(conjugated estrogens/bazedoxifene)
8 USE IN SPECIFIC POPULATIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
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).
8.2 Lactation
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)].
8.3 Females and Males of Reproductive Potential
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)].
8.5 Geriatric Use
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)].
8.6 Renal Impairment
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.
8.7 Hepatic 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.
8.8 Body Mass Index (BMI)
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)].
PATIENT INFORMATIONDUAVEE® (DEW' AH-VEE) (CONJUGATED ESTROGENS/BAZEDOXIFENE)TABLETS
Patient Information DUAVEE® (DEW' ah-vee) (conjugated estrogens/bazedoxifene) Tablets
Read this Patient Information before you start taking DUAVEE and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is the most important information I should know about DUAVEE?
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What is DUAVEE?
DUAVEE is a prescription medicine that contains a mixture of estrogens and bazedoxifene.
What is DUAVEE used for?
DUAVEE is used after menopause for women with a uterus to:
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- reduce moderate to severe hot flushes
Estrogens are hormones made by a woman's ovaries. The ovaries normally stop making estrogens when a woman is between 45 and 55 years old. This drop in body estrogen levels causes the "change of life" or menopause (the end of monthly menstrual periods). Sometimes both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes "surgical menopause."
When the estrogen levels begin dropping, some women get very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense episodes of heat and sweating ("hot flashes" or "hot flushes"). In some women, the symptoms are mild, and they will not need to take medicines. In other women, symptoms can be more severe. - •
- help reduce your chances of developing osteoporosis (thin, weak bones)
If you use DUAVEE only to prevent osteoporosis due to menopause, talk with your healthcare provider about whether a different treatment or medicine without estrogens might be better for you.
DUAVEE should be taken for the shortest time possible and only for as long as treatment is needed.
You and your healthcare provider should talk regularly about whether you still need treatment with DUAVEE.
DUAVEE is not for use in children.
It is not known if DUAVEE is safe and effective in people with kidney problems.
Who should not take DUAVEE?
Do not take DUAVEE if you:
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- currently have or have had blood clots
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- are allergic to estrogens or bazedoxifene, the active ingredients in DUAVEE, or any of its ingredients.
See the list of ingredients in DUAVEE at the end of this leaflet. - •
- have unusual vaginal bleeding. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
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- currently have or have had certain cancers. Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or have had cancer, talk with your healthcare provider about whether you should use DUAVEE.
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- currently have or have had liver problems
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- have been diagnosed with a bleeding disorder
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- are pregnant. DUAVEE is not for pregnant women. If you think you may be pregnant, you should have a pregnancy test and know the results. Do not take DUAVEE if the test is positive and talk to your healthcare provider.
What should I tell my healthcare provider before taking DUAVEE?
Before you take DUAVEE, tell your healthcare provider if you:
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- have any unusual vaginal bleeding.
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- have any other medical conditions. Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, or problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
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- are going to have surgery or will be on bed rest. Your healthcare provider will let you know if you need to stop taking DUAVEE.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Especially tell your healthcare provider if you take other hormonal medicines, including progestins or other medicines like DUAVEE. Ask your healthcare provider if you do not know if you take any of these medicines.
Some medicines may affect how DUAVEE works. DUAVEE may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take DUAVEE?
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- DUAVEE comes in a blister package.
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- Record the date you open the foil pouch in the space provided on the blister package label. Do not use if the blister package has been open for more than 60 days.
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- Take DUAVEE exactly as your healthcare provider tells you to take it.
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- Take 1 DUAVEE tablet at the same time each day.
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- DUAVEE should be swallowed whole.
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- Take DUAVEE with or without food.
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- You should not remove DUAVEE from the blister until right before you are ready to take it. Remove 1 tablet at a time from the blister package. Do not place DUAVEE in pill boxes or pill organizers.
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- If you miss a dose of DUAVEE, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time unless your healthcare provider tells you to. If you are not sure about your dosing, call your healthcare provider.
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- If you take a calcium or vitamin D supplement, you may take it at the same time you take DUAVEE.
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- If you take too much DUAVEE, call your healthcare provider. Symptoms of taking too much DUAVEE include:
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What are the possible side effects of DUAVEE?
Side effects are grouped by how serious they are and how often they happen when you are treated.
Serious side effects include:
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- blood clots
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- stroke
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- heart attack
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- cancer of the lining of the uterus
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- breast cancer
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- cancer of the ovary
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- dementia
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- gallbladder problems
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- loss of vision
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- high blood pressure
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- increased fats in your blood
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- liver problems
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- thyroid problems
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- fluid retention
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- low calcium
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- swelling of your mouth or tongue
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- worsening of other medical problems such as asthma, diabetes, epilepsy, migraines, a genetic problem called porphyria, lupus and liver problems
Call your healthcare provider right away if you get any of the following warning signs, or any other unusual symptoms that concern you:
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- new breast lumps
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- unusual vaginal bleeding
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- changes in vision or speech
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- sudden new severe headaches
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- severe pains in your chest or legs with or without shortness of breath, weakness and fatigue
Less serious, but common side effects include:
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- muscle spasms
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- nausea
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- diarrhea
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- upset stomach
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- abdominal pain
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- throat pain
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- dizziness
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- neck pain
These are not all the possible side effects of DUAVEE. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effects that bother you or do not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What can I do to lower my chances of a serious side effect with DUAVEE?
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- Talk with your healthcare provider regularly about whether you should continue taking DUAVEE.
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- See your healthcare provider right away if you get vaginal bleeding while taking DUAVEE.
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- Have a pelvic exam, breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else.
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- If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
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- If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances of getting heart disease.
Ask your healthcare provider for ways to lower your chances of getting heart disease.
How do I store DUAVEE?
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- Store DUAVEE at room temperature between 68°F to 77°F (20°C to 25°C).
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- Keep DUAVEE in the blister until you are ready to take it to protect the tablet from moisture.
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- Do not place DUAVEE in pill boxes or pill organizers.
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- After opening the foil pouch the DUAVEE blisters come in, DUAVEE must be used within 60 days.
Keep DUAVEE and all other medicines out of the reach of children.
General information about the safe and effective use of DUAVEE
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use DUAVEE for a condition for which it was not prescribed. Do not give DUAVEE to other people, even if they have the same symptoms you have. It may harm them.
This Patient Information summarizes the most important information about DUAVEE. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about DUAVEE that is written for health professionals.
What are the ingredients in DUAVEE?
Active Ingredients: conjugated estrogens and bazedoxifene. Conjugated estrogens are a mixture of sodium estrone sulfate and sodium equilin sulfate and other components, including sodium sulfate conjugates, 17α-dihydroequilin, 17α-estradiol, and 17β-dihydroequilin.
Inactive Ingredients: calcium phosphate tribasic, hydroxypropyl cellulose, microcrystalline cellulose, powdered cellulose, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, sucrose, ascorbic acid, sucrose palmitic acid ester, hydroxyethylcellulose, titanium dioxide, red iron oxide, yellow iron oxide, black iron oxide, povidone, polydextrose, maltitol, poloxamer 188, propylene glycol, isopropyl alcohol.
This Patient Information has been approved by the U.S. Food and Drug Administration.
This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com or call 1-800-438-1985.
LAB-0583-6.0
Revised December 2022
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