bazedoxifene/conjugated estrogens

Action and Spectrum

Actions and Spectrum:  

The actions of bazedoxifene/conjugated estrogens are complex and involve multiple mechanisms of action. The conjugated estrogens component of the medication helps to alleviate the symptoms of menopause by replacing the estrogen that is no longer produced by the ovaries.

bazedoxifene, on the other hand, works as a SERM, which means that it has a mixed agonist/antagonist effect on estrogen receptors in different tissues. The spectrum of bazedoxifene/conjugated estrogens includes a range of effects on different tissues in the body, including:  

Bone: bazedoxifene/conjugated estrogens helps to prevent bone loss and reduce the risk of fractures in postmenopausal women by increasing bone mineral density.  

Vagina: The medication helps to alleviate vaginal dryness and improve vaginal health by restoring vaginal tissue thickness and elasticity.  

Brain: bazedoxifene/conjugated estrogens may protect cognitive function and memory in postmenopausal women.  

Cardiovascular system: The medication may have both beneficial and harmful effects on the cardiovascular system, depending on the dose and duration of treatment. 

Drug Interaction

Adverse Reaction

Frequency defined   

1-10% 

Dyspepsia (7%) 

Neck pain (5%) 

Upper abdominal pain (7%) 

Oropharyngeal pain (7%) 

Muscle spasms (9%) 

Diarrhea (8%) 

Dizziness (5%) 

Nausea (8%) 

Black Box Warning

Black Box Warning:  

The black box warning highlights the serious risks associated with bazedoxifene/conjugated estrogens, including the increased risk of endometrial cancer, cardiovascular disorders, breast cancer, and probable dementia.  

Contraindication / Caution

Contraindication/Caution:  

History of blood clots: If a woman has a history of blood clots or has an increased risk of developing them, bazedoxifene/conjugated estrogens should be avoided as the medication may heighten the risk of clotting.  

Liver disease: bazedoxifene/conjugated estrogens is metabolized by the liver, so women with liver disease should not use this medication.  

Pregnancy: It is not advisable to use bazedoxifene/conjugated estrogens during pregnancy as it can negatively impact the development of the fetus.  

Breast cancer: If a woman has a history of breast cancer or has a significant family history of the disease, using bazedoxifene/conjugated estrogens is not recommended as it may raise the chances of breast cancer recurrence.  

Abnormal vaginal bleeding: Women who experience abnormal vaginal bleeding should not use bazedoxifene/conjugated estrogens, as it can mask the underlying cause of the bleeding.  

Allergic reaction: Women who are allergic to any of the components of bazedoxifene/conjugated estrogens should not use this medication. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category  

Pharmacology

Pharmacology:  

bazedoxifene/conjugated estrogens is a drug prescribed to manage moderate to severe vasomotor symptoms that are linked with menopause. Additionally, this medication is also used for preventing osteoporosis. It is a combination of bazedoxifene, a selective estrogen receptor modulator (SERM), and conjugated estrogens, a mixture of estrogen hormones. 

Pharmacodynamics: 

The pharmacodynamics of bazedoxifene/conjugated estrogens can be explained as follows: 

bazedoxifene is a SERM that acts as an estrogen receptor agonist in some tissues (e.g., bone and brain) and as an antagonist in others (e.g., breast and endometrium). It binds to estrogen receptors and modifies the way they function, which leads to a reduction in bone resorption and an increase in bone density. bazedoxifene also has a tissue-specific estrogenic effect on the brain, which can help reduce hot flashes. 

conjugated estrogens, on the other hand, contain a mixture of estrogen hormones, including estrone, equilin, and 17β-estradiol. They bind to estrogen receptors in various tissues and produce estrogenic effects, including the proliferation of uterine and vaginal epithelium, the maintenance of bone density, and the regulation of body temperature. conjugated estrogens can also help reduce the frequency and intensity of hot flashes.  

MOA: bazedoxifene is a non-steroidal compound that selectively binds to estrogen receptors in certain tissues, acting as an estrogen agonist in some tissues, such as bone, and as an antagonist in others, such as breast tissue. This mechanism results in the maintenance of bone density and reduction in the risk of fractures without increasing the risk of endometrial or breast cancer. 

conjugated estrogens, on the other hand, act as an estrogen replacement therapy, supplementing the low levels of estrogen in menopausal women. The estrogen receptors that conjugated estrogens bind to include estrogen receptor alpha and beta. The activation of these receptors leads to a variety of effects, including maintenance of vaginal lubrication, bone density, and reduction in vasomotor symptoms.  

Pharmacokinetics: 

Absorption 

bazedoxifene/conjugated estrogens are available in tablet form, and they are taken orally. The asorption of the medication occurs in the small intestine. 

Distribution  

Once absorbed, the medication is distributed throughout the body through the bloodstream. conjugated estrogens bind to serum albumin and sex hormone-binding globulin, while bazedoxifene binds to plasma proteins. Both components have a high volume of distribution and cross the blood-brain barrier. 

Metabolism 

conjugated estrogens are metabolized in the liver to form a variety of metabolites, including equilin, equilenin, and estrone. These metabolites are further metabolized by glucuronidation and sulfation. bazedoxifene is primarily metabolized by the liver through glucuronidation and CYP3A4-mediated oxidation. 

Excretion and elimination 

The metabolites of conjugated estrogens and bazedoxifene are eliminated primarily through the kidneys. A small portion of the metabolites may be eliminated in the feces. The half-life of bazedoxifene is approximately 30 hours, while the half-life of conjugated estrogens is variable. 

Adminstartion

Administration:   

Dosage: The prescribed amount of bazedoxifene/conjugated estrogens is a single tablet to be taken orally once a day, with or without food.  

Timing: For the purpose of sustaining steady hormone levels in the body, it is advisable to consume the tablet at the same time every day.  

Swallowing: The tablet should be swallowed whole and not chewed or crushed.  

Duration: The length of treatment with bazedoxifene/conjugated estrogens will depend on the severity of symptoms and individual patient factors. It is important to follow the treatment plan prescribed by the healthcare provider. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: bazedoxifene/conjugated estrogens 

Why do we use bazedoxifene/conjugated estrogens?  

bazedoxifene/conjugated estrogens is a medication used in postmenopausal women to treat symptoms such as hot flashes, vaginal dryness, and osteoporosis. bazedoxifene is categorized as a selective estrogen receptor modulator (SERM) due to its ability to attach to estrogen receptors and simulate some of estrogen’s impacts in specific tissues while obstructing its effects in other tissues.

Conjugated estrogens refer to a blend of estrogen hormones that are employed to supplement the levels of estrogen that the body stops producing following menopause. bazedoxifene/conjugated estrogens are prescribed to women who have undergone menopause and are experiencing symptoms of estrogen deficiency, such as hot flashes and vaginal dryness.