Dosing & Uses
Dosage Forms & Strengths
vaginal cream
- 0.1mg/g (0.01%) (Estrace Vaginal)
vaginal insert
- 4mcg (Imvexxy)
- 10mcg (Imvexxy, Vagifem, Yuvafem)
vaginal ring
- 2mg/ring (releases ~7.5mcg/24hr) (Estring)
- 12.4mg/ring (releases 0.05mg/24hr for 3 months) (Femring)
- 24.8mg/ring (releases 0.1mg/24hr for 3 months) (Femring)
Menopausal Vasomotor Symptoms
Femring
- Indicated for treatment of moderate-to-severe vasomotor symptoms caused by menopause
- 1 ring intravaginally for 90 days; replace with new ring at 90 days if continuing therapy
- Initiate with lowest effective dose and the shortest duration consistent with treatment goals
- Initial: 0.05 mg/day; dosage adjustment should be guided by the clinical response
- Attempts to taper or discontinue the medication should be made at 3-6 month intervals
Menopausal Vulvar and Vaginal Atrophy
Estrace Vaginal
- Indicated for treatment of vulvar and vaginal atrophy
- Initial: 2-4 g (marked on the applicator) intravaginally qDay x1-2 weeks, then gradually reduced to 50% of initial dosage for a similar period
- Maintenance: 1 g intravaginally 1-3 times/week may be used after restoration of the vaginal mucosa has been achieved
Estring
- Indicated for treatment of moderate-to-severe vulvar and vaginal atrophy caused by menopause
- 1 ring (2 mg) inserted intravaginally for 90 days; replace with new ring at 90 days if continuing therapy
- Attempts to taper or discontinue the medication should be made at 3-6 month intervals
Femring
- Indicated for treatment of moderate-to-severe vulvar and vaginal atrophy caused by menopause
- 1 ring intravaginally for 90 days; replace with new ring at 90 days if continuing therapy
- Initiate with lowest effective dose and the shortest duration consistent with treatment goals
- Initial: 0.05 mg/day; dosage adjustment should be guided by the clinical response
- Attempts to taper or discontinue the medication should be made at 3-6 month intervals
Vagifem, Yuvafem
- Indicated for treatment of atrophic vaginitis caused by menopause
- Administer intravaginally using the supplied applicator
- Insert one 10 mcg-insert vaginally qDay x2 weeks; followed by one 10 mcg-insert twice weekly (eg, Tuesday and Friday)
- Generally, women should be started with 10 mcg/day
Dyspareunia
Imvexxy
- Indicated for moderate-to-severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause
- Administer 1 insert intravaginally qDay at ~same time for 2 weeks, followed by 1 insert twice weekly, every 3-4 days (eg, Monday and Thursday)
- Generally, women should start at 4 mcg; dosage adjustment based on clinical response
- Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman
- Re-evaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary
- Also see Administration
Not indicated
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (52)
- abametapir
estradiol vaginal will increase the level or effect of abametapir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- amobarbital
amobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- apalutamide
apalutamide will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atazanavir
atazanavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- bosentan
bosentan will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butabarbital
butabarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butalbital
butalbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- carbamazepine
carbamazepine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clarithromycin
clarithromycin will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- cobicistat
cobicistat will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- conivaptan
conivaptan will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- dabrafenib
dabrafenib will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- darunavir
darunavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- dexamethasone
dexamethasone will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- efavirenz
efavirenz will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- enzalutamide
enzalutamide will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- etravirine
etravirine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosamprenavir
fosamprenavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- fosphenytoin
fosphenytoin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- grapefruit
grapefruit will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- idelalisib
idelalisib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- imatinib
imatinib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- indinavir
indinavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- isoniazid
isoniazid will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- itraconazole
itraconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- ketoconazole
ketoconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- levoketoconazole
levoketoconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
estradiol vaginal will increase the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities. - lopinavir
lopinavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mitotane
mitotane will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nafcillin
nafcillin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nefazodone
nefazodone will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- nelfinavir
nelfinavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- nevirapine
nevirapine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nicardipine
nicardipine will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pentobarbital
pentobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- phenobarbital
phenobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- phenytoin
phenytoin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- posaconazole
posaconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- primidone
primidone will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifabutin
rifabutin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifapentine
rifapentine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ritonavir
ritonavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- saquinavir
saquinavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- secobarbital
secobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- somapacitan
estradiol vaginal decreases effects of somapacitan by Other (see comment). Modify Therapy/Monitor Closely. Comment: Oral estrogens may reduce the serum IGF-1 response to somapacitan. Patients may require higher somapacitan dosages. See drug monograph for starting dose recommendations.
- St John's Wort
St John's Wort will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tipranavir
tipranavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
- voriconazole
voriconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.
Minor (27)
- amiodarone
amiodarone will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- aprepitant
aprepitant will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- bicalutamide
bicalutamide will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ceritinib
ceritinib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- clotrimazole
clotrimazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- crizotinib
crizotinib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclosporine
cyclosporine will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- diltiazem
diltiazem will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- doxycycline
doxycycline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dronedarone
dronedarone will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- erythromycin base
erythromycin base will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- erythromycin stearate
erythromycin stearate will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fluconazole
fluconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fosaprepitant
fosaprepitant will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- haloperidol
haloperidol will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- iloperidone
iloperidone will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lapatinib
lapatinib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- metronidazole
metronidazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ribociclib
ribociclib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- schisandra
schisandra will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sertraline
sertraline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- tetracycline
tetracycline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- verapamil
verapamil will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10%
Headache (5-16%)
1-10%
Vulvovaginal mycotic infection (5-8%)
Vulvovaginal pruritus (8%)
Back pain (7%)
Abdominal pain (7%)
Diarrhea (5%)
Postmarketing Reports
Causality not confirmed
Reproductive system and breast disorders: Breast cancer, endometrial cancer, endometrial hyperplasia, vulvovaginal burning sensation, vulvovaginal pain, vaginismus, vaginal ulceration, genital pruritus, vulvovaginal rash, vulvovaginal swelling
Cardiovascular: Deep vein thrombosis
Gastrointestinal: Diarrhea
Skin and subcutaneous tissue disorders: Rash, rash erythematous, rash pruritic urticaria
Central nervous system: Aggravated migraine, depression, insomnia
Miscellaneous: Fluid retention, weight increase, drug ineffectiveness, hypersensitivity, blood estrogen increase
Immune system disorders: Hypersensitivity
Metabolism and nutrition disorders: Fluid retention
Psychiatric disorders: Depression, insomnia
Genitourinary system: Vaginal discharge
Warnings
Black Box Warnings
Increased risk of endometrial cancer
- Close clinical surveillance of all women taking estrogens is important
- Risk of endometrial cancer in women with a uterus increases with use of unopposed estrogens; adding progestin to estrogen therapy may reduce risk of endometrial hyperplasia, a precursor to endometrial cancer
- Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding
Cardiovascular risks
- Estrogens with and without progestins should not be used to prevent cardiovascular disease
- Estrogens plus progestins: Women’s Health Initiative (WHI) Estrogen Plus Progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary embolism (PE), and deep vein thrombosis (DVT) in postmenopausal women (50-79 years) during 5.6 years of treatment with daily PO conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) in comparison with placebo
- Estrogens alone: Substudy of WHI study reported increased risk of stroke and DVT in postmenopausal women (50-79 years) during 6.8 years of treatment with PO conjugated estrogens (0.625 mg/day) alone in comparison with placebo
Dementia risks
- Estrogens with and without progestins should not be used to prevent dementia
- Women's Health Initiative Memory Study (WHIMS), substudy of WHI study, reported increased risk of developing probable dementia in postmenopausal women ≥65 years during 4 years of treatment with daily PO conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) in comparison with placebo
- Estrogens alone: Substudy of WHIMS reported increased risk of developing probable dementia in postmenopausal women ≥65 years during 5.2 years of treatment with conjugated estrogens (0.625 mg/day) alone in comparison with placebo
- Unknown whether these findings apply to younger postmenopausal women
Breast cancer
- The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer; prescribe estrogens with or without progestins at the lowest doses and for the shortest duration
Dose & duration
- In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and medroxyprogesterone acetate, as well as for other combinations and dosage forms of estrogens and progestins
- Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose and for shortest duration consistent with treatment goals and individual risks
Contraindications
Undiagnosed abnormal genital bleeding
Known, suspected, or history of breast cancer
Known or suspected estrogen-dependent neoplasia
Active DVT, PE, or history of these conditions
Active arterial thromboembolic disease (eg, stroke, MI), or a history of these conditions
Known anaphylactic reaction or angioedema to estrogen
Known liver impairment or disease
Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Known or suspected pregnancy
Cautions
System absorption occurs with intravaginal administration; consider warnings, precautions, and adverse effects associated with systemic estrogen-alone therapy
Increased risk of stroke and DVT reported with estrogen-alone therapy; increased risk of PE, DVT, stroke, and MI reported with estrogen plus progestin therapy; discontinue drug immediately if these conditions occur or are suspected (see Black Box Warnings)
The WHI estrogen plus progestin substudy reported a statistically nonsignificant increased risk of ovarian cancer (4 vs 3 cases per 10,000 women-years)
Estrogen with or without progesterone may increase risk of dementia (see Black Box Warnings)
Increased risk of gallbladder disease (2- to 4-fold) requiring surgery in postmenopausal women receiving estrogen has been reported
Severe hypercalcemia in women with breast cancer and bone metastases reported with estrogen use; if hypercalcemia occurs, discontinue estrogen and initiate appropriate treatment to reduce serum calcium level
Retinal vascular thrombosis reported; discontinue estrogen pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine; if papilledema or retinal vascular lesions diagnosed, permanently discontinue estrogens
Rare occurrences reported of substantial blood pressure increases that were attributed to idiosyncratic reactions to estrogens
May cause elevated triglycerides that lead to pancreatitis in women with preexisting hypertriglyceridemia; discontinue estrogens if pancreatitis occurs
Estrogens may be poorly metabolized with hepatic impairment; if cholestatic jaundice occurs, discontinued estrogens; exercise caution in any woman with a history of cholestatic jaundice associated with past estrogen use or with pregnancy
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, however, women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy; monitor thyroid function in these women during treatment to maintain their free thyroid hormone levels in an acceptable range
Estrogens may cause some degree of fluid retention; women with conditions that might be influenced by this factor (eg, cardiac or renal impairment) warrant careful observation; monitor any woman with a condition(s) that might predispose her to fluid retention, such as cardiac or renal impairment; discontinue estrogen-alone therapy with evidence of medically concerning fluid retention
Malignant transformation of residual endometrial implants have been reported in women treated posthysterectomy with estrogen-alone therapy; if residual endometriosis posthysterectomy exists, the addition of progestin should be considered
Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema; consider whether benefits of estrogen therapy outweigh risks in such women
Estrogen therapy may exacerbate asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas; consider whether benefits of estrogen therapy outweigh risks in women with these conditions
Local abrasion induced by vaginal tablet applicator reported
Serum follicle stimulating hormone (FSH) and estradiol levels not shown for the management of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause
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 and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity
Estrogen-induced hypocalcemia may occur in women with hypoparathyroidism; consider whether benefits of estrogen therapy outweigh risks in such women
Endometrial cancer
- Increased risk of endometrial cancer reported with use of unopposed estrogen therapy in a woman with a uterus (see Black Box Warnings); clinical surveillance of all women using estrogen-alone or estrogen plus progestogen therapy is important
- There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose
- Adding a progestogen to estrogen therapy in postmenopausal women has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer
Breast cancer
- The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the Women’s Health Initiative (WHI) substudy of daily PO conjugated estrogens (CE) (0.625 mg)-alone
- In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE-alone was not associated with an increased risk of invasive breast cancer (see Black Box Warnings)
Drug interactions overview
- CYP3A4 inducers or inhibitors may affect estrogen drug metabolism
- CYP3A4 inducers (eg, St. John's wort [Hypericum perforatum] preparations, phenobarbital, carbamazepine, and rifampin) may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile
- CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, grapefruit juice) may increase plasma concentrations of estrogens and may result in side effects
Pregnancy & Lactation
Pregnancy
Not indicated for use in pregnancy; there are no data with use in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy
Lactation
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 breastfeeding is well-established; the clinical need for therapy and any potential adverse effects on breastfed child or from underlying maternal condition. developmental and health benefits of breastfeeding should be considered along with the mother’s
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics
Absorption
Estrogen drug products are well absorbed through the skin, mucous membranes, and the GI tract
Vaginal delivery of estrogens circumvents first-pass metabolism
Peak plasma concentration (Imvexxy): 4.8-7.3 pg/mL
Distribution
Distribution of exogenous estrogens is similar to that of endogenous estrogens
Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs
Estrogens circulate in the blood largely bound to sex hormone-binding globulin (SHBG) and albumin
Metabolism
Exogenous estrogens are metabolized in the same manner as endogenous estrogens
Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions that take place mainly in the liver
Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite
Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption
In postmenopausal women, a significant portion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens
Elimination
Excretion: Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates
Administration
Intravaginal Administration
Intravaginal ring
- Insert in upper third of vaginal vault; the ring is to remain in place continuously for 3 months, after which it is to be removed and, if appropriate, replaced by a new ring
- Should the ring be removed or fall out at any time during the 90-day treatment period, rinse the ring in lukewarm water and reinsert (by the patient, or, if necessary, by a physician or nurse)
Vaginal tablet or cream
- Use applicator provided with drug to insert vaginal tablet or measure dose of vaginal cream
- Lay on back with pelvis slightly tilted upward, or stand with one knee bent (ie, foot on seat of chair or toilet), insert the prescribed dose with applicator
- The applicator should be inserted (without forcing) as far as comfortably possible, or until half of the applicator is inside vagina
- Note: The vaginal tablet dissolves gradually over several hours, so bedtime application may be desired
Vaginal insert
- Administer intravaginally
- Insert with the smaller end up for a depth of about 2 inches into the vaginal canal
Storage
- Estrace Vaginal: Room temperature; protect from temperatures exceeding 40°C (104°F)
- Estring: Controlled room temperature 15-25°C (59-77°F)
- Vagifem: Controlled room temperature 25°C (77°F), excursions permitted to 15-30°C (59-86°F); do not refrigerate
- Femring: Controlled room temperature 25°C (77°F), excursions permitted to 15-30°C (59-86°F); do not store out of the protective pouch; insert immediately upon remove from the protective pouch
- Imvexxy: Store at 20-25°C (68-77°F), excursions permitted to 15-30°C (59-86°F)
Images
BRAND | FORM. | UNIT PRICE | PILL IMAGE |
---|---|---|---|
Femring vaginal - | 0.1 mg/24 hr ring | ![]() | |
Femring vaginal - | 0.05 mg/24 hr ring | ![]() |
Copyright © 2010 First DataBank, Inc.
Patient Handout
estradiol acetate vaginal
ESTRADIOL ACETATE RING - VAGINAL
(ES-tra-DYE-ol AS-e-tate)
COMMON BRAND NAME(S): Femring
WARNING: Estrogens, either used alone or with another hormone (progestin), have rarely caused very serious side effects. Discuss the risks and benefits of hormone treatment with your doctor. Estrogens should not be used to prevent heart disease or dementia.Estrogens can increase the risk of cancer of the uterus (endometrial cancer). Taking a progestin as directed by your doctor can help decrease this risk. Tell your doctor right away if you have any unusual vaginal bleeding.In postmenopausal women, estrogens, taken with or without a progestin, increase the risk of cancer of the breast/ovaries, stroke, dementia, and serious blood clots. When used along with a progestin, estrogens also increase the risk of heart disease (such as heart attacks).The risk for serious side effects may depend on the dose of estrogen and the length of time it is used. This medication should be used at the lowest effective dose and for the shortest amount of time. Discuss the use of this medication with your doctor and check with him/her regularly (for example, every 3 to 6 months) to see if you still need to take this medication. If you will be taking this medication long-term, you should have regular complete physical exams (for example, once a year) as directed by your doctor. See also Notes section.
USES: This medication is a female hormone (estrogen). It is used by women to help reduce symptoms of menopause (such as hot flashes, vaginal dryness). These symptoms are caused by the body making less estrogen. If you are using this medication to treat symptoms only in and around the vagina, other products applied directly inside the vagina (such as cream, vaginal tablet) should be considered before this product.
HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using this medication and each time you get a refill. Learn how to use this medication properly. If you have any questions, ask your doctor or pharmacist.Wash and dry your hands before handling the ring. Insert the ring high into the vagina as directed. The ring is usually left in place for 3 months and then removed and replaced with a new ring if treatment is to be continued. Do not leave a ring in place for longer than 3 months. Follow the dosing schedule carefully.The dosage is based on your medical condition and response to treatment.If the ring is put in properly, you should not be able to feel it and it will not interfere with sexual intercourse. If you are able to feel the ring or feel slight discomfort from the ring, it may mean that the ring is not high enough. Gently push the ring higher with your finger.If the ring falls out of the vagina, rinse the ring with lukewarm water and put it back into the vagina. Contact your doctor if the ring falls out often.The ring is removed by hooking your finger through the ring and gently pulling it out. Contact your doctor if you have trouble removing the ring. Discard the used ring in the trash. Do not flush it down the toilet.Tell your doctor if your condition does not improve or if it worsens.
SIDE EFFECTS: See also Warning section.Nausea/vomiting, bloating, breast tenderness, headache, or weight changes may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn't stop, mental/mood changes (such as depression, memory loss), breast lumps, unusual vaginal bleeding (such as spotting, breakthrough bleeding, prolonged/recurrent bleeding), increased or new vaginal irritation/itching/odor/discharge, severe stomach/abdominal pain, yellowing eyes/skin, dark urine, swelling hands/ankles/feet, increased thirst/urination.This medication may rarely cause serious problems from blood clots (such as heart attacks, strokes, deep vein thrombosis, pulmonary embolism). Get medical help right away if you have any serious side effects, including: chest/jaw/left arm pain, unusual sweating, sudden/severe headache, weakness on one side of the body, confusion, trouble speaking, sudden vision changes (such as partial/complete blindness), pain/redness/swelling of legs, tingling/weakness/numbness in the arms/legs, trouble breathing, coughing up blood, sudden dizziness/fainting.Vaginal rings have rarely caused a very serious (possibly fatal) bacterial infection (toxic shock syndrome-TSS). Remove this product and get medical help right away if you have any symptoms of toxic shock syndrome, including: high fever, sudden dizziness/fainting, unusual muscle pain, sunburn-like rash, diarrhea.A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before using estradiol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: vaginal bleeding of unknown cause, certain cancers (such as breast cancer, cancer of the uterus/ovaries), blood clots (such as in the legs, eyes, lungs), blood clotting disorders (such as protein C or protein S deficiency), stroke, heart disease (such as heart attack), liver disease, kidney disease, family medical history (especially breast lumps, cancer, blood clots), family or personal history of a certain swelling disorder (angioedema), blood clotting disorders (such as protein C or protein S deficiency), high blood pressure, diabetes, high cholesterol/triglyceride levels, obesity, lupus, underactive thyroid (hypothyroidism), mineral imbalance (low or high level of calcium in the blood), a certain hormone problem (hypoparathyroidism), uterus problems (such as fibroids, endometriosis), gallbladder disease, asthma, seizures, migraine headaches, mental/mood disorders (such as dementia, depression), a certain blood disorder (porphyria), frequent vaginal infections.Do not smoke or use tobacco. Estrogens combined with smoking further increases your risk of stroke, blood clots, high blood pressure, and heart attack, especially in women older than 35.Tell your doctor if you just had or will be having surgery, or if you will be confined to a chair or bed for a long time (such as a long plane flight). These conditions increase your risk of getting blood clots, especially if you are using an estrogen product. You may need to stop this medication for a time or take special precautions.This medication may cause blotchy, dark areas on your face and skin (melasma). Sunlight may worsen this effect. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors.If you are nearsighted or wear contact lenses, you may develop vision problems or trouble wearing your contact lenses. Contact your eye doctor if these problems occur.If you get a vaginal infection while using this ring, you may leave the ring in place while the infection is being treated. Consult your doctor or pharmacist for treatment options.This medication should not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor right away.This medication passes into breast milk. It may reduce the quality and amount of breast milk produced. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: aromatase inhibitors (such as anastrozole, exemestane, letrozole), fulvestrant, ospemifene, raloxifene, tamoxifen, toremifene, tranexamic acid.This medication may interfere with certain laboratory tests, possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.
OVERDOSE: This medicine may be harmful if swallowed. If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe nausea/vomiting, unusual vaginal bleeding.
NOTES: Do not share this medication with others.Regular complete physical exams which include lab and/or medical tests (such as blood pressure, breast exam/mammogram, pelvic exam, Pap smear) should be done while you are using this medication. Follow your doctor's instructions for examining your breasts, and report any lumps right away. Keep all medical and lab appointments. Consult your doctor for more details.Preventing or controlling high blood pressure, high cholesterol, and diabetes can help to reduce your chances of heart disease and stroke. Lifestyle changes that can help to control or prevent these diseases include reducing stress, eating a low fat/salt diet, losing weight if overweight, exercising regularly, and stopping smoking. Keep your mind active with mental exercises (such as reading, solving crossword puzzles) to help prevent dementia. Talk to your doctor about lifestyle changes that might benefit you.Lifestyle changes that may help reduce hot flashes include stopping smoking, dressing lightly or in layers, avoiding/limiting certain foods (spicy foods, caffeine, alcohol), reducing stress, and exercising regularly.
MISSED DOSE: Not applicable. However, if you have not inserted a new ring after 3 months, ask your doctor or pharmacist right away for a new dosing schedule.
STORAGE: Store at room temperature. Do not remove the ring from the pouch until ready for use. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised January 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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