bazedoxifene/conjugated estrogens

Both bazedoxifene and conjugated estrogens bind to α and β estrogen receptors. Conjugated estrogen acts as an agonist at these receptors. Bazedoxifene acts as an agonist in some tissues and an antagonist in other tissues, including the uterus. The combined effect is estrogen replacement while minimizing the risk of endometrial hyperplasia and prevention of postmenopausal osteoporosis.

Therapeutic effects:

Reduced vasomotor symptoms of menopause with reduced risk of endometrial hyperplasia and prevention of postmenopausal osteoporosis.

Pharmacokinetics ⬆ ⬇

Bazedoxifene

Absorption: 6% absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 98–99%.

Metabolism/Excretion: Undergoes extensive metabolism by UGT enzymes in the intestinal tract and liver, undergoes biliary excretion with enterohepatic recycling and elimination in feces (85%).

Half-Life: 30 hr.

Conjugated Estrogens

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed; higher concentrations found in sex hormone target organs; enters breast milk.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; some metabolites are hormonally active. Metabolites are renally excreted.

Half-Life: 17 hr (estrone).

Time/Action Profile ⬆ ⬇

(effect on vasomotor symptoms‡)

ROUTE	ONSET	PEAK	DURATION
PO	within 4 wk	12 wk	duration of treatment

‡effects on osteoporosis were noted at 12–24 mo and lasted throughout treatment (5 yr).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Undiagnosed/abnormal vaginal bleeding;
Hepatic or renal impairment or BMI > 27 kg/m² (↑ risk of endometrial hyperplasia;
History of known/suspected breast cancer or other estrogen-dependent cancer;
Active or past history of thromboembolism including stroke, myocardial infarction, or pulmonary embolism;
Known protein C, protein S, or antithrombin deficiency or other thrombophilic disorders;
OB: Pregnancy;
Lactation: Lactation;
Rep: Women of reproductive potential;
Geri: Not recommended for use in patients 75 yr; has been associated with dementia in patients 65 yr.

Use Cautiously in:

Risk factors for thromboembolic phenomenon including diabetes, family history, obesity, or systemic lupus erythematosus.
History of cholestatic jaundice associated with estrogen use.
Hypothyroidism (may need ↑ dose of thyroid replacement).
History of hereditary angioedema (estrogen may provoke).
History of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, or hepatic hemangiomas (estrogen may exacerbate these conditions).

Adv. Reactions/Side Effects ⬆ ⬇

CV: ↑BP, edema, THROMBOEMBOLISM

Derm: hot flash

EENT: retinal vascular thrombosis

F and E: hypocalemia

GI: cholestatic jaundice, diarrhea, dyspepsia, gall bladder disease, nausea, oropharyngeal pain, upper abdominal pain

MS: muscle spasms, neck pain

Interactions ⬆ ⬇

Drug-drug:

UGT inducers, including carbamazepine, phenobarbital, phenytoin, and rifampin, may ↓ bazedoxifene levels and result in ↑ risk of endometrial hyperplasia.
CYP3A4 inhibitors, including clarithromycin, erythromycin, itraconazole, , ketoconazole, and ritonavir , may ↑ levels of conjugated estrogens and the risk of endometrial hyperplasia.
CYP3A4 inducers, including carbamazepine, phenobarbital, and rifampin, may ↓ levels and effectiveness of conjugated estrogens and alter uterine bleeding patterns.
Progestins, other estrogens, or estrogen agonist/antagonists may alter the effectiveness or treatment and/or ↑ risk of adverse reactions; avoid concurrent use.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness of conjugated estrogens and alter uterine bleeding patterns.

Grapefruit juice may ↑ levels of conjugated estrogens and the risk of endometrial hyperplasia.

Route/Dosage ⬆ ⬇

PO (Adults ): One tablet (bazedoxifene 20 mg/conjugated estrogen 0.45 mg) once daily.

Availability ⬆ ⬇

Tablets: bazedoxifene 20 mg/conjugated estrogens 0.45 mg

Assessment ⬆ ⬇

Assess for frequency and intensity of postmenopausal vasomotor symptoms (hot flashes).
Assess BP before and periodically during therapy.
Monitor intake and output ratios and weekly weight. Report significant discrepancies or steady weight gain.

Lab Test Considerations:

May cause hypocalcemia.
- May cause ↑ HDL and triglycerides, and ↓ serum LDL concentrations.
- May cause ↑ prothrombin time, partial thromboplastin time, and platelet aggregation time. May ↑ factors II, VII, VIII, IX, X, XII levels. May ↓ antithrombin III and ↑ levels of fibrinogen and fibrinogen activity and plasminogen antigen and activity.
- May cause ↑ thyroid-binding globulin, causing increased circulating total thyroid hormone; may require higher doses of thyroid replacement therapy.
- May cause impaired glucose tolerance.

Implementation ⬆ ⬇

Supplement calcium and/or vitamin D if diet is inadequate.
PO: Administer once daily without regard to meals. DNC: Swallow tablets whole; do not crush, break, or chew.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Advise patient to keep Duavee in original container to protect from moisture; avoid placing in pill boxes or organizers. Open only one blister pouch and one tablet at a time; record date opened and discard after 60 days. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Advise patient to avoid grapefruit juice during therapy.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products, especially progestins, additional estrogens, or additional estrogen agonist/antagonists, without consulting health care professional; may increase risk of uterine cancer.
Advise patient to report signs and symptoms of fluid retention (swelling of ankles and feet, weight gain), thromboembolic disorders (pain, swelling, tenderness in extremities; headache; chest pain; blurred vision), new breast lumps, changes in vision or speech, sudden new severe headaches, severe pains in chest or legs with or without shortness or breath, weakness, fatigue, or abnormal vaginal bleeding to health care professional.
Caution patient that cigarette smoking during estrogen therapy may increase risk of serious side effects, especially for women over age 35.
Advise patient treated for osteoporosis that exercise has been found to arrest and reverse bone loss. Discuss any exercise limitations with health care professional before beginning program.
Emphasize the importance of routine follow-up physical exams, including BP; breast, abdomen, and pelvic examinations; Papanicolaou smears every 6–12 mo; and mammogram every 12 mo or as directed. Health care professional will evaluate possibility of discontinuing medication every 3–6 mo.
Advise patient to notify health care professional promptly if unusual vaginal bleeding occurs during therapy. Vaginal bleeding after menopause may be a sign of uterine cancer.
Rep: May cause fetal harm. Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

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