY STUDY OF WHI
REPORTED AN
INCREASED RISK OF PROBABLE DEMENTIA IN POSTMENOPAUSAL WOMEN 65 YEARS
OF AGE
AND OLDER (5.4)
Treatment of moderate to severe vasomotor symptoms associated with
menopause (1.1)
Prevention of postmenopausal osteoporosis (1.2)
Take one tablet orally once daily (2)
Undiagnosed abnormal uterine bleeding (4, 5.3)
Known, suspected, or past history of breast cancer (4, 5.3)
Known or suspected estrogen-d